ID ARAF_HUMAN STANDARD; PRT; 606 AA. AC P10398; P07557; Q5H9B3; DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1996, sequence version 2. DT 30-MAY-2006, entry version 77. DE A-Raf proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) (A- DE raf-1) (Proto-oncogene Pks). GN Name=ARAF; Synonyms=ARAF1, PKS, PKS2; 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=87146380; PubMed=3029685; RA Beck T.W., Huleihel M., Gunnell M., Bonner T.I., Rapp U.R.; RT "The complete coding sequence of the human A-raf-1 oncogene and RT transforming activity of a human A-raf carrying retrovirus."; RL Nucleic Acids Res. 15:595-609(1987). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Placenta; RX MEDLINE=94292185; PubMed=8020955; RA Lee J.-E., Beck T.W., Brennscheidt U., DeGennaro L.J., Rapp U.R.; RT "The complete sequence and promoter activity of the human A-raf-1 gene RT (ARAF1)."; RL Genomics 20:43-55(1994). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor RT vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15772651; DOI=10.1038/nature03440; RA Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., RA Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., RA Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., RA Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S., RA Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., RA Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., RA Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., RA Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., RA Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., RA Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., RA Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., RA Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., RA Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., RA Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., RA Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., RA Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., RA Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., RA Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., RA Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., RA Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., RA Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., RA Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., RA Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., RA Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., RA Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., RA Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., RA Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., RA de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., RA Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., RA Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., RA Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., RA Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., RA McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., RA Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., RA Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., RA Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., RA Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., RA Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., RA Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., RA Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., RA Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., RA Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., RA Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., RA Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., RA Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., RA Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., RA Williams G., Williams L., Williamson A., Williamson H., Wilming L., RA Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., RA Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., RA Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., RA Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., RA Nelson D.L., Weinstock G., Sulston J.E., Durbin R., Hubbard T., RA Gibbs R.A., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence of the human X chromosome."; RL Nature 434:325-337(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Kidney; 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 [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 292-589. RX MEDLINE=86313571; PubMed=3529082; RA Mark G.E., Seeley T.W., Shows T.B., Mountz J.D.; RT "Pks, a raf-related sequence in humans."; RL Proc. Natl. Acad. Sci. U.S.A. 83:6312-6316(1986). RN [7] RP INTERACTION WITH NELFD. RX MEDLINE=21948648; PubMed=11952167; DOI=10.1023/A:1014437024129; RA Yin X.L., Chen S., Gu J.X.; RT "Identification of TH1 as an interaction partner of A-Raf kinase."; RL Mol. Cell. Biochem. 231:69-74(2002). CC -!- FUNCTION: Involved in the transduction of mitogenic signals from CC the cell membrane to the nucleus. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- COFACTOR: Binds 2 zinc ions per subunit (By similarity). CC -!- SUBUNIT: Interacts with TH1L/NELFD. CC -!- INTERACTION: CC P00966:ASS; NbExp=3; IntAct=EBI-365961, EBI-536842; CC O94906:C20orf14; NbExp=4; IntAct=EBI-365961, EBI-536755; CC Q9UNS2:COPS3; NbExp=3; IntAct=EBI-365961, EBI-350590; CC P31327:CPS1; NbExp=3; IntAct=EBI-365961, EBI-536811; CC Q12805:EFEMP1; NbExp=3; IntAct=EBI-365961, EBI-536772; CC O95848:NUDT14; NbExp=3; IntAct=EBI-365961, EBI-536866; CC Q96KB5:PBK; NbExp=3; IntAct=EBI-365961, EBI-536853; CC P53611:RABGGTB; NbExp=3; IntAct=EBI-365961, EBI-536715; CC P62070:RRAS2; NbExp=3; IntAct=EBI-365961, EBI-491037; CC Q8IXH7:TH1L; NbExp=4; IntAct=EBI-365961, EBI-536725; CC O43615:TIMM44; NbExp=3; IntAct=EBI-365961, EBI-861737; CC Q96FJ5:TIMM50; NbExp=2; IntAct=EBI-365961, EBI-536874; CC -!- TISSUE SPECIFICITY: Predominantly in urogenital tissues (By CC similarity). CC -!- SIMILARITY: Belongs to the Ser/Thr protein kinase family. RAF CC subfamily. CC -!- SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC -!- SIMILARITY: Contains 1 RBD (Ras-binding) 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; X04790; CAA28476.1; -; mRNA. DR EMBL; L24038; AAA65219.1; -; Genomic_DNA. DR EMBL; U01337; AAB03517.1; -; Genomic_DNA. DR EMBL; BT019864; AAV38667.1; -; mRNA. DR EMBL; Z84466; CAI42468.1; -; Genomic_DNA. DR EMBL; BC002466; AAH02466.1; -; mRNA. DR EMBL; M13829; AAB08754.1; -; mRNA. DR PIR; A53026; TVHUAF. DR UniGene; Hs.446641; -. DR PDB; 1WXM; NMR; A=19-91. DR SMR; P10398; 96-146, 303-576. DR IntAct; P10398; -. DR Ensembl; ENSG00000078061; Homo sapiens. DR H-InvDB; HIX0016762; -. DR HGNC; HGNC:646; ARAF. DR MIM; 311010; gene. DR GO; GO:0005524; F:ATP binding; NAS. DR GO; GO:0005515; F:protein binding; IPI. DR GO; GO:0004674; F:protein serine/threonine kinase activity; NAS. DR GO; GO:0006468; P:protein amino acid phosphorylation; NAS. DR InterPro; IPR002219; DAG_PE_bd. DR InterPro; IPR011009; Kinase_like. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR003116; Raf_like_ras_bd. DR InterPro; IPR008271; Ser_thr_pkin_AS. DR Pfam; PF00130; C1_1; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF02196; RBD; 1. DR PRINTS; PR00008; DAGPEDOMAIN. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00109; C1; 1. DR SMART; SM00455; RBD; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR PROSITE; PS50898; RBD; 1. DR PROSITE; PS00479; ZF_DAG_PE_1; 1. DR PROSITE; PS50081; ZF_DAG_PE_2; 1. KW 3D-structure; ATP-binding; Kinase; Metal-binding; Nucleotide-binding; KW Phorbol-ester binding; Proto-oncogene; KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger. FT CHAIN 1 606 A-Raf proto-oncogene serine/threonine- FT protein kinase. FT /FTId=PRO_0000085622. FT DOMAIN 19 91 RBD. FT DOMAIN 310 570 Protein kinase. FT ZN_FING 98 144 Phorbol-ester/DAG-type. FT NP_BIND 316 324 ATP (By similarity). FT ACT_SITE 429 429 Proton acceptor (By similarity). FT METAL 99 99 Zinc 1 (By similarity). FT METAL 112 112 Zinc 2 (By similarity). FT METAL 115 115 Zinc 2 (By similarity). FT METAL 125 125 Zinc 1 (By similarity). FT METAL 128 128 Zinc 1 (By similarity). FT METAL 133 133 Zinc 2 (By similarity). FT METAL 136 136 Zinc 2 (By similarity). FT METAL 144 144 Zinc 1 (By similarity). FT BINDING 336 336 ATP (By similarity). FT CONFLICT 368 368 L -> P (in Ref. 6). FT CONFLICT 378 378 F -> V (in Ref. 6). FT CONFLICT 469 469 S -> P (in Ref. 6). FT CONFLICT 478 478 I -> T (in Ref. 6). FT STRAND 19 24 FT STRAND 26 28 FT STRAND 30 34 FT STRAND 37 38 FT STRAND 40 41 FT HELIX 42 50 FT TURN 51 52 FT STRAND 56 67 FT STRAND 69 72 FT STRAND 74 78 FT TURN 79 80 FT STRAND 82 83 FT STRAND 85 90 SQ SEQUENCE 606 AA; 67585 MW; D23E5711304AA468 CRC64; MEPPRGPPAN GAEPSRAVGT VKVYLPNKQR TVVTVRDGMS VYDSLDKALK VRGLNQDCCV VYRLIKGRKT VTAWDTAIAP LDGEELIVEV LEDVPLTMHN FVRKTFFSLA FCDFCLKFLF HGFRCQTCGY KFHQHCSSKV PTVCVDMSTN RQQFYHSVQD LSGGSRQHEA PSNRPLNELL TPQGPSPRTQ HCDPEHFPFP APANAPLQRI RSTSTPNVHM VSTTAPMDSN LIQLTGQSFS TDAAGSRGGS DGTPRGSPSP ASVSSGRKSP HSKSPAEQRE RKSLADDKKK VKNLGYRDSG YYWEVPPSEV QLLKRIGTGS FGTVFRGRWH GDVAVKVLKV SQPTAEQAQA FKNEMQVLRK TRHVNILLFM GFMTRPGFAI ITQWCEGSSL YHHLHVADTR FDMVQLIDVA RQTAQGMDYL HAKNIIHRDL KSNNIFLHEG LTVKIGDFGL ATVKTRWSGA QPLEQPSGSV LWMAAEVIRM QDPNPYSFQS DVYAYGVVLY ELMTGSLPYS HIGCRDQIIF MVGRGYLSPD LSKISSNCPK AMRRLLSDCL KFQREERPLF PQILATIELL QRSLPKIERS ASEPSLHRTQ ADELPACLLS AARLVP // ID ARAF_MOUSE STANDARD; PRT; 604 AA. AC P04627; Q99J44; Q9CTT5; Q9D6R6; Q9DBU7; DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot. DT 02-AUG-2002, sequence version 2. DT 30-MAY-2006, entry version 81. DE A-Raf proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1). GN Name=Araf; Synonyms=A-raf, Araf1; 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 [LARGE SCALE MRNA]. RC TISSUE=Mammary gland; 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-283. RC STRAIN=C57BL/6J; TISSUE=Lung, Tongue, and Urinary bladder; 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 [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 168-604. RX MEDLINE=87064566; PubMed=3491291; RA Huleihel M., Goldsborough M., Cleveland J., Gunnell M., Bonner T., RA Rapp U.R.; RT "Characterization of murine A-raf, a new oncogene related to the v-raf RT oncogene."; RL Mol. Cell. Biol. 6:2655-2662(1986). CC -!- FUNCTION: Involved in the transduction of mitogenic signals from CC the cell membrane to the nucleus. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- COFACTOR: Binds 2 zinc ions per subunit (By similarity). CC -!- SUBUNIT: Interacts with TH1L/NELFD (By similarity). CC -!- SIMILARITY: Belongs to the Ser/Thr protein kinase family. RAF CC subfamily. CC -!- SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC -!- SIMILARITY: Contains 1 RBD (Ras-binding) 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; BC004757; AAH04757.1; -; mRNA. DR EMBL; AK004741; BAB23522.1; -; mRNA. DR EMBL; AK010060; BAB26674.1; -; mRNA. DR EMBL; AK020547; BAB32131.3; -; mRNA. DR EMBL; D00024; BAA00018.1; -; mRNA. DR PIR; A25382; TVMSRF. DR UniGene; Mm.220946; -. DR HSSP; P04049; 1FAR. DR SMR; P04627; 20-91, 96-146, 301-574. DR Ensembl; ENSMUSG00000001127; Mus musculus. DR MGI; MGI:88065; Araf. DR GO; GO:0005739; C:mitochondrion; IDA. DR GO; GO:0005515; F:protein binding; IPI. DR InterPro; IPR002219; DAG_PE_bd. DR InterPro; IPR011009; Kinase_like. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR003116; Raf_like_ras_bd. DR InterPro; IPR008271; Ser_thr_pkin_AS. DR Pfam; PF00130; C1_1; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF02196; RBD; 1. DR PRINTS; PR00008; DAGPEDOMAIN. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00109; C1; 1. DR SMART; SM00455; RBD; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR PROSITE; PS50898; RBD; 1. DR PROSITE; PS00479; ZF_DAG_PE_1; 1. DR PROSITE; PS50081; ZF_DAG_PE_2; 1. KW ATP-binding; Kinase; Metal-binding; Nucleotide-binding; KW Phorbol-ester binding; Proto-oncogene; KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger. FT CHAIN 1 604 A-Raf proto-oncogene serine/threonine- FT protein kinase. FT /FTId=PRO_0000085623. FT DOMAIN 19 91 RBD. FT DOMAIN 308 568 Protein kinase. FT ZN_FING 98 144 Phorbol-ester/DAG-type. FT NP_BIND 314 322 ATP (By similarity). FT ACT_SITE 427 427 Proton acceptor (By similarity). FT METAL 99 99 Zinc 1 (By similarity). FT METAL 112 112 Zinc 2 (By similarity). FT METAL 115 115 Zinc 2 (By similarity). FT METAL 125 125 Zinc 1 (By similarity). FT METAL 128 128 Zinc 1 (By similarity). FT METAL 133 133 Zinc 2 (By similarity). FT METAL 136 136 Zinc 2 (By similarity). FT METAL 144 144 Zinc 1 (By similarity). FT BINDING 334 334 ATP (By similarity). FT CONFLICT 169 169 E -> K (in Ref. 3). FT CONFLICT 186 186 S -> R (in Ref. 2; BAB23522/BAB26674). FT CONFLICT 326 326 R -> L (in Ref. 3). SQ SEQUENCE 604 AA; 67581 MW; 05F8262F99DDD087 CRC64; MEPPRGPPVS GAEPSRAVGT VKVYLPNKQR TVVTVREGMS VYDSLDKALK VRGLNQDCCV VYRLIKGRKT VTAWDTAIAP LDGEELIVEV LEDVPLTMHN FVRKTFFSLA FCDFCLKFLF HGFRCQTCGY KFHQHCSSKV PTVCVDMSTN RRQFYHSIQD LSGGSRQQEA PSNLSVNELL TPQGPSPFTQ QRDQEHFSFP APANPPLQRI RSTSTPNVHM VSTTAPMDSS LMQFTAQSFS TDAAGRGGDG APRGSPSPAS VSSGRKSPHS KLPSEQRERK SLADEKKKVK NLGYRDSGYY WEVPPSEVQL LKRIGTGSFG TVFRGRWHGD VAVKVLKVAQ PTAEQAQAFK NEMQVLRKTR HVNILLFMGF MTRPGFAIIT QWCEGSSLYH HLHVADTRFD MVQLIDVARQ TAQGMDYLHA KNIIHRDLKS NNIFLHEGLT VKIGDFGLAT VKTRWSGAQP LEQPSGSVLW MAAEVIRMQD PNPYSFQSDV YAYGVVLYEL MTGSLPYSHI GSRDQIIFMV GRGYLSPDLS KIFSNCPKAM RRLLTDCLKF QREERPLFPQ ILATIELLQR SLPKIERSAS EPSLHRTQAD ELPACLLSAA RLVP // ID ARAF_PIG STANDARD; PRT; 606 AA. AC O19004; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 30-MAY-2006, entry version 53. DE A-Raf proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) (A- DE Raf-1). GN Name=ARAF; Synonyms=ARAF1; OS Sus scrofa (Pig). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Laurasiatheria; Cetartiodactyla; Suina; Suidae; OC Sus. OX NCBI_TaxID=9823; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=Landrace; TISSUE=Liver; RX MEDLINE=97343844; PubMed=9166601; DOI=10.1007/s003359900473; RA Yasue H., Adams L., Ozawa A., Hanazono M., Li N., Lin Z.H., RA Kusumoto H.; RT "Assignment of ARAF1 to porcine chromosome Xp11.2-p13 by fluorescence RT in situ hybridization."; RL Mamm. Genome 8:457-458(1997). CC -!- FUNCTION: Involved in the transduction of mitogenic signals from CC the cell membrane to the nucleus (By similarity). CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- COFACTOR: Binds 2 zinc ions per subunit (By similarity). CC -!- SUBUNIT: Interacts with TH1L/NELFD (By similarity). CC -!- SIMILARITY: Belongs to the Ser/Thr protein kinase family. RAF CC subfamily. CC -!- SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC -!- SIMILARITY: Contains 1 RBD (Ras-binding) 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; D88385; BAA22379.1; -; mRNA. DR UniGene; Ssc.2370; -. DR HSSP; P04049; 1FAR. DR SMR; O19004; 20-91, 96-146, 303-576. DR LinkHub; O19004; -. DR InterPro; IPR002219; DAG_PE_bd. DR InterPro; IPR011009; Kinase_like. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR003116; Raf_like_ras_bd. DR InterPro; IPR008271; Ser_thr_pkin_AS. DR Pfam; PF00130; C1_1; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF02196; RBD; 1. DR PRINTS; PR00008; DAGPEDOMAIN. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00109; C1; 1. DR SMART; SM00455; RBD; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR PROSITE; PS50898; RBD; 1. DR PROSITE; PS00479; ZF_DAG_PE_1; 1. DR PROSITE; PS50081; ZF_DAG_PE_2; 1. KW ATP-binding; Kinase; Metal-binding; Nucleotide-binding; KW Phorbol-ester binding; Proto-oncogene; KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger. FT CHAIN 1 606 A-Raf proto-oncogene serine/threonine- FT protein kinase. FT /FTId=PRO_0000085624. FT DOMAIN 19 91 RBD. FT DOMAIN 310 570 Protein kinase. FT ZN_FING 98 144 Phorbol-ester/DAG-type. FT NP_BIND 316 324 ATP (By similarity). FT ACT_SITE 429 429 Proton acceptor (By similarity). FT METAL 99 99 Zinc 1 (By similarity). FT METAL 112 112 Zinc 2 (By similarity). FT METAL 115 115 Zinc 2 (By similarity). FT METAL 125 125 Zinc 1 (By similarity). FT METAL 128 128 Zinc 1 (By similarity). FT METAL 133 133 Zinc 2 (By similarity). FT METAL 136 136 Zinc 2 (By similarity). FT METAL 144 144 Zinc 1 (By similarity). FT BINDING 336 336 ATP (By similarity). SQ SEQUENCE 606 AA; 67538 MW; 1A7EEB9A5D9DE152 CRC64; MEPPRGPPAN GAEPSRAVGT VKVYLPNKQR TVVTVRDGMS VYDSLDKALK VRGLNQDCCV VYRLIKGRKT VTAWDTAIAP LDGEELIVEV LEDVPLTMHN FVRKTFFSLA FCDFCLKFLF HGFRCQTCGY KFHQHCSSKV PTVCVDMSTN RRQFYHSVQD LSGGSRQHET PSNRPLNEPL TPQGPSSCTQ HRDPEHFPFP APANAPLQRI RSTSTPNVHM VSTTAPMDSG LVQLTAQSFN TDAAGNRGGG DGAPRGSPSP ASVSSGRKSP HSKSPSEQRE RKSLADDKKK VKNLGYRDSG YYWEVPPSEV QLLKRIGTGS FGTVFRGRWH GDVAVKVLKV AQPTAEQAQA FKNEMQVLRK TRHVNILLFM GFMTRPGFAI ITQWCEGSSL YHHLHVADTR FDMVQLIDVA RQTAQGMDYL HAKNIIHRDL KSNNIFLHEG LTVKIGDFGL ATVKTRWSGA QPLEQPSGSV LWMAAEVIRM QDPNPYSFQS DVYAYGVVLY ELMTGSLPYS HIGSRDQIIF MVGRGYLSPD LSKISSNCPK AMRRLLSDCL KFQREERPLF PQILATIELL QRSLPKIERS ASEPSLHRTQ ADELPACLLS AARLVP // ID ARAF_RAT STANDARD; PRT; 604 AA. AC P14056; DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1990, sequence version 1. DT 30-MAY-2006, entry version 65. DE A-Raf proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1). GN Name=Araf; Synonyms=A-raf, Araf1; 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 STRAIN=Fischer; TISSUE=Liver; RX MEDLINE=88217324; PubMed=3449797; RA Ishikawa F., Takaku F., Nagao M., Sugimura T.; RT "The complete primary structure of the rat A-raf cDNA coding region: RT conservation of the putative regulatory regions present in rat c- RT raf."; RL Oncogene Res. 1:243-253(1987). CC -!- FUNCTION: Involved in the transduction of mitogenic signals from CC the cell membrane to the nucleus. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- COFACTOR: Binds 2 zinc ions per subunit (By similarity). CC -!- SUBUNIT: Interacts with TH1L/NELFD (By similarity). CC -!- SIMILARITY: Belongs to the Ser/Thr protein kinase family. RAF CC subfamily. CC -!- SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC -!- SIMILARITY: Contains 1 RBD (Ras-binding) 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; X06942; CAA30023.1; -; mRNA. DR PIR; S00726; S00726. DR UniGene; Rn.1714; -. DR HSSP; P04049; 1FAR. DR SMR; P14056; 20-91, 96-146, 301-574. DR Ensembl; ENSRNOG00000010838; Rattus norvegicus. DR RGD; 2148; Araf. DR GO; GO:0005829; C:cytosol; IDA. DR GO; GO:0005626; C:insoluble fraction; IDA. DR GO; GO:0004709; F:MAP kinase kinase kinase activity; TAS. DR GO; GO:0006468; P:protein amino acid phosphorylation; TAS. DR GO; GO:0007243; P:protein kinase cascade; TAS. DR InterPro; IPR002219; DAG_PE_bd. DR InterPro; IPR011009; Kinase_like. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR003116; Raf_like_ras_bd. DR InterPro; IPR008271; Ser_thr_pkin_AS. DR Pfam; PF00130; C1_1; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF02196; RBD; 1. DR PRINTS; PR00008; DAGPEDOMAIN. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00109; C1; 1. DR SMART; SM00455; RBD; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR PROSITE; PS50898; RBD; 1. DR PROSITE; PS00479; ZF_DAG_PE_1; 1. DR PROSITE; PS50081; ZF_DAG_PE_2; 1. KW ATP-binding; Kinase; Metal-binding; Nucleotide-binding; KW Phorbol-ester binding; Proto-oncogene; KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger. FT CHAIN 1 604 A-Raf proto-oncogene serine/threonine- FT protein kinase. FT /FTId=PRO_0000085625. FT DOMAIN 19 91 RBD. FT DOMAIN 308 568 Protein kinase. FT ZN_FING 98 144 Phorbol-ester/DAG-type. FT NP_BIND 314 322 ATP (By similarity). FT ACT_SITE 427 427 Proton acceptor (By similarity). FT METAL 99 99 Zinc 1 (By similarity). FT METAL 112 112 Zinc 2 (By similarity). FT METAL 115 115 Zinc 2 (By similarity). FT METAL 125 125 Zinc 1 (By similarity). FT METAL 128 128 Zinc 1 (By similarity). FT METAL 133 133 Zinc 2 (By similarity). FT METAL 136 136 Zinc 2 (By similarity). FT METAL 144 144 Zinc 1 (By similarity). FT BINDING 334 334 ATP (By similarity). SQ SEQUENCE 604 AA; 67551 MW; FF24FB2170B0B115 CRC64; MEPPRGPPAS GAEPSRAVGT VKVYLPNKQR TVVTVRDGMS VYDSLDKALK VRGLNQDCCV VYRLIKGRKT VTAWDTAIAP LDGEELIVEV LEDVPLTMHN FVRKTFFSLA FCDFCLKFLF HGFRCQTCGY KFHQHCSSKV PTVCVDMSTN RRQFYHSIQD LSGGSRQQEV PSNLSVNELL TPQGPSPFTQ QRDQEHFSFP APANPPLQRI RSTSTPNVHM VSTTAPMDSS LMQFTAQSFS TDAAGRGGDG APRGSPSPAS VSSGRKSPHS KLPAEQRERK SLADEKKKVK NLGYRDSGYY WEVPPSEVQL LKRIGTGSFG TVFRGRWHGD VAVKVLKVAQ PTAEQAQAFK NEMQVLRKTR HVNILLFMGF MTRPGFAIIT QWCEGSSLYH HLHVADTRFD MVQLIDVARQ TAQGMDYLHA KNIIHRDLKS NNIFLHEGLT VKIGDFGLAT VKTRWSGAQP LEQPSGSVLW MAAEVIRMQD PNPYSFQSDV YAYGVVLYEL MTGSLPYSHI GSRDQIIFMV GRGYLSPDLS KIFSNCPKAM RRLLTDCLKF QREERPLFPQ ILATIELLQR SLPKIERSAS EPSLHRTQAD ELPACLLSAA RLVP // ID ARHG2_HUMAN STANDARD; PRT; 893 AA. AC Q92974; O75142; Q15079; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1999, sequence version 3. DT 30-MAY-2006, entry version 55. DE Rho/Rac guanine nucleotide exchange factor 2 (GEF-H1 protein) DE (Proliferating cell nucleolar antigen p40). GN Name=ARHGEF2; Synonyms=KIAA0651, LFP40; 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]. RC TISSUE=Cervix carcinoma; RX MEDLINE=99074271; PubMed=9857026; DOI=10.1074/jbc.273.52.34954; RA Ren Y., Li R., Zheng Y., Busch H.; RT "Cloning and characterization of GEF-H1, a microtubule-associated RT guanine nucleotide exchange factor for Rac and Rho GTPases."; RL J. Biol. Chem. 273:34954-34960(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX MEDLINE=98403880; PubMed=9734811; DOI=10.1093/dnares/5.3.169; RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., RA Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. X. RT The complete sequences of 100 new cDNA clones from brain which can RT code for large proteins in vitro."; RL DNA Res. 5:169-176(1998). RN [3] RP SEQUENCE REVISION. RA Ishikawa K., Nagase T., Suyama M., Miyajima N., Tanaka A., Kotani H., RA Nomura N., Ohara O.; RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 630-893. RX MEDLINE=89168219; PubMed=2466560; RA Reddy A.B., Chatterjee A., Rothblum L.I., Black A., Busch H.; RT "Isolation and characterization of complementary DNA to proliferating RT cell nucleolar antigen P40."; RL Cancer Res. 49:1763-1767(1989). RN [5] RP PHOSPHORYLATION AT SER-163 AND SER-695, AND MASS SPECTROMETRY. RX PubMed=16565220; DOI=10.1073/pnas.0507066103; RA Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R.; RT "Phosphoproteome analysis of the human mitotic spindle."; RL Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006). CC -!- FUNCTION: Stimulates guanine nucleotide exchange of Rac and Rho CC but is inactive toward CDC42, TC10, or Ras. Binds to Rac and Rho CC proteins in both the GDP- and guanosine 5'-3-O-(thio)triphosphate- CC bound states without detectable affinity for CDC42 or Ras. May CC have a direct role in activation of Rac and/or Rho and in bringing CC the activated GTPase to specific target sites such as CC microtubules. CC -!- SUBCELLULAR LOCATION: Cytoplasm. Colocalizes with microtubules CC through the C-terminal coiled-coil domain. CC -!- SIMILARITY: Contains 1 DH (DBL-homology) domain. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger. CC -!- CAUTION: The sequence shown here comes from the figure of Ref.1, CC apparently the submitted sequence is wrong. CC -!- CAUTION: Ref.2 sequence differs from that shown due to a CC frameshift in position 886. 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; U72206; AAC97383.1; ALT_SEQ; mRNA. DR EMBL; AB014551; BAA31626.3; ALT_FRAME; mRNA. DR EMBL; X15610; CAA33634.1; -; mRNA. DR UniGene; Hs.568509; -. DR Ensembl; ENSG00000116584; Homo sapiens. DR HGNC; HGNC:682; ARHGEF2. DR MIM; 607560; gene. DR GO; GO:0005874; C:microtubule; ISS. DR GO; GO:0008017; F:microtubule binding; ISS. DR GO; GO:0048365; F:Rac GTPase binding; ISS. DR GO; GO:0030676; F:Rac guanyl-nucleotide exchange factor activity; ISS. DR GO; GO:0017048; F:Rho GTPase binding; ISS. DR GO; GO:0005089; F:Rho guanyl-nucleotide exchange factor activity; ISS. DR GO; GO:0008270; F:zinc ion binding; ISS. DR GO; GO:0007015; P:actin filament organization; ISS. DR GO; GO:0007166; P:cell surface receptor linked signal transdu...; TAS. DR GO; GO:0000902; P:cellular morphogenesis; ISS. DR GO; GO:0006886; P:intracellular protein transport; ISS. DR GO; GO:0007026; P:negative regulation of microtubule depolyme...; ISS. DR GO; GO:0042127; P:regulation of cell proliferation; ISS. DR GO; GO:0035023; P:regulation of Rho protein signal transduction; ISS. DR InterPro; IPR002219; DAG_PE_bd. DR InterPro; IPR001331; GDS_CDC24. DR InterPro; IPR001849; PH. DR InterPro; IPR011993; PH_type. DR InterPro; IPR000219; RhoGEF. DR Pfam; PF00130; C1_1; 1. DR Pfam; PF00169; PH; 1. DR Pfam; PF00621; RhoGEF; 1. DR SMART; SM00109; C1; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00325; RhoGEF; 1. DR PROSITE; PS00741; DH_1; FALSE_NEG. DR PROSITE; PS50010; DH_2; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS00479; ZF_DAG_PE_1; 1. DR PROSITE; PS50081; ZF_DAG_PE_2; 1. KW Coiled coil; Guanine-nucleotide releasing factor; Metal-binding; KW Phorbol-ester binding; Phosphorylation; Zinc; Zinc-finger. FT CHAIN 1 893 Rho/Rac guanine nucleotide exchange FT factor 2. FT /FTId=PRO_0000080909. FT DOMAIN 234 431 DH. FT DOMAIN 485 571 PH. FT ZN_FING 39 86 Phorbol-ester/DAG-type. FT COILED 589 610 Potential. FT COILED 797 868 Potential. FT MOD_RES 163 163 Phosphoserine. FT MOD_RES 695 695 Phosphoserine. FT CONFLICT 1 20 MSRIESLTRARIDRSRELAS -> IVGAAGHGRALSLCFDN FT GPLEQVPLALEETASIGMPRPQGGPLPADPRRTGHLSGTGH FT QGGYASRLDQDSCHPSAGPLDHSATGMLSKSVPVSGINCLL FT DRSDTDGNVSQSSAIDLRKRCSQLEGHSGTRVGSSLRQTFS FT FLSGMTGKA (in Ref. 2). FT CONFLICT 579 579 S -> P (in Ref. 2). FT CONFLICT 867 867 Q -> P (in Ref. 2). SQ SEQUENCE 893 AA; 101174 MW; 80AC8FA7F762E9C3 CRC64; MSRIESLTRA RIDRSRELAS KTREKEKMKE AKDARYTNGH LFTTISVSGM TMCYACNKSI TAKEALICPT CNVTIHNRCK DTLANCTKVK QKQQKAALLK NNTALQSVSL RSKTTIRERP SSAIYPSDSF RQSLLGSRRG RSSLSLAKSV STTNIAGHFN DESPLGLRRI LSQSTDSLNM RNRTLSVESL IDEEVIYSEL MSDFEMDEKD FAADSWSLAV DSSFLQQHKK EVMKQQDVIY ELIQTELHHV RTLKIMTRLF RTGMLEELHL EPGVVQGLFP CVDELSDIHT RFLSQLLERR RQALCPGSTR NFVIHRLGDL LISQFSGPSA EQMCKTYSEF CSRHSKALKL YKELYARDKR FQQFIRKVTR PAVLKRHGVQ ECILLVTQRI TKYPLLISRI LQHSHGIEEE RQDLTTALGL VKELLSNVDE GIYQLEKGAR LQEIYNRMDP RAQTPVPGKG PFGREELLRR KLIHDGCLLW KTATGRFKDV LVLLMTDVLV FLQEKDQKYI FPTLDKPSVV SLQNLIVRDI ANQEKGMFLI SAAPPEMYEV HTASRDDRST WIRVIQQSVR TCPSREDFSL IETEDEAYLR RIKMELQQKD RALVELLREK VGLFAEMTHF QAEEDGGSGM ALPTLPRGLF RSESLESPRG ERLLQDAIRE VEGLKDLLVG PGVELLLTPR EPALPLEPDS GGNTSPGVTA NGEARTFNGS IELCRADSDS SQRDRNGNQL RSPQEEALQR LVNLYGLLHG LQAAVAQQDT LMEARFPEGP ERREKLCRAN SRDGEAGRAG AAPVAPEKQA TELALLQRQH ALLQEELRRC RRLGEERATE AGSLEARLRE SEQARALLER EAEEARRQLA ALGQTEQLPA EAPWARRPVD PRRRSSPQAM PCT // ID ARHG2_MOUSE STANDARD; PRT; 596 AA. AC Q60875; O09115; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 2. DT 30-MAY-2006, entry version 43. DE Rho/Rac guanine nucleotide exchange factor 2 (Lymphoid blast crisis- DE like 1) (LBC'S first cousin) (Oncogene LFC) (RHOBIN). GN Name=Arhgef2; Synonyms=Lbcl1, Lfc; 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]. RC TISSUE=Myeloid; RX MEDLINE=95355462; PubMed=7629163; DOI=10.1074/jbc.270.31.18388; RA Whitehead I., Kirk H., Tognon C., Trigo-Gonzalez G., Kay R.; RT "Expression cloning of lfc, a novel oncogene with structural RT similarities to guanine nucleotide exchange factors and to the RT regulatory region of protein kinase C."; RL J. Biol. Chem. 270:18388-18395(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=BALB/c; RA Olofsson B.; RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Stimulates guanine nucleotide exchange of Rac and Rho CC but is inactive toward CDC42, TC10, or Ras. Binds to Rac and Rho CC proteins in both the GDP- and guanosine 5'-3-O-(thio)triphosphate- CC bound states without detectable affinity for CDC42 or Ras. May CC have a direct role in activation of Rac and/or Rho and in bringing CC the activated GTPase to specific target sites such as microtubules CC (By similarity). CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). Colocalizes with CC microtubules through the C-terminal coiled-coil domain (By CC similarity). CC -!- TISSUE SPECIFICITY: Ubiquitous, with the exception of liver CC tissue. Levels are high in hemopoietic tissues (thymus, spleen, CC bone marrow) as well as in kidney and lung. CC -!- SIMILARITY: Contains 1 DH (DBL-homology) domain. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger. 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; U28495; AAC52234.1; -; mRNA. DR EMBL; X95761; CAA65067.1; -; mRNA. DR PIR; I49342; I49342. DR UniGene; Mm.239329; -. DR Ensembl; ENSMUSG00000028059; Mus musculus. DR MGI; MGI:103264; Arhgef2. DR InterPro; IPR002219; DAG_PE_bd. DR InterPro; IPR001331; GDS_CDC24. DR InterPro; IPR001849; PH. DR InterPro; IPR011993; PH_type. DR InterPro; IPR000219; RhoGEF. DR Pfam; PF00130; C1_1; 1. DR Pfam; PF00169; PH; 1. DR Pfam; PF00621; RhoGEF; 1. DR SMART; SM00109; C1; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00325; RhoGEF; 1. DR PROSITE; PS00741; DH_1; FALSE_NEG. DR PROSITE; PS50010; DH_2; 1. DR PROSITE; PS50003; PH_DOMAIN; 1. DR PROSITE; PS00479; ZF_DAG_PE_1; 1. DR PROSITE; PS50081; ZF_DAG_PE_2; 1. KW Guanine-nucleotide releasing factor; Metal-binding; KW Phorbol-ester binding; Phosphorylation; Proto-oncogene; Zinc; KW Zinc-finger. FT CHAIN 1 596 Rho/Rac guanine nucleotide exchange FT factor 2. FT /FTId=PRO_0000080910. FT DOMAIN 236 433 DH. FT DOMAIN 487 573 PH. FT ZN_FING 39 86 Phorbol-ester/DAG-type. FT COMPBIAS 493 496 Poly-Leu. FT MOD_RES 163 163 Phosphoserine (By similarity). FT CONFLICT 1 21 MSRIESLTRARIDRSKEQATK -> MSGNRRQPSRRGQ FT (in Ref. 2). FT CONFLICT 156 156 A -> V (in Ref. 2). FT CONFLICT 574 596 Missing (in Ref. 1). SQ SEQUENCE 596 AA; 68585 MW; E168508BDC7C6E13 CRC64; MSRIESLTRA RIDRSKEQAT KTREKEKMKE AKDARYTNGH LFTTISVSGM TMCYACNKSI TAKEALICPT CNVTIHNRCK DTLANCTKVK QKQQKAALLR NNTALQSVSL RSKTTTRERP TSAIYPSDSF RQSLLGSRRG LSSLSLAKSV STTNIAGHFN DESPLGLRQI LSQSTDSLNM RNRTLSVESL IDEGVEVFYN ELMSDFEMDE KDFEADSWSL AVDSSFLQQH KKEVMKKQDV IYELIQTELH HVRTLKIMTR LFRTGMLEEL QMEPEVVQGL FPCVDELSDI HTRFLNQLLE RRRQALCPGS TRNFVIHRLG DLLISQFSGS NAEQMRKTYS EFCSRHTKAL KLYKELYARD KRFQQFIRKM TRSAVLKRHG VQECILLVTQ RITKYPVLIN RILQNSHGVE EEYQDLASAL GLVKELLSNV DQDVHELEKE ARLQEIYNRM DPRAQTPVPG KGPFGRDELL RRKLIHEGCL LWKTATGRFK DVLLLLMTDV LVFLQEKDQK YIFTSLDKPS VVSLQNLIVR DIANQAKGMF LISSGPPEMY EVHAASRDDR TTWIRVIQQS VRLCPSREDF PLIETEDKAY LRRIKS // ID ATX1_ARATH STANDARD; PRT; 1062 AA. AC Q9C5X4; Q84WP4; Q9SIP3; DT 02-MAY-2006, integrated into UniProtKB/Swiss-Prot. DT 02-MAY-2006, sequence version 2. DT 30-MAY-2006, entry version 23. DE Histone-lysine N-methyltransferase, H3 lysine-4 specific ATX1 DE (EC 2.1.1.43) (H3-K4-HMTase) (Trithorax-homolog protein 1) (TRX- DE homolog protein 1) (Protein SET DOMAIN GROUP 27). GN Name=ATX1; Synonyms=SDG27, SET27, TRX1; OrderedLocusNames=At2g31650; GN ORFNames=T9H9.17; OS Arabidopsis thaliana (Mouse-ear cress). OC Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta; OC Spermatophyta; Magnoliophyta; eudicotyledons; core eudicotyledons; OC rosids; eurosids II; Brassicales; Brassicaceae; Arabidopsis. OX NCBI_TaxID=3702; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RC STRAIN=cv. Wassilewskija; RX MEDLINE=21311636; PubMed=11418242; DOI=10.1016/S0378-1119(01)00524-8; RA Alvarez-Venegas R., Avramova Z.; RT "Two Arabidopsis homologs of the animal trithorax genes: a new RT structural domain is a signature feature of the trithorax gene RT family."; RL Gene 271:215-221(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=cv. Columbia; RX MEDLINE=20083487; PubMed=10617197; DOI=10.1038/45471; RA Lin X., Kaul S., Rounsley S.D., Shea T.P., Benito M.-I., Town C.D., RA Fujii C.Y., Mason T.M., Bowman C.L., Barnstead M.E., Feldblyum T.V., RA Buell C.R., Ketchum K.A., Lee J.J., Ronning C.M., Koo H.L., RA Moffat K.S., Cronin L.A., Shen M., Pai G., Van Aken S., Umayam L., RA Tallon L.J., Gill J.E., Adams M.D., Carrera A.J., Creasy T.H., RA Goodman H.M., Somerville C.R., Copenhaver G.P., Preuss D., RA Nierman W.C., White O., Eisen J.A., Salzberg S.L., Fraser C.M., RA Venter J.C.; RT "Sequence and analysis of chromosome 2 of the plant Arabidopsis RT thaliana."; RL Nature 402:761-768(1999). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC STRAIN=cv. Columbia; RX MEDLINE=22954850; PubMed=14593172; DOI=10.1126/science.1088305; RA Yamada K., Lim J., Dale J.M., Chen H., Shinn P., Palm C.J., RA Southwick A.M., Wu H.C., Kim C.J., Nguyen M., Pham P.K., Cheuk R.F., RA Karlin-Newmann G., Liu S.X., Lam B., Sakano H., Wu T., Yu G., RA Miranda M., Quach H.L., Tripp M., Chang C.H., Lee J.M., Toriumi M.J., RA Chan M.M., Tang C.C., Onodera C.S., Deng J.M., Akiyama K., Ansari Y., RA Arakawa T., Banh J., Banno F., Bowser L., Brooks S.Y., Carninci P., RA Chao Q., Choy N., Enju A., Goldsmith A.D., Gurjal M., Hansen N.F., RA Hayashizaki Y., Johnson-Hopson C., Hsuan V.W., Iida K., Karnes M., RA Khan S., Koesema E., Ishida J., Jiang P.X., Jones T., Kawai J., RA Kamiya A., Meyers C., Nakajima M., Narusaka M., Seki M., Sakurai T., RA Satou M., Tamse R., Vaysberg M., Wallender E.K., Wong C., Yamamura Y., RA Yuan S., Shinozaki K., Davis R.W., Theologis A., Ecker J.R.; RT "Empirical analysis of transcriptional activity in the Arabidopsis RT genome."; RL Science 302:842-846(2003). RN [4] RP NOMENCLATURE. RX MEDLINE=21550130; PubMed=11691919; DOI=10.1093/nar/29.21.4319; RA Baumbusch L.O., Thorstensen T., Krauss V., Fischer A., Naumann K., RA Assalkhou R., Schulz I., Reuter G., Aalen R.B.; RT "The Arabidopsis thaliana genome contains at least 29 active genes RT encoding SET domain proteins that can be assigned to four RT evolutionarily conserved classes."; RL Nucleic Acids Res. 29:4319-4333(2001). RN [5] RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX MEDLINE=22586056; PubMed=12699618; DOI=10.1016/S0960-9822(03)00243-4; RA Alvarez-Venegas R., Pien S., Sadder M., Witmer X., Grossniklaus U., RA Avramova Z.; RT "ATX-1, an Arabidopsis homolog of trithorax, activates flower homeotic RT genes."; RL Curr. Biol. 13:627-637(2003). RN [6] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PIP5. RX DOI=10.1073/pnas.0600944103; RA Alvarez-Vnegas R., Sadder M., Hlavacka A., Baluska F., Xia Y., Lu G., RA Firsov A., Sarath G., Moriyama H., Dubrovsky J.G., Avramova Z.; RT "The Arabidopsis homolog of trithorax, ATX1, binds RT phosphatidylinositol 5-phosphate, and the two regulate a common set of RT target genes."; RL Proc. Natl. Acad. Sci. U.S.A. 103:6049-6054(2006). CC -!- FUNCTION: Histone methyltransferase. Methylates Lys-4 of histone CC H3. H3 Lys-4 methylation represents a specific tag for epigenetic CC transcriptional activation. Required to maintain the active state CC of class A (AP1 and AP2), class B (PI and AP3) and class C (AG) CC floral homeotic genes at early stages of flower development. CC Regulates floral organ identity and flowering transition. CC Functions as a receptor for the lipid messenger CC phosphatidylinositol 5-phosphate (PI5P), which regulates CC negatively its transcriptional activation activity. CC -!- CATALYTIC ACTIVITY: S-adenosyl-L-methionine + histone L-lysine = CC S-adenosyl-L-homocysteine + histone N(6)-methyl-L-lysine. CC -!- SUBUNIT: Interacts with PIP5. CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Shifts from nucleus to CC cytoplasm as PIP5 levels increase. When in the nucleus, associated CC with chromatin. When cytopasmic, mostly localized along the plasma CC membrane, associated with PIP5. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9C5X4-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9C5X4-2; Sequence=VSP_018132; CC Note=No experimental confirmation available; CC -!- TISSUE SPECIFICITY: Ubiquitous with higher levels in dividing CC tissues, including inflorescence meristem and flower primordia. CC -!- DEVELOPMENTAL STAGE: Expression is associated with the initiation CC of flower organs and ovules. CC -!- SIMILARITY: Belongs to the TRX/MLL family. CC -!- SIMILARITY: Contains 1 PHD-type zinc finger. CC -!- SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger. CC -!- SIMILARITY: Contains 1 post-SET domain. CC -!- SIMILARITY: Contains 1 PWWP domain. CC -!- SIMILARITY: Contains 1 SET domain. CC -!- CAUTION: Ref.2 sequence differs from that shown due to erroneous CC gene model prediction. 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; AF329273; AAK01237.1; -; mRNA. DR EMBL; AC007071; AAD24842.1; ALT_SEQ; Genomic_DNA. DR EMBL; BT002941; AAO22754.1; -; mRNA. DR PIR; D84723; D84723. DR UniGene; At.14356; -. DR GenomeReviews; CT485783_GR; AT2G31650. DR TAIR; At2g31650; -. DR PROSITE; PS50868; POST_SET; 1. DR PROSITE; PS50812; PWWP; 1. DR PROSITE; PS50280; SET; 1. DR PROSITE; PS00479; ZF_DAG_PE_1; FALSE_NEG. DR PROSITE; PS50081; ZF_DAG_PE_2; 1. DR PROSITE; PS01359; ZF_PHD_1; 1. DR PROSITE; PS50016; ZF_PHD_2; 1. KW Alternative splicing; Chromatin regulator; Metal-binding; KW Methyltransferase; Nuclear protein; Phorbol-ester binding; KW Transferase; Zinc; Zinc-finger. FT CHAIN 1 1062 Histone-lysine N-methyltransferase, H3 FT lysine-4 specific ATX1. FT /FTId=PRO_0000233354. FT DOMAIN 301 365 PWWP. FT DOMAIN 897 1020 SET. FT DOMAIN 1022 1038 Post-SET. FT ZN_FING 591 647 Phorbol-ester/DAG-type. FT ZN_FING 609 660 PHD-type. FT REGION 599 1062 Interaction with PIP5. FT VAR_SEQ 1 583 Missing (in isoform 2). FT /FTId=VSP_018132. FT CONFLICT 4 4 F -> V (in Ref. 1). FT CONFLICT 23 23 R -> H (in Ref. 1). FT CONFLICT 194 194 V -> I (in Ref. 1). FT CONFLICT 313 313 A -> S (in Ref. 1). FT CONFLICT 667 667 R -> Q (in Ref. 1). SQ SEQUENCE 1062 AA; 119711 MW; 8949A2C5F414B726 CRC64; MACFSNETQI EIDVHDLVEA PIRYDSIESI YSIPSSALCC VNAVGSHSLM SKKVKAQKLP MIEQFEIEGS GVSASDDCCR SDDYKLRIQR PEIVRVYYRR RKRPLRECLL DQAVAVKTES VELDEIDCFE EKKRRKIGNC ELVKSGMESI GLRRCKENNA FSGNKQNGSS RRKGSSSKNQ DKATLASRSA KKWVRLSYDG VDPTSFIGLQ CKVFWPLDAL WYEGSIVGYS AERKRYTVKY RDGCDEDIVF DREMIKFLVS REEMELLHLK FCTSNVTVDG RDYDEMVVLA ATLDECQDFE PGDIVWAKLA GHAMWPAVIV DESIIGERKG LNNKVSGGGS LLVQFFGTHD FARIKVKQAI SFIKGLLSPS HLKCKQPRFE EGMQEAKMYL KAHRLPERMS QLQKGADSVD SDMANSTEEG NSGGDLLNDG EVWLRPTEHV DFRHIIGDLL IINLGKVVTD SQFFKDENHI WPEGYTAMRK FTSLTDHSAS ALYKMEVLRD AETKTHPLFI VTADSGEQFK GPTPSACWNK IYNRIKKVQN SDSPNILGEE LNGSGTDMFG LSNPEVIKLV QDLSKSRPSS HVSMCKNSLG RHQNQPTGYR PVRVDWKDLD KCNVCHMDEE YENNLFLQCD KCRMMVHAKC YGELEPCDGA LWLCNLCRPG APDMPPRCCL CPVVGGAMKP TTDGRWAHLA CAIWIPETCL SDVKKMEPID GVNKVSKDRW KLMCTICGVS YGACIQCSNN SCRVAYHPLC ARAAGLCVEL ENDMSVEGEE ADQCIRMLSF CKRHRQTSTA CLGSEDRIKS ATHKTSEYLP PPNPSGCART EPYNCFGRRG RKEPEALAAA SSKRLFVENQ PYVIGGYSRL EFSTYKSIHG SKVSQMNTPS NILSMAEKYR YMRETYRKRL AFGKSGIHGF GIFAKLPHRA GDMMIEYTGE LVRPSIADKR EQLIYNSMVG AGTYMFRIDD ERVIDATRTG SIAHLINHSC VPNCYSRVIT VNGDEHIIIF AKRHIPKWEE LTYDYRFFSI GERLSCSCGF PGCRGVVNDT EAEEQHAKIC VPRCDLIDWT AE // ID BRAF1_CHICK STANDARD; PRT; 806 AA. AC Q04982; Q8AV85; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1994, sequence version 1. DT 30-MAY-2006, entry version 57. DE B-Raf proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) DE (Rmil serine/threonine-protein kinase) (c-Rmil). GN Name=BRAF; Synonyms=RMIL; 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 [MRNA] (ISOFORMS LONG AND SHORT). RC TISSUE=Fibroblast, and Lymphocyte; RX MEDLINE=93312327; PubMed=8323553; RA Calogeraki I., Barnier J.V., Eychene A., Felder M.-P., Calothy G., RA Marx M.; RT "Genomic organization and nucleotide sequence of the coding region of RT the chicken c-Rmil(B-raf-1) proto-oncogene."; RL Biochem. Biophys. Res. Commun. 193:1324-1331(1993). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 55-806 (ISOFORM SHORT). RC TISSUE=Bursa of Fabricius; RA Brummer T., Naegele H., Reth M., Misawa Y.; RT "Feedback phosphorylation of B-Raf by ERK in activated B cells."; RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: May play a role in transducing specific signals in CC neural cells. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- COFACTOR: Binds 2 zinc ions per subunit (Potential). CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Long; CC IsoId=Q04982-1; Sequence=Displayed; CC Name=Short; CC IsoId=Q04982-2; Sequence=VSP_004798; CC -!- TISSUE SPECIFICITY: Expressed preferentially in neural tissue. CC -!- PTM: Phosphorylated. CC -!- SIMILARITY: Belongs to the Ser/Thr protein kinase family. RAF CC subfamily. CC -!- SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC -!- SIMILARITY: Contains 1 RBD (Ras-binding) 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; X67052; CAA47436.1; -; mRNA. DR EMBL; AF449458; AAO13358.1; -; mRNA. DR PIR; JN0612; JN0612. DR UniGene; Gga.719; -. DR HSSP; P04049; 1FAR. DR SMR; Q04982; 232-283, 488-763. DR Ensembl; ENSGALG00000012865; Gallus gallus. DR InterPro; IPR002219; DAG_PE_bd. DR InterPro; IPR011009; Kinase_like. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR003116; Raf_like_ras_bd. DR InterPro; IPR008271; Ser_thr_pkin_AS. DR Pfam; PF00130; C1_1; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF02196; RBD; 1. DR PRINTS; PR00008; DAGPEDOMAIN. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00109; C1; 1. DR SMART; SM00455; RBD; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR PROSITE; PS50898; RBD; 1. DR PROSITE; PS00479; ZF_DAG_PE_1; 1. DR PROSITE; PS50081; ZF_DAG_PE_2; 1. KW Alternative splicing; ATP-binding; Kinase; Metal-binding; KW Nuclear protein; Nucleotide-binding; Phorbol-ester binding; KW Phosphorylation; Proto-oncogene; Serine/threonine-protein kinase; KW Transferase; Zinc; Zinc-finger. FT CHAIN 1 806 B-Raf proto-oncogene serine/threonine- FT protein kinase. FT /FTId=PRO_0000085667. FT DOMAIN 155 227 RBD. FT DOMAIN 497 757 Protein kinase. FT ZN_FING 234 280 Phorbol-ester/DAG-type. FT NP_BIND 503 511 ATP (By similarity). FT COMPBIAS 122 129 Poly-Ser. FT COMPBIAS 248 280 Cys-rich. FT ACT_SITE 616 616 Proton acceptor (By similarity). FT METAL 235 235 Zinc 1 (By similarity). FT METAL 248 248 Zinc 2 (By similarity). FT METAL 251 251 Zinc 2 (By similarity). FT METAL 261 261 Zinc 1 (By similarity). FT METAL 264 264 Zinc 1 (By similarity). FT METAL 269 269 Zinc 2 (By similarity). FT METAL 272 272 Zinc 2 (By similarity). FT METAL 280 280 Zinc 1 (By similarity). FT BINDING 523 523 ATP (By similarity). FT VAR_SEQ 393 432 Missing (in isoform Short). FT /FTId=VSP_004798. SQ SEQUENCE 806 AA; 89366 MW; 8F3FA4D5274FB75C CRC64; MAALSSGSSA EGASLFNGDM EPEPPPPVLG ACYAGSGGGD PAIPEEVWNI KQMIKLTQEH IEALLDKFGG EHNPPSIYLE AYEEYTSKLD ALQQREQQLL ESMGNGTDFS VSSSASTDTV ASSSSSSLSV APSSLSVYQN PTDMSRNNPK SPQKPIVRVF LPNKQRTVVP ARCGVTVRDS LKKALMMRGL IPECCAVYRI QDGEKKPIGW DTDISWLTGE ELHVEVLENV PLTTHNFVRK TFFTLAFCDF CRKLLFQGFR CQTCGYKFHQ RCSTEVPLMC VNYDQLDLLF VSKFFEHHPI SQEETTLGET TPASGSYPSV PPSDSVGPPI LPSPSPSKSI PIPQPFRPAD EDHRNQFGQR DRSSSAPNVH INTIEPVNID DLIRDQGVRG EGAPLNQLMR CLRKYQSRTP SPLLHSVPSE IVFDFEPGPV FRGSTAGLSA TPPASLPGSL TNVKALQKSP GPQRERKSSS SSEDRNRMKT LGRRDSSDDW EIPDGQITVG QRIGSGSFGT VYKGKWHGDV AVKMLNVTAP TPQQLQAFKN EVGVLRKTRH VNILLFMGYS TKPQLAIVTQ WCEGSSLYHH LHIIETKFEM IKLIDIARQT AQGMDYLHAK SIIHRDLKSN NIFLHEDLTV KIGDFGLATV KSRWSGSHQF EQLSGSILWM APEVIRMQDK NPYSFQSDVY AFGIVLYELM TGQLPYSNIN NRDQIIFMVG RGYLSPDLSK VRSNCPKAMK RLMAECLKKK RDERPLFPQI LASIELLARS LPKIHRSASE PSLNRAGFQT EDFSLYACAS PKTPIQAGGY GGFPVH // ID BRAF1_COTJA STANDARD; PRT; 807 AA. AC P34908; DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1994, sequence version 1. DT 30-MAY-2006, entry version 57. DE B-Raf proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) DE (RMIL serine/threonine-protein kinase) (c-RMIL). GN Name=BRAF; Synonyms=RMIL; OS Coturnix coturnix japonica (Japanese quail). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Archosauria; Aves; Neognathae; Galliformes; Phasianidae; Phasianinae; OC Coturnix. OX NCBI_TaxID=93934; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT). RX MEDLINE=92319540; PubMed=1620546; RA Eychene A., Barnier J.V., Dezelee P., Marx M., Laugier D., RA Calogeraki I., Calothy G.; RT "Quail neuroretina c-Rmil(B-raf) proto-oncogene cDNAs encode two RT proteins of 93.5 and 95 kDa resulting from alternative splicing."; RL Oncogene 7:1315-1323(1992). CC -!- FUNCTION: May play a role in transducing specific signals in CC neural cells. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- COFACTOR: Binds 2 zinc ions per subunit (Potential). CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Long; CC IsoId=P34908-1; Sequence=Displayed; CC Name=Short; CC IsoId=P34908-2; Sequence=VSP_004799; CC -!- TISSUE SPECIFICITY: Expressed preferentially in neural tissue. CC -!- PTM: Phosphorylated. CC -!- SIMILARITY: Belongs to the Ser/Thr protein kinase family. RAF CC subfamily. CC -!- SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC -!- SIMILARITY: Contains 1 RBD (Ras-binding) 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; M80846; AAA49493.1; -; mRNA. DR EMBL; M80845; AAA49492.1; -; mRNA. DR HSSP; P04049; 1FAR. DR SMR; P34908; 232-283, 488-763. DR InterPro; IPR002219; DAG_PE_bd. DR InterPro; IPR011009; Kinase_like. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR003116; Raf_like_ras_bd. DR InterPro; IPR008271; Ser_thr_pkin_AS. DR Pfam; PF00130; C1_1; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF02196; RBD; 1. DR PRINTS; PR00008; DAGPEDOMAIN. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00109; C1; 1. DR SMART; SM00455; RBD; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR PROSITE; PS50898; RBD; 1. DR PROSITE; PS00479; ZF_DAG_PE_1; 1. DR PROSITE; PS50081; ZF_DAG_PE_2; 1. KW Alternative splicing; ATP-binding; Kinase; Metal-binding; KW Nuclear protein; Nucleotide-binding; Phorbol-ester binding; KW Phosphorylation; Proto-oncogene; Serine/threonine-protein kinase; KW Transferase; Zinc; Zinc-finger. FT CHAIN 1 807 B-Raf proto-oncogene serine/threonine- FT protein kinase. FT /FTId=PRO_0000085668. FT DOMAIN 155 227 RBD. FT DOMAIN 497 757 Protein kinase. FT ZN_FING 234 280 Phorbol-ester/DAG-type. FT NP_BIND 503 511 ATP (By similarity). FT COMPBIAS 122 129 Poly-Ser. FT COMPBIAS 248 280 Cys-rich. FT ACT_SITE 616 616 Proton acceptor (By similarity). FT METAL 235 235 Zinc 1 (By similarity). FT METAL 248 248 Zinc 2 (By similarity). FT METAL 251 251 Zinc 2 (By similarity). FT METAL 261 261 Zinc 1 (By similarity). FT METAL 264 264 Zinc 1 (By similarity). FT METAL 269 269 Zinc 2 (By similarity). FT METAL 272 272 Zinc 2 (By similarity). FT METAL 280 280 Zinc 1 (By similarity). FT BINDING 523 523 ATP (By similarity). FT VAR_SEQ 393 432 Missing (in isoform Short). FT /FTId=VSP_004799. SQ SEQUENCE 807 AA; 89522 MW; 1F9700AE65242FB7 CRC64; MAALSSGSSA EGASLFNGDM EPEPPPPVLG ACYAGSGGGD PAIPEEVWNI KQMIKLTQEH IEALLDKFGG EHNPPSIYLE AYEEYTSKLD ALQQREQQLL ESMGNGTDFS VSSSASTDTV ASSSSSSLSV APSSLSVYQN PTDMSRNNPK SPQKPIVRVF LPNKQRTVVP ARCGVTVRDS LKKALMMRGL IPECCAVYRI QDGEKKPIGW DTDISWLTGE ELHVEVLENV PLTTHNFVRK TFFTLAFCDF CRKLLFQGFR CQTCGYKFHQ RCSTEVPLMC VNYDQLDLLF VSKFFEHHPI SQEETTLGET TPASGSYPSV PPSDSVGPPI LPSPSPSKSI PIPQPFRPAD EDHRNQFGQR DRSSSAPNVH INTIEPVNID DLIRDQGVRG EGAPLNQLMR CLRKYQSRTP SPLLHSVPSE IVFDFEPGPV FRGSTAGLSA TPPASLPGSL TNVKALQKSP GPQRERKSSS SSEDRNRMKT LGRRDSSDDW EIPDGQITVG QRIGSGSFGT VYKGKWHGDV AVKMLNVTAP TPQQLQAFKN EVGVLRKTRH VNILLFMGYS TKPQLAIVTQ WCEGSSLYHH LHIIETKFEM IKLIDIARQT AQGMDYLHAK SIIHRDLKSN NIFLHEDLTV KIGDFGLATV KSRWSGSHQF EQLSGSILWM APEVIRMQDK NPYSFQSDVY AFGIVLYELM TGQLPYSNIN NRDQIIFMVG RGYLSPDLSK VRSNCPKAMK RLMAECLKKK RDERPLFPQI LASIELLARS LPKIHRSASE PSLNRAGFQT EDFSLYACAS PKTPIQAGGY GEFAAFK // ID BRAF1_HUMAN STANDARD; PRT; 766 AA. AC P15056; Q13878; Q9Y6T3; DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot. DT 19-JUL-2004, sequence version 4. DT 30-MAY-2006, entry version 77. DE B-Raf proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) DE (p94) (v-Raf murine sarcoma viral oncogene homolog B1). GN Name=BRAF; Synonyms=BRAF1, RAFB1; 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, PARTIAL PROTEIN SEQUENCE, AND PHOSPHORYLATION AT RP THR-373. RC TISSUE=Testis; RX MEDLINE=92375040; PubMed=1508179; RA Stephens R.M., Sithanandam G., Copeland T.D., Kaplan D.R., Rapp U.R., RA Morrison D.K.; RT "95-kilodalton B-Raf serine/threonine kinase: identification of the RT protein and its major autophosphorylation site."; RL Mol. Cell. Biol. 12:3733-3742(1992). RN [2] RP SEQUENCE REVISION TO 31-33. RA Albert S., Wixler L., Rapp U.R.; RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX MEDLINE=22737999; PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., RA Waterston R.H., Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [4] RP NUCLEOTIDE SEQUENCE OF 1-200. RC TISSUE=Placenta; RX MEDLINE=92334878; PubMed=1630826; RA Eychene A., Barnier J.V., Apiou F., Dutrillaux B., Calothy G.; RT "Chromosomal assignment of two human B-raf(Rmil) proto-oncogene loci: RT B-raf-1 encoding the p94Braf/Rmil and B-raf-2, a processed RT pseudogene."; RL Oncogene 7:1657-1660(1992). RN [5] RP NUCLEOTIDE SEQUENCE OF 117-766. RC TISSUE=Testis; RX MEDLINE=91133728; PubMed=2284096; RA Sithanandam G., Kolch W., Duh F.-M., Rapp U.R.; RT "Complete coding sequence of a human B-raf cDNA and detection of B-raf RT protein kinase with isozyme specific antibodies."; RL Oncogene 5:1775-1780(1990). RN [6] RP NUCLEOTIDE SEQUENCE OF 439-766. RX MEDLINE=88302178; PubMed=3043188; RA Ikawa S., Fukui M., Ueyama Y., Tamaoki N., Yamamoto T., Toyoshima K.; RT "B-raf, a new member of the raf family, is activated by DNA RT rearrangement."; RL Mol. Cell. Biol. 8:2651-2654(1988). RN [7] RP PHOSPHORYLATION AT THR-401 AND SER-729. RX PubMed=15302935; DOI=10.1073/pnas.0404720101; RA Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., RA Li J., Cohn M.A., Cantley L.C., Gygi S.P.; RT "Large-scale characterization of HeLa cell nuclear phosphoproteins."; RL Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004). RN [8] RP VARIANTS LUNG CANCER VAL-466 AND ARG-597. RX MEDLINE=22349173; PubMed=12460919; RA Naoki K., Chen T.-H., Richards W.G., Sugarbaker D.J., Meyerson M.; RT "Missense mutations of the BRAF gene in human lung adenocarcinoma."; RL Cancer Res. 62:7001-7003(2002). RN [9] RP VARIANTS CANCER GLU-464; VAL-464; ALA-466; GLU-466; VAL-466; ALA-469; RP GLU-469; LYS-586; LEU-595; ARG-596; ARG-597; VAL-597; GLU-600 AND RP ASP-600, AND CHARACTERIZATION OF VARIANTS CANCER VAL-464; ALA-469; RP VAL-597 AND GLU-600. RX MEDLINE=22082291; PubMed=12068308; DOI=10.1038/nature00766; RA Davies H., Bignell G.R., Cox C., Stephens P., Edkins S., Clegg S., RA Teague J., Woffendin H., Garnett M.J., Bottomley W., Davis N., RA Dicks E., Ewing R., Floyd Y., Gray K., Hall S., Hawes R., Hughes J., RA Kosmidou V., Menzies A., Mould C., Parker A., Stevens C., Watt S., RA Hooper S., Wilson R., Jayatilake H., Gusterson B.A., Cooper C., RA Shipley J., Hargrave D., Pritchard-Jones K., Maitland N., RA Chenevix-Trench G., Riggins G.J., Bigner D.D., Palmieri G., Cossu A., RA Flanagan A., Nicholson A., Ho J.W.C., Leung S.Y., Yuen S.T., RA Weber B.L., Seigler H.F., Darrow T.L., Paterson H., Marais R., RA Marshall C.J., Wooster R., Stratton M.R., Futreal P.A.; RT "Mutations of the BRAF gene in human cancer."; RL Nature 417:949-954(2002). RN [10] RP VARIANTS COLORECTAL CANCER ILE-462; SER-463; GLU-464; GLU-600 AND RP GLU-601. RX MEDLINE=22187000; PubMed=12198537; DOI=10.1038/418934a; RA Rajagopalan H., Bardelli A., Lengauer C., Kinzler K.W., Vogelstein B., RA Velculescu V.E.; RT "Tumorigenesis: RAF/RAS oncogenes and mismatch-repair status."; RL Nature 418:934-934(2002). RN [11] RP VARIANTS NHL ALA-469; ARG-469 AND GLY-594. RX MEDLINE=22973595; PubMed=14612909; DOI=10.1038/sj.bjc.6601371; RA Lee J.W., Yoo N.J., Soung Ark W.S., Kim S.Y., Lee J.H., Park J.Y., RA Cho Y.G., Kim C.J., Ko Y.H., Kim S.H., Nam S.W., Lee J.Y., Lee S.H.; RT "BRAF mutations in non-Hodgkin's lymphoma."; RL Br. J. Cancer 89:1958-1960(2003). RN [12] RP CHARACTERIZATION OF VARIANT MELANOMA GLU-600. RX MEDLINE=22861930; PubMed=14500344; RA Hingorani S.R., Jacobetz M.A., Robertson G.P., Herlyn M., RA Tuveson D.A.; RT "Suppression of BRAF(V599E) in human melanoma abrogates RT transformation."; RL Cancer Res. 63:5198-5202(2003). RN [13] RP INVOLVEMENT IN CARDIOFACIOCUTANEOUS SYNDROME, AND VARIANTS CFC RP SYNDROME PRO-246; ARG-257; GLU-469; PHE-485; GLU-499; LYS-501; GLY-501 RP AND ASP-581. RX PubMed=16474404; DOI=10.1038/ng1749; RA Niihori T., Aoki Y., Narumi Y., Neri G., Cave H., Verloes A., RA Okamoto N., Hennekam R.C., Gillessen-Kaesbach G., Wieczorek D., RA Kavamura M.I., Kurosawa K., Ohashi H., Wilson L., Heron D., RA Bonneau D., Corona G., Kaname T., Naritomi K., Baumann C., RA Matsumoto N., Kato K., Kure S., Matsubara Y.; RT "Germline KRAS and BRAF mutations in cardio-facio-cutaneous RT syndrome."; RL Nat. Genet. 38:294-296(2006). CC -!- FUNCTION: Involved in the transduction of mitogenic signals from CC the cell membrane to the nucleus. May play a role in the CC postsynaptic responses of hippocampal neuron. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- COFACTOR: Binds 2 zinc ions per subunit (By similarity). CC -!- SUBUNIT: Interacts with RIT1 (By similarity). CC -!- SUBCELLULAR LOCATION: Cytoplasm. CC -!- TISSUE SPECIFICITY: Brain and testis. CC -!- DISEASE: Defects in BRAF are a cause of cardiofaciocutaneous CC syndrome (CFC syndrome) [MIM:115150]; also known as cardio-facio- CC cutaneous syndrome. CFC syndrome is characterized by a distinctive CC facial appearance, heart defects and mental retardation. Heart CC defects include pulmonic stenosis, atrial septal defects and CC hypertrophic cardiomyopathy. Some affected individuals present CC with ectodermal abnormalities such as sparse, friable hair, CC hyperkeratotic skin lesions and a generalized ichthyosis-like CC condition. Typical facial features are similar to Noonan syndrome. CC They include high forehead with bitemporal constriction, CC hypoplastic supraorbital ridges, downslanting palpebral fissures, CC a depressed nasal bridge, and posteriorly angulated ears with CC prominent helices. The inheritance of CFC syndrome is autosomal CC dominant. CC -!- DISEASE: Defects in BRAF are involved in a wide range of cancers. CC -!- DISEASE: Defects in BRAF are involved in lung cancer [MIM:211980]. CC -!- DISEASE: Defects in BRAF are involved in non-Hodgkin lymphoma CC (NHL) [MIM:605027]. CC -!- SIMILARITY: Belongs to the Ser/Thr protein kinase family. RAF CC subfamily. CC -!- SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC -!- SIMILARITY: Contains 1 RBD (Ras-binding) domain. CC -!- CAUTION: Ref.3 sequence differs from that shown due to erroneous CC gene model prediction. CC -!- WEB RESOURCE: NAME=GeneReviews; CC URL="http://www.genetests.org/query?gene=BRAF". 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; M95712; AAA35609.2; -; mRNA. DR EMBL; AC006344; AAD43193.1; ALT_SEQ; Genomic_DNA. DR EMBL; X65187; CAA46301.1; -; Genomic_DNA. DR EMBL; M21001; AAA96495.1; -; mRNA. DR PIR; A57977; TVHUBF. DR UniGene; Hs.550061; -. DR PDB; 1UWH; X-ray; A/B=448-723. DR PDB; 1UWJ; X-ray; A/B=448-723. DR SMR; P15056; 232-283. DR IntAct; P15056; -. DR Ensembl; ENSG00000157764; Homo sapiens. DR HGNC; HGNC:1097; BRAF. DR MIM; 115150; phenotype. DR MIM; 164757; gene. DR MIM; 211980; phenotype. DR MIM; 605027; phenotype. DR LinkHub; P15056; -. DR GO; GO:0004672; F:protein kinase activity; TAS. DR GO; GO:0006916; P:anti-apoptosis; TAS. DR GO; GO:0009887; P:organ morphogenesis; TAS. DR GO; GO:0006468; P:protein amino acid phosphorylation; TAS. DR InterPro; IPR002219; DAG_PE_bd. DR InterPro; IPR000719; Prot_kinase. DR InterPro; IPR003116; Raf_like_ras_bd. DR InterPro; IPR008271; Ser_thr_pkin_AS. DR Pfam; PF00130; C1_1; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF02196; RBD; 1. DR PRINTS; PR00008; DAGPEDOMAIN. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00109; C1; 1. DR SMART; SM00455; RBD; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR PROSITE; PS50898; RBD; 1. DR PROSITE; PS00479; ZF_DAG_PE_1; 1. DR PROSITE; PS50081; ZF_DAG_PE_2; 1. KW 3D-structure; ATP-binding; Cardiomyopathy; Direct protein sequencing; KW Disease mutation; Kinase; Metal-binding; Nucleotide-binding; KW Phorbol-ester binding; Phosphorylation; Proto-oncogene; KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger. FT CHAIN 1 766 B-Raf proto-oncogene serine/threonine- FT protein kinase. FT /FTId=PRO_0000085665. FT DOMAIN 155 227 RBD. FT DOMAIN 457 717 Protein kinase. FT ZN_FING 234 280 Phorbol-ester/DAG-type. FT NP_BIND 463 471 ATP (By similarity). FT COMPBIAS 6 11 Poly-Gly. FT COMPBIAS 122 129 Poly-Ser. FT COMPBIAS 428 432 Poly-Ser. FT ACT_SITE 576 576 Proton acceptor (By similarity). FT METAL 235 235 Zinc 1 (By similarity). FT METAL 248 248 Zinc 2 (By similarity). FT METAL 251 251 Zinc 2 (By similarity). FT METAL 261 261 Zinc 1 (By similarity). FT METAL 264 264 Zinc 1 (By similarity). FT METAL 269 269 Zinc 2 (By similarity). FT METAL 272 272 Zinc 2 (By similarity). FT METAL 280 280 Zinc 1 (By similarity). FT BINDING 483 483 ATP (By similarity). FT MOD_RES 373 373 Phosphothreonine (by autocatalysis). FT MOD_RES 401 401 Phosphothreonine. FT MOD_RES 729 729 Phosphoserine. FT VARIANT 246 246 A -> P (in CFC syndrome). FT /FTId=VAR_026113. FT VARIANT 257 257 Q -> R (in CFC syndrome). FT /FTId=VAR_026114. FT VARIANT 462 462 R -> I (in colorectal cancer). FT /FTId=VAR_018613. FT VARIANT 463 463 I -> S (in colorectal cancer). FT /FTId=VAR_018614. FT VARIANT 464 464 G -> E (in colorectal cancer). FT /FTId=VAR_018615. FT VARIANT 464 464 G -> V (in a colorectal cancer cell line; FT elevated kinase activity; efficiently FT induces cell transformation). FT /FTId=VAR_018616. FT VARIANT 466 466 G -> A (in melanoma). FT /FTId=VAR_018617. FT VARIANT 466 466 G -> E (in melanoma). FT /FTId=VAR_018618. FT VARIANT 466 466 G -> V (in lung cancer). FT /FTId=VAR_018512. FT VARIANT 469 469 G -> A (in NHL; also in a lung cancer FT cell line; elevated kinase activity; FT efficiently induces cell transformation). FT /FTId=VAR_018620. FT VARIANT 469 469 G -> E (in CFC syndrome and colon FT cancer). FT /FTId=VAR_018621. FT VARIANT 469 469 G -> R (in NHL). FT /FTId=VAR_018622. FT VARIANT 485 485 L -> F (in CFC syndrome). FT /FTId=VAR_026115. FT VARIANT 499 499 K -> E (in CFC syndrome). FT /FTId=VAR_026116. FT VARIANT 501 501 E -> G (in CFC syndrome). FT /FTId=VAR_026117. FT VARIANT 501 501 E -> K (in CFC syndrome). FT /FTId=VAR_026118. FT VARIANT 581 581 N -> D (in CFC syndrome). FT /FTId=VAR_026119. FT VARIANT 586 586 E -> K (in ovarian cancer). FT /FTId=VAR_018623. FT VARIANT 594 594 D -> G (in NHL). FT /FTId=VAR_018624. FT VARIANT 595 595 F -> L (in colon cancer). FT /FTId=VAR_018625. FT VARIANT 596 596 G -> R (in a colon cancer cell line). FT /FTId=VAR_018626. FT VARIANT 597 597 L -> R (in lung cancer and ovarian FT cancer). FT /FTId=VAR_018513. FT VARIANT 597 597 L -> V (in a lung cancer cell line; FT elevated kinase activity; efficiently FT induces cell transformation). FT /FTId=VAR_018627. FT VARIANT 600 600 V -> D (in a melanoma cell line; requires FT 2 nucleotide substitutions). FT /FTId=VAR_018628. FT VARIANT 600 600 V -> E (in colorectal cancer, melanoma, FT ovarian cancer and sarcoma; most common FT mutation; elevated kinase activity; FT efficiently induces cell transformation; FT suppression of mutation in melanoma FT causes growth arrest and promotes FT apoptosis). FT /FTId=VAR_018629. FT VARIANT 601 601 K -> E (in colorectal cancer). FT /FTId=VAR_018630. FT CONFLICT 766 766 H -> D (in Ref. 6). FT STRAND 451 451 FT TURN 454 455 FT STRAND 461 465 FT STRAND 467 468 FT STRAND 470 484 FT STRAND 488 489 FT TURN 492 493 FT HELIX 494 505 FT TURN 506 507 FT TURN 511 512 FT STRAND 513 513 FT STRAND 516 520 FT STRAND 522 524 FT STRAND 526 530 FT STRAND 534 536 FT HELIX 537 542 FT TURN 543 543 FT STRAND 544 544 FT HELIX 550 569 FT TURN 570 571 FT STRAND 575 575 FT HELIX 579 581 FT STRAND 582 585 FT TURN 586 587 FT STRAND 588 592 FT STRAND 598 598 FT HELIX 617 619 FT HELIX 622 625 FT TURN 626 627 FT STRAND 629 630 FT HELIX 635 651 FT STRAND 652 653 FT TURN 655 658 FT HELIX 662 670 FT TURN 671 672 FT STRAND 673 673 FT HELIX 678 680 FT STRAND 681 681 FT TURN 683 684 FT HELIX 687 696 FT TURN 697 697 FT STRAND 699 700 FT HELIX 701 703 FT STRAND 704 704 FT HELIX 707 719 FT TURN 720 720 SQ SEQUENCE 766 AA; 84437 MW; 0798C2AAB487E813 CRC64; MAALSGGGGG GAEPGQALFN GDMEPEAGAG AGAAASSAAD PAIPEEVWNI KQMIKLTQEH IEALLDKFGG EHNPPSIYLE AYEEYTSKLD ALQQREQQLL ESLGNGTDFS VSSSASMDTV TSSSSSSLSV LPSSLSVFQN PTDVARSNPK SPQKPIVRVF LPNKQRTVVP ARCGVTVRDS LKKALMMRGL IPECCAVYRI QDGEKKPIGW DTDISWLTGE ELHVEVLENV PLTTHNFVRK TFFTLAFCDF CRKLLFQGFR CQTCGYKFHQ RCSTEVPLMC VNYDQLDLLF VSKFFEHHPI PQEEASLAET ALTSGSSPSA PASDSIGPQI LTSPSPSKSI PIPQPFRPAD EDHRNQFGQR DRSSSAPNVH INTIEPVNID DLIRDQGFRG DGGSTTGLSA TPPASLPGSL TNVKALQKSP GPQRERKSSS SSEDRNRMKT LGRRDSSDDW EIPDGQITVG QRIGSGSFGT VYKGKWHGDV AVKMLNVTAP TPQQLQAFKN EVGVLRKTRH VNILLFMGYS TKPQLAIVTQ WCEGSSLYHH LHIIETKFEM IKLIDIARQT AQGMDYLHAK SIIHRDLKSN NIFLHEDLTV KIGDFGLATV KSRWSGSHQF EQLSGSILWM APEVIRMQDK NPYSFQSDVY AFGIVLYELM TGQLPYSNIN NRDQIIFMVG RGYLSPDLSK VRSNCPKAMK RLMAECLKKK RDERPLFPQI LASIELLARS LPKIHRSASE PSLNRAGFQT EDFSLYACAS PKTPIQAGGY GAFPVH // ID CHIN_HUMAN STANDARD; PRT; 459 AA. AC P15882; Q96FB0; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 11-JUL-2002, sequence version 3. DT 30-MAY-2006, entry version 67. DE N-chimaerin (NC) (N-chimerin) (Alpha chimerin) (A-chimaerin) (Rho- DE GTPase-activating protein 2). GN Name=CHN1; Synonyms=ARHGAP2, CHN; 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 (ISOFORM ALPHA-1). RC TISSUE=Retina; RX MEDLINE=90133942; PubMed=2299665; RA Hall C., Monfries C., Smith P., Lim H.H., Kozma R., Ahmed S., RA Vanniasingham V., Leung T., Lim L.; RT "Novel human brain cDNA encoding a 34,000 Mr protein n-chimaerin, RT related to both the regulatory domain of protein kinase C and BCR, the RT product of the breakpoint cluster region gene."; RL J. Mol. Biol. 211:11-16(1990). RN [2] RP SEQUENCE REVISION. RX MEDLINE=93074974; PubMed=1445199; RA Lim H.H., Michael G.J., Smith P., Lim L., Hall C.; RT "Developmental regulation and neuronal expression of the mRNA of rat RT n-chimaerin, a p21rac GAP:cDNA sequence."; RL Biochem. J. 287:415-422(1992). RN [3] RP NUCLEOTIDE SEQUENCE (ISOFORM ALPHA-2). RX MEDLINE=93330292; PubMed=8336731; RA Hall C., Sin W.C., Teo M., Michael G.J., Smith P., Dong J.M., RA Lim H.H., Manser E., Spurr N.K., Jones T.A., Lim L.; RT "Alpha 2-chimerin, an SH2-containing GTPase-activating protein for the RT ras-related protein p21rac derived by alternate splicing of the human RT n-chimerin gene, is selectively expressed in brain regions and RT testes."; RL Mol. Cell. Biol. 13:4986-4998(1993). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA-2). RC TISSUE=Eye; 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 PARTIAL NUCLEOTIDE SEQUENCE (ISOFORM ALPHA-1). RC TISSUE=Fibroblast; RX MEDLINE=95172046; PubMed=7867622; RA Dong J.M., Smith P., Hall C., Lim L.; RT "Promoter region of the transcriptional unit for human alpha 1- RT chimaerin, a neuron-specific GTPase-activating protein for p21rac."; RL Eur. J. Biochem. 227:636-646(1995). RN [6] RP PHORBOL-ESTER BINDING. RX MEDLINE=91097509; PubMed=2268301; RA Ahmed S., Kozma R., Monfries C., Hall C., Lim H.H., Smith P., Lim L.; RT "Human brain n-chimaerin cDNA encodes a novel phorbol ester RT receptor."; RL Biochem. J. 272:767-773(1990). CC -!- FUNCTION: GTPase-activating protein for p21-rac and a phorbol CC ester receptor. May play an important role in neuronal signal- CC transduction mechanisms. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Alpha-2; CC IsoId=P15882-1; Sequence=Displayed; CC Name=Alpha-1; CC IsoId=P15882-2; Sequence=VSP_001636; CC -!- TISSUE SPECIFICITY: In neurons in brain regions that are involved CC in learning and memory processes. CC -!- DEVELOPMENTAL STAGE: Increases in amount during brain development CC coincident with synaptogenesis. CC -!- SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger. CC -!- SIMILARITY: Contains 1 Rho-GAP 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; X51408; CAA35769.1; ALT_INIT; mRNA. DR EMBL; Z22641; CAA80354.1; -; mRNA. DR EMBL; BC011393; AAH11393.1; -; mRNA. DR EMBL; S75654; AAB33506.1; -; Genomic_DNA. DR UniGene; Hs.380138; -. DR HSSP; P28867; 1PTQ. DR SMR; P15882; 13-459. DR Ensembl; ENSG00000128656; Homo sapiens. DR H-InvDB; HIX0002610; -. DR HGNC; HGNC:1943; CHN1. DR MIM; 118423; gene. DR LinkHub; P15882; -. DR GO; GO:0005070; F:SH3/SH2 adaptor activity; TAS. DR InterPro; IPR002219; DAG_PE_bd. DR InterPro; IPR008936; Rho_GAP. DR InterPro; IPR000198; RhoGAP. DR InterPro; IPR000980; SH2. DR Pfam; PF00130; C1_1; 1. DR Pfam; PF00620; RhoGAP; 1. DR Pfam; PF00017; SH2; 1. DR PRINTS; PR00008; DAGPEDOMAIN. DR PRINTS; PR00401; SH2DOMAIN. DR ProDom; PD000093; SH2; 1. DR SMART; SM00109; C1; 1. DR SMART; SM00324; RhoGAP; 1. DR SMART; SM00252; SH2; 1. DR PROSITE; PS50238; RHOGAP; 1. DR PROSITE; PS50001; SH2; 1. DR PROSITE; PS00479; ZF_DAG_PE_1; 1. DR PROSITE; PS50081; ZF_DAG_PE_2; 1. KW Alternative splicing; GTPase activation; Metal-binding; KW Phorbol-ester binding; SH2 domain; Zinc; Zinc-finger. FT CHAIN 1 459 N-chimaerin. FT /FTId=PRO_0000056694. FT DOMAIN 49 135 SH2. FT DOMAIN 268 459 Rho-GAP. FT ZN_FING 205 255 Phorbol-ester/DAG-type. FT VAR_SEQ 1 183 MALTLFDTDEYRPPVWKSYLYQLQQEAPHPRRITCTCEVEN FT RPKYYGREFHGMISREAADQLLIVAEGSYLIRESQRQPGTY FT TLALRFGSQTRNFRLYYDGKHFVGEKRFESIHDLVTDGLIT FT LYIETKAAEYIAKMTINPIYEHVGYTTLNREPAYKKHMPVL FT KETHDERDSTGQDGVSEKR -> MPSKESWSGRKTNRAAVH FT KSKQEGRQQDLLIAALGMKLGSPKSSVTIWQPLKLFAYSQ FT (in isoform Alpha-1). FT /FTId=VSP_001636. SQ SEQUENCE 459 AA; 53172 MW; 04C4CC9BCC611389 CRC64; MALTLFDTDE YRPPVWKSYL YQLQQEAPHP RRITCTCEVE NRPKYYGREF HGMISREAAD QLLIVAEGSY LIRESQRQPG TYTLALRFGS QTRNFRLYYD GKHFVGEKRF ESIHDLVTDG LITLYIETKA AEYIAKMTIN PIYEHVGYTT LNREPAYKKH MPVLKETHDE RDSTGQDGVS EKRLTSLVRR ATLKENEQIP KYEKIHNFKV HTFRGPHWCE YCANFMWGLI AQGVKCADCG LNVHKQCSKM VPNDCKPDLK HVKKVYSCDL TTLVKAHTTK RPMVVDMCIR EIESRGLNSE GLYRVSGFSD LIEDVKMAFD RDGEKADISV NMYEDINIIT GALKLYFRDL PIPLITYDAY PKFIESAKIM DPDEQLETLH EALKLLPPAH CETLRYLMAH LKRVTLHEKE NLMNAENLGI VFGPTLMRSP ELDAMAALND IRYQRLVVEL LIKNEDILF // ID CHIN_MOUSE STANDARD; PRT; 334 AA. AC Q91V57; DT 11-JUL-2002, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 02-MAY-2006, entry version 41. DE N-chimaerin (NC) (N-chimerin) (Alpha chimerin) (A-chimaerin) (Rho- DE GTPase-activating protein 2). GN Name=Chn1; Synonyms=Arhgap2; 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]. RC STRAIN=ILS, and ISS; RX MEDLINE=21363810; PubMed=11471062; DOI=10.1007/s00335-001-1001-x; RA Ehringer M.A., Thompson J., Conroy O., Xu Y., Yang F., Canniff J., RA Beeson M., Gordon L., Bennett B., Johnson T.E., Sikela J.M.; RT "High-throughput sequence identification of gene coding variants RT within alcohol-related QTLs."; RL Mamm. Genome 12:657-663(2001). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Brain; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Colon, and Eye; 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: GTPase-activating protein for p21-rac and a phorbol CC ester receptor. May play an important role in neuronal signal- CC transduction mechanisms (By similarity). CC -!- SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger. 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; AF332069; AAK56097.1; -; mRNA. DR EMBL; AF332070; AAK56098.1; -; mRNA. DR EMBL; AK075606; BAC35853.1; -; mRNA. DR EMBL; BC010825; AAH10825.1; -; mRNA. DR EMBL; BC024796; AAH24796.1; -; mRNA. DR EMBL; BC025023; AAH25023.1; -; mRNA. DR UniGene; Mm.257073; -. DR HSSP; P28867; 1PTQ. DR Ensembl; ENSMUSG00000056486; Mus musculus. DR MGI; MGI:1915674; Chn1. DR InterPro; IPR002219; DAG_PE_bd. DR InterPro; IPR008936; Rho_GAP. DR InterPro; IPR000198; RhoGAP. DR Pfam; PF00130; C1_1; 1. DR Pfam; PF00620; RhoGAP; 1. DR PRINTS; PR00008; DAGPEDOMAIN. DR SMART; SM00109; C1; 1. DR SMART; SM00324; RhoGAP; 1. DR PROSITE; PS50238; RHOGAP; 1. DR PROSITE; PS00479; ZF_DAG_PE_1; 1. DR PROSITE; PS50081; ZF_DAG_PE_2; 1. KW GTPase activation; Metal-binding; Phorbol-ester binding; Zinc; KW Zinc-finger. FT CHAIN 1 334 N-chimaerin. FT /FTId=PRO_0000056695. FT DOMAIN 143 334 Rho-GAP. FT ZN_FING 80 130 Phorbol-ester/DAG-type. SQ SEQUENCE 334 AA; 38121 MW; 9EC5DA66D58A36C4 CRC64; MPSKESWSGR KANRATVHKA KPEGRQQGLL IAALGMKLGS QKSSVTIWQP LKLFAYSQLT SLVRRATLKE NEQIPKYEKV HNFKVHTFRG PHWCEYCANF MWGLIAQGVK CADCGLNVHK QCSKMVPNDC KPDLKHVKKV YSCDLTTLVK AHITKRPMVV DMCIREIESR GLNSEGLYRV SGFSDLIEDV KMAFDRDGEK ADISVNMYED INIITGALKL YFRDLPIPLI TYDAYPKFIE SAKIMDPDEQ LETLHEALRS LPPAHCETLR YLMAHLKRVT LHEKENLMSA ENLGIVFGPT LMRSPELDPM AALNDIRYQR LVVELLIKNE DILF // ID CHIN_RAT STANDARD; PRT; 334 AA. AC P30337; DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot. DT 01-APR-1993, sequence version 1. DT 04-APR-2006, entry version 48. DE N-chimaerin (NC) (N-chimerin) (Alpha chimerin) (A-chimaerin) (Rho- DE GTPase-activating protein 2). GN Name=Chn1; Synonyms=Arhgap2, Chn; 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 STRAIN=Wistar; TISSUE=Brain; RX MEDLINE=93074974; PubMed=1445199; RA Lim H.H., Michael G.J., Smith P., Lim L., Hall C.; RT "Developmental regulation and neuronal expression of the mRNA of rat RT n-chimaerin, a p21rac GAP:cDNA sequence."; RL Biochem. J. 287:415-422(1992). CC -!- FUNCTION: GTPase-activating protein for p21-rac and a phorbol CC ester receptor. May play an important role in neuronal signal- CC transduction mechanisms. CC -!- TISSUE SPECIFICITY: In neurons in brain regions that are involved CC in learning and memory processes. CC -!- DEVELOPMENTAL STAGE: Increases in amount during brain development CC coincident with synaptogenesis. CC -!- SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger. 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; X67250; CAA47672.1; -; mRNA. DR PIR; S29128; S29128. DR UniGene; Rn.11166; -. DR HSSP; P28867; 1PTQ. DR RGD; 620139; Chn1. DR GO; GO:0005096; F:GTPase activator activity; TAS. DR GO; GO:0001565; F:phorbol ester receptor activity; TAS. DR GO; GO:0007165; P:signal transduction; TAS. DR InterPro; IPR002219; DAG_PE_bd. DR InterPro; IPR008936; Rho_GAP. DR InterPro; IPR000198; RhoGAP. DR Pfam; PF00130; C1_1; 1. DR Pfam; PF00620; RhoGAP; 1. DR PRINTS; PR00008; DAGPEDOMAIN. DR SMART; SM00109; C1; 1. DR SMART; SM00324; RhoGAP; 1. DR PROSITE; PS50238; RHOGAP; 1. DR PROSITE; PS00479; ZF_DAG_PE_1; 1. DR PROSITE; PS50081; ZF_DAG_PE_2; 1. KW GTPase activation; Metal-binding; Phorbol-ester binding; Zinc; KW Zinc-finger. FT CHAIN 1 334 N-chimaerin. FT /FTId=PRO_0000056696. FT DOMAIN 143 334 Rho-GAP. FT ZN_FING 80 130 Phorbol-ester/DAG-type. SQ SEQUENCE 334 AA; 38210 MW; D7F828C63683528B CRC64; MPSKESWSGR KTNRATVHKS NQEGRQQDLL IAALGMKLGS QKSSVTIWQP LKLFAYSQLT SLVRRATLKE NEQIPKYEKV HNFKVHTFRG PHWCEYCANF MWGLIAQGVK CADCGLNVHK QCSKMVPNDC KPDLKHVKKV YSCDLTTLVK AHITKRPMVV DMCIREIESR GLNSEGLYRV SGFSDLIEDV KMAFDRDGEK ADISVNMYED INIITGALKL YFRDLPIPLI TYDAYPKFIE SAKIVDPDEQ LETLHEALRS LPPAHCETLR YLMAHLKRVT LHEKENLMSA ENLGIVFGPT LMRSPELDPM AALNDIRYQR LVVELLIKNE DILF // ID CHIO_HUMAN STANDARD; PRT; 468 AA. AC P52757; Q75MM2; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 2. DT 30-MAY-2006, entry version 59. DE Beta-chimaerin (Beta-chimerin) (Rho-GTPase-activating protein 3). GN Name=CHN2; Synonyms=ARHGAP3, BCH; 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]. RC TISSUE=Cerebellum; RX MEDLINE=94230370; PubMed=8175705; RA Leung T., How B.-E., Manser E., Lim L.; RT "Cerebellar beta 2-chimaerin, a GTPase-activating protein for p21 ras- RT related rac is specifically expressed in granule cells and has a RT unique N-terminal SH2 domain."; RL J. Biol. Chem. 269:12888-12892(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Fetal brain; RX MEDLINE=95339337; PubMed=7614486; RA Yuan S., Miller D.W., Barnett G.H., Hahn J.F., Williams B.R.G.; RT "Identification and characterization of human beta 2-chimaerin: RT association with malignant transformation in astrocytoma."; RL Cancer Res. 55:3456-3461(1995). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 18-468. RX MEDLINE=22737999; PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., RA Waterston R.H., Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). CC -!- FUNCTION: GTPase-activating protein for p21-rac. Insufficient CC expression of beta-2 chimaerin is expected to lead to higher Rac CC activity and could therefore play a role in the progression from CC low-grade to high-grade tumors. CC -!- SUBCELLULAR LOCATION: Membrane; peripheral membrane protein CC (Potential). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Beta-2; CC IsoId=P52757-1; Sequence=Displayed; CC Name=Beta-1; CC IsoId=P52757-2; Sequence=Not described; CC -!- TISSUE SPECIFICITY: Highest levels in the brain and pancreas. Also CC expressed in the heart, placenta, and weakly in the kidney and CC liver. Expression is much reduced in the malignant gliomas, CC compared to normal brain or low-grade astrocytomas. CC -!- SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger. CC -!- SIMILARITY: Contains 1 Rho-GAP 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; L29126; AAA19191.1; -; mRNA. DR EMBL; U07223; AAA16836.1; -; mRNA. DR EMBL; U28926; AAA86528.1; -; mRNA. DR EMBL; AC004417; AAC06177.1; -; Genomic_DNA. DR EMBL; AC007255; AAS07498.1; -; Genomic_DNA. DR PIR; A53764; A53764. DR UniGene; Hs.151880; -. DR UniGene; Hs.594763; -. DR PDB; 1XA6; X-ray; A=7-468. DR Ensembl; ENSG00000106069; Homo sapiens. DR HGNC; HGNC:1944; CHN2. DR MIM; 602857; gene. DR LinkHub; P52757; -. DR GO; GO:0005096; F:GTPase activator activity; TAS. DR GO; GO:0005070; F:SH3/SH2 adaptor activity; TAS. DR InterPro; IPR002219; DAG_PE_bd. DR InterPro; IPR008936; Rho_GAP. DR InterPro; IPR000198; RhoGAP. DR InterPro; IPR000980; SH2. DR Pfam; PF00130; C1_1; 1. DR Pfam; PF00620; RhoGAP; 1. DR Pfam; PF00017; SH2; 1. DR PRINTS; PR00008; DAGPEDOMAIN. DR PRINTS; PR00401; SH2DOMAIN. DR ProDom; PD000093; SH2; 1. DR SMART; SM00109; C1; 1. DR SMART; SM00324; RhoGAP; 1. DR SMART; SM00252; SH2; 1. DR PROSITE; PS50238; RHOGAP; 1. DR PROSITE; PS50001; SH2; 1. DR PROSITE; PS00479; ZF_DAG_PE_1; 1. DR PROSITE; PS50081; ZF_DAG_PE_2; 1. KW 3D-structure; Alternative splicing; GTPase activation; Metal-binding; KW Phorbol-ester binding; Polymorphism; SH2 domain; Zinc; Zinc-finger. FT CHAIN 1 468 Beta-chimaerin. FT /FTId=PRO_0000056697. FT DOMAIN 59 127 SH2. FT DOMAIN 277 468 Rho-GAP. FT ZN_FING 214 264 Phorbol-ester/DAG-type. FT VARIANT 204 204 H -> R (in dbSNP:3750103). FT /FTId=VAR_022118. FT CONFLICT 1 6 MAASSN -> MRLL (in Ref. 1). FT STRAND 25 26 FT HELIX 29 36 FT STRAND 37 37 FT STRAND 42 42 FT STRAND 47 48 FT STRAND 52 53 FT STRAND 55 56 FT STRAND 58 63 FT HELIX 66 73 FT STRAND 75 75 FT TURN 77 78 FT STRAND 79 84 FT STRAND 86 88 FT TURN 89 90 FT STRAND 92 98 FT TURN 99 100 FT STRAND 101 104 FT STRAND 108 114 FT STRAND 116 118 FT STRAND 123 124 FT HELIX 125 138 FT STRAND 139 139 FT HELIX 141 146 FT TURN 147 148 FT STRAND 149 150 FT HELIX 153 155 FT STRAND 156 161 FT STRAND 219 220 FT STRAND 223 224 FT STRAND 227 227 FT TURN 229 231 FT STRAND 234 234 FT TURN 237 240 FT STRAND 242 243 FT STRAND 246 248 FT STRAND 252 252 FT TURN 254 254 FT HELIX 255 257 FT TURN 258 259 FT STRAND 260 260 FT STRAND 262 262 FT TURN 266 269 FT STRAND 270 270 FT TURN 275 276 FT STRAND 277 277 FT HELIX 279 286 FT TURN 287 287 FT STRAND 289 290 FT HELIX 292 303 FT STRAND 304 304 FT STRAND 306 308 FT TURN 309 313 FT STRAND 314 314 FT HELIX 318 328 FT STRAND 329 330 FT TURN 331 334 FT STRAND 335 335 FT STRAND 339 342 FT TURN 345 345 FT HELIX 346 358 FT STRAND 360 361 FT TURN 363 364 FT STRAND 366 366 FT TURN 367 368 FT HELIX 369 373 FT TURN 374 377 FT HELIX 381 392 FT TURN 393 394 FT STRAND 395 395 FT HELIX 397 405 FT TURN 406 410 FT HELIX 411 414 FT TURN 415 419 FT STRAND 420 420 FT HELIX 424 431 FT TURN 432 434 FT STRAND 435 435 FT STRAND 441 441 FT TURN 443 444 FT HELIX 445 448 FT TURN 449 449 FT HELIX 450 462 FT TURN 463 463 FT HELIX 464 467 SQ SEQUENCE 468 AA; 53924 MW; 63254958E0B5804C CRC64; MAASSNSSLS GSSVSSDAEE YQPPIWKSYL YQLQQEAPRP KRIICPREVE NRPKYYGREF HGIISREQAD ELLGGVEGAY ILRESQRQPG CYTLALRFGN QTLNYRLFHD GKHFVGEKRF ESIHDLVTDG LITLYIETKA AEYISKMTTN PIYEHIGYAT LLREKVSRRL SRSKNEPRKT NVTHEEHTAV EKISSLVRRA ALTHNDNHFN YEKTHNFKVH TFRGPHWCEY CANFMWGLIA QGVRCSDCGL NVHKQCSKHV PNDCQPDLKR IKKVYCCDLT TLVKAHNTQR PMVVDICIRE IEARGLKSEG LYRVSGFTEH IEDVKMAFDR DGEKADISAN VYPDINIITG ALKLYFRDLP IPVITYDTYS KFIDAAKISN ADERLEAVHE VLMLLPPAHY ETLRYLMIHL KKVTMNEKDN FMNAENLGIV FGPTLMRPPE DSTLTTLHDM RYQKLIVQIL IENEDVLF // ID CHIO_MOUSE STANDARD; PRT; 332 AA. AC Q80XD1; Q9D9W2; Q9ER57; DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot. DT 21-JUN-2005, sequence version 2. DT 30-MAY-2006, entry version 30. DE Beta-chimaerin (Beta-chimerin) (Rho-GTPase-activating protein 3). GN Name=Chn2; Synonyms=Arhgap3, Bch; 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] (ISOFORM 3). RC TISSUE=Testis; RA Prumer A., Heinlein U.A.O.; RT "Characterization of mouse beta chimaerin."; RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC STRAIN=C57BL/6J; TISSUE=Testis; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; 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: GTPase-activating protein for p21-rac (By similarity). CC -!- SUBCELLULAR LOCATION: Membrane; peripheral membrane protein CC (Potential). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q80XD1-1; Sequence=Displayed; CC Name=2; CC IsoId=Q80XD1-2; Sequence=VSP_014244, VSP_014245; CC Name=3; CC IsoId=Q80XD1-3; Sequence=VSP_014243, VSP_014246, VSP_014247; CC -!- SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger. 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; AJ279014; CAC08453.1; -; mRNA. DR EMBL; AK006398; BAB24568.1; -; mRNA. DR EMBL; BC051139; AAH51139.1; -; mRNA. DR UniGene; Mm.321147; -. DR HSSP; Q98935; 1F7C. DR SMR; Q80XD1; 75-332. DR Ensembl; ENSMUSG00000004633; Mus musculus. DR MGI; MGI:1917243; Chn2. DR InterPro; IPR002219; DAG_PE_bd. DR InterPro; IPR008936; Rho_GAP. DR InterPro; IPR000198; RhoGAP. DR Pfam; PF00130; C1_1; 1. DR Pfam; PF00620; RhoGAP; 1. DR PRINTS; PR00008; DAGPEDOMAIN. DR SMART; SM00109; C1; 1. DR SMART; SM00324; RhoGAP; 1. DR PROSITE; PS50238; RHOGAP; 1. DR PROSITE; PS00479; ZF_DAG_PE_1; 1. DR PROSITE; PS50081; ZF_DAG_PE_2; 1. KW Alternative splicing; GTPase activation; Membrane; Metal-binding; KW Phorbol-ester binding; Zinc; Zinc-finger. FT CHAIN 1 332 Beta-chimaerin. FT /FTId=PRO_0000056698. FT DOMAIN 141 332 Rho-GAP. FT ZN_FING 78 128 Phorbol-ester/DAG-type. FT VAR_SEQ 1 55 Missing (in isoform 3). FT /FTId=VSP_014243. FT VAR_SEQ 1 50 Missing (in isoform 2). FT /FTId=VSP_014244. FT VAR_SEQ 51 56 LFACSQ -> MALQCR (in isoform 2). FT /FTId=VSP_014245. FT VAR_SEQ 56 56 Q -> M (in isoform 3). FT /FTId=VSP_014246. FT VAR_SEQ 303 332 PEDSTLTTLHDMRYQKLIVQILIENEDVLF -> LRTAPSP FT PSMTCGTKS (in isoform 3). FT /FTId=VSP_014247. FT CONFLICT 138 138 V -> G (in Ref. 3; AAH51139). SQ SEQUENCE 332 AA; 38218 MW; 164E8E735053E744 CRC64; MCSQELWLEN ERKCAMVRKS KPSRKRQELL AIAFGVKVGL KGGFLWSPLK LFACSQISSL VRRAALTHND NHFNYEKTHN FKVHTFRGPH WCEYCANFMW GLIAQGVRCS DCGLNVHKQC SKHVPNDCQP DLKRIKKVYC CDLTTLVKAH NTQRPMVVDI CIREIEARGL KSEGLYRVSG FTEHIEDVKM AFDRDGEKAD ISANIYPDIN IITGALKLYF RDLPIPIITY DTYSKFIEAA KISNADERLE AVHEVLMLLP PAHYETLRYL MIHLKKVTMN EKDNLMNAEN LGIVFGPTLM RPPEDSTLTT LHDMRYQKLI VQILIENEDV LF // ID CHIO_RAT STANDARD; PRT; 295 AA. AC Q03070; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1995, sequence version 1. DT 16-MAY-2006, entry version 52. DE Beta-chimaerin (Beta-chimerin) (Rho-GTPase-activating protein 3). GN Name=Chn2; Synonyms=Arhgap3, Bch; 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 STRAIN=Wistar; TISSUE=Testis; RX MEDLINE=93179371; PubMed=8440677; RA Leung T., How B.E., Manser E., Lim L.; RT "Germ cell beta-chimaerin, a new GTPase-activating protein for p21rac, RT is specifically expressed during the acrosomal assembly stage in rat RT testis."; RL J. Biol. Chem. 268:3813-3816(1993). CC -!- FUNCTION: GTPase-activating protein for p21-rac. CC -!- SUBCELLULAR LOCATION: Membrane; peripheral membrane protein CC (Potential). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Beta-1; CC IsoId=Q03070-1; Sequence=Displayed; CC Name=Beta-2; CC IsoId=Q03070-2; Sequence=Not described; CC -!- TISSUE SPECIFICITY: Found in cerebellum and testis. CC -!- DEVELOPMENTAL STAGE: Expressed specifically in late stage CC spermatocytes. In the cerebellum, emergence of beta-2 isoform CC coincides with granule cells maturation and exhibits postnatal CC developmental increases. Expression is specifically reduced in CC weaver mutant. CC -!- SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger. 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; X69489; CAA49244.1; -; mRNA. DR EMBL; L07494; AAA40809.1; -; mRNA. DR PIR; A45485; S29956. DR UniGene; Rn.10521; -. DR HSSP; Q98935; 1F7C. DR SMR; Q03070; 38-295. DR Ensembl; ENSRNOG00000009411; Rattus norvegicus. DR RGD; 620140; Chn2. DR GO; GO:0001565; F:phorbol ester receptor activity; TAS. DR GO; GO:0030675; F:Rac GTPase activator activity; IDA. DR GO; GO:0001675; P:acrosome formation; IEP. DR InterPro; IPR002219; DAG_PE_bd. DR InterPro; IPR008936; Rho_GAP. DR InterPro; IPR000198; RhoGAP. DR Pfam; PF00130; C1_1; 1. DR Pfam; PF00620; RhoGAP; 1. DR PRINTS; PR00008; DAGPEDOMAIN. DR SMART; SM00109; C1; 1. DR SMART; SM00324; RhoGAP; 1. DR PROSITE; PS50238; RHOGAP; 1. DR PROSITE; PS00479; ZF_DAG_PE_1; 1. DR PROSITE; PS50081; ZF_DAG_PE_2; 1. KW Alternative splicing; GTPase activation; Membrane; Metal-binding; KW Phorbol-ester binding; SH2 domain; Zinc; Zinc-finger. FT CHAIN 1 295 Beta-chimaerin. FT /FTId=PRO_0000056699. FT DOMAIN 104 295 Rho-GAP. FT ZN_FING 41 91 Phorbol-ester/DAG-type. SQ SEQUENCE 295 AA; 33837 MW; D7692D957B4816BD CRC64; MLCTSPVNCL DSVCCTSINI SSLVRRAALT HNDNHFNYEK THNFKVHTFR GPHWCEYCAN FMWGLIAQGV RCSDCGLNVH KQCSKHVPND CQPDLKRIKK VYCCDLTTLV KAHNTQRPMV VDICIREIEA RGLKSEGLYR VSGFTEHIED VKMAFDRDGE KADISANIYP DINIITGALK LYFRDLPIPI ITYDTYTKFI EAAKISNADE RLEAVHEVLM LLPPAHYETL RYLMIHLKKV TMNEKDNLMN AENLGIVFGP TLMRPPEDST LTTLHDMRYQ KLIVQILIEN EDVLF // ID CTRO_HUMAN STANDARD; PRT; 2027 AA. AC O14578; Q6XUH8; Q86UQ9; Q9UPZ7; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 04-JAN-2005, sequence version 2. DT 30-MAY-2006, entry version 48. DE Citron Rho-interacting kinase (EC 2.7.11.1) (CRIK) (Rho-interacting, DE serine/threonine-protein kinase 21). GN Name=CIT; Synonyms=KIAA0949, STK21; 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 1). RA Huang C.Q., Wu S.L., Shan Y.X., Liu S., Xiao P.J.; RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RA Mao Y., Xie Y., Wu Q.; RT "Cloning and characterizing a novel human CRIK-SK gene."; RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Brain; RX MEDLINE=99246063; PubMed=10231032; DOI=10.1093/dnares/6.1.63; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., RA Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XIII. RT The complete sequences of 100 new cDNA clones from brain which code RT for large proteins in vitro."; RL DNA Res. 6:63-70(1999). RN [4] RP SEQUENCE REVISION. RA Ohara O., Nagase T., Kikuno R.; RL Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16541075; DOI=10.1038/nature04569; RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., RA Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., RA Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., RA Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., RA Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., RA Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., RA Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., RA Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., RA Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., RA Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., RA Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., RA Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., RA Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., RA Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., RA Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., RA Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., RA Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., RA Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., RA Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., RA Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., RA Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., RA Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., RA Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., RA Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., RA Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., RA Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., RA Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., RA Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., RA Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., RA Kucherlapati R., Weinstock G., Gibbs R.A.; RT "The finished DNA sequence of human chromosome 12."; RL Nature 440:346-351(2006). RN [6] RP PHOSPHORYLATION AT SER-440, AND MASS SPECTROMETRY. RX PubMed=16565220; DOI=10.1073/pnas.0507066103; RA Nousiainen M., Sillje H.H.W., Sauer G., Nigg E.A., Koerner R.; RT "Phosphoproteome analysis of the human mitotic spindle."; RL Proc. Natl. Acad. Sci. U.S.A. 103:5391-5396(2006). CC -!- FUNCTION: Putative RHO/RAC effector that binds to the GTP-bound CC forms of RHO and RAC1. It probably binds p21 with a tighter CC specificity in vivo. Dual specificity protein kinase activity CC catalyzing autophosphorylation and phosphorylation of exogenous CC substrates on both serine/threonine and tyrosine residues. Plays CC an important role in the regulation of cytokinesis and the CC development of the central nervous system (By similarity). CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- SUBCELLULAR LOCATION: Cytoplasm (By similarity). CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=Long; CC IsoId=O14578-1; Sequence=Displayed; CC Name=2; Synonyms=Short, CRIK-SK; CC IsoId=O14578-2; Sequence=VSP_012434, VSP_012435; CC Name=3; CC IsoId=O14578-3; Sequence=VSP_014507, VSP_014508, VSP_014509; CC Note=No experimental confirmation available; CC -!- SIMILARITY: Belongs to the Ser/Thr protein kinase family. CC -!- SIMILARITY: Contains 1 CNH domain. CC -!- SIMILARITY: Contains 1 PH domain. CC -!- SIMILARITY: Contains 1 phorbol-ester/DAG-type zinc finger. 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; AY257469; AAP13528.1; -; mRNA. DR EMBL; AY209000; AAP43922.1; -; mRNA. DR EMBL; AB023166; BAA76793.2; ALT_INIT; mRNA. DR EMBL; AC002563; AAB71327.1; -; Genomic_DNA. DR EMBL; AC079317; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC004813; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR UniGene; Hs.119594; -. DR HSSP; P31751; 1MRV. DR Ensembl; ENSG00000122966; Homo sapiens. DR HGNC; HGNC:1985; CIT. DR MIM; 605629; gene. DR GO; GO:0005622; C:intracellular; ISS. DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS. DR GO; GO:0004713; F:protein-tyrosine kinase activity; ISS. DR GO; GO:0007067; P:mitosis; ISS. DR GO; GO:0048699; P:neurogenesis; ISS. DR InterPro; IPR001180; Citron. DR InterPro; IPR002219; DAG_PE_bd. 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; IPR000861; REM_rpt_rho_bd. DR InterPro; IPR008271; Ser_thr_pkin_AS. DR InterPro; IPR002290; Ser_thr_pkinase. DR Pfam; PF00130; C1_1; 1. DR Pfam; PF00780; CNH; 1. DR Pfam; PF00169; PH; 1. DR Pfam; PF00069; Pkinase; 1. DR Pfam; PF00433; Pkinase_C; 1. DR ProDom; PD000001; Prot_kinase; 1. DR SMART; SM00109; C1; 1. DR SMART; SM00036; CNH; 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. DR PROSITE; PS00479; ZF_DAG_PE_1; 1. DR PROSITE; PS50081; ZF_DAG_PE_2; 1. KW Alternative splicing; ATP-binding; Cell cycle; Cell division; KW Coiled coil; Developmental protein; Differentiation; Kinase; KW Metal-binding; Mitosis; Neurogenesis; Nucleotide-binding; KW Phorbol-ester bindi