ARAF_HUMAN
ID ARAF_HUMAN Reviewed; 606 AA.
AC P10398; P07557; Q5H9B2; Q5H9B3;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 234.
DE RecName: Full=Serine/threonine-protein kinase A-Raf;
DE EC=2.7.11.1;
DE AltName: Full=Proto-oncogene A-Raf;
DE AltName: Full=Proto-oncogene A-Raf-1;
DE AltName: Full=Proto-oncogene Pks;
GN Name=ARAF; Synonyms=ARAF1, PKS, PKS2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=3029685; DOI=10.1093/nar/15.2.595;
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 PubMed=8020955; DOI=10.1006/geno.1994.1125;
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 [MRNA] (ISOFORM 2), FUNCTION (ISOFORM 2), AND
RP ALTERNATIVE SPLICING.
RX PubMed=17535970; DOI=10.1083/jcb.200703195;
RA Yokoyama T., Takano K., Yoshida A., Katada F., Sun P., Takenawa T.,
RA Andoh T., Endo T.;
RT "DA-Raf1, a competent intrinsic dominant-negative antagonist of the Ras-ERK
RT pathway, is required for myogenic differentiation.";
RL J. Cell Biol. 177:781-793(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [6]
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., Lovell F.L.,
RA Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C.,
RA Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A.,
RA Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P.,
RA Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D.,
RA Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D.,
RA Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L.,
RA Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P.,
RA Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G.,
RA Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J.,
RA Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D.,
RA Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L.,
RA Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z.,
RA Chinault C., 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., Delgado O.,
RA Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H.,
RA Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T.,
RA Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L.,
RA Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R.,
RA Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y.,
RA Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K.,
RA Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J.,
RA Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L.,
RA Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S.,
RA Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A.,
RA Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L.,
RA Liu W., 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., Milne S.,
RA Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C.,
RA Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S.,
RA Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V.,
RA Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K.,
RA Rhodes S., 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., Teague B.,
RA Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C.,
RA d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q.,
RA Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N.,
RA Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A.,
RA Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J.,
RA Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A.,
RA Rosenthal A., 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., Nelson D.L.,
RA Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S.,
RA Rogers J., Bentley D.R.;
RT "The DNA sequence of the human X chromosome.";
RL Nature 434:325-337(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 292-589 (ISOFORM 1).
RX PubMed=3529082; DOI=10.1073/pnas.83.17.6312;
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 [9]
RP INTERACTION WITH NELFD.
RX 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).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-257, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-318, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [19]
RP FUNCTION IN TOR SIGNALING.
RX PubMed=22609986; DOI=10.1038/ncb2507;
RA Gan X., Wang J., Wang C., Sommer E., Kozasa T., Srinivasula S., Alessi D.,
RA Offermanns S., Simon M.I., Wu D.;
RT "PRR5L degradation promotes mTORC2-mediated PKC-delta phosphorylation and
RT cell migration downstream of Galpha12.";
RL Nat. Cell Biol. 14:686-696(2012).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-157; SER-162; THR-253;
RP SER-257 AND SER-269, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-181; SER-186 AND SER-257, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [22]
RP STRUCTURE BY NMR OF 19-91.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the N-terminal RAS-binding domain (RBD) in human A-
RT RAF kinase.";
RL Submitted (JUL-2005) to the PDB data bank.
RN [23]
RP VARIANTS [LARGE SCALE ANALYSIS] THR-98; CYS-331 AND ASP-578.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Involved in the transduction of mitogenic signals from the
CC cell membrane to the nucleus. May also regulate the TOR signaling
CC cascade. {ECO:0000269|PubMed:22609986}.
CC -!- FUNCTION: [Isoform 2]: Serves as a positive regulator of myogenic
CC differentiation by inducing cell cycle arrest, the expression of
CC myogenin and other muscle-specific proteins, and myotube formation.
CC {ECO:0000269|PubMed:22609986}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250};
CC -!- SUBUNIT: Interacts with TH1L/NELFD. {ECO:0000269|PubMed:11952167}.
CC -!- INTERACTION:
CC P10398; P00966: ASS1; NbExp=4; IntAct=EBI-365961, EBI-536842;
CC P10398; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-365961, EBI-350590;
CC P10398; P31327: CPS1; NbExp=3; IntAct=EBI-365961, EBI-536811;
CC P10398; Q12805: EFEMP1; NbExp=3; IntAct=EBI-365961, EBI-536772;
CC P10398; P01112: HRAS; NbExp=3; IntAct=EBI-365961, EBI-350145;
CC P10398; P08238: HSP90AB1; NbExp=9; IntAct=EBI-365961, EBI-352572;
CC P10398; O43187: IRAK2; NbExp=2; IntAct=EBI-365961, EBI-447733;
CC P10398; Q92985: IRF7; NbExp=2; IntAct=EBI-365961, EBI-968267;
CC P10398; P36507: MAP2K2; NbExp=9; IntAct=EBI-365961, EBI-1056930;
CC P10398; Q8IXH7: NELFCD; NbExp=5; IntAct=EBI-365961, EBI-536725;
CC P10398; O95848: NUDT14; NbExp=3; IntAct=EBI-365961, EBI-536866;
CC P10398; Q96KB5: PBK; NbExp=3; IntAct=EBI-365961, EBI-536853;
CC P10398; O94906: PRPF6; NbExp=4; IntAct=EBI-365961, EBI-536755;
CC P10398; P53611: RABGGTB; NbExp=3; IntAct=EBI-365961, EBI-536715;
CC P10398; P62070: RRAS2; NbExp=3; IntAct=EBI-365961, EBI-491037;
CC P10398; P31947: SFN; NbExp=3; IntAct=EBI-365961, EBI-476295;
CC P10398; O43615: TIMM44; NbExp=3; IntAct=EBI-365961, EBI-861737;
CC P10398; Q3ZCQ8: TIMM50; NbExp=4; IntAct=EBI-365961, EBI-355175;
CC P10398; P58753: TIRAP; NbExp=2; IntAct=EBI-365961, EBI-528644;
CC P10398; P62258: YWHAE; NbExp=4; IntAct=EBI-365961, EBI-356498;
CC P10398; P63104: YWHAZ; NbExp=7; IntAct=EBI-365961, EBI-347088;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P10398-1; Sequence=Displayed;
CC Name=2; Synonyms=DA-Raf1;
CC IsoId=P10398-2; Sequence=VSP_045609, VSP_045610;
CC -!- TISSUE SPECIFICITY: Predominantly in urogenital tissues.
CC -!- MISCELLANEOUS: [Isoform 2]: Has a wider tissue distribution than
CC isoform 1, and acts as dominant-negative antagonist. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. RAF subfamily. {ECO:0000305}.
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DR EMBL; X04790; CAA28476.1; -; mRNA.
DR EMBL; L24038; AAA65219.1; -; Genomic_DNA.
DR EMBL; U01337; AAB03517.1; -; Genomic_DNA.
DR EMBL; AB158254; BAE66645.1; -; mRNA.
DR EMBL; BT019864; AAV38667.1; -; mRNA.
DR EMBL; AL542736; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; Z84466; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002466; AAH02466.1; -; mRNA.
DR EMBL; M13829; AAB08754.1; -; mRNA.
DR CCDS; CCDS35232.1; -. [P10398-1]
DR CCDS; CCDS59164.1; -. [P10398-2]
DR PIR; A53026; TVHUAF.
DR RefSeq; NP_001243125.1; NM_001256196.1.
DR RefSeq; NP_001243126.1; NM_001256197.1. [P10398-2]
DR RefSeq; NP_001645.1; NM_001654.4. [P10398-1]
DR RefSeq; XP_011542210.1; XM_011543908.2.
DR PDB; 1WXM; NMR; -; A=19-91.
DR PDB; 2MSE; NMR; -; D=19-91.
DR PDBsum; 1WXM; -.
DR PDBsum; 2MSE; -.
DR AlphaFoldDB; P10398; -.
DR BMRB; P10398; -.
DR SMR; P10398; -.
DR BioGRID; 106864; 375.
DR CORUM; P10398; -.
DR DIP; DIP-31374N; -.
DR IntAct; P10398; 126.
DR MINT; P10398; -.
DR STRING; 9606.ENSP00000290277; -.
DR BindingDB; P10398; -.
DR ChEMBL; CHEMBL1169596; -.
DR DrugBank; DB00171; ATP.
DR DrugCentral; P10398; -.
DR GuidetoPHARMACOLOGY; 1933; -.
DR GlyGen; P10398; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P10398; -.
DR PhosphoSitePlus; P10398; -.
DR BioMuta; ARAF; -.
DR DMDM; 1730068; -.
DR CPTAC; CPTAC-1339; -.
DR CPTAC; CPTAC-1343; -.
DR CPTAC; CPTAC-1344; -.
DR CPTAC; CPTAC-1345; -.
DR CPTAC; CPTAC-1547; -.
DR EPD; P10398; -.
DR jPOST; P10398; -.
DR MassIVE; P10398; -.
DR MaxQB; P10398; -.
DR PaxDb; P10398; -.
DR PeptideAtlas; P10398; -.
DR PRIDE; P10398; -.
DR ProteomicsDB; 52601; -. [P10398-1]
DR ProteomicsDB; 62876; -.
DR TopDownProteomics; P10398-1; -. [P10398-1]
DR Antibodypedia; 11388; 723 antibodies from 39 providers.
DR CPTC; P10398; 5 antibodies.
DR DNASU; 369; -.
DR Ensembl; ENST00000377039.2; ENSP00000366238.1; ENSG00000078061.14. [P10398-2]
DR Ensembl; ENST00000377045.9; ENSP00000366244.4; ENSG00000078061.14. [P10398-1]
DR GeneID; 369; -.
DR KEGG; hsa:369; -.
DR MANE-Select; ENST00000377045.9; ENSP00000366244.4; NM_001654.5; NP_001645.1.
DR UCSC; uc031tjj.2; human. [P10398-1]
DR CTD; 369; -.
DR DisGeNET; 369; -.
DR GeneCards; ARAF; -.
DR HGNC; HGNC:646; ARAF.
DR HPA; ENSG00000078061; Low tissue specificity.
DR MalaCards; ARAF; -.
DR MIM; 311010; gene.
DR neXtProt; NX_P10398; -.
DR OpenTargets; ENSG00000078061; -.
DR PharmGKB; PA24928; -.
DR VEuPathDB; HostDB:ENSG00000078061; -.
DR eggNOG; KOG0193; Eukaryota.
DR GeneTree; ENSGT00940000159633; -.
DR HOGENOM; CLU_023684_1_1_1; -.
DR InParanoid; P10398; -.
DR OrthoDB; 243095at2759; -.
DR PhylomeDB; P10398; -.
DR TreeFam; TF317006; -.
DR BRENDA; 2.7.10.2; 2681.
DR PathwayCommons; P10398; -.
DR Reactome; R-HSA-5673000; RAF activation.
DR Reactome; R-HSA-5674135; MAP2K and MAPK activation.
DR Reactome; R-HSA-5675221; Negative regulation of MAPK pathway.
DR Reactome; R-HSA-6802946; Signaling by moderate kinase activity BRAF mutants.
DR Reactome; R-HSA-6802948; Signaling by high-kinase activity BRAF mutants.
DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions.
DR Reactome; R-HSA-6802955; Paradoxical activation of RAF signaling by kinase inactive BRAF.
DR Reactome; R-HSA-9649948; Signaling downstream of RAS mutants.
DR Reactome; R-HSA-9656223; Signaling by RAF1 mutants.
DR Reactome; R-HSA-9726840; SHOC2 M1731 mutant abolishes MRAS complex function.
DR Reactome; R-HSA-9726842; Gain-of-function MRAS complexes activate RAF signaling.
DR SignaLink; P10398; -.
DR SIGNOR; P10398; -.
DR BioGRID-ORCS; 369; 13 hits in 743 CRISPR screens.
DR ChiTaRS; ARAF; human.
DR EvolutionaryTrace; P10398; -.
DR GeneWiki; ARAF; -.
DR GenomeRNAi; 369; -.
DR Pharos; P10398; Tchem.
DR PRO; PR:P10398; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P10398; protein.
DR Bgee; ENSG00000078061; Expressed in hindlimb stylopod muscle and 183 other tissues.
DR ExpressionAtlas; P10398; baseline and differential.
DR Genevisible; P10398; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004709; F:MAP kinase kinase kinase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0000165; P:MAPK cascade; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0036211; P:protein modification process; TAS:ProtInc.
DR GO; GO:0006468; P:protein phosphorylation; IEA:Ensembl.
DR GO; GO:0032434; P:regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0032006; P:regulation of TOR signaling; IMP:UniProtKB.
DR CDD; cd00029; C1; 1.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR020454; DAG/PE-bd.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR003116; RBD_dom.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF02196; RBD; 1.
DR PRINTS; PR00008; DAGPEDOMAIN.
DR SMART; SM00109; C1; 1.
DR SMART; SM00455; RBD; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57889; SSF57889; 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.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Kinase; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Proto-oncogene; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..606
FT /note="Serine/threonine-protein kinase A-Raf"
FT /id="PRO_0000085622"
FT DOMAIN 19..91
FT /note="RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00262"
FT DOMAIN 310..570
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ZN_FING 98..144
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 160..207
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 240..290
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 160..188
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 240..271
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 272..290
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 429
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 99
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 112
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 115
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 125
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 128
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 133
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 136
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 144
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 316..324
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 336
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 157
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 162
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 181
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 253
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 257
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 269
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 318
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT VAR_SEQ 186
FT /note="S -> R (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17535970, ECO:0000303|Ref.5"
FT /id="VSP_045609"
FT VAR_SEQ 187..606
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:17535970, ECO:0000303|Ref.5"
FT /id="VSP_045610"
FT VARIANT 98
FT /note="M -> T (in dbSNP:rs56197559)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040375"
FT VARIANT 331
FT /note="G -> C (in a colorectal adenocarcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040376"
FT VARIANT 578
FT /note="E -> D (in dbSNP:rs55852926)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040377"
FT CONFLICT 368
FT /note="L -> P (in Ref. 8; AAB08754)"
FT /evidence="ECO:0000305"
FT CONFLICT 378
FT /note="F -> V (in Ref. 8; AAB08754)"
FT /evidence="ECO:0000305"
FT CONFLICT 469
FT /note="S -> P (in Ref. 8; AAB08754)"
FT /evidence="ECO:0000305"
FT CONFLICT 478
FT /note="I -> T (in Ref. 8; AAB08754)"
FT /evidence="ECO:0000305"
FT STRAND 19..24
FT /evidence="ECO:0007829|PDB:1WXM"
FT STRAND 26..28
FT /evidence="ECO:0007829|PDB:1WXM"
FT STRAND 30..34
FT /evidence="ECO:0007829|PDB:1WXM"
FT HELIX 42..50
FT /evidence="ECO:0007829|PDB:1WXM"
FT TURN 51..53
FT /evidence="ECO:0007829|PDB:2MSE"
FT STRAND 56..67
FT /evidence="ECO:0007829|PDB:1WXM"
FT STRAND 69..72
FT /evidence="ECO:0007829|PDB:1WXM"
FT STRAND 74..78
FT /evidence="ECO:0007829|PDB:1WXM"
FT HELIX 79..81
FT /evidence="ECO:0007829|PDB:2MSE"
FT STRAND 82..84
FT /evidence="ECO:0007829|PDB:2MSE"
FT STRAND 85..90
FT /evidence="ECO:0007829|PDB:1WXM"
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
