ID 3BP2_HUMAN STANDARD; PRT; 561 AA. AC P78314; O00500; O15373; P78315; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 15-JUL-1998, sequence version 2. DT 30-MAY-2006, entry version 53. DE SH3 domain-binding protein 2 (3BP-2). GN Name=SH3BP2; Synonyms=3BP2; ORFNames=RES4-23; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). RX MEDLINE=97446134; PubMed=9299232; DOI=10.1006/geno.1997.4849; RA Bell S.M., Shaw M., Jou Y.-S., Myers R.M., Knowles M.A.; RT "Identification and characterization of the human homologue of SH3BP2, RT an SH3 binding domain protein within a common region of deletion at RT 4p16.3 involved in bladder cancer."; RL Genomics 44:163-170(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT), AND TISSUE RP SPECIFICITY. RC TISSUE=Brain; RX MEDLINE=98403881; PubMed=9734812; DOI=10.1093/dnares/5.3.177; RA Hadano S., Ishida Y., Ikeda J.-E.; RT "The primary structure and genomic organization of five novel RT transcripts located close to the Huntington's disease gene on human RT chromosome 4p16.3."; RL DNA Res. 5:177-186(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG). RC TISSUE=Tonsil; RA Gokemeijer J., Deligiannidis K.E., Ligris K., Ernst T.J.; RT "3BP2 binds to phosphatidylinositols; linking the hemopoietic tyrosine RT kinase c-FES to the cytoplasmic membrane in a phosphorylation RT dependent mechanism."; RL Blood 88:473A-473A(1996). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG). RC TISSUE=Cervix; RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length human RT and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [5] RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S). RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8; RA Hillman R.T., Green R.E., Brenner S.E.; RT "An unappreciated role for RNA surveillance."; RL Genome Biol. 5:RESEARCH008.1-RESEARCH008.16(2004). RN [6] RP VARIANTS CRBM GLN-415; PRO-415; ARG-418; HIS-418; LEU-418; ARG-420 AND RP GLU-420. RX MEDLINE=21275962; PubMed=11381256; DOI=10.1038/88832; RA Ueki Y., Tiziani V., Santanna C., Fukai N., Maulik C., Garfinkle J., RA Ninomiya C., doAmaral C., Peters H., Habal M., Rhee-Morris L., RA Doss J.B., Kreiborg S., Olsen B.R., Reichenberger E.; RT "Mutations in the gene encoding c-Abl-binding protein SH3BP2 cause RT cherubism."; RL Nat. Genet. 28:125-126(2001). RN [7] RP VARIANT CRBM ARG-420. RX MEDLINE=22781491; PubMed=12900899; DOI=10.1002/ajmg.a.20226; RA Lo B., Faiyaz-Ul-Haque M., Kennedy S., Aviv R., Tsui L.C., Teebi A.S.; RT "Novel mutation in the gene encoding c-Abl-binding protein SH3BP2 RT causes cherubism."; RL Am. J. Med. Genet. A 121:37-40(2003). RN [8] RP VARIANT CRBM ARG-418. RX PubMed=14577811; DOI=10.1597/1545-1569(2003)040<0632:AMMITS>2.0.CO;2; RA Imai Y., Kanno K., Moriya T., Kayano S., Seino H., Matsubara Y., RA Yamada A.; RT "A missense mutation in the SH3BP2 gene on chromosome 4p16.3 found in RT a case of nonfamilial cherubism."; RL Cleft Palate Craniofac. J. 40:632-638(2003). CC -!- FUNCTION: Binds differentially to the SH3 domains of certain CC proteins of signal transduction pathways. Binds to CC phosphatidylinositols; linking the hemopoietic tyrosine kinase fes CC to the cytoplasmic membrane in a phosphorylation dependent CC mechanism. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Long; CC IsoId=P78314-1; Sequence=Displayed; CC Name=Short; CC IsoId=P78314-2; Sequence=VSP_004085, VSP_004086; CC Note=May be produced at very low levels due to a premature stop CC codon in the mRNA, leading to nonsense-mediated mRNA decay; CC -!- TISSUE SPECIFICITY: Expressed in a variety of tissues including CC lung, liver, skeletal muscle, kidney and pancreas. CC -!- DISEASE: Defects in SH3BP2 are the cause of cherubism (CRBM) CC [MIM:118400]. CRBM is an autosomal dominant inherited syndrome CC characterized by excessive bone degradation of the upper and lower CC jaws, which often begins around three years of age. It is followed CC by development of fibrous tissue masses, which causes a CC characteristic facial swelling. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 SH2 domain. CC -!- WEB RESOURCE: NAME=GeneReviews; CC URL="http://www.genetests.org/query?gene=SH3BP2". CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; U56386; AAB72034.1; -; mRNA. DR EMBL; AB000462; BAA19119.1; -; mRNA. DR EMBL; AB000463; BAA19120.1; -; mRNA. DR EMBL; AF000936; AAB59973.1; -; mRNA. DR EMBL; BC022996; AAH22996.1; -; mRNA. DR UniGene; Hs.167679; -. DR PDB; 2CR4; NMR; A=444-558. DR Ensembl; ENSG00000087266; Homo sapiens. DR H-InvDB; HIX0004037; -. DR HGNC; HGNC:10825; SH3BP2. DR MIM; 118400; phenotype. DR MIM; 602104; gene. DR GO; GO:0005070; F:SH3/SH2 adaptor activity; TAS. DR GO; GO:0007165; P:signal transduction; TAS. DR InterPro; IPR001849; PH. DR InterPro; IPR011993; PH_type. DR InterPro; IPR000980; SH2. DR Pfam; PF00169; PH; 1. DR Pfam; PF00017; SH2; 1. DR ProDom; PD000093; SH2; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00252; SH2; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS50001; SH2; 1. KW 3D-structure; Alternative splicing; Disease mutation; SH2 domain; KW SH3-binding. FT CHAIN 1 561 SH3 domain-binding protein 2. FT /FTId=PRO_0000064365. FT DOMAIN 26 130 PH. FT DOMAIN 457 555 SH2. FT MOTIF 201 210 SH3-binding. FT COMPBIAS 205 212 Poly-Pro. FT COMPBIAS 236 240 Poly-Pro. FT VAR_SEQ 81 97 VMRAAEETTSNNVFPFK -> QPRPQPAQALSQTEAGP FT (in isoform Short). FT /FTId=VSP_004085. FT VAR_SEQ 98 561 Missing (in isoform Short). FT /FTId=VSP_004086. FT VARIANT 415 415 R -> P (in CRBM). FT /FTId=VAR_013257. FT VARIANT 415 415 R -> Q (in CRBM). FT /FTId=VAR_013258. FT VARIANT 418 418 P -> H (in CRBM). FT /FTId=VAR_013259. FT VARIANT 418 418 P -> L (in CRBM). FT /FTId=VAR_013260. FT VARIANT 418 418 P -> R (in CRBM). FT /FTId=VAR_013261. FT VARIANT 420 420 G -> E (in CRBM). FT /FTId=VAR_013262. FT VARIANT 420 420 G -> R (in CRBM). FT /FTId=VAR_013263. FT CONFLICT 27 27 V -> L (in Ref. 3). FT CONFLICT 224 224 H -> N (in Ref. 3). FT CONFLICT 249 249 L -> R (in Ref. 3). FT CONFLICT 251 251 A -> P (in Ref. 3). SQ SEQUENCE 561 AA; 62244 MW; 69E6846A4F6D8F15 CRC64; MAAEEMHWPV PMKAIGAQNL LTMPGGVAKA GYLHKKGGTQ LQLLKWPLRF VIIHKRCVYY FKSSTSASPQ GAFSLSGYNR VMRAAEETTS NNVFPFKIIH ISKKHRTWFF SASSEEERKS WMALLRREIG HFHEKKDLPL DTSDSSSDTD SFYGAVERPV DISLSPYPTD NEDYEHDDED DSYLEPDSPE PGRLEDALMH PPAYPPPPVP TPRKPAFSDM PRAHSFTSKG PGPLLPPPPP KHGLPDVGLA AEDSKRDPLC PRRAEPCPRV PATPRRMSDP PLSTMPTAPG LRKPPCFRES ASPSPEPWTP GHGACSTSSA AIMATATSRN CDKLKSFHLS PRGPPTSEPP PVPANKPKFL KIAEEDPPRE AAMPGLFVPP VAPRPPALKL PVPEAMARPA VLPRPEKPQL PHLQRSPPDG QSFRSFSFEK PRQPSQADTG GDDSDEDYEK VPLPNSVFVN TTESCEVERL FKATSPRGEP QDGLYCIRNS STKSGKVLVV WDETSNKVRN YRIFEKDSKF YLEGEVLFVS VGSMVEHYHT HVLPSHQSLL LRHPYGYTGP R // ID 3BP2_MOUSE STANDARD; PRT; 559 AA. AC Q06649; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 1. DT 04-APR-2006, entry version 36. DE SH3 domain-binding protein 2 (3BP-2). GN Name=Sh3bp2; Synonyms=3bp2; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=93174278; PubMed=8438166; RA Ren R., Mayer B.J., Cicchetti P., Baltimore D.; RT "Identification of a ten-amino acid proline-rich SH3 binding site."; RL Science 259:1157-1161(1993). CC -!- FUNCTION: Binds differentially to the SH3 domains of certain CC proteins of signal transduction pathways. Binds to CC phosphatidylinositols; linking the hemopoietic tyrosine kinase fes CC to the cytoplasmic membrane in a phosphorylation dependent CC mechanism (By similarity). CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 SH2 domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; L14543; AAA37121.1; -; mRNA. DR PIR; I49444; I49444. DR UniGene; Mm.5012; -. DR HSSP; Q9HB21; 1EAZ. DR Ensembl; ENSMUSG00000054520; Mus musculus. DR MGI; MGI:1346349; Sh3bp2. DR InterPro; IPR001849; PH. DR InterPro; IPR011993; PH_type. DR InterPro; IPR000980; SH2. DR Pfam; PF00169; PH; 1. DR Pfam; PF00017; SH2; 1. DR ProDom; PD000093; SH2; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00252; SH2; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS50001; SH2; 1. KW SH2 domain; SH3-binding. FT CHAIN 1 559 SH3 domain-binding protein 2. FT /FTId=PRO_0000064366. FT DOMAIN 26 130 PH. FT DOMAIN 455 553 SH2. FT MOTIF 201 210 SH3-binding. FT COMPBIAS 205 212 Poly-Pro. FT COMPBIAS 236 240 Poly-Pro. SQ SEQUENCE 559 AA; 62208 MW; EDFE1F11B259646E CRC64; MAAEEMQWPV PMKAIGAQNL LTMPGGVAKA GYLHKKGGTQ LQLLKWPLRF VIIHKRCIYY FKSSTSASPQ GAFSLSGYNR VMRAAEETTS NNVFPFKIIH ISKKHRTWFF SASSEDERKS WMAFVRREIG HFHEKKELPL DTSDSSSDTD SFYGAVERPI DISLSSYPMD NEDYEHEDED DSYLEPDSPG PMKLEDALTY PPAYPPPPVP VPRKPAFSDL PRAHSFTSKS PSPLLPPPPP KRGLPDTGSA PEDAKDALGL RRVEPGLRVP ATPRRMSDPP MSNVPTVPNL RKHPCFRDSV NPGLEPWTPG HGTSSVSSST TMAVATSRNC DKLKSFHLSS RGPPTSEPPP VPANKPKFLK IAEEPSPREA AKFAPVPPVA PRPPVQKMPM PEATVRPAVL PRPENTPLPH LQRSPPDGQS FRGFSFEKAR QPSQADTGEE DSDEDYEKVP LPNSVFVNTT ESCEVERLFK ATDPRGEPQD GLYCIRNSST KSGKVLVVWD ESSNKVRNYR IFEKDSKFYL EGEVLFASVG SMVEHYHTHV LPSHQSLLLR HPYGYAGPR // ID AB1IP_BRARE STANDARD; PRT; 646 AA. AC Q6PFT9; DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 30-MAY-2006, entry version 19. DE Amyloid beta A4 precursor protein-binding family B member 1- DE interacting protein (APBB1-interacting protein 1). GN Name=apbb1ip; OS Brachydanio rerio (Zebrafish) (Danio rerio). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes; OC Cyprinidae; Danio. OX NCBI_TaxID=7955; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Kidney; RG NIH - Zebrafish Gene Collection (ZGC) project; RL Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Appears to function in the signal transduction from Ras CC activation to actin cytoskeletal remodelling. CC -!- SUBCELLULAR LOCATION: Cell membrane; peripheral membrane (By CC similarity). CC -!- SIMILARITY: Belongs to the MRL family. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 Ras-associating domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; BC057421; AAH57421.1; -; mRNA. DR UniGene; Dr.28408; -. DR Ensembl; ENSDARG00000016505; Danio rerio. DR ZFIN; ZDB-GENE-040426-1318; apbb1ip. DR InterPro; IPR011009; Kinase_like. DR InterPro; IPR001849; PH. DR InterPro; IPR011993; PH_type. DR InterPro; IPR000159; RA. DR Pfam; PF00169; PH; 1. DR Pfam; PF00788; RA; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00314; RA; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS50200; RA; 1. KW Cytoskeleton. FT CHAIN 1 646 Amyloid beta A4 precursor protein-binding FT family B member 1-interacting protein. FT /FTId=PRO_0000181350. FT DOMAIN 162 248 Ras-associating. FT DOMAIN 292 401 PH. FT COMPBIAS 127 135 Pro-rich. FT COMPBIAS 138 142 Poly-Glu. FT COMPBIAS 436 626 Pro-rich. SQ SEQUENCE 646 AA; 71002 MW; A8CF0551E9932FA3 CRC64; MDDIDAMFSD MLQEMDLLTQ SLDAEVDSAP LAKPPTIPEP QEMNFSIGFA NFNESLNDLE DNDLDALMAD LVADISATEE KFATERDTSK GSVPVAPAPS KPQSNFSLPA SFDSSKPATS SNSIAAPPPP PAFKPSKEEE EEQLKADKIK LALEKLKEAK VKKLVVKVEI TDGSSKTLMV DERQTVRDVM DNLFEKTHCD CNVDWSVCET NPDLQTERAF EDHENLVEPL STWTRDTENK VLFQEKKHKY EVFKNPQIFY LWKKDKKSLK DMKEKDKEQL LEENFCGASV IVPDLEGVLY LKEDGKKSWK QRYFLLRASG LYYSPKGKTK ASRDLVCLVQ FDNVNVYYCK EYRIKYKAPT DHCFMLKHPQ IQKESQYIKF MCCDDEWSMN LWVTGIRVAK YGKQLYDNYK AAVRKASGSA SWANRTIQAS STASTPSPTP KAKAANGHAP QPPVENKVPS NQSSLPPPPP SMDFLPPPPP DPMFPPPPPA PPAPPAPPVP VSSTKVNKFP PPPKFPQSSF PPPPMDDLPP PPPPPEIADL PPDFLPPPPP SFVSHGGESL PPPPPDPVAS LPPPPPAFTS AGGAPPPPPP PPPPPAPAPA VNNPAGSVRK VAPPPPKRTT PQLAAPSGGD FMSELMNAMQ KKRTQP // ID AB1IP_CHICK STANDARD; PRT; 485 AA. AC Q5ZL23; DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot. DT 23-NOV-2004, sequence version 1. DT 30-MAY-2006, entry version 12. DE Amyloid beta A4 precursor protein-binding family B member 1- DE interacting protein (APBB1-interacting protein 1). GN Name=APBB1IP; ORFNames=RCJMB04_8c12; OS Gallus gallus (Chicken). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Archosauria; Aves; Neognathae; Galliformes; Phasianidae; Phasianinae; OC Gallus. OX NCBI_TaxID=9031; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=CB; TISSUE=Bursa of Fabricius; RX PubMed=15642098; DOI=10.1186/gb-2004-6-1-r6; RA Caldwell R.B., Kierzek A.M., Arakawa H., Bezzubov Y., Zaim J., RA Fiedler P., Kutter S., Blagodatski A., Kostovska D., Koter M., RA Plachy J., Carninci P., Hayashizaki Y., Buerstedde J.-M.; RT "Full-length cDNAs from chicken bursal lymphocytes to facilitate gene RT function analysis."; RL Genome Biol. 6:RESEARCH006.1-RESEARCH006.9(2005). CC -!- FUNCTION: Appears to function in the signal transduction from Ras CC activation to actin cytoskeletal remodelling. CC -!- SUBCELLULAR LOCATION: Cell membrane; peripheral membrane (By CC similarity). CC -!- SIMILARITY: Belongs to the MRL family. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 Ras-associating domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AJ719911; CAG31570.1; -; mRNA. DR UniGene; Gga.22233; -. DR InterPro; IPR001849; PH. DR InterPro; IPR011993; PH_type. DR InterPro; IPR000159; RA. DR Pfam; PF00169; PH; 1. DR Pfam; PF00788; RA; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00314; RA; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS50200; RA; 1. KW Cytoskeleton. FT CHAIN 1 485 Amyloid beta A4 precursor protein-binding FT family B member 1-interacting protein. FT /FTId=PRO_0000181349. FT DOMAIN 175 262 Ras-associating. FT DOMAIN 305 414 PH. FT COMPBIAS 126 147 Pro-rich. SQ SEQUENCE 485 AA; 54748 MW; C4EE1C5B1283EE34 CRC64; MEQTCDDIDE MFSNLLGEMD MLTQSLGVET VQTPSPKVTN EEFSFTVGFK DLNESLNALE DKDLDALMAD LVADINEVEQ RTLQAQKTSG NQQSVVTQPS TGTNNDFCSK LSPCATITGQ FKNDLPPPPP APDLDLPPPP PPPPPEPLSQ EEQEARAKAD KIKLALEKLK EAKIKKLVVK VHMYDNSTKS LMVDERQVTR DVLDNLFEKT HCDCSVDWCL YEVYPELQIE RFFEDHENVV EVLSDWTRDS ENKVLFLEKK EKYALFKNPQ NFYLANKGKN ESKEMNDKSK EALLEESFCG ASVIVPELEG ALYLKEDGKK SWKRRYFLLR ASGIYYVPKG KTKTSRDLMC FIQFENMNVY YGSQHKVKYK APTDHCFVLK HPQIQKESQY IKYLCCDDRA TLHQWVTGIR IAKYGKTLYD NYKCAVKKAG LSSQWANQGT LEPAAPTGSL SAGAVQANGQ IPRVVLPSSA EVAETQKKVD PAIRA // ID AB1IP_HUMAN STANDARD; PRT; 666 AA. AC Q7Z5R6; Q8IWS8; Q8IZZ7; DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2003, sequence version 1. DT 30-MAY-2006, entry version 25. DE Amyloid beta A4 precursor protein-binding family B member 1- DE interacting protein (APBB1-interacting protein 1) (Rap1-GTP- DE interacting adapter molecule) (RIAM) (Proline-rich EVH1 ligand 1) DE (PREL-1) (Proline-rich protein 73) (Retinoic acid-responsive proline- DE rich protein 1) (RARP-1). GN Name=APBB1IP; Synonyms=PREL1, RARP1, RIAM; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY. RC TISSUE=Thymus; RX PubMed=14530287; DOI=10.1074/jbc.M308016200; RA Inagaki T., Suzuki S., Miyamoto T., Takeda T., Yamashita K., RA Komatsu A., Yamauchi K., Hashizume K.; RT "The retinoic acid-responsive proline-rich protein is identified in RT promyeloleukemic HL-60 cells."; RL J. Biol. Chem. 278:51685-51692(2003). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE RP SPECIFICITY, AND INTERACTION WITH RAP1A; PFN1; VASP AND ENAH. RC TISSUE=T-cell; RX PubMed=15469846; DOI=10.1016/j.devcel.2004.07.021; RA Lafuente E.M., van Puijenbroek A.A., Krause M., Carman C.V., RA Freeman G.J., Berezovskaya A., Constantine E., Springer T.A., RA Gertler F.B., Boussiotis V.A.; RT "RIAM, an Ena/VASP and profilin ligand, interacts with Rap1-GTP and RT mediates Rap1-induced adhesion."; RL Dev. Cell 7:585-595(2004). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Cervix carcinoma; RX PubMed=15642358; DOI=10.1016/j.febslet.2004.10.110; RA Jenzora A., Behrendt B., Small J.V., Wehland J., Stradal T.E.; RT "PREL1 provides a link from Ras signalling to the actin cytoskeleton RT via Ena/VASP proteins."; RL FEBS Lett. 579:455-463(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15164054; DOI=10.1038/nature02462; RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P., RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., RA Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., RA Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., RA Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., RA Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., RA Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., RA Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., RA Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., RA Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., RA Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., RA Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., RA Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., RA Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., RA Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., RA Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., RA Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., RA Siebert R., Fechtel K., Bentley D., Durbin R., Hubbard T., RA Doucette-Stamm L., Beck S., Smith D.R., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 10."; RL Nature 429:375-381(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length human RT and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). CC -!- FUNCTION: Appears to function in the signal transduction from Ras CC activation to actin cytoskeletal remodelling. Suppresses insulin- CC induced promoter activities through AP1 and SRE. Mediates Rap1- CC induced adhesion. CC -!- SUBUNIT: Interacts, through the N-terminal Pro-rich region, with CC the WW domain of APBB1. Interacts with RAP1A, PFN1, VASP and ENAH. CC -!- SUBCELLULAR LOCATION: Cell membrane; peripheral membrane (By CC similarity). Colocalizes with ENA/VASP proteins at lamellipodia CC tips and focal adhesions, and F-actin at the leading edge. At the CC membrane surface, associates, via the PH domain, preferentially CC with the inositol phosphates, PtdIns(5)P and PtdIns(3)P. This CC binding appears to be necessary for the efficient interaction of CC the RA domain to Ras-GTPases (By similarity). CC -!- TISSUE SPECIFICITY: Widely expressed with high expression in CC thymus, spleen, lymph node, bone marrow and peripheral leukocytes. CC -!- INDUCTION: Induced by all-trans-retinoic acid. CC -!- DOMAIN: The two Pro-rich regions are required for the suppression CC of AP1 transcription activity. CC -!- SIMILARITY: Belongs to the MRL family. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 Ras-associating domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AB085852; BAC41256.1; -; mRNA. DR EMBL; AY152730; AAN75525.1; -; mRNA. DR EMBL; AL160287; CAH70339.1; -; Genomic_DNA. DR EMBL; BC054516; AAH54516.1; -; mRNA. DR UniGene; Hs.310421; -. DR UniGene; Hs.621989; -. DR Ensembl; ENSG00000077420; Homo sapiens. DR HGNC; HGNC:17379; APBB1IP. DR MIM; 609036; gene. DR LinkHub; Q7Z5R6; -. DR InterPro; IPR001849; PH. DR InterPro; IPR011993; PH_type. DR InterPro; IPR000159; RA. DR Pfam; PF00169; PH; 1. DR Pfam; PF00788; RA; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00314; RA; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS50200; RA; 1. KW Cytoskeleton. FT CHAIN 1 666 Amyloid beta A4 precursor protein-binding FT family B member 1-interacting protein. FT /FTId=PRO_0000181347. FT DOMAIN 176 263 Ras-associating. FT DOMAIN 310 419 PH. FT COMPBIAS 129 148 Pro-rich. FT COMPBIAS 152 155 Poly-Glu. FT COMPBIAS 503 640 Pro-rich. FT CONFLICT 423 423 L -> F (in Ref. 1). FT CONFLICT 599 599 Missing (in Ref. 2). SQ SEQUENCE 666 AA; 73183 MW; 525C906C490D8D97 CRC64; MGESSEDIDQ MFSTLLGEMD LLTQSLGVDT LPPPDPNPPR AEFNYSVGFK DLNESLNALE DQDLDALMAD LVADISEAEQ RTIQAQKESL QNQHHSASLQ ASIFSGAASL GYGTNVAATG ISQYEDDLPP PPADPVLDLP LPPPPPEPLS QEEEEAQAKA DKIKLALEKL KEAKVKKLVV KVHMNDNSTK SLMVDERQLA RDVLDNLFEK THCDCNVDWC LYEIYPELQI ERFFEDHENV VEVLSDWTRD TENKILFLEK EEKYAVFKNP QNFYLDNRGK KESKETNEKM NAKNKESLLE ESFCGTSIIV PELEGALYLK EDGKKSWKRR YFLLRASGIY YVPKGKTKTS RDLACFIQFE NVNIYYGTQH KMKYKAPTDY CFVLKHPQIQ KESQYIKYLC CDDTRTLNQW VMGIRIAKYG KTLYDNYQRA VAKAGLASRW TNLGTVNAAA PAQPSTGPKT GTTQPNGQIP QATHSVSAVL QEAQRHAETS KDKKPALGNH HDPAVPRAPH APKSSLPPPP PVRRSSDTSG SPATPLKAKG TGGGGLPAPP DDFLPPPPPP PPLDDPELPP PPPDFMEPPP DFVPPPPPSY AGIAGSELPP PPPPPPAPAP APVPDSARPP PAVAKRPPVP PKRQENPGHP GGAGGGEQDF MSDLMKALQK KRGNVS // ID AB1IP_MOUSE STANDARD; PRT; 670 AA. AC Q8R5A3; O35329; Q8BRU0; Q99KV8; DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot. DT 22-NOV-2005, sequence version 2. DT 30-MAY-2006, entry version 26. DE Amyloid beta A4 precursor protein-binding family B member 1- DE interacting protein (APBB1-interacting protein 1) (Proline-rich EVH1 DE ligand 1) (PREL-1) (Proline-rich protein 48). GN Name=Apbb1ip; Synonyms=Prel1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, RP AND INTERACTION WITH ENAH; VASP AND RAP1A. RC TISSUE=Cervix carcinoma; RX PubMed=15642358; DOI=10.1016/j.febslet.2004.10.110; RA Jenzora A., Behrendt B., Small J.V., Wehland J., Stradal T.E.; RT "PREL1 provides a link from Ras signalling to the actin cytoskeleton RT via Ena/VASP proteins."; RL FEBS Lett. 579:455-463(2005). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Czech II, and FVB/N; TISSUE=Mammary tumor; RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length human RT and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-282. RC STRAIN=C57BL/6J; TISSUE=Thymus; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., RA Davis M.J., Wilming L.G., Aidinis V., Allen J.E., RA Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., RA Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., RA Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., RA Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., RA di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., RA Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., RA Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., RA Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., RA Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., RA Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., RA Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., RA Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., RA Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., RA Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., RA Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., RA Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., RA Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., RA Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., RA Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., RA Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., RA Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., RA Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., RA Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., RA Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., RA Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., RA Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., RA Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., RA Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., RA Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., RA Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 66-670, TISSUE SPECIFICITY, AND RP INTERACTION WITH APBB1. RX MEDLINE=98070482; PubMed=9407065; DOI=10.1074/jbc.272.52.32869; RA Ermekova K.S., Zambrano N., Linn H., Minopoli G., Gertler F., RA Russo T., Sudol M.; RT "The WW domain of neural protein FE65 interacts with proline-rich RT motifs in Mena, the mammalian homolog of Drosophila enabled."; RL J. Biol. Chem. 272:32869-32877(1997). CC -!- FUNCTION: Appears to function in the signal transduction from Ras CC activation to actin cytoskeletal remodelling. Suppresses insulin- CC induced promoter activities through AP1 and SRE. Mediates Rap1- CC induced adhesion (By similarity). CC -!- SUBUNIT: Interacts, through the N-terminal Pro-rich region, with CC the WW domain of APBB1. Interacts with RAP1A, PFN1, VASP and ENAH. CC -!- SUBCELLULAR LOCATION: Cell membrane; peripheral membrane. CC Colocalizes with ENA/VASP proteins at lamellipodia tips and focal CC adhesions, and F-actin at the leading edge. At the membrane CC surface, associates, via the PH domain, preferentially with the CC inositol phosphates, PtdIns(5)P and PtdIns(3)P. This binding CC appears to be necessary for the efficient interaction of the RA CC domain to Ras-GTPases. CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with high expression in CC the haematopoietic system. CC -!- SIMILARITY: Belongs to the MRL family. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 Ras-associating domain. CC -!- CAUTION: Ref.4 sequence differs from that shown due to frameshifts CC in positions 348 and 477. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; BC003991; AAH03991.1; -; mRNA. DR EMBL; BC023110; AAH23110.1; -; mRNA. DR EMBL; AK041552; BAC30983.1; -; mRNA. DR EMBL; AF020313; AAB94880.1; ALT_FRAME; mRNA. DR UniGene; Mm.14255; -. DR Ensembl; ENSMUSG00000026786; Mus musculus. DR MGI; MGI:1861354; Apbb1ip. DR InterPro; IPR001849; PH. DR InterPro; IPR011993; PH_type. DR InterPro; IPR000159; RA. DR Pfam; PF00169; PH; 1. DR Pfam; PF00788; RA; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00314; RA; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS50200; RA; 1. KW Cytoskeleton. FT CHAIN 1 670 Amyloid beta A4 precursor protein-binding FT family B member 1-interacting protein. FT /FTId=PRO_0000181348. FT DOMAIN 179 266 Ras-associating. FT DOMAIN 313 422 PH. FT COMPBIAS 129 149 Pro-rich. FT COMPBIAS 155 158 Poly-Glu. FT COMPBIAS 517 635 Pro-rich. FT CONFLICT 66 69 ALMA -> EFKP (in Ref. 4). FT CONFLICT 127 127 A -> D (in Ref. 2; AAH03991). FT CONFLICT 141 141 Missing (in Ref. 1, 2 and 4). FT CONFLICT 142 142 Missing (in Ref. 1, 2; AAH23110 and 4). FT CONFLICT 461 461 S -> P (in Ref. 2; AAH03991). FT CONFLICT 549 549 T -> S (in Ref. 2; AAH03991). SQ SEQUENCE 670 AA; 74319 MW; 39EB28E468C479C8 CRC64; MGESNEDIDQ MFSTLLGEMD LLTQSLGVDT LPPPDPNPPR EEFNYTVGFK DLNESLNALE DQDLDALMAD LVADISEAEQ RTIQAQKESS QNQDRFALLR ASDGQGTASG GYGASAAAID VSHHEEALPP PPVEPMLDLL PPPPPPPPPE LLSKEEEEAK AKADKIKLAL EKLKEAKVKK LVVKVHMDDS STKSLMVDER QLARDVLDNL FEKTHCDCNV DWCLYEIYPE LQIERVFEDH ENVVEVLSDW TRDTENKVLF LEKEERYAVF KNPQNFYLDN KGKKENKETN EKMNAKNKEY LLEESFCGTS IIVPELEGAL YLKEDGKKSW KRRYFLLRAS GIYYVPKGKT KTSRDLACFI QFENVNIYYG IQCKMKYKAP TDHCFVLKHP QIQKESQYIK YLCCDDARTL SQWVMGIRIA KYGKTLYDNY QRAVARAGLA SRWTNLGTVG TPMPAQPSTV SSGLKTGTSQ PNGQMPQAIP SAGPPLQEAQ TQIETTKDEK QGLGNHSPGA TRENHRPKSS LPPPPPPVRR SSDTCGSPAL PSKVKGPGTC TFPHPPENFL PPPPPPPPEE DNSGLLPPPP PPPYLEEPPD FVPPPPPPAA VEDSALPPPP PPPPCLSQEI TKSSPLPPKK PLVPPKRQEN QGLPGAPGNS EQDFMSDLMK ALQKKRGNIP // ID AB1IP_XENLA STANDARD; PRT; 653 AA. AC Q6DCV1; DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot. DT 22-NOV-2005, sequence version 2. DT 30-MAY-2006, entry version 18. DE Amyloid beta A4 precursor protein-binding family B member 1- DE interacting protein (APBB1-interacting protein 1). GN Name=apbb1ip; OS Xenopus laevis (African clawed frog). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Amphibia; Batrachia; Anura; Mesobatrachia; Pipoidea; Pipidae; OC Xenopodinae; Xenopus; Xenopus. OX NCBI_TaxID=8355; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Spleen; RG NIH - Xenopus Gene Collection (XGC) project; RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Appears to function in the signal transduction from Ras CC activation to actin cytoskeletal remodelling. CC -!- SUBCELLULAR LOCATION: Cell membrane; peripheral membrane (By CC similarity). CC -!- SIMILARITY: Belongs to the MRL family. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 Ras-associating domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; BC077889; AAH77889.1; ALT_INIT; mRNA. DR UniGene; Xl.48402; -. DR InterPro; IPR001849; PH. DR InterPro; IPR011993; PH_type. DR InterPro; IPR000159; RA. DR Pfam; PF00169; PH; 1. DR Pfam; PF00788; RA; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00314; RA; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS50200; RA; 1. KW Cytoskeleton. FT CHAIN 1 653 Amyloid beta A4 precursor protein-binding FT family B member 1-interacting protein. FT /FTId=PRO_0000181351. FT DOMAIN 165 253 Ras-associating. FT DOMAIN 295 404 PH. FT COMPBIAS 88 137 Pro-rich. FT COMPBIAS 492 623 Pro-rich. SQ SEQUENCE 653 AA; 72681 MW; CB6633CE6D496DDE CRC64; MDEIDEMFSN LLGEMDLLTQ SLEIETLPPP TRSASTTEIN FSVGFKDLNE SLNALEDNDL DALMAELVAD ITDAEQNVAT YNNKSTAPFP PADASNSYHF HPPPMPSIIT EDLSLLPPPP EFDPHYPPPP PDPLTEPKTQ EELESKAKAN KINLALSKMK EAKVKKRIVK VHMIDSSTKT LMVEEHQTVR DVLDNLFEKT HCDCSIEWCL FEVTPELQIE RFFEDHENIV EILANWTRDS VNTIHFLEKN EKYAVFKKPQ NFYMATKGSA DLKDMNEKNK VSLLEQSFCG ASVTVPELEA ALYLKEDGKK SWKKRYFLLR ASGIYYVPKG KTKTSRDLAC FVQFDNVNVY YGTQYRMKYK APTDHCFVLK HPQIQKESQY IKYLCCEDPW LLHQWVTGIR IAKYGKILYD NYKTAVQRGG LASHWSTLGS SSVSTAAGSS QGNGQICQNV TTISSSFSDA WKHGEANKQE KKSSEVNKPE TKSATPTVTK RPPPTPRRAS SISRVTDHPA FPPKPKAINT DIMSGPPQFP PPEPLQPADD FLPPPPPDFF DAPPDFLPPS PPSFMSNAEN PPPPPVTQLQ MSNAPAPPPP PPPPAPAANV PPLPVKKHPP KPPKRQSIVG PMPGTNAHGG AGGQPDFMSD LMKALQKKRE PPT // ID ABR_HUMAN STANDARD; PRT; 859 AA. AC Q12979; Q13693; Q13694; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 30-MAY-2006, entry version 45. DE Active breakpoint cluster region-related protein. GN Name=ABR; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE. RC TISSUE=Hippocampus; RX MEDLINE=94086546; PubMed=8262969; RA Tan E.-C., Leung T., Manser E., Lim L.; RT "The human active breakpoint cluster region-related gene encodes a RT brain protein with homology to guanine nucleotide exchange proteins RT and GTPase-activating proteins."; RL J. Biol. Chem. 268:27291-27298(1993). RN [2] RP NUCLEOTIDE SEQUENCE OF 39-859 (ISOFORMS LONG AND SHORT). RC TISSUE=Fibroblast; RX MEDLINE=93352461; PubMed=8349582; RA Heisterkamp N., Kaartinen V., van Soest S., Bokoch G.M., Groffen J.; RT "Human ABR encodes a protein with GAPrac activity and homology to the RT DBL nucleotide exchange factor domain."; RL J. Biol. Chem. 268:16903-16906(1993). RN [3] RP NUCLEOTIDE SEQUENCE OF 436-597. RX MEDLINE=90067847; PubMed=2587217; RA Heisterkamp N., Morris C., Groffen J.; RT "ABR, an active BCR-related gene."; RL Nucleic Acids Res. 17:8821-8831(1989). CC -!- FUNCTION: GTPase-activating protein for RAC and CDC42. Promotes CC the exchange of RAC or CDC42-bound GDP by GTP, thereby activating CC them. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Long; CC IsoId=Q12979-1; Sequence=Displayed; CC Name=Short; CC IsoId=Q12979-2; Sequence=VSP_001815; CC -!- TISSUE SPECIFICITY: Highly enriched in the brain. Much weaker CC expression in heart, lung and muscle. CC -!- SIMILARITY: Contains 1 C2 domain. CC -!- SIMILARITY: Contains 1 DH (DBL-homology) domain. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 Rho-GAP domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; U01147; AAC50063.1; -; mRNA. DR EMBL; L19704; AAC37519.1; -; Unassigned_DNA. DR EMBL; L19705; AAC37518.1; ALT_INIT; Unassigned_DNA. DR PIR; A49307; A49307. DR UniGene; Hs.159306; -. DR HSSP; Q98935; 1F7C. DR Ensembl; ENSG00000159842; Homo sapiens. DR HGNC; HGNC:81; ABR. DR MIM; 600365; gene. DR GO; GO:0005096; F:GTPase activator activity; TAS. DR GO; GO:0007264; P:small GTPase mediated signal transduction; TAS. DR InterPro; IPR000008; C2_Ca-dep. DR InterPro; IPR001331; GDS_CDC24. DR InterPro; IPR001849; PH. DR InterPro; IPR011993; PH_type. DR InterPro; IPR008936; Rho_GAP. DR InterPro; IPR000198; RhoGAP. DR InterPro; IPR000219; RhoGEF. DR Pfam; PF00168; C2; 1. DR Pfam; PF00169; PH; 1. DR Pfam; PF00620; RhoGAP; 1. DR Pfam; PF00621; RhoGEF; 1. DR SMART; SM00239; C2; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00324; RhoGAP; 1. DR SMART; SM00325; RhoGEF; 1. DR PROSITE; PS50004; C2_DOMAIN; 1. DR PROSITE; PS00741; DH_1; 1. DR PROSITE; PS50010; DH_2; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS50238; RHOGAP; 1. KW Alternative splicing; Guanine-nucleotide releasing factor. FT CHAIN 1 859 Active breakpoint cluster region-related FT protein. FT /FTId=PRO_0000080902. FT DOMAIN 91 284 DH. FT DOMAIN 301 459 PH. FT DOMAIN 463 595 C2. FT DOMAIN 647 845 Rho-GAP. FT COMPBIAS 417 420 Poly-Leu. FT VAR_SEQ 1 82 MEPLSHRGLPRLSWIDTLYSNFSYGTDEYDGEGNEEQKGPP FT EGSETMPYIDESPTMSPQLSARSQGRGDGVSPTPPEGLAPG FT -> MEEEEEAIGLLDKVLEDEDVFLLEECELGTPTSPGSGS FT PFLVAVK (in isoform Short). FT /FTId=VSP_001815. FT CONFLICT 67 67 R -> G (in Ref. 2). FT CONFLICT 657 660 RSKV -> VQGA (in Ref. 2). FT CONFLICT 761 761 L -> V (in Ref. 2). SQ SEQUENCE 859 AA; 97697 MW; 9FD50CD54FA99483 CRC64; MEPLSHRGLP RLSWIDTLYS NFSYGTDEYD GEGNEEQKGP PEGSETMPYI DESPTMSPQL SARSQGRGDG VSPTPPEGLA PGVEAGKGLE MRKLVLSGFL ASEEIYINQL EALLLPMKPL KATATTSQPV LTIQQIETIF YKIQDIYEIH KEFYDNLCPK VQQWDSQVTM GHLFQKLASQ LGVYKAFVDN YKVALETAEK CSQSNNQFQK ISEELKVKGP KDSKDSHTSV TMEALLYKPI DRVTRSTLVL HDLLKHTPVD HPDYPLLQDA LRISQNFLSS INEDIDPRRT AVTTPKGETR QLVKDGFLVE VSESSRKLRH VFLFTDVLLC AKLKKTSAGK HQQYDCKWYI PLADLVFPSP EESEASPQVH PFPDHELEDM KMKISALKSE IQKEKANKGQ SRAIERLKKK MFENEFLLLL NSPTIPFRIH NRNGKSYLFL LSSDYERSEW REAIQKLQKK DLQAFVLSSV ELQVLTGSCF KLRTVHNIPV TSNKDDDESP GLYGFLHVIV HSAKGFKQSA NLYCTLEVDS FGYFVSKAKT RVFRDTAEPK WDEEFEIELE GSQSLRILCY EKCYDKTKVN KDNNEIVDKI MGKGQIQLDP QTVETKNWHT DVIEMNGIKV EFSMKFTSRD MSLKRTPSKK QTGVFGVKIS VVTKRERSKV PYIVRQCVEE VEKRGIEEVG IYRISGVATD IQALKAVFDA NNKDILLMLS DMDINAIAGT LKLYFRELPE PLLTDRLYPA FMEGIALSDP AAKENCMMHL LRSLPDPNLI TFLFLLEHLK RVAEKEPINK MSLHNLATVF GPTLLRPSEV ESKAHLTSAA DIWSHDVMAQ VQVLLYYLQH PPISFAELKR NTLYFSTDV // ID AKT1_BOVIN STANDARD; PRT; 480 AA. AC Q01314; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 30-MAY-2006, entry version 55. DE RAC-alpha serine/threonine-protein kinase (EC 2.7.11.1) (RAC-PK-alpha) DE (Protein kinase B) (PKB). GN Name=AKT1; Synonyms=PKB; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Laurasiatheria; Cetartiodactyla; Ruminantia; OC Pecora; Bovidae; Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Brain; RX MEDLINE=92037600; PubMed=1718748; RA Coffer P.J., Woodgett J.R.; RT "Molecular cloning and characterisation of a novel putative protein- RT serine kinase related to the cAMP-dependent and protein kinase C RT families."; RL Eur. J. Biochem. 201:475-481(1991). RN [2] RP ERRATUM, AND SEQUENCE REVISION. RX MEDLINE=92249329; PubMed=1533586; RA Coffer P.J., Woodgett J.R.; RL Eur. J. Biochem. 205:1217-1218(1992). RN [3] RP DEPHOSPHORYLATION AT SER-473 BY PHLPP. RX PubMed=15808505; DOI=10.1016/j.molcel.2005.03.008; RA Gao T., Furnari F., Newton A.C.; RT "PHLPP: a phosphatase that directly dephosphorylates Akt, promotes RT apoptosis, and suppresses tumor growth."; RL Mol. Cell 18:13-24(2005). CC -!- FUNCTION: General protein kinase capable of phosphorylating CC several known proteins. Phosphorylates TBC1D4. Signals downstream CC of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects CC of various growth factors such as platelet-derived growth factor CC (PDGF), epidermal growth factor (EGF), insulin and insulin-like CC growth factor I (IGF-I). Plays a role in glucose transport by CC mediating insulin-induced translocation of the GLUT4 glucose CC transporter to the cell surface. Mediates the antiapoptotic CC effects of IGF-I. Mediates insulin-stimulated protein synthesis, CC partly by playing a role in both insulin-induced phosphorylation CC of 4E-BP1 and in insulin-induced activation of p70 S6 kinase. CC Promotes glycogen synthesis by mediating the insulin-induced CC activation of glycogen synthase (By similarity). CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- INTERACTION: CC Q9R269:Ppl (xeno); NbExp=1; IntAct=EBI-368344, EBI-368293; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Nucleus after activation CC by integrin-linked protein kinase 1 (ILK1). CC -!- DOMAIN: Binding of the PH domain to the phosphatidylinositol 3- CC kinase alpha (PI(3)K) results in its targeting to the plasma CC membrane. CC -!- PTM: Phosphorylation on Thr-308, Ser-473 and Tyr-474 is required CC for full activity. Ser-473 phosphorylation favors Thr-308 CC phosphorylation (By similarity). Ser-473 is dephosphorylated by CC PHLPP. CC -!- SIMILARITY: Belongs to the Ser/Thr protein kinase family. RAC CC subfamily. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; X61036; CAA43371.1; -; mRNA. DR PIR; S62117; S62117. DR UniGene; Bt.4843; -. DR HSSP; P31749; 1H10. DR SMR; Q01314; 3-121. DR IntAct; Q01314; -. DR GO; GO:0005515; F:protein binding; IPI. DR InterPro; IPR011009; Kinase_like. DR InterPro; IPR001849; PH. DR InterPro; IPR011993; PH_type. DR InterPro; IPR000961; Pkinase_C. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR008271; Ser_thr_pkin_AS. DR InterPro; IPR002290; Ser_thr_pkinase. DR Pfam; PF00169; PH; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF00433; Pkinase_C; 1. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00133; S_TK_X; 1. DR SMART; SM00220; S_TKc; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. KW Apoptosis; ATP-binding; Carbohydrate metabolism; Glucose metabolism; KW Glycogen biosynthesis; Glycogen metabolism; Kinase; Nuclear protein; KW Nucleotide-binding; Phosphorylation; Serine/threonine-protein kinase; KW Sugar transport; Transferase; Translation regulation; Transport. FT CHAIN 1 480 RAC-alpha serine/threonine-protein FT kinase. FT /FTId=PRO_0000085604. FT DOMAIN 5 108 PH. FT DOMAIN 150 408 Protein kinase. FT NP_BIND 156 164 ATP (By similarity). FT ACT_SITE 274 274 Proton acceptor (By similarity). FT BINDING 179 179 ATP (By similarity). FT MOD_RES 308 308 Phosphothreonine (By similarity). FT MOD_RES 473 473 Phosphoserine. FT MOD_RES 474 474 Phosphotyrosine (By similarity). SQ SEQUENCE 480 AA; 55617 MW; 0BACA4123ED5A848 CRC64; MNDVAIVKEG WLHKRGEYIK TWRPRYFLLK NDGTFIGYKE RPQDLEQRES PLNNFSVAQC QLMKTERPRP NTFIIRCLQW TTVIERTFHV ETPEEREEWT TAIQTVADGL KRQEEETMDF RSGSPGENSG AEEMEVSLAK PKHRVTMNEF EYVKLLGKGT FGKVILVKEK ATAAYYAMKI LKKEVIVAKD EVAHTLTENR VLQNSRHPSL TALKYSFQTH DRLCFVMEYA NGGELFFHLS RERVFSEDRA RFYGAEIVSA LDYLHSEKEV VYRDLKLENL MLDKDGHIKI TDFGLCKEGI KDGATMKTFC GTPEYLAPEV LEDNDYGRAV DWWGLGVVMY EMMCGRLPFY NQDHEKLFEL ILMEEIRFPR TLSPEAKSLL SGLLKKDPKQ RLGGGSEDAK EIMQHRFFAS IVWQDVYEKK LSPPFKPQVT SETDTRYFDE EFTAQMITIT PPDQDDSMEG VDSERRPHFP QFSYSASATA // ID AKT1_CAEEL STANDARD; PRT; 541 AA. AC Q17941; Q17942; DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1998, sequence version 2. DT 30-MAY-2006, entry version 50. DE Serine/threonine-protein kinase akt-1 (EC 2.7.11.1) (Protein kinase B DE akt-1) (PKB akt-1). GN Name=akt-1; ORFNames=C12D8.10; OS Caenorhabditis elegans. OC Eukaryota; Metazoa; Nematoda; Chromadorea; Rhabditida; Rhabditoidea; OC Rhabditidae; Peloderinae; Caenorhabditis. OX NCBI_TaxID=6239; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B), FUNCTION, MUTAGENESIS RP OF ALA-183, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX MEDLINE=98382502; PubMed=9716402; RA Paradis S., Ruvkun G.; RT "Caenorhabditis elegans Akt/PKB transduces insulin receptor-like RT signals from AGE-1 PI3 kinase to the DAF-16 transcription factor."; RL Genes Dev. 12:2488-2498(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Bristol N2; RX MEDLINE=99069613; PubMed=9851916; DOI=10.1126/science.282.5396.2012; RG The C. elegans sequencing consortium; RT "Genome sequence of the nematode C. elegans: a platform for RT investigating biology."; RL Science 282:2012-2018(1998). RN [3] RP SEQUENCE REVISION, AND ALTERNATIVE SPLICING. RG WormBase consortium; RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases. RN [4] RP FUNCTION. RX MEDLINE=99292684; PubMed=10364160; RA Paradis S., Ailion M., Toker A., Thomas J.H., Ruvkun G.; RT "A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 RT kinase signals that regulate diapause in Caenorhabditis elegans."; RL Genes Dev. 13:1438-1452(1999). RN [5] RP FUNCTION. RX MEDLINE=21614652; PubMed=11747825; DOI=10.1016/S0960-9822(01)00594-2; RA Henderson S.T., Johnson T.E.; RT "daf-16 integrates developmental and environmental inputs to mediate RT aging in the nematode Caenorhabditis elegans."; RL Curr. Biol. 11:1975-1980(2001). RN [6] RP FUNCTION. RX PubMed=11381260; DOI=10.1038/88850; RA Lin K., Hsin H., Libina N., Kenyon C.; RT "Regulation of the Caenorhabditis elegans longevity protein DAF-16 by RT insulin/IGF-1 and germline signaling."; RL Nat. Genet. 28:139-145(2001). RN [7] RP INTERACTION WITH PDK-1; SGK-1; AKT-2 AND DAF-16, AND FUNCTION. RX PubMed=15068796; DOI=10.1016/S1534-5807(04)00095-4; RA Hertweck M., Goebel C., Baumeister R.; RT "C. elegans SGK-1 is the critical component in the Akt/PKB kinase RT complex to control stress response and life span."; RL Dev. Cell 6:577-588(2004). CC -!- FUNCTION: Acts downstream age-1 and pdk-1 in the daf-2/insulin CC receptor-like transduction pathway, which controls longevity and CC prevents developmental arrest at the dauer stage. Phosphorylates CC Forkhead-related daf-16 transcription factor, which inhibits its CC entry into the nucleus and antagonizes its function. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- SUBUNIT: Interacts with pdk-1, sgk-1, akt-2 and daf-16. Part of a CC complex containing sgk-1, akt-1 and akt-2. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=a; CC IsoId=Q17941-1; Sequence=Displayed; CC Name=b; CC IsoId=Q17941-2; Sequence=VSP_017044, VSP_017045, VSP_017046; CC -!- TISSUE SPECIFICITY: Expressed in neurons, muscle cells of the CC pharynx, rectal gland cells, and spermatheca. CC -!- DEVELOPMENTAL STAGE: Expressed in late stage embryos and CC throughout life. CC -!- SIMILARITY: Belongs to the Ser/Thr protein kinase family. RAC CC subfamily. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF072379; AAC62466.1; -; mRNA. DR EMBL; AF072380; AAC62467.1; -; mRNA. DR EMBL; Z73969; CAA98238.1; -; Genomic_DNA. DR EMBL; Z73969; CAA98240.1; -; Genomic_DNA. DR PIR; T43232; T43232. DR PIR; T43233; T43233. DR UniGene; Cel.5036; -. DR HSSP; P31751; 1MRY. DR Ensembl; C12D8.10; Caenorhabditis elegans. DR WormBase; WBGene00000102; akt-1. DR WormPep; C12D8.10a; CE15612. DR WormPep; C12D8.10b; CE05274. DR GO; GO:0005622; C:intracellular; IDA. DR InterPro; IPR011009; Kinase_like. DR InterPro; IPR001849; PH. DR InterPro; IPR011993; PH_type. DR InterPro; IPR000961; Pkinase_C. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR008271; Ser_thr_pkin_AS. DR InterPro; IPR002290; Ser_thr_pkinase. DR Pfam; PF00169; PH; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF00433; Pkinase_C; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00133; S_TK_X; 1. DR SMART; SM00220; S_TKc; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. KW Alternative splicing; ATP-binding; Complete proteome; KW Developmental protein; Kinase; Nucleotide-binding; KW Serine/threonine-protein kinase; Transferase. FT CHAIN 1 541 Serine/threonine-protein kinase akt-1. FT /FTId=PRO_0000085615. FT DOMAIN 15 118 PH. FT DOMAIN 193 450 Protein kinase. FT NP_BIND 199 207 ATP (By similarity). FT ACT_SITE 316 316 Proton acceptor (By similarity). FT BINDING 222 222 ATP (By similarity). FT VAR_SEQ 262 287 EQHYLCFVMQFANGGELFTHVRKCGT -> TNDRLCFVMEF FT AIGGDLYYHLNREVQMNKEG (in isoform b). FT /FTId=VSP_017044. FT VAR_SEQ 298 298 A -> S (in isoform b). FT /FTId=VSP_017045. FT VAR_SEQ 309 317 RCDIVYRDM -> ANSIVYRDL (in isoform b). FT /FTId=VSP_017046. FT MUTAGEN 183 183 A->T: In mg144; suppresses the dauer FT arrest phenotype of the age-1(mg44) null FT mutant. SQ SEQUENCE 541 AA; 62200 MW; 17FEDD1109926950 CRC64; MSMTSLSTKS RRQEDVVIEG WLHKKGEHIR NWRPRYFMIF NDGALLGFRA KPKEGQPFPE PLNDFMIKDA ATMLFEKPRP NMFMVRCLQW TTVIERTFYA ESAEVRQRWI HAIESISKKY KGTNANPQEE LMETNQQPKI DEDSEFAGAA HAIMGQPSSG HGDNCSIDFR ASMISIADTS EAAKRDKITM EDFDFLKVLG KGTFGKVILC KEKRTQKLYA IKILKKDVII AREEVAHTLT ENRVLQRCKH PFLTELKYSF QEQHYLCFVM QFANGGELFT HVRKCGTFSE PRARFYGAEI VLALGYLHRC DIVYRDMKLE NLLLDKDGHI KIADFGLCKE EISFGDKTST FCGTPEYLAP EVLDDHDYGR CVDWWGVGVV MYEMMCGRLP FYSKDHNKLF ELIMAGDLRF PSKLSQEART LLTGLLVKDP TQRLGGGPED ALEICRADFF RTVDWEATYR KEIEPPYKPN VQSETDTSYF DNEFTSQPVQ LTPPSRSGAL ATVDEQEEMQ SNFTQFSFHN VMGSINRIHE ASEDNEDYDM G // ID AKT1_DROME STANDARD; PRT; 611 AA. AC Q8INB9; Q24293; Q24469; Q24470; Q7JN11; Q8T9A5; Q9VEY7; DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot. DT 07-DEC-2004, sequence version 3. DT 30-MAY-2006, entry version 31. DE RAC serine/threonine-protein kinase (EC 2.7.11.1) (DRAC-PK) (Akt) DE (Dakt1) (Protein kinase B) (PKB). GN Name=Akt1; ORFNames=CG4006; OS Drosophila melanogaster (Fruit fly). OC Eukaryota; Metazoa; Arthropoda; Hexapoda; Insecta; Pterygota; OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; OC Ephydroidea; Drosophilidae; Drosophila. OX NCBI_TaxID=7227; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A). RX MEDLINE=94134407; PubMed=8302573; RA Franke T.F., Tartof K.D., Tsichlis P.N.; RT "The SH2-like Akt homology (AH) domain of c-akt is present in multiple RT copies in the genome of vertebrate and invertebrate eucaryotes. RT Cloning and characterisation of the Drosophila melanogaster c-akt RT homolog Dakt1."; RL Oncogene 9:141-148(1994). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE INITIATION (ISOFORMS A RP AND C), ENZYME ACTIVITY, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=7876156; DOI=10.1074/jbc.270.8.4066; RA Andjelkovic M., Jones P.F., Grossniklaus U., Cron P., Schier A.F., RA Dick M., Bilbe G., Hemmings B.A.; RT "Developmental regulation of expression and activity of multiple forms RT of the Drosophila RAC protein kinase."; RL J. Biol. Chem. 270:4066-4075(1995). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley; RX MEDLINE=20196006; PubMed=10731132; DOI=10.1126/science.287.5461.2185; RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., RA Brandon R.C., Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., RA Wan K.H., Doyle C., Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., RA Abril J.F., Agbayani A., An H.-J., Andrews-Pfannkoch C., Baldwin D., RA Ballew R.M., Basu A., Baxendale J., Bayraktaroglu L., Beasley E.M., RA Beeson K.Y., Benos P.V., Berman B.P., Bhandari D., Bolshakov S., RA Borkova D., Botchan M.R., Bouck J., Brokstein P., Brottier P., RA Burtis K.C., Busam D.A., Butler H., Cadieu E., Center A., Chandra I., RA Cherry J.M., Cawley S., Dahlke C., Davenport L.B., Davies P., RA de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., Dietz S.M., RA Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., Dunn P., RA Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., Fleischmann W., RA Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., Glasser K., RA Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., RA Hostin D., Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., RA Jalali M., Kalush F., Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., RA Kimmel B.E., Kodira C.D., Kraft C., Kravitz S., Kulp D., Lai Z., RA Lasko P., Lei Y., Levitsky A.A., Li J.H., Li Z., Liang Y., Lin X., RA Liu X., Mattei B., McIntosh T.C., McLeod M.P., McPherson D., RA Merkulov G., Milshina N.V., Mobarry C., Morris J., Moshrefi A., RA Mount S.M., Moy M., Murphy B., Murphy L., Muzny D.M., Nelson D.L., RA Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., Pacleb J.M., RA Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., Reese M.G., RA Reinert K., Remington K., Saunders R.D.C., Scheeler F., Shen H., RA Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T., RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., RA Svirskas R., Tector C., Turner R., Venter E., Wang A.H., Wang X., RA Wang Z.-Y., Wassarman D.A., Weinstock G.M., Weissenbach J., RA Williams S.M., Woodage T., Worley K.C., Wu D., Yang S., Yao Q.A., RA Ye J., Yeh R.-F., Zaveri J.S., Zhan M., Zhang G., Zhao Q., Zheng L., RA Zheng X.H., Zhong F.N., Zhong W., Zhou X., Zhu S., Zhu X., Smith H.O., RA Gibbs R.A., Myers E.W., Rubin G.M., Venter J.C.; RT "The genome sequence of Drosophila melanogaster."; RL Science 287:2185-2195(2000). RN [4] RP GENOME REANNOTATION, AND ALTERNATIVE INITIATION. RX MEDLINE=22426069; PubMed=12537572; RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A., RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., RA Stapleton M., Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., RA Lewis S.E.; RT "Annotation of the Drosophila melanogaster euchromatic genome: a RT systematic review."; RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A). RC STRAIN=Berkeley; TISSUE=Embryo; RX MEDLINE=22426066; PubMed=12537569; RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., RA George R.A., Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., RA Rubin G.M., Celniker S.E.; RT "A Drosophila full-length cDNA resource."; RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002). RN [6] RP FUNCTION, AND MUTAGENESIS OF PHE-408. RX MEDLINE=98263952; PubMed=9601646; DOI=10.1016/S0960-9822(98)70231-3; RA Staveley B.E., Ruel L., Jin J., Stambolic V., Mastronardi F.G., RA Heitzler P., Woodgett J.R., Manoukian A.S.; RT "Genetic analysis of protein kinase B (AKT) in Drosophila."; RL Curr. Biol. 8:599-602(1998). RN [7] RP FUNCTION, AND MUTAGENESIS OF LYS-295. RX PubMed=10587646; DOI=10.1038/70293; RA Verdu J., Buratovich M.A., Wilder E.L., Birnbaum M.J.; RT "Cell-autonomous regulation of cell and organ growth in Drosophila by RT Akt/PKB."; RL Nat. Cell Biol. 1:500-506(1999). RN [8] RP FUNCTION, AND PHOSPHORYLATION AT SER-586. RX PubMed=10962553; DOI=10.1038/sj.onc.1203739; RA Scanga S.E., Ruel L., Binari R.C., Snow B., Stambolic V., Bouchard D., RA Peters M., Calvieri B., Mak T.W., Woodgett J.R., Manoukian A.S.; RT "The conserved PI3'K/PTEN/Akt signaling pathway regulates both cell RT size and survival in Drosophila."; RL Oncogene 19:3971-3977(2000). RN [9] RP FUNCTION. RX MEDLINE=21606145; PubMed=11740943; DOI=10.1016/S1534-5807(01)00090-9; RA Jin J., Anthopoulos N., Wetsch B., Binari R.C., Isaac D.D., RA Andrew D.J., Woodgett J.R., Manoukian A.S.; RT "Regulation of Drosophila tracheal system development by protein RT kinase B."; RL Dev. Cell 1:817-827(2001). RN [10] RP PHOSPHORYLATION. RX PubMed=11344272; DOI=10.1073/pnas.101596998; RA Cho K.S., Lee J.H., Kim S., Kim D., Koh H., Lee J., Kim C., Kim J., RA Chung J.; RT "Drosophila phosphoinositide-dependent kinase-1 regulates apoptosis RT and growth via the phosphoinositide 3-kinase-dependent signaling RT pathway."; RL Proc. Natl. Acad. Sci. U.S.A. 98:6144-6149(2001). RN [11] RP FUNCTION. RX PubMed=11752451; DOI=10.1073/pnas.011318098; RA Rintelen F., Stocker H., Thomas G., Hafen E.; RT "PDK1 regulates growth through Akt and S6K in Drosophila."; RL Proc. Natl. Acad. Sci. U.S.A. 98:15020-15025(2001). RN [12] RP FUNCTION. RX PubMed=12172554; DOI=10.1038/ncb840; RA Potter C.J., Pedraza L.G., Xu T.; RT "Akt regulates growth by directly phosphorylating Tsc2."; RL Nat. Cell Biol. 4:658-665(2002). RN [13] RP FUNCTION, AND MUTAGENESIS OF GLY-180 AND PHE-408. RX MEDLINE=21893748; PubMed=11872800; DOI=10.1126/science.1068094; RA Stocker H., Andjelkovic M., Oldham S., Laffargue M., Wymann M.P., RA Hemmings B.A., Hafen E.; RT "Living with lethal PIP3 levels: viability of flies lacking PTEN RT restored by a PH domain mutation in Akt/PKB."; RL Science 295:2088-2091(2002). RN [14] RP FUNCTION. RX PubMed=14525946; DOI=10.1096/fj.03-0040fje; RA Lavenburg K.R., Ivey J., Hsu T., Muise-Helmericks R.C.; RT "Coordinated functions of Akt/PKB and ETS1 in tubule formation."; RL FASEB J. 17:2278-2280(2003). RN [15] RP FUNCTION. RX PubMed=12893776; DOI=10.1101/gad.1098703; RA Puig O., Marr M.T., Ruhf M.L., Tjian R.; RT "Control of cell number by Drosophila FOXO: downstream and feedback RT regulation of the insulin receptor pathway."; RL Genes Dev. 17:2006-2020(2003). RN [16] RP FUNCTION. RX PubMed=15466161; DOI=10.1101/gad.1240504; RA Dong J., Pan D.; RT "Tsc2 is not a critical target of Akt during normal Drosophila RT development."; RL Genes Dev. 18:2479-2484(2004). RN [17] RP FUNCTION, AND DEVELOPMENTAL STAGE. RX PubMed=15712201; DOI=10.1002/dvdy.20333; RA Cavaliere V., Donati A., Hsouna A., Hsu T., Gargiulo G.; RT "dAkt kinase controls follicle cell size during Drosophila RT oogenesis."; RL Dev. Dyn. 232:845-854(2005). RN [18] RP PHOSPHORYLATION AT SER-586. RX PubMed=15718470; DOI=10.1126/science.1106148; RA Sarbassov D.D., Guertin D.A., Ali S.M., Sabatini D.M.; RT "Phosphorylation and regulation of Akt/PKB by the rictor-mTOR RT complex."; RL Science 307:1098-1101(2005). CC -!- FUNCTION: Serine/threonine kinase involved in various CC developmental processes. During early embryogenesis, acts as a CC survival protein. During mid-embryogenesis, phosphorylates and CC activates trh, a transcription factor required for tracheal cell CC fate determination. Also regulates tracheal cell migration. Later CC in development, acts downstream of PI3K and Pk61C/PDK1 in the CC insulin receptor transduction pathway which regulates cell growth CC and organ size, by phosphorylating and antagonizing FOXO CC transcription factor. Controls follicle cell size during CC oogenesis. May also stimulate cell growth by phosphorylating CC Gig/Tsc2 and inactivating the Tsc complex. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- INTERACTION: CC Q9VR24:CG15631; NbExp=1; IntAct=EBI-162210, EBI-98854; CC Q9VPE1:CG32425; NbExp=1; IntAct=EBI-162210, EBI-147129; CC Q9VPR4:Nle; NbExp=1; IntAct=EBI-162210, EBI-176424; CC O76136:PHDP; NbExp=2; IntAct=EBI-162210, EBI-466449; CC -!- SUBCELLULAR LOCATION: Cytoplasm; cytosol. Cell membrane. Recruited CC to plasma membrane upon activation. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative initiation; Named isoforms=2; CC Name=C; Synonyms=PK85; CC IsoId=Q8INB9-1; Sequence=Displayed; CC Name=A; Synonyms=PK66; CC IsoId=Q8INB9-2; Sequence=VSP_018833; CC Note=Major form; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed. Present in ovary, CC where it is concentrated at the basal side of follicle cells. CC -!- DEVELOPMENTAL STAGE: Strongly expressed in embryo and pupa. Weakly CC expressed in larva. Mildly expressed in adult. CC -!- DOMAIN: Binding of the PH domain to the phosphatidylinositol 3- CC kinase alpha (PI(3)K) results in its targeting to the plasma CC membrane (Probable). CC -!- PTM: Phosphorylated and activated by Pk61C/PDK1. Phosphorylated on CC Ser-586 by the rictor-Tor complex. CC -!- MISCELLANEOUS: Flies lacking Akt1 die at the first instar larval CC stage. CC -!- SIMILARITY: Belongs to the Ser/Thr protein kinase family. RAC CC subfamily. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; Z26242; CAA81204.1; -; mRNA. DR EMBL; X83510; CAA58499.2; -; Genomic_DNA. DR EMBL; X83510; CAA58500.1; -; Genomic_DNA. DR EMBL; AE003711; AAF55276.1; -; Genomic_DNA. DR EMBL; AE003711; AAN13699.3; -; Genomic_DNA. DR EMBL; AY069856; AAL40001.1; -; mRNA. DR PIR; A55888; A55888. DR UniGene; Dm.1219; -. DR HSSP; Q63450; 1A06. DR IntAct; Q8INB9; -. DR FlyBase; FBgn0010379; Akt1. DR GO; GO:0005886; C:plasma membrane; NAS. DR GO; GO:0035091; F:phosphoinositide binding; NAS. DR GO; GO:0005515; F:protein binding; IPI. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA. DR GO; GO:0006916; P:anti-apoptosis; IMP. DR GO; GO:0008362; P:embryonic cuticle biosynthesis (sensu Insecta); IGI. DR GO; GO:0008286; P:insulin receptor signaling pathway; IDA. DR GO; GO:0007242; P:intracellular signaling cascade; IGI. DR GO; GO:0009993; P:oogenesis (sensu Insecta); IMP. DR GO; GO:0040018; P:positive regulation of body size; TAS. DR GO; GO:0030307; P:positive regulation of cell growth; IMP. DR GO; GO:0046622; P:positive regulation of organ size; IMP. DR GO; GO:0006468; P:protein amino acid phosphorylation; IDA. DR GO; GO:0008360; P:regulation of cell shape; IMP. DR GO; GO:0042306; P:regulation of protein import into nucleus; TAS. DR GO; GO:0007427; P:tracheal epithelial cell migration (sensu I...; IMP. DR InterPro; IPR011009; Kinase_like. DR InterPro; IPR001849; PH. DR InterPro; IPR011993; PH_type. DR InterPro; IPR000961; Pkinase_C. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR008271; Ser_thr_pkin_AS. DR InterPro; IPR002290; Ser_thr_pkinase. DR Pfam; PF00169; PH; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF00433; Pkinase_C; 1. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00133; S_TK_X; 1. DR SMART; SM00220; S_TKc; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. KW Alternative initiation; Apoptosis; ATP-binding; Complete proteome; KW Developmental protein; Growth regulation; Kinase; Membrane; KW Nucleotide-binding; Phosphorylation; Serine/threonine-protein kinase; KW Transferase. FT CHAIN 1 611 RAC serine/threonine-protein kinase. FT /FTId=PRO_0000045784. FT DOMAIN 106 211 PH. FT DOMAIN 266 523 Protein kinase. FT NP_BIND 272 280 ATP (By similarity). FT ACT_SITE 389 389 Proton acceptor (By similarity). FT BINDING 295 295 ATP (Probable). FT MOD_RES 586 586 Phosphoserine. FT VAR_SEQ 1 81 Missing (in isoform A). FT /FTId=VSP_018833. FT MUTAGEN 180 180 G->S: Fails to be recruited at the FT membrane upon activation. FT MUTAGEN 260 260 K->A: Abolishes enzymatic activity. FT MUTAGEN 295 295 K->M: Abolishes enzymatic activity. FT MUTAGEN 408 408 F->I: Abolishes enzymatic activity. FT CONFLICT 73 73 A -> T (in Ref. 2; CAA58499). FT CONFLICT 200 201 QQ -> HE (in Ref. 1). SQ SEQUENCE 611 AA; 68485 MW; C139380152580934 CRC64; MNYLPFVLQR RSTVVASAPA PGSASRIPES PTTTGSNIIN IIYSQSTHPN SSPTSGSAEK FSWQQSWPSR TSAAPTHDSG TMSINTTFDL SSPSVTSGHA LTEQTQVVKE GWLMKRGEHI KNWRQRYFVL HSDGRLMGYR SKPADSASTP SDFLLNNFTV RGCQIMTVDR PKPFTFIIRG LQWTTVIERT FAVESELERQ QWTEAIRNVS SRLIDVGEVA MTPSEQTDMT DVDMATIAED ELSEQFSVQG TTCNSSGVKK VTLENFEFLK VLGKGTFGKV ILCREKATAK LYAIKILKKE VIIQKDEVAH TLTESRVLKS TNHPFLISLK YSFQTNDRLC FVMQYVNGGE LFWHLSHERI FTEDRTRFYG AEIISALGYL HSQGIIYRDL KLENLLLDKD GHIKVADFGL CKEDITYGRT TKTFCGTPEY LAPEVLDDND YGQAVDWWGT GVVMYEMICG RLPFYNRDHD VLFTLILVEE VKFPRNITDE AKNLLAGLLA KDPKKRLGGG KDDVKEIQAH PFFASINWTD LVLKKIPPPF KPQVTSDTDT RYFDKEFTGE SVELTPPDPT GPLGSIAEEP LFPQFSYQGD MASTLGTSSH ISTSTSLASM Q // ID AKT1_HUMAN STANDARD; PRT; 480 AA. AC P31749; Q9BWB6; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-2005, sequence version 2. DT 30-MAY-2006, entry version 76. DE RAC-alpha serine/threonine-protein kinase (EC 2.7.11.1) (RAC-PK-alpha) DE (Protein kinase B) (PKB) (C-AKT). GN Name=AKT1; Synonyms=PKB, RAC; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX MEDLINE=91239529; PubMed=1851997; RA Jones P.F., Jakubowicz T., Pitossi F.J., Maurer F., Hemmings B.A.; RT "Molecular cloning and identification of a serine/threonine protein RT kinase of the second-messenger subfamily."; RL Proc. Natl. Acad. Sci. U.S.A. 88:4171-4175(1991). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX MEDLINE=21399046; PubMed=11508278; DOI=10.1007/s001250100577; RA Matsubara A., Wasson J.C., Donelan S.S., Welling C.M., Glaser B., RA Permutt M.A.; RT "Isolation and characterization of the human AKT1 gene, identification RT of 13 single nucleotide polymorphisms (SNPs), and their lack of RT association with Type II diabetes."; RL Diabetologia 44:910-913(2001). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Muscle, and Ovary; RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length human RT and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [4] RP NUCLEOTIDE SEQUENCE OF 63-480. RC TISSUE=Foreskin; RX MEDLINE=92037600; PubMed=1718748; RA Coffer P.J., Woodgett J.R.; RT "Molecular cloning and characterisation of a novel putative protein- RT serine kinase related to the cAMP-dependent and protein kinase C RT families."; RL Eur. J. Biochem. 201:475-481(1991). RN [5] RP ERRATUM, AND SEQUENCE REVISION. RX MEDLINE=92249329; PubMed=1533586; RA Coffer P.J., Woodgett J.R.; RL Eur. J. Biochem. 205:1217-1218(1992). RN [6] RP CHARACTERIZATION. RX MEDLINE=98409636; PubMed=9736715; DOI=10.1073/pnas.95.19.11211; RA Delcommenne M., Tan C., Gray V., Rue L., Woodgett J.R., Dedhar S.; RT "Phosphoinositide-3-OH kinase-dependent regulation of glycogen RT synthase kinase 3 and protein kinase B/AKT by the integrin-linked RT kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 95:11211-11216(1998). RN [7] RP MUTAGENESIS OF THR-308 AND SER-473, AND PHOSPHORYLATION AT THR-308 AND RP SER-473. RX MEDLINE=97133284; PubMed=8978681; RA Alessi D.R., Andjelkovic M., Caudwell F.B., Cron P., Morrice N., RA Cohen P., Hemmings B.A.; RT "Mechanism of activation of protein kinase B by insulin and IGF-1."; RL EMBO J. 15:6541-6551(1996). RN [8] RP PHOSPHORYLATION OF TBC1D4. RX MEDLINE=22063368; PubMed=11994271; DOI=10.1074/jbc.C200198200; RA Kane S., Sano H., Liu S.C.H., Asara J.M., Lane W.S., Garner C.C., RA Lienhard G.E.; RT "A method to identify serine kinase substrates. Akt phosphorylates a RT novel adipocyte protein with a Rab GTPase-activating protein (GAP) RT domain."; RL J. Biol. Chem. 277:22115-22118(2002). RN [9] RP PHOSPHORYLATION AT TYR-474, AND MUTAGENESIS OF TYR-474. RX MEDLINE=22254844; PubMed=12149249; DOI=10.1074/jbc.M203387200; RA Conus N.M., Hannan K.M., Cristiano B.E., Hemmings B.A., Pearson R.B.; RT "Direct identification of tyrosine 474 as a regulatory phosphorylation RT site for the Akt protein kinase."; RL J. Biol. Chem. 277:38021-38028(2002). RN [10] RP INTERACTION WITH CENTG1, AND PHOSPHORYLATION AT SER-473. RX PubMed=14761976; DOI=10.1074/jbc.M312175200; RA Ahn J.-Y., Rong R., Kroll T.G., Van Meir E.G., Snyder S.H., Ye K.; RT "PIKE (phosphatidylinositol 3-kinase enhancer)-A GTPase stimulates Akt RT activity and mediates cellular invasion."; RL J. Biol. Chem. 279:16441-16451(2004). RN [11] RP INTERACTION WITH CENTG1. RX PubMed=15118108; DOI=10.1073/pnas.0400921101; RA Ahn J.-Y., Hu Y., Kroll T.G., Allard P., Ye K.; RT "PIKE-A is amplified in human cancers and prevents apoptosis by up- RT regulating Akt."; RL Proc. Natl. Acad. Sci. U.S.A. 101:6993-6998(2004). RN [12] RP PHOSPHORYLATION AT THR-308 AND SER-473. RX PubMed=15718470; DOI=10.1126/science.1106148; RA Sarbassov D.D., Guertin D.A., Ali S.M., Sabatini D.M.; RT "Phosphorylation and regulation of Akt/PKB by the rictor-mTOR RT complex."; RL Science 307:1098-1101(2005). CC -!- FUNCTION: General protein kinase capable of phosphorylating CC several known proteins. Phosphorylates TBC1D4. Signals downstream CC of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects CC of various growth factors such as platelet-derived growth factor CC (PDGF), epidermal growth factor (EGF), insulin and insulin-like CC growth factor I (IGF-I). Plays a role in glucose transport by CC mediating insulin-induced translocation of the GLUT4 glucose CC transporter to the cell surface. Mediates the antiapoptotic CC effects of IGF-I. Mediates insulin-stimulated protein synthesis, CC partly by playing a role in both insulin-induced phosphorylation CC of 4E-BP1 and in insulin-induced activation of p70 S6 kinase. CC Promotes glycogen synthesis by mediating the insulin-induced CC activation of glycogen synthase. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- SUBUNIT: Interacts with CENTG1 isoform 2 (PIKE-A) in the presence CC of guanine nucleotides. CC -!- INTERACTION: CC Self; NbExp=1; IntAct=EBI-296087, EBI-296087; CC Q16543:CDC37; NbExp=1; IntAct=EBI-296087, EBI-295634; CC O60437:PPL; NbExp=1; IntAct=EBI-296087, EBI-368321; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Nucleus after activation CC by integrin-linked protein kinase 1 (ILK1). CC -!- TISSUE SPECIFICITY: In all human cell types so far analyzed. CC -!- DOMAIN: Binding of the PH domain to the phosphatidylinositol 3- CC kinase alpha (PI(3)K) results in its targeting to the plasma CC membrane. CC -!- PTM: Phosphorylation on Thr-308, Ser-473 and Tyr-474 is required CC for full activity. Ser-473 phosphorylation by the Rictor-mTor CC complex favors Thr-308 phosphorylation by PDPK1. Ser-473 CC phosphorylation is enhanced by interaction with CENTG1 isoform 2 CC (PIKE-A). CC -!- SIMILARITY: Belongs to the Ser/Thr protein kinase family. RAC CC subfamily. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; M63167; AAA36539.1; -; mRNA. DR EMBL; AF283830; AAL55732.1; -; Genomic_DNA. DR EMBL; AF283819; AAL55732.1; JOINED; Genomic_DNA. DR EMBL; AF283820; AAL55732.1; JOINED; Genomic_DNA. DR EMBL; AF283821; AAL55732.1; JOINED; Genomic_DNA. DR EMBL; AF283822; AAL55732.1; JOINED; Genomic_DNA. DR EMBL; AF283823; AAL55732.1; JOINED; Genomic_DNA. DR EMBL; AF283824; AAL55732.1; JOINED; Genomic_DNA. DR EMBL; AF283825; AAL55732.1; JOINED; Genomic_DNA. DR EMBL; AF283826; AAL55732.1; JOINED; Genomic_DNA. DR EMBL; AF283827; AAL55732.1; JOINED; Genomic_DNA. DR EMBL; AF283828; AAL55732.1; JOINED; Genomic_DNA. DR EMBL; AF283829; AAL55732.1; JOINED; Genomic_DNA. DR EMBL; BC000479; AAH00479.1; -; mRNA. DR EMBL; BC084538; AAH84538.1; -; mRNA. DR EMBL; X61037; CAA43372.1; -; mRNA. DR PIR; A39360; A39360. DR UniGene; Hs.525622; -. DR UniGene; Hs.594927; -. DR PDB; 1H10; X-ray; A=1-123. DR PDB; 1UNP; X-ray; A=1-121. DR PDB; 1UNQ; X-ray; A=1-123. DR PDB; 1UNR; X-ray; A=1-123. DR IntAct; P31749; -. DR Ensembl; ENSG00000142208; Homo sapiens. DR H-InvDB; HIX0012019; -. DR HGNC; HGNC:391; AKT1. DR MIM; 164730; gene. DR Reactome; P31749; -. DR GO; GO:0005737; C:cytoplasm; ISS. DR GO; GO:0042802; F:identical protein binding; IPI. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA. DR GO; GO:0006916; P:anti-apoptosis; TAS. DR GO; GO:0007186; P:G-protein coupled receptor protein signalin...; TAS. DR GO; GO:0008286; P:insulin receptor signaling pathway; IMP. DR GO; GO:0048009; P:insulin-like growth factor receptor signali...; IMP. DR GO; GO:0006809; P:nitric oxide biosynthesis; TAS. DR GO; GO:0006468; P:protein amino acid phosphorylation; IDA. DR GO; GO:0009408; P:response to heat; TAS. DR GO; GO:0007165; P:signal transduction; TAS. DR InterPro; IPR011009; Kinase_like. DR InterPro; IPR001849; PH. DR InterPro; IPR011993; PH_type. DR InterPro; IPR000961; Pkinase_C. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR008271; Ser_thr_pkin_AS. DR InterPro; IPR002290; Ser_thr_pkinase. DR Pfam; PF00169; PH; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF00433; Pkinase_C; 1. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00133; S_TK_X; 1. DR SMART; SM00220; S_TKc; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. KW 3D-structure; Apoptosis; ATP-binding; Carbohydrate metabolism; KW Glucose metabolism; Glycogen biosynthesis; Glycogen metabolism; KW Kinase; Nuclear protein; Nucleotide-binding; Phosphorylation; KW Serine/threonine-protein kinase; Sugar transport; Transferase; KW Translation regulation; Transport. FT CHAIN 1 480 RAC-alpha serine/threonine-protein FT kinase. FT /FTId=PRO_0000085605. FT DOMAIN 5 108 PH. FT DOMAIN 150 408 Protein kinase. FT NP_BIND 156 164 ATP (By similarity). FT ACT_SITE 274 274 Proton acceptor (By similarity). FT BINDING 179 179 ATP (By similarity). FT MOD_RES 308 308 Phosphothreonine (by PDPK1). FT MOD_RES 473 473 Phosphoserine. FT MOD_RES 474 474 Phosphotyrosine. FT MUTAGEN 308 308 T->D: 5-fold activation and 18-fold FT activation; when associated with D-473. FT MUTAGEN 473 473 S->D: 7-fold activation and 25-fold FT activation; when associated with D-308. FT MUTAGEN 474 474 Y->F: 55% inhibition of activation. FT CONFLICT 173 174 GR -> A (in Ref. 4). FT CONFLICT 202 202 L -> Q (in Ref. 4). FT CONFLICT 212 212 A -> R (in Ref. 4). FT CONFLICT 246 246 S -> A (in Ref. 4). FT CONFLICT 409 409 A -> T (in Ref. 4). FT CONFLICT 476 476 A -> P (in Ref. 4). FT CONFLICT 478 478 G -> A (in Ref. 4). FT CONFLICT 478 478 G -> S (in Ref. 1 and 2). FT TURN 1 1 FT HELIX 2 4 FT STRAND 6 15 FT STRAND 17 19 FT STRAND 22 30 FT TURN 31 32 FT STRAND 33 40 FT STRAND 44 44 FT HELIX 45 48 FT TURN 49 49 FT STRAND 50 50 FT STRAND 52 56 FT TURN 58 59 FT STRAND 61 65 FT STRAND 67 69 FT TURN 70 71 FT STRAND 72 79 FT TURN 80 81 FT STRAND 82 89 FT STRAND 91 92 FT HELIX 93 115 SQ SEQUENCE 480 AA; 55686 MW; 6EAFF4F8AD436714 CRC64; MSDVAIVKEG WLHKRGEYIK TWRPRYFLLK NDGTFIGYKE RPQDVDQREA PLNNFSVAQC QLMKTERPRP NTFIIRCLQW TTVIERTFHV ETPEEREEWT TAIQTVADGL KKQEEEEMDF RSGSPSDNSG AEEMEVSLAK PKHRVTMNEF EYLKLLGKGT FGKVILVKEK ATGRYYAMKI LKKEVIVAKD EVAHTLTENR VLQNSRHPFL TALKYSFQTH DRLCFVMEYA NGGELFFHLS RERVFSEDRA RFYGAEIVSA LDYLHSEKNV VYRDLKLENL MLDKDGHIKI TDFGLCKEGI KDGATMKTFC GTPEYLAPEV LEDNDYGRAV DWWGLGVVMY EMMCGRLPFY NQDHEKLFEL ILMEEIRFPR TLGPEAKSLL SGLLKKDPKQ RLGGGSEDAK EIMQHRFFAG IVWQHVYEKK LSPPFKPQVT SETDTRYFDE EFTAQMITIT PPDQDDSMEC VDSERRPHFP QFSYSASGTA // ID AKT1_MOUSE STANDARD; PRT; 480 AA. AC P31750; Q62274; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1993, sequence version 1. DT 30-MAY-2006, entry version 64. DE RAC-alpha serine/threonine-protein kinase (EC 2.7.11.1) (RAC-PK-alpha) DE (AKT1 kinase) (Protein kinase B) (PKB) (C-AKT) (Thymoma viral proto- DE oncogene). GN Name=Akt1; Synonyms=Akt, Rac; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Bousquets X., Powell C.T.; RT "Complete nucleotide coding sequence for murine rac (related to A and RT C kinases) protein kinase."; RL Submitted (JUN-1992) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY. RC STRAIN=AKR/J; TISSUE=Thymus; RX MEDLINE=93173519; PubMed=8437858; RA Bellacosa A., Franke T.F., Gonzalez-Portal M.E., Datta K., Taguchi T., RA Gardner J., Cheng J.Q., Testa J.R., Tsichlis P.N.; RT "Structure, expression and chromosomal mapping of c-akt: relationship RT to v-akt and its implications."; RL Oncogene 8:745-754(1993). RN [3] RP FUNCTION, AND MUTAGENESIS OF LYS-179. RX PubMed=9415393; DOI=10.1210/me.11.13.1881; RA Cong L.N., Chen H., Li Y., Zhou L., McGibbon M.A., Taylor S.I., RA Quon M.J.; RT "Physiological role of Akt in insulin-stimulated translocation of RT GLUT4 in transfected rat adipose cells."; RL Mol. Endocrinol. 11:1881-1890(1997). RN [4] RP FUNCTION. RX PubMed=11282895; RA Yamashita K., Kajstura J., Discher D.J., Wasserlauf B.J., RA Bishopric N.H., Anversa P., Webster K.A.; RT "Reperfusion-activated Akt kinase prevents apoptosis in transgenic RT mouse hearts overexpressing insulin-like growth factor-1."; RL Circ. Res. 88:609-614(2001). RN [5] RP PHOSPHORYLATION OF TBC1D4. RX MEDLINE=22063368; PubMed=11994271; DOI=10.1074/jbc.C200198200; RA Kane S., Sano H., Liu S.C.H., Asara J.M., Lane W.S., Garner C.C., RA Lienhard G.E.; RT "A method to identify serine kinase substrates. Akt phosphorylates a RT novel adipocyte protein with a Rab GTPase-activating protein (GAP) RT domain."; RL J. Biol. Chem. 277:22115-22118(2002). CC -!- FUNCTION: General protein kinase capable of phosphorylating CC several known proteins. Phosphorylates TBC1D4. Signals downstream CC of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects CC of various growth factors such as platelet-derived growth factor CC (PDGF), epidermal growth factor (EGF), insulin and insulin-like CC growth factor I (IGF-I). Plays a role in glucose transport by CC mediating insulin-induced translocation of the GLUT4 glucose CC transporter to the cell surface. Mediates the antiapoptotic CC effects of IGF-I. Mediates insulin-stimulated protein synthesis, CC partly by playing a role in both insulin-induced phosphorylation CC of 4E-BP1 and in insulin-induced activation of p70 S6 kinase. CC Promotes glycogen synthesis by mediating the insulin-induced CC activation of glycogen synthase. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- INTERACTION: CC Q8K4K2:Trib3; NbExp=5; IntAct=EBI-298707, EBI-448962; CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By CC similarity). Nucleus after activation by integrin-linked protein CC kinase 1 (ILK1) (By similarity). CC -!- TISSUE SPECIFICITY: Widely expressed. Low levels found in liver CC with slightly higher levels present in thymus and testis. CC -!- DOMAIN: Binding of the PH domain to the phosphatidylinositol 3- CC kinase alpha (PI(3)K) results in its targeting to the plasma CC membrane. CC -!- PTM: Phosphorylation on Thr-308, Ser-473 and Tyr-474 is required CC for full activity. Ser-473 phosphorylation favors Thr-308 CC phosphorylation (By similarity). CC -!- SIMILARITY: Belongs to the Ser/Thr protein kinase family. RAC CC subfamily. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; M94335; AAA18254.1; -; mRNA. DR EMBL; X65687; CAA46620.1; -; mRNA. DR PIR; S33364; S33364. DR UniGene; Mm.6645; -. DR HSSP; P31749; 1H10. DR SMR; P31750; 3-121. DR IntAct; P31750; -. DR Ensembl; ENSMUSG00000001729; Mus musculus. DR MGI; MGI:87986; Akt1. DR GO; GO:0005737; C:cytoplasm; IDA. DR GO; GO:0030027; C:lamellipodium; IDA. DR GO; GO:0005819; C:spindle; IDA. DR GO; GO:0005515; F:protein binding; IPI. DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS. DR GO; GO:0042640; P:anagen; IMP. DR GO; GO:0006915; P:apoptosis; IDA. DR GO; GO:0008637; P:apoptotic mitochondrial changes; IDA. DR GO; GO:0007281; P:germ cell development; IDA. DR GO; GO:0015758; P:glucose transport; IMP. DR GO; GO:0006954; P:inflammatory response; IDA. DR GO; GO:0008286; P:insulin receptor signaling pathway; IMP. DR GO; GO:0048009; P:insulin-like growth factor receptor signali...; ISS. DR GO; GO:0043066; P:negative regulation of apoptosis; IMP. DR GO; GO:0006468; P:protein amino acid phosphorylation; ISS. DR GO; GO:0030163; P:protein catabolism; IDA. DR GO; GO:0016567; P:protein ubiquitination; IDA. DR GO; GO:0045884; P:regulation of survival gene product activity; IDA. DR InterPro; IPR011009; Kinase_like. DR InterPro; IPR001849; PH. DR InterPro; IPR011993; PH_type. DR InterPro; IPR000961; Pkinase_C. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR008271; Ser_thr_pkin_AS. DR InterPro; IPR002290; Ser_thr_pkinase. DR Pfam; PF00169; PH; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF00433; Pkinase_C; 1. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00133; S_TK_X; 1. DR SMART; SM00220; S_TKc; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. KW Apoptosis; ATP-binding; Carbohydrate metabolism; Glucose metabolism; KW Glycogen biosynthesis; Glycogen metabolism; Kinase; Nuclear protein; KW Nucleotide-binding; Phosphorylation; Serine/threonine-protein kinase; KW Sugar transport; Transferase; Translation regulation; Transport. FT CHAIN 1 480 RAC-alpha serine/threonine-protein FT kinase. FT /FTId=PRO_0000085606. FT DOMAIN 5 108 PH. FT DOMAIN 150 408 Protein kinase. FT NP_BIND 156 164 ATP (By similarity). FT ACT_SITE 274 274 Proton acceptor (By similarity). FT BINDING 179 179 ATP. FT MOD_RES 308 308 Phosphothreonine (By similarity). FT MOD_RES 473 473 Phosphoserine (By similarity). FT MOD_RES 474 474 Phosphotyrosine (By similarity). FT MUTAGEN 179 179 K->A: Lacks kinase activity. FT Overexpression inhibits insulin- FT stimulated translocation of GLUT4 in a FT dominant negative manner. FT CONFLICT 367 367 A -> R (in Ref. 2). SQ SEQUENCE 480 AA; 55622 MW; 18D21018593B5A98 CRC64; MNDVAIVKEG WLHKRGEYIK TWRPRYFLLK NDGTFIGYKE RPQDVDQRES PLNNFSVAQC QLMKTERPRP NTFIIRCLQW TTVIERTFHV ETPEEREEWA TAIQTVADGL KRQEEETMDF RSGSPSDNSG AEEMEVSLAK PKHRVTMNEF EYLKLLGKGT FGKVILVKEK ATGRYYAMKI LKKEVIVAKD EVAHTLTENR VLQNSRHPFL TALKYSFQTH DRLCFVMEYA NGGELFFHLS RERVFSEDRA RFYGAEIVSA LDYLHSEKNV VYRDLKLENL MLDKDGHIKI TDFGLCKEGI KDGATMKTFC GTPEYLAPEV LEDNDYGRAV DWWGLGVVMY EMMCGRLPFY NQDHEKLFEL ILMEEIAFPR TLGPEAKSLL SGLLKKDPTQ RLGGGSEDAK EIMQHRFFAN IVWQDVYEKK LSPPFKPQVT SETDTRYFDE EFTAQMITIT PPDQDDSMEC VDSERRPHFP QFSYSASGTA // ID AKT1_RAT STANDARD; PRT; 480 AA. AC P47196; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1996, sequence version 1. DT 30-MAY-2006, entry version 53. DE RAC-alpha serine/threonine-protein kinase (EC 2.7.11.1) (RAC-PK-alpha) DE (Protein kinase B) (PKB). GN Name=Akt1; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Sciurognathi; OC Muroidea; Muridae; Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Testis; RX MEDLINE=95091823; PubMed=7999118; RA Konishi H., Shinomura T., Kuroda S.I., Ono Y., Kikkawa U.; RT "Molecular cloning of rat RAC protein kinase alpha and beta and their RT association with protein kinase C zeta."; RL Biochem. Biophys. Res. Commun. 205:817-825(1994). RN [2] RP FUNCTION, AND MUTAGENESIS OF LYS-179; THR-308 AND SER-473. RX PubMed=9632753; RA Kitamura T., Ogawa W., Sakaue H., Hino Y., Kuroda S., Takata M., RA Matsumoto M., Maeda T., Konishi H., Kikkawa U., Kasuga M.; RT "Requirement for activation of the serine-threonine kinase Akt RT (protein kinase B) in insulin stimulation of protein synthesis but not RT of glucose transport."; RL Mol. Cell. Biol. 18:3708-3717(1998). RN [3] RP FUNCTION, AND MUTAGENESIS OF LYS-179; THR-308 AND SER-473. RX PubMed=10400692; DOI=10.1074/jbc.274.29.20611; RA Takata M., Ogawa W., Kitamura T., Hino Y., Kuroda S., Kotani K., RA Klip A., Gingras A.C., Sonenberg N., Kasuga M.; RT "Requirement for Akt (protein kinase B) in insulin-induced activation RT of glycogen synthase and phosphorylation of 4E-BP1 (PHAS-1)."; RL J. Biol. Chem. 274:20611-20618(1999). CC -!- FUNCTION: General protein kinase capable of phosphorylating CC several known proteins. Phosphorylates TBC1D4. Signals downstream CC of phosphatidylinositol 3-kinase (PI(3)K) to mediate the effects CC of various growth factors such as platelet-derived growth factor CC (PDGF), epidermal growth factor (EGF), insulin and insulin-like CC growth factor I (IGF-I). Plays a role in glucose transport by CC mediating insulin-induced translocation of the GLUT4 glucose CC transporter to the cell surface. Mediates the antiapoptotic CC effects of IGF-I (By similarity). Mediates insulin-stimulated CC protein synthesis, partly by playing a role in both insulin- CC induced phosphorylation of 4E-BP1 and in insulin-induced CC activation of p70 S6 kinase. Promotes glycogen synthesis by CC mediating the insulin-induced activation of glycogen synthase. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By CC similarity). Nucleus after activation by integrin-linked protein CC kinase 1 (ILK1) (By similarity). CC -!- TISSUE SPECIFICITY: Widely expressed. Low levels found in liver CC with slightly higher levels present in thymus and testis. CC -!- DOMAIN: Binding of the PH domain to the phosphatidylinositol 3- CC kinase alpha (PI(3)K) results in its targeting to the plasma CC membrane. CC -!- PTM: Phosphorylation on Thr-308, Ser-473 and Tyr-474 is required CC for full activity. Ser-473 phosphorylation favors Thr-308 CC phosphorylation. CC -!- SIMILARITY: Belongs to the Ser/Thr protein kinase family. RAC CC subfamily. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; D30040; BAA06279.1; -; mRNA. DR PIR; JC2437; JC2437. DR UniGene; Rn.11422; -. DR HSSP; P31749; 1H10. DR SMR; P47196; 3-121. DR Ensembl; ENSRNOG00000028629; Rattus norvegicus. DR RGD; 2081; Akt1. DR GO; GO:0005737; C:cytoplasm; IDA. DR GO; GO:0005515; F:protein binding; IDA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS. DR GO; GO:0006916; P:anti-apoptosis; IMP. DR GO; GO:0005978; P:glycogen biosynthesis; IMP. DR GO; GO:0008286; P:insulin receptor signaling pathway; IMP. DR GO; GO:0048009; P:insulin-like growth factor receptor signali...; ISS. DR GO; GO:0030307; P:positive regulation of cell growth; IDA. DR GO; GO:0006468; P:protein amino acid phosphorylation; ISS. DR GO; GO:0006412; P:protein biosynthesis; IMP. DR GO; GO:0007165; P:signal transduction; IDA. DR InterPro; IPR011009; Kinase_like. DR InterPro; IPR001849; PH. DR InterPro; IPR011993; PH_type. DR InterPro; IPR000961; Pkinase_C. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR008271; Ser_thr_pkin_AS. DR InterPro; IPR002290; Ser_thr_pkinase. DR Pfam; PF00169; PH; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF00433; Pkinase_C; 1. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00133; S_TK_X; 1. DR SMART; SM00220; S_TKc; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. KW Apoptosis; ATP-binding; Carbohydrate metabolism; Glucose metabolism; KW Glycogen biosynthesis; Glycogen metabolism; Kinase; Nuclear protein; KW Nucleotide-binding; Phosphorylation; Serine/threonine-protein kinase; KW Sugar transport; Transferase; Translation regulation; Transport. FT CHAIN 1 480 RAC-alpha serine/threonine-protein FT kinase. FT /FTId=PRO_0000085607. FT DOMAIN 5 108 PH. FT DOMAIN 150 408 Protein kinase. FT NP_BIND 156 164 ATP (By similarity). FT ACT_SITE 274 274 Proton acceptor (By similarity). FT BINDING 179 179 ATP. FT MOD_RES 308 308 Phosphothreonine. FT MOD_RES 473 473 Phosphoserine. FT MOD_RES 474 474 Phosphotyrosine (By similarity). FT MUTAGEN 179 179 K->D: Lacks kinase activity. Inhibits FT insulin-induced activation of glycogen FT synthase when expressed. FT MUTAGEN 308 308 T->A: Inhibits insulin-induced activation FT of endogenous Akt1, insulin-stimulated FT protein synthesis, insulin-induced FT activation of glycogen synthase and FT insulin-induced phosphorylation of 4E-BP1 FT in a dominant negative manner when FT overexpressed; when associated with A- FT 473. FT MUTAGEN 473 473 S->A: Inhibits insulin-induced activation FT of endogenous Akt1, insulin-stimulated FT protein synthesis, insulin-induced FT activation of glycogen synthase and FT insulin-induced phosphorylation of 4E-BP1 FT in a dominant negative manner when FT overexpressed; when associated with A- FT 308. SQ SEQUENCE 480 AA; 55735 MW; 5DCAAE7134366D04 CRC64; MNDVAIVKEG WLHKRGEYIK TWRPRYFLLK NDGTFIGYKE RPQDVEQRES PLNNFSVAQC QLMKTERPRP NTFIIRCLQW TTVIERTFHV ETPEEREEWT TAIQTVADGL KRQEEETMDF RSGSPSDNSG AEEMEVALAK PKHRVTMNEF EYLKLLGKGT FGKVILVKEK ATGRYYAMKI LKKEVIVAKD EVAHTLTENR VLQNSRHPFL TALKYSFQTH DRLCFVMEYA NGGELFFHLS RERVFSEDRA RFYGAEIVSA LDYLHSEKNV VYRDLKLENL MLDKDGHIKI TDFGLCKEGI KDGATMKTFC GTPEYLAPEV LEDNDYGRAV DWWGLGVVMY EMMCGRLPFY NQDHEKLFEL ILMEEIRFPR TLGPEAKSLL SGLLKKDPTQ RLGGGSEDAK EIMQHRFFAN IVWQDVYEKK LSPPFKPQVT SETDTRYFDE EFTAQMITIT PPDQDDSMEC VDSERRPHFP QFSYSASGTA // ID AKT1_XENLA STANDARD; PRT; 481 AA. AC Q98TY9; DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 1. DT 30-MAY-2006, entry version 30. DE RAC-alpha serine/threonine-protein kinase (EC 2.7.11.1) (RAC-PK-alpha) DE (Protein kinase Akt-1) (Protein kinase B, alpha) (PKB alpha) (xAkt). GN Name=akt1; OS Xenopus laevis (African clawed frog). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Amphibia; Batrachia; Anura; Mesobatrachia; Pipoidea; Pipidae; OC Xenopodinae; Xenopus; Xenopus. OX NCBI_TaxID=8355; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ENZYME REGULATION, AND TISSUE RP SPECIFICITY. RC TISSUE=Oocyte; RX PubMed=12374568; DOI=10.1042/BJ20021243; RA Andersen C.B., Sakaue H., Nedachi T., Kovacina K.S., Clayberger C., RA Conti M., Roth R.A.; RT "Protein kinase B/Akt is essential for the insulin- but not RT progesterone-stimulated resumption of meiosis in Xenopus oocytes."; RL Biochem. J. 369:227-238(2003). CC -!- FUNCTION: General protein kinase capable of phosphorylating CC several known proteins. Signals downstream of phosphatidylinositol CC 3-kinase (PI(3)K) to mediate the effects of various growth factors CC such as platelet-derived growth factor (PDGF), epidermal growth CC factor (EGF), insulin and insulin-like growth factor I (IGF-I). CC Plays a role in glucose transport by mediating insulin-induced CC translocation of the GLUT4 glucose transporter to the cell CC surface. Mediates the antiapoptotic effects of IGF-I. Mediates CC insulin-stimulated protein synthesis, partly by playing a role in CC both insulin-induced phosphorylation of 4E-BP1 and in insulin- CC induced activation of p70 S6 kinase. Promotes glycogen synthesis CC by mediating the insulin-induced activation of glycogen synthase CC (By similarity). Required for insulin-stimulated meiotic CC reinitiation during oocyte maturation. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- ENZYME REGULATION: Activated in response to insulin. CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Nucleus (By CC similarity). Nucleus after activation by integrin-linked protein CC kinase 1 (ILK1) (By similarity). CC -!- TISSUE SPECIFICITY: Expressed in the oocyte. CC -!- DOMAIN: Binding of the PH domain to the phosphatidylinositol 3- CC kinase alpha (PI(3)K) results in its targeting to the plasma CC membrane. CC -!- SIMILARITY: Belongs to the Ser/Thr protein kinase family. RAC CC subfamily. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF317656; AAG59601.1; -; mRNA. DR UniGene; Xl.738; -. DR HSSP; P31751; 1MRY. DR SMR; Q98TY9; 1-116. DR GO; GO:0005737; C:cytoplasm; ISS. DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS. DR GO; GO:0015758; P:glucose transport; ISS. DR GO; GO:0008286; P:insulin receptor signaling pathway; ISS. DR GO; GO:0048009; P:insulin-like growth factor receptor signali...; ISS. DR GO; GO:0043066; P:negative regulation of apoptosis; ISS. DR GO; GO:0006468; P:protein amino acid phosphorylation; ISS. DR InterPro; IPR011009; Kinase_like. DR InterPro; IPR001849; PH. DR InterPro; IPR011993; PH_type. DR InterPro; IPR000961; Pkinase_C. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR008271; Ser_thr_pkin_AS. DR InterPro; IPR002290; Ser_thr_pkinase. DR Pfam; PF00169; PH; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF00433; Pkinase_C; 1. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00133; S_TK_X; 1. DR SMART; SM00220; S_TKc; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. KW ATP-binding; Carbohydrate metabolism; Glucose metabolism; KW Glycogen biosynthesis; Kinase; Nuclear protein; Nucleotide-binding; KW Phosphorylation; Serine/threonine-protein kinase; Sugar transport; KW Transferase; Transport. FT CHAIN 1 481 RAC-alpha serine/threonine-protein FT kinase. FT /FTId=PRO_0000223507. FT DOMAIN 5 108 PH. FT DOMAIN 151 409 Protein kinase. FT NP_BIND 157 165 ATP (By similarity). FT ACT_SITE 275 275 Proton acceptor (By similarity). FT BINDING 180 180 ATP (By similarity). SQ SEQUENCE 481 AA; 56042 MW; FF56CFB9A6454303 CRC64; MNEVAIVKEG WLHKRGEYIK TWRPRYFLLK SDGTFIGYKE RPQDVDQLET PLNNFSVAKC QLMKTERPKP NTFIIRCLQW TTVIERTFHV DSPEEREEWI QVIQHVADNL KKQEEEMMEV RSGDSPSDNS GAEEMEVSHS KPKHKVTMNE FEYLKLLGKG TFGKVILVKE KATGRYYAMK ILKKEVIVAK DEVAHTLTEN RVLQNSRHPF LTALKYSFQT HDRLCFVMEY ANGGELFFHL SRERIFSEDR ARFYGAEIVS ALDYLHSEKN VVYRDLKLEN LMLDKDGHIK ITDFGLCKEG IKDGATMKTF CGTPEYLAPE VLEDNDYGRA VDWWGLGVVM YEMMCGRLPF YNQDHEKLFE LILMEEIRFP RTLLPEAKSL LSGLLKKDPK QRLGGGPDDA KEIMQHKFFA GIVWQDVYEK KLVPPFKPQV TSETDTRYFD EEFTAQMITI TPPDQDDNFE FVDNERRPHF PQFSYSASGN A // ID AKT2A_XENLA STANDARD; PRT; 486 AA. AC Q7ZX15; DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2003, sequence version 1. DT 30-MAY-2006, entry version 27. DE RAC-beta serine/threonine-protein kinase-A (EC 2.7.11.1) (RAC-PK-beta- DE A) (Protein kinase Akt-2-A) (Protein kinase B, beta-A) (PKB beta-A). GN Name=akt2-A; OS Xenopus laevis (African clawed frog). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Amphibia; Batrachia; Anura; Mesobatrachia; Pipoidea; Pipidae; OC Xenopodinae; Xenopus; Xenopus. OX NCBI_TaxID=8355; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Embryo; RG NIH - Xenopus Gene Collection (XGC) project; RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: General protein kinase capable of phosphorylating CC several known proteins (By similarity). CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- SIMILARITY: Belongs to the Ser/Thr protein kinase family. RAC CC subfamily. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; BC046261; AAH46261.1; -; mRNA. DR UniGene; Xl.5248; -. DR HSSP; P31751; 1MRY. DR SMR; Q7ZX15; 1-113. DR InterPro; IPR011009; Kinase_like. DR InterPro; IPR001849; PH. DR InterPro; IPR011993; PH_type. DR InterPro; IPR000961; Pkinase_C. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR008271; Ser_thr_pkin_AS. DR InterPro; IPR002290; Ser_thr_pkinase. DR Pfam; PF00169; PH; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF00433; Pkinase_C; 1. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00133; S_TK_X; 1. DR SMART; SM00220; S_TKc; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. KW ATP-binding; Kinase; Nucleotide-binding; KW Serine/threonine-protein kinase; Transferase. FT CHAIN 1 486 RAC-beta serine/threonine-protein kinase- FT A. FT /FTId=PRO_0000223508. FT DOMAIN 5 110 PH. FT DOMAIN 157 414 Protein kinase. FT NP_BIND 163 171 ATP (By similarity). FT ACT_SITE 280 280 Proton acceptor (By similarity). FT BINDING 186 186 ATP (By similarity). SQ SEQUENCE 486 AA; 56310 MW; F124CAE30758016B CRC64; MNEVMVIKEG WLQKRGEYIK TWRPRYFLLK SDGSFIGYKE KPESTEHNVV LPPLNNFSVA ECQLMKTERP RPNTFVIRCL QWTTVIERTF HVDTPEEREE WIIAIQTVAN GLKNQVPEDE EEEAMEVKYG SPSDVSSAEQ MDVAMSKGHP KVTMNDFDYL KLLGKGTFGK VILVREKATG RYYAMKILRK EVIIAKDEVA HTLTESRVLQ NTKHPFLTAL KYAFQTSDRL CFVMEYANGG ELFFHLSRER VFTEDRARFY GAEIVSALEY LHSRNVVYRD IKLENLMLDK DGHVKITDFG LCKEGITDGA TMRTFCGTPE YLAPEVLEDN DYGRAVDWWG LGVVMYEMMC GRLPFYNQDH ERLFELILME EIRFPRTLSP EAKSLLAGLL KKDPKQRLGG GPNDAQEVMS HRFFVSINWQ DVTERKLTPP FKPQVTSEID TRYFDDEFTA QSITLTPPDR YDNLDALESD QRPHFPQFSY SASIRE // ID AKT2B_XENLA STANDARD; PRT; 485 AA. AC Q6IP76; DT 21-FEB-2006, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 30-MAY-2006, entry version 22. DE RAC-beta serine/threonine-protein kinase-B (EC 2.7.11.1) (RAC-PK-beta- DE B) (Protein kinase Akt-2-B) (Protein kinase B, beta-B) (PKB beta-B). GN Name=akt2-B; OS Xenopus laevis (African clawed frog). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Amphibia; Batrachia; Anura; Mesobatrachia; Pipoidea; Pipidae; OC Xenopodinae; Xenopus; Xenopus. OX NCBI_TaxID=8355; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Spleen; RG NIH - Xenopus Gene Collection (XGC) project; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: General protein kinase capable of phosphorylating CC several known proteins (By similarity). CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- SIMILARITY: Belongs to the Ser/Thr protein kinase family. RAC CC subfamily. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; BC072041; AAH72041.1; -; mRNA. DR UniGene; Xl.16885; -. DR HSSP; P05132; 1ATP. DR SMR; Q6IP76; 1-112. DR InterPro; IPR011009; Kinase_like. DR InterPro; IPR001849; PH. DR InterPro; IPR011993; PH_type. DR InterPro; IPR000961; Pkinase_C. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR008271; Ser_thr_pkin_AS. DR InterPro; IPR002290; Ser_thr_pkinase. DR Pfam; PF00169; PH; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF00433; Pkinase_C; 1. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00133; S_TK_X; 1. DR SMART; SM00220; S_TKc; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. KW ATP-binding; Kinase; Nucleotide-binding; KW Serine/threonine-protein kinase; Transferase. FT CHAIN 1 485 RAC-beta serine/threonine-protein kinase- FT B. FT /FTId=PRO_0000223509. FT DOMAIN 5 109 PH. FT DOMAIN 156 413 Protein kinase. FT NP_BIND 162 170 ATP (By similarity). FT ACT_SITE 279 279 Proton acceptor (By similarity). FT BINDING 185 185 ATP (By similarity). SQ SEQUENCE 485 AA; 56024 MW; 27D584109098CC56 CRC64; MNEVMVIKEG WLQKRGEYIK TWRPRYFLLK SDGSFIGYKE KPDSTEHSLL PPLNNFSVAE CQLMKTERPR PNTFVIRCLQ WTTVIERTFH VDTPEEREEW IIAIQTVANG LKNQVPEDEE EEAMEVKYGS PSDVSSAEQM DVAMSKGRPK VTMNDFDYLK LLGKGTFGKV ILVREKATGL YYAMKILRKE VIIAKDEVAH TLTESRVLQN TKHPFLTGLK YAFQTSDRLC FVMEYANGGE LFFHLSRERV FTEDRARFYG AEIVSALEYL HSRNVVYRDI KLENLMLDKD GHVKITDFGL CKEGITDGAT MRTFCGTPEY LAPEVLEDND YGRAVDWWGL GVVMYEMMCG RLPFYNQDHE RLFELILMEE TRFPRTLSPE AKSLLAGLLK KDPKQRLGGG PDDAQEVMSH GFFASINWQD VTERKLSPPF KPQVTSEIDT RYFDDEFTAQ SITLTPPDRY DNLDALESEQ RPHFPQFSYS SSIRE // ID AKT2_CAEEL STANDARD; PRT; 528 AA. AC Q9XTG7; O77145; DT 24-JAN-2006, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 30-MAY-2006, entry version 48. DE Serine/threonine-protein kinase akt-2 (EC 2.7.11.1) (Protein kinase B DE akt-2) (PKB akt-2). GN Name=akt-2; ORFNames=F28H6.1; OS Caenorhabditis elegans. OC Eukaryota; Metazoa; Nematoda; Chromadorea; Rhabditida; Rhabditoidea; OC Rhabditidae; Peloderinae; Caenorhabditis. OX NCBI_TaxID=6239; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), FUNCTION, TISSUE SPECIFICITY, RP AND DEVELOPMENTAL STAGE. RX MEDLINE=98382502; PubMed=9716402; RA Paradis S., Ruvkun G.; RT "Caenorhabditis elegans Akt/PKB transduces insulin receptor-like RT signals from AGE-1 PI3 kinase to the DAF-16 transcription factor."; RL Genes Dev. 12:2488-2498(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Bristol N2; RX MEDLINE=99069613; PubMed=9851916; DOI=10.1126/science.282.5396.2012; RG The C. elegans sequencing consortium; RT "Genome sequence of the nematode C. elegans: a platform for RT investigating biology."; RL Science 282:2012-2018(1998). RN [3] RP SEQUENCE REVISION, AND ALTERNATIVE SPLICING. RG WormBase consortium; RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases. RN [4] RP FUNCTION. RX MEDLINE=99292684; PubMed=10364160; RA Paradis S., Ailion M., Toker A., Thomas J.H., Ruvkun G.; RT "A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 RT kinase signals that regulate diapause in Caenorhabditis elegans."; RL Genes Dev. 13:1438-1452(1999). RN [5] RP FUNCTION. RX MEDLINE=21614652; PubMed=11747825; DOI=10.1016/S0960-9822(01)00594-2; RA Henderson S.T., Johnson T.E.; RT "daf-16 integrates developmental and environmental inputs to mediate RT aging in the nematode Caenorhabditis elegans."; RL Curr. Biol. 11:1975-1980(2001). RN [6] RP FUNCTION. RX PubMed=11381260; DOI=10.1038/88850; RA Lin K., Hsin H., Libina N., Kenyon C.; RT "Regulation of the Caenorhabditis elegans longevity protein DAF-16 by RT insulin/IGF-1 and germline signaling."; RL Nat. Genet. 28:139-145(2001). RN [7] RP INTERACTION WITH PDK-1; SGK-1; AKT-1 AND DAF-16, AND FUNCTION. RX PubMed=15068796; DOI=10.1016/S1534-5807(04)00095-4; RA Hertweck M., Goebel C., Baumeister R.; RT "C. elegans SGK-1 is the critical component in the Akt/PKB kinase RT complex to control stress response and life span."; RL Dev. Cell 6:577-588(2004). CC -!- FUNCTION: Acts downstream age-1 and pdk-1 in the daf-2/insulin CC receptor-like transduction pathway, which controls longevity and CC prevents developmental arrest at the dauer stage. Phosphorylates CC Forkhead-related daf-16 transcription factor, which inhibits its CC entry into the nucleus and antagonizes its function. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- SUBUNIT: Interacts with pdk-1, sgk-1, akt-1 and daf-16. Part of a CC complex containing sgk-1, akt-1 and akt-2. CC -!- INTERACTION: CC P34766:pal-1; NbExp=1; IntAct=EBI-320656, EBI-311911; CC Q22847:T28C6.7; NbExp=1; IntAct=EBI-320656, EBI-316760; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=a; CC IsoId=Q9XTG7-1; Sequence=Displayed; CC Name=b; CC IsoId=Q9XTG7-2; Sequence=VSP_017047, VSP_017048; CC -!- TISSUE SPECIFICITY: Expressed in neurons, muscle cells of the CC pharynx, rectal gland cells, and spermatheca. CC -!- DEVELOPMENTAL STAGE: Expressed in late stage embryos and CC throughout life. CC -!- SIMILARITY: Belongs to the Ser/Thr protein kinase family. RAC CC subfamily. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF072381; AAC62468.1; -; mRNA. DR EMBL; AL031621; CAA20936.1; -; Genomic_DNA. DR EMBL; Z92837; CAA20936.1; JOINED; Genomic_DNA. DR EMBL; Z92837; CAB07403.1; -; Genomic_DNA. DR EMBL; AL031621; CAB07403.1; JOINED; Genomic_DNA. DR EMBL; AL031621; CAC70087.1; -; Genomic_DNA. DR EMBL; Z92837; CAC70087.1; JOINED; Genomic_DNA. DR EMBL; Z92837; CAD21654.1; -; Genomic_DNA. DR EMBL; AL031621; CAD21654.1; JOINED; Genomic_DNA. DR PIR; T21523; T21523. DR PIR; T43234; T43234. DR UniGene; Cel.18147; -. DR HSSP; P31751; 1MRY. DR IntAct; Q9XTG7; -. DR Ensembl; F28H6.1; Caenorhabditis elegans. DR WormBase; WBGene00000103; akt-2. DR WormPep; F28H6.1a; CE18646. DR WormPep; F28H6.1b; CE29298. DR GO; GO:0005622; C:intracellular; IDA. DR GO; GO:0005515; F:protein binding; IPI. DR InterPro; IPR011009; Kinase_like. DR InterPro; IPR001849; PH. DR InterPro; IPR011993; PH_type. DR InterPro; IPR000961; Pkinase_C. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR008271; Ser_thr_pkin_AS. DR InterPro; IPR002290; Ser_thr_pkinase. DR Pfam; PF00169; PH; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF00433; Pkinase_C; 1. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00133; S_TK_X; 1. DR SMART; SM00220; S_TKc; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. KW Alternative splicing; ATP-binding; Complete proteome; KW Developmental protein; Kinase; Nucleotide-binding; KW Serine/threonine-protein kinase; Transferase. FT CHAIN 1 528 Serine/threonine-protein kinase akt-2. FT /FTId=PRO_0000085616. FT DOMAIN 12 115 PH. FT DOMAIN 180 437 Protein kinase. FT NP_BIND 186 194 ATP (By similarity). FT ACT_SITE 303 303 Proton acceptor (By similarity). FT BINDING 209 209 ATP (By similarity). FT VAR_SEQ 470 483 EFTSMPVQLTPPRR -> VRYVSILLKVSEAI (in FT isoform b). FT /FTId=VSP_017047. FT VAR_SEQ 484 528 Missing (in isoform b). FT /FTId=VSP_017048. SQ SEQUENCE 528 AA; 61058 MW; 9750E8F0AE4F6AE7 CRC64; MSTENAHLQK EDIVIESWLH KKGEHIRNWR PRYFILFRDG TLLGFRSKPK EDQPLPEPLN NFMIRDAATV CLDKPRPNMF IVRCLQWTTV IERTFYADSA DFRQMWIEAI QAVSSHNRLK ENAGNTSMQE EDTNGNPSGE SDVNMDATST RSDNDFESTV MNIDEPEEVP RKNTVTMDDF DFLKVLGQGT FGKVILCREK SSDKLYAIKI IRKEMVVDRS EVAHTLTENR VLYACVHPFL TLLKYSFQAQ YHICFVMEFA NGGELFTHLQ RCKTFSEART RFYGSEIILA LGYLHHRNIV YRDMKLENLL LDRDGHIKIT DFGLCKEEIK YGDKTSTFCG TPEYLAPEVI EDIDYDRSVD WWGVGVVMYE MMCGRLPFSA KENGKLFELI TTCDLKFPNR LSPEAVTLLS GLLERVPAKR LGAGPDDARE VSRAEFFKDV DWEATLRKEV EPPFKPNVMS ETDTSFFDRE FTSMPVQLTP PRRGEELPTV DEEEELQANF IQFASYYVSG SLERSYDTNR SADKYEIR // ID AKT2_HUMAN STANDARD; PRT; 481 AA. AC P31751; Q68GC0; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 2. DT 30-MAY-2006, entry version 61. DE RAC-beta serine/threonine-protein kinase (EC 2.7.11.1) (RAC-PK-beta) DE (Protein kinase Akt-2) (Protein kinase B, beta) (PKB beta). GN Name=AKT2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE. RC TISSUE=Epithelium; RX MEDLINE=92198987; PubMed=1801921; RA Jones P.F., Jakubowicz T., Hemmings B.A.; RT "Molecular cloning of a second form of rac protein kinase."; RL Cell Regul. 2:1001-1009(1991). RN [2] RP NUCLEOTIDE SEQUENCE. RX MEDLINE=93028445; PubMed=1409633; RA Cheng J.Q., Godwin A.K., Bellacosa A., Taguchi T., Franke T.F., RA Hamilton T.C., Tsichlis P.N., Testa J.R.; RT "AKT2, a putative oncogene encoding a member of a subfamily of RT protein-serine/threonine kinases, is amplified in human ovarian RT carcinomas."; RL Proc. Natl. Acad. Sci. U.S.A. 89:9267-9271(1992). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 237-277. RA Rieder M.J., Livingston R.J., Braun A.C., Montoya M.A., Chung M.-W., RA Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D., RA Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A.; RT "NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department RT of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)."; RL Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: General protein kinase capable of phosphorylating CC several known proteins. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- INTERACTION: CC Q16543:CDC37; NbExp=1; IntAct=EBI-296058, EBI-295634; CC -!- TISSUE SPECIFICITY: In all human cell types so far analyzed. CC -!- DISEASE: Alterations of AKT2 may contribute to the pathogenesis of CC ovarian carcinomas. CC -!- SIMILARITY: Belongs to the Ser/Thr protein kinase family. RAC CC subfamily. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; M77198; AAA36585.1; -; mRNA. DR EMBL; M95936; AAA58364.1; -; mRNA. DR EMBL; AY708392; AAT97984.1; -; Genomic_DNA. DR PIR; A46288; A46288. DR UniGene; Hs.541273; -. DR PDB; 1GZK; X-ray; A=146-460. DR PDB; 1GZN; X-ray; A=146-480. DR PDB; 1GZO; X-ray; A=146-460. DR PDB; 1MRV; X-ray; A=143-481. DR PDB; 1MRY; X-ray; A=143-481. DR PDB; 1O6K; X-ray; A=146-481. DR PDB; 1O6L; X-ray; A=146-467. DR IntAct; P31751; -. DR Ensembl; ENSG00000105221; Homo sapiens. DR HGNC; HGNC:392; AKT2. DR MIM; 164731; gene. DR GO; GO:0005515; F:protein binding; IPI. DR GO; GO:0004674; F:protein serine/threonine kinase activity; TAS. DR GO; GO:0006464; P:protein modification; TAS. DR InterPro; IPR011009; Kinase_like. DR InterPro; IPR001849; PH. DR InterPro; IPR011993; PH_type. DR InterPro; IPR000961; Pkinase_C. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR008271; Ser_thr_pkin_AS. DR InterPro; IPR002290; Ser_thr_pkinase. DR Pfam; PF00169; PH; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF00433; Pkinase_C; 1. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00133; S_TK_X; 1. DR SMART; SM00220; S_TKc; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. KW 3D-structure; ATP-binding; Kinase; Nucleotide-binding; KW Serine/threonine-protein kinase; Transferase. FT CHAIN 1 481 RAC-beta serine/threonine-protein kinase. FT /FTId=PRO_0000085608. FT DOMAIN 5 108 PH. FT DOMAIN 152 409 Protein kinase. FT NP_BIND 158 166 ATP (By similarity). FT ACT_SITE 275 275 Proton acceptor (By similarity). FT BINDING 181 181 ATP (By similarity). FT CONFLICT 478 481 SIRE -> FREEKDLLMSLFVSLILFSDFSSLKSHSFSSNF FT ILLSFSSLKK (in Ref. 1). FT HELIX 149 151 FT STRAND 152 160 FT STRAND 162 171 FT TURN 172 174 FT STRAND 177 184 FT HELIX 185 190 FT TURN 191 192 FT HELIX 194 200 FT TURN 203 205 FT STRAND 206 206 FT TURN 210 211 FT STRAND 212 212 FT STRAND 215 220 FT STRAND 222 230 FT TURN 233 234 FT STRAND 236 236 FT HELIX 237 241 FT STRAND 245 245 FT HELIX 249 260 FT HELIX 263 267 FT STRAND 272 272 FT TURN 278 279 FT STRAND 280 283 FT TURN 285 286 FT STRAND 287 287 FT STRAND 289 291 FT TURN 295 296 FT STRAND 298 298 FT STRAND 300 300 FT STRAND 307 307 FT STRAND 311 312 FT HELIX 314 316 FT HELIX 319 322 FT STRAND 323 325 FT STRAND 327 327 FT TURN 329 330 FT HELIX 331 345 FT STRAND 34