Full text data of ARAF
ARAF
(ARAF1, PKS, PKS2)
[Confidence: low (only semi-automatic identification from reviews)]
Serine/threonine-protein kinase A-Raf; 2.7.11.1 (Proto-oncogene A-Raf; Proto-oncogene A-Raf-1; Proto-oncogene Pks)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Serine/threonine-protein kinase A-Raf; 2.7.11.1 (Proto-oncogene A-Raf; Proto-oncogene A-Raf-1; Proto-oncogene Pks)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P10398
ID ARAF_HUMAN Reviewed; 606 AA.
AC P10398; P07557; Q5H9B2; Q5H9B3;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-1996, sequence version 2.
DT 22-JAN-2014, entry version 167.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT Ras-ERK 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
RT 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.,
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.M., 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 [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
RT project: 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.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-257, AND MASS
RP SPECTROMETRY.
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
RT phosphorylation 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.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, AND MASS
RP SPECTROMETRY.
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
RT the 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 MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation 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.,
RA Buerckstuemmer T., 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.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [19]
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
RT human A-RAF kinase.";
RL Submitted (JUL-2005) to the PDB data bank.
RN [20]
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.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., 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
CC the cell membrane to the nucleus.
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
CC formation.
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:ASS1; NbExp=4; IntAct=EBI-365961, EBI-536842;
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 P08238:HSP90AB1; NbExp=3; IntAct=EBI-365961, EBI-352572;
CC O43187:IRAK2; NbExp=2; IntAct=EBI-365961, EBI-447733;
CC Q92985:IRF7; NbExp=2; IntAct=EBI-365961, EBI-968267;
CC P36507:MAP2K2; NbExp=4; IntAct=EBI-365961, EBI-1056930;
CC Q8IXH7:NELFCD; NbExp=5; IntAct=EBI-365961, EBI-536725;
CC O95848:NUDT14; NbExp=3; IntAct=EBI-365961, EBI-536866;
CC Q96KB5:PBK; NbExp=3; IntAct=EBI-365961, EBI-536853;
CC O94906:PRPF6; NbExp=4; IntAct=EBI-365961, EBI-536755;
CC P53611:RABGGTB; NbExp=3; IntAct=EBI-365961, EBI-536715;
CC P62070:RRAS2; NbExp=3; IntAct=EBI-365961, EBI-491037;
CC O43615:TIMM44; NbExp=3; IntAct=EBI-365961, EBI-861737;
CC Q3ZCQ8:TIMM50; NbExp=3; IntAct=EBI-365961, EBI-355175;
CC P58753:TIRAP; NbExp=2; IntAct=EBI-365961, EBI-528644;
CC P63104:YWHAZ; NbExp=3; 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 Note=Has a wider tissue distribution than isoform 1, and acts as
CC dominant-negative antagonist;
CC -!- TISSUE SPECIFICITY: Predominantly in urogenital tissues.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. RAF 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.
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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; CAI42468.1; -; Genomic_DNA.
DR EMBL; Z84466; CAI42469.1; -; Genomic_DNA.
DR EMBL; BC002466; AAH02466.1; -; mRNA.
DR EMBL; M13829; AAB08754.1; -; mRNA.
DR PIR; A53026; TVHUAF.
DR RefSeq; NP_001243125.1; NM_001256196.1.
DR RefSeq; NP_001243126.1; NM_001256197.1.
DR RefSeq; NP_001645.1; NM_001654.4.
DR UniGene; Hs.446641; -.
DR PDB; 1WXM; NMR; -; A=19-91.
DR PDBsum; 1WXM; -.
DR ProteinModelPortal; P10398; -.
DR SMR; P10398; 20-91, 96-146, 273-576.
DR DIP; DIP-31374N; -.
DR IntAct; P10398; 37.
DR MINT; MINT-88835; -.
DR STRING; 9606.ENSP00000366244; -.
DR ChEMBL; CHEMBL1169596; -.
DR DrugBank; DB00171; Adenosine triphosphate.
DR GuidetoPHARMACOLOGY; 1933; -.
DR PhosphoSite; P10398; -.
DR DMDM; 1730068; -.
DR PaxDb; P10398; -.
DR PRIDE; P10398; -.
DR DNASU; 369; -.
DR Ensembl; ENST00000377039; ENSP00000366238; ENSG00000078061.
DR Ensembl; ENST00000377045; ENSP00000366244; ENSG00000078061.
DR GeneID; 369; -.
DR KEGG; hsa:369; -.
DR UCSC; uc011mlp.3; human.
DR CTD; 369; -.
DR GeneCards; GC0XP047429; -.
DR HGNC; HGNC:646; ARAF.
DR MIM; 311010; gene.
DR neXtProt; NX_P10398; -.
DR PharmGKB; PA24928; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000252972; -.
DR HOVERGEN; HBG001886; -.
DR KO; K08845; -.
DR OMA; LFHTTRL; -.
DR OrthoDB; EOG7F5128; -.
DR BRENDA; 2.7.10.2; 2681.
DR SignaLink; P10398; -.
DR EvolutionaryTrace; P10398; -.
DR GeneWiki; ARAF; -.
DR GenomeRNAi; 369; -.
DR NextBio; 1545; -.
DR PRO; PR:P10398; -.
DR ArrayExpress; P10398; -.
DR Bgee; P10398; -.
DR CleanEx; HS_ARAF; -.
DR Genevestigator; P10398; -.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; NAS:UniProtKB.
DR GO; GO:0004709; F:MAP kinase kinase kinase activity; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
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:0032434; P:regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0032006; P:regulation of TOR signaling cascade; IMP:UniProtKB.
DR InterPro; IPR020454; DAG/PE-bd.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR002219; Prot_Kinase_C-like_PE/DAG-bd.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR003116; Raf-like_ras-bd.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF07714; Pkinase_Tyr; 1.
DR Pfam; PF02196; RBD; 1.
DR PRINTS; PR00008; DAGPEDOMAIN.
DR SMART; SM00109; C1; 1.
DR SMART; SM00455; RBD; 1.
DR SUPFAM; SSF56112; SSF56112; 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; Complete proteome;
KW Kinase; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Polymorphism; Proto-oncogene; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
FT CHAIN 1 606 Serine/threonine-protein kinase A-Raf.
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 MOD_RES 186 186 Phosphoserine.
FT MOD_RES 257 257 Phosphoserine.
FT MOD_RES 318 318 Phosphothreonine.
FT VAR_SEQ 186 186 S -> R (in isoform 2).
FT /FTId=VSP_045609.
FT VAR_SEQ 187 606 Missing (in isoform 2).
FT /FTId=VSP_045610.
FT VARIANT 98 98 M -> T (in dbSNP:rs56197559).
FT /FTId=VAR_040375.
FT VARIANT 331 331 G -> C (in a colorectal adenocarcinoma
FT sample; somatic mutation).
FT /FTId=VAR_040376.
FT VARIANT 578 578 E -> D (in dbSNP:rs55852926).
FT /FTId=VAR_040377.
FT CONFLICT 368 368 L -> P (in Ref. 8; AAB08754).
FT CONFLICT 378 378 F -> V (in Ref. 8; AAB08754).
FT CONFLICT 469 469 S -> P (in Ref. 8; AAB08754).
FT CONFLICT 478 478 I -> T (in Ref. 8; AAB08754).
FT STRAND 19 24
FT STRAND 26 28
FT STRAND 30 34
FT HELIX 42 50
FT STRAND 56 67
FT STRAND 69 72
FT STRAND 74 78
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_HUMAN Reviewed; 606 AA.
AC P10398; P07557; Q5H9B2; Q5H9B3;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-1996, sequence version 2.
DT 22-JAN-2014, entry version 167.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT Ras-ERK 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
RT 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.,
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.M., 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 [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
RT project: 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.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-257, AND MASS
RP SPECTROMETRY.
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
RT phosphorylation 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.,
RA Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for
RT efficient phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186, AND MASS
RP SPECTROMETRY.
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
RT the 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 MASS
RP SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation 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.,
RA Buerckstuemmer T., 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.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [19]
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
RT human A-RAF kinase.";
RL Submitted (JUL-2005) to the PDB data bank.
RN [20]
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.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., 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
CC the cell membrane to the nucleus.
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
CC formation.
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:ASS1; NbExp=4; IntAct=EBI-365961, EBI-536842;
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 P08238:HSP90AB1; NbExp=3; IntAct=EBI-365961, EBI-352572;
CC O43187:IRAK2; NbExp=2; IntAct=EBI-365961, EBI-447733;
CC Q92985:IRF7; NbExp=2; IntAct=EBI-365961, EBI-968267;
CC P36507:MAP2K2; NbExp=4; IntAct=EBI-365961, EBI-1056930;
CC Q8IXH7:NELFCD; NbExp=5; IntAct=EBI-365961, EBI-536725;
CC O95848:NUDT14; NbExp=3; IntAct=EBI-365961, EBI-536866;
CC Q96KB5:PBK; NbExp=3; IntAct=EBI-365961, EBI-536853;
CC O94906:PRPF6; NbExp=4; IntAct=EBI-365961, EBI-536755;
CC P53611:RABGGTB; NbExp=3; IntAct=EBI-365961, EBI-536715;
CC P62070:RRAS2; NbExp=3; IntAct=EBI-365961, EBI-491037;
CC O43615:TIMM44; NbExp=3; IntAct=EBI-365961, EBI-861737;
CC Q3ZCQ8:TIMM50; NbExp=3; IntAct=EBI-365961, EBI-355175;
CC P58753:TIRAP; NbExp=2; IntAct=EBI-365961, EBI-528644;
CC P63104:YWHAZ; NbExp=3; 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 Note=Has a wider tissue distribution than isoform 1, and acts as
CC dominant-negative antagonist;
CC -!- TISSUE SPECIFICITY: Predominantly in urogenital tissues.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. RAF 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.
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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; CAI42468.1; -; Genomic_DNA.
DR EMBL; Z84466; CAI42469.1; -; Genomic_DNA.
DR EMBL; BC002466; AAH02466.1; -; mRNA.
DR EMBL; M13829; AAB08754.1; -; mRNA.
DR PIR; A53026; TVHUAF.
DR RefSeq; NP_001243125.1; NM_001256196.1.
DR RefSeq; NP_001243126.1; NM_001256197.1.
DR RefSeq; NP_001645.1; NM_001654.4.
DR UniGene; Hs.446641; -.
DR PDB; 1WXM; NMR; -; A=19-91.
DR PDBsum; 1WXM; -.
DR ProteinModelPortal; P10398; -.
DR SMR; P10398; 20-91, 96-146, 273-576.
DR DIP; DIP-31374N; -.
DR IntAct; P10398; 37.
DR MINT; MINT-88835; -.
DR STRING; 9606.ENSP00000366244; -.
DR ChEMBL; CHEMBL1169596; -.
DR DrugBank; DB00171; Adenosine triphosphate.
DR GuidetoPHARMACOLOGY; 1933; -.
DR PhosphoSite; P10398; -.
DR DMDM; 1730068; -.
DR PaxDb; P10398; -.
DR PRIDE; P10398; -.
DR DNASU; 369; -.
DR Ensembl; ENST00000377039; ENSP00000366238; ENSG00000078061.
DR Ensembl; ENST00000377045; ENSP00000366244; ENSG00000078061.
DR GeneID; 369; -.
DR KEGG; hsa:369; -.
DR UCSC; uc011mlp.3; human.
DR CTD; 369; -.
DR GeneCards; GC0XP047429; -.
DR HGNC; HGNC:646; ARAF.
DR MIM; 311010; gene.
DR neXtProt; NX_P10398; -.
DR PharmGKB; PA24928; -.
DR eggNOG; COG0515; -.
DR HOGENOM; HOG000252972; -.
DR HOVERGEN; HBG001886; -.
DR KO; K08845; -.
DR OMA; LFHTTRL; -.
DR OrthoDB; EOG7F5128; -.
DR BRENDA; 2.7.10.2; 2681.
DR SignaLink; P10398; -.
DR EvolutionaryTrace; P10398; -.
DR GeneWiki; ARAF; -.
DR GenomeRNAi; 369; -.
DR NextBio; 1545; -.
DR PRO; PR:P10398; -.
DR ArrayExpress; P10398; -.
DR Bgee; P10398; -.
DR CleanEx; HS_ARAF; -.
DR Genevestigator; P10398; -.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; NAS:UniProtKB.
DR GO; GO:0004709; F:MAP kinase kinase kinase activity; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
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:0032434; P:regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:UniProtKB.
DR GO; GO:0032006; P:regulation of TOR signaling cascade; IMP:UniProtKB.
DR InterPro; IPR020454; DAG/PE-bd.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR002219; Prot_Kinase_C-like_PE/DAG-bd.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR003116; Raf-like_ras-bd.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF07714; Pkinase_Tyr; 1.
DR Pfam; PF02196; RBD; 1.
DR PRINTS; PR00008; DAGPEDOMAIN.
DR SMART; SM00109; C1; 1.
DR SMART; SM00455; RBD; 1.
DR SUPFAM; SSF56112; SSF56112; 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; Complete proteome;
KW Kinase; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Polymorphism; Proto-oncogene; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
FT CHAIN 1 606 Serine/threonine-protein kinase A-Raf.
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 MOD_RES 186 186 Phosphoserine.
FT MOD_RES 257 257 Phosphoserine.
FT MOD_RES 318 318 Phosphothreonine.
FT VAR_SEQ 186 186 S -> R (in isoform 2).
FT /FTId=VSP_045609.
FT VAR_SEQ 187 606 Missing (in isoform 2).
FT /FTId=VSP_045610.
FT VARIANT 98 98 M -> T (in dbSNP:rs56197559).
FT /FTId=VAR_040375.
FT VARIANT 331 331 G -> C (in a colorectal adenocarcinoma
FT sample; somatic mutation).
FT /FTId=VAR_040376.
FT VARIANT 578 578 E -> D (in dbSNP:rs55852926).
FT /FTId=VAR_040377.
FT CONFLICT 368 368 L -> P (in Ref. 8; AAB08754).
FT CONFLICT 378 378 F -> V (in Ref. 8; AAB08754).
FT CONFLICT 469 469 S -> P (in Ref. 8; AAB08754).
FT CONFLICT 478 478 I -> T (in Ref. 8; AAB08754).
FT STRAND 19 24
FT STRAND 26 28
FT STRAND 30 34
FT HELIX 42 50
FT STRAND 56 67
FT STRAND 69 72
FT STRAND 74 78
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
//
MIM
311010
*RECORD*
*FIELD* NO
311010
*FIELD* TI
*311010 V-RAF MURINE SARCOMA 3611 VIRAL ONCOGENE HOMOLOG 1; ARAF1
;;ONCOGENE ARAF1;;
read moreRAFA1;;
ONCOGENE PKS2
*FIELD* TX
CLONING
By screening a fetal liver cDNA library at reduced stringency for
v-raf-related sequences, Mark et al. (1986) found a sequence in addition
to the expected RAF1 (164760). This sequence, which they called PKS
(presumably for 'protein kinase sequence'), showed 71% nucleotide
homology to RAF1. The predicted amino acid sequence of the kinase domain
was sufficiently like the sequence of v-raf to suggest that PKS may
encode a polypeptide with serine/threonine kinase activity. Mark et al.
(1986) found that expression of PKS mRNA (2.7 kb) was elevated in
peripheral blood mononuclear cells isolated from 2 patients with
angioimmunoblastic lymphadenopathy with dysproteinemia, a disease in
which autoantibodies are produced following the lymphoproliferative
activation of B cells.
By screening a mouse cDNA library with a v-raf oncogene probe, Huebner
et al. (1986) also isolated a transforming raf-related cDNA, A-raf, that
represented a gene distinct from RAF1. As an initial step in the
analysis of this RAF1-related cDNA, they isolated a human ARAF cDNA and
used it to map the genes in mouse and man.
Beck et al. (1987) deduced the complete 606-amino acid sequence of the
human ARAF1 oncogene from the 2,453-nucleotide sequence of the cDNA.
Yuryev et al. (2000) stated that ARAF contains an N-terminal regulatory
domain and a C-terminal catalytic domain. The regulatory domain contains
a RAS (HRAS; 190020)-binding domain and a cysteine-rich domain.
Immunohistochemical analysis and immunoelectron microscopy of
fractionated rat liver revealed that a portion of Araf localized to
mitochondria.
GENE FUNCTION
Because of an 80% homology to RAF1 in its kinase domain, Huebner et al.
(1986) speculated that the ARAF1 gene product may have
serine/threonine-specific kinase activity.
The RAF protooncogenes encode cytoplasmic protein serine/threonine
kinases that play a critical role in cell growth and development. Araf1
in the mouse is expressed predominantly in urogenital tissues (Lee et
al., 1994).
Pelkmans and Zerial (2005) explored the role of some kinases in caveolae
dynamics. Using RNAi, they identified functions at distinct steps of the
caveolar cycle. In the first step, the silencing of ARAF1, a
serine/threonine kinase involved in mitogenic signaling, resulted in
diffuse CAV1 (601047)-GFP staining that was laterally mobile, in
addition to the characteristic spot-like pattern. The authors suggested
that in the absence of ARAF1, the caveolar coat is less stable or
inefficiently assembled. Their observations revealed new principles in
caveolae trafficking and suggested that the dynamic properties of
caveolae and their transport competence are regulated by different
kinases operating at several levels.
Using yeast 2-hybrid analysis of HeLa cells, Yuryev et al. (2000) showed
that the N-terminal regulatory domain of ARAF interacted with the
putative mitochondrial proteins TOM (PPRF6; 613979) and TIM44 (TIMM44;
605058).
GENE STRUCTURE
Lee et al. (1994) demonstrated that the ARAF1 gene in the human
comprises 16 exons encoded by a minimum of 10,776 nucleotides.
MAPPING
Huebner et al. (1986) used a human ARAF cDNA to map the genes in mouse
and man. The mouse gene cosegregated with the X chromosome in Chinese
hamster-mouse hybrid cells. In humans, 2 independently segregating loci,
designated ARAF1 and ARAF2, were mapped to chromosomes X and 7,
respectively. (Huebner et al. (1986) had not conclusively shown that the
ARAF2 locus on chromosome 7 is transcribed, and indeed the ARAF2 locus,
now designated ARAF2P, has been shown to be a pseudogene (Lee et al.,
1994).) The single X-linked ARAF locus of the mouse and the ARAF1 locus
of man are actively transcribed in several mouse and human cell lines.
By in situ hybridization, Huebner et al. (1986) mapped the ARAF1 gene to
Xp21-q11, with most grains at Xp13-p11. Popescu and Mark (1989)
regionalized the gene to Xp11.4-p11.2 by in situ hybridization.
Avner et al. (1987) found that in the mouse the A-raf oncogene is on the
X chromosome, 10 to 17 cM proximal to the Hprt gene. The localization
was considered compatible with the presence of the ARAF oncogene on the
short arm of the X chromosome between the centromere and Xp21 in man.
*FIELD* RF
1. Avner, P.; Bucan, M.; Arnaud, D.; Lehrach, H.; Rapp, U.: A-raf
oncogene localizes on mouse X chromosome to region some 10-17 centimorgans
proximal to hypoxanthine phosphoribosyltransferase gene. Somat. Cell
Molec. Genet. 13: 267-272, 1987.
2. Beck, T. W.; Huleihel, M.; Gunnell, M.; Bonner, T. I.; Rapp, U.
R.: The complete coding sequence of the human A-raf-1 oncogene and
transforming activity of a human A-raf carrying retrovirus. Nucleic
Acids Res. 15: 595-609, 1987.
3. Huebner, K.; ar-Rushdi, A.; Griffin, C. A.; Isobe, M.; Kozak, C.;
Emanuel, B. S.; Nagarajan, L.; Cleveland, J. L.; Bonner, T. I.; Goldsborough,
M. D.; Croce, C. M.; Rapp, U.: Actively transcribed genes in the
raf oncogene group, located on the X chromosome in mouse and human. Proc.
Nat. Acad. Sci. 83: 3934-3938, 1986.
4. Lee, J.-E.; Beck, T. W.; Brennscheidt, U.; DeGennaro, L. J.; Rapp,
U. R.: The complete sequence and promoter activity of the human A-raf-1
gene (ARAF1). Genomics 20: 43-55, 1994.
5. Mark, G. E.; Seeley, T. W.; Shows, T. B.; Mountz, J. D.: Pks,
a raf-related sequence in humans. Proc. Nat. Acad. Sci. 83: 6312-6316,
1986.
6. Pelkmans, L.; Zerial, M.: Kinase-regulated quantal assemblies
and kiss-and-run recycling of caveolae. Nature 436: 128-133, 2005.
7. Popescu, N. C.; Mark, G. E.: Localization of the pKs gene, a raf
related sequence on human chromosomes X and 7. Oncogene 4: 517-519,
1989.
8. Yuryev, A.; Ono, M.; Goff, S. A.; Macaluso, F.; Wennogle, L. P.
: Isoform-specific localization of A-RAF in mitochondria. Molec.
Cell. Biol. 20: 4870-4878, 2000.
*FIELD* CN
Patricia A. Hartz - updated: 6/1/2011
Ada Hamosh - updated: 8/3/2005
*FIELD* CD
Victor A. McKusick: 6/25/1986
*FIELD* ED
mgross: 06/09/2011
terry: 6/1/2011
alopez: 8/4/2005
terry: 8/3/2005
carol: 3/14/2000
alopez: 8/21/1997
mark: 2/29/1996
carol: 5/31/1994
mimadm: 2/28/1994
supermim: 3/17/1992
carol: 10/21/1991
supermim: 3/20/1990
ddp: 10/26/1989
*RECORD*
*FIELD* NO
311010
*FIELD* TI
*311010 V-RAF MURINE SARCOMA 3611 VIRAL ONCOGENE HOMOLOG 1; ARAF1
;;ONCOGENE ARAF1;;
read moreRAFA1;;
ONCOGENE PKS2
*FIELD* TX
CLONING
By screening a fetal liver cDNA library at reduced stringency for
v-raf-related sequences, Mark et al. (1986) found a sequence in addition
to the expected RAF1 (164760). This sequence, which they called PKS
(presumably for 'protein kinase sequence'), showed 71% nucleotide
homology to RAF1. The predicted amino acid sequence of the kinase domain
was sufficiently like the sequence of v-raf to suggest that PKS may
encode a polypeptide with serine/threonine kinase activity. Mark et al.
(1986) found that expression of PKS mRNA (2.7 kb) was elevated in
peripheral blood mononuclear cells isolated from 2 patients with
angioimmunoblastic lymphadenopathy with dysproteinemia, a disease in
which autoantibodies are produced following the lymphoproliferative
activation of B cells.
By screening a mouse cDNA library with a v-raf oncogene probe, Huebner
et al. (1986) also isolated a transforming raf-related cDNA, A-raf, that
represented a gene distinct from RAF1. As an initial step in the
analysis of this RAF1-related cDNA, they isolated a human ARAF cDNA and
used it to map the genes in mouse and man.
Beck et al. (1987) deduced the complete 606-amino acid sequence of the
human ARAF1 oncogene from the 2,453-nucleotide sequence of the cDNA.
Yuryev et al. (2000) stated that ARAF contains an N-terminal regulatory
domain and a C-terminal catalytic domain. The regulatory domain contains
a RAS (HRAS; 190020)-binding domain and a cysteine-rich domain.
Immunohistochemical analysis and immunoelectron microscopy of
fractionated rat liver revealed that a portion of Araf localized to
mitochondria.
GENE FUNCTION
Because of an 80% homology to RAF1 in its kinase domain, Huebner et al.
(1986) speculated that the ARAF1 gene product may have
serine/threonine-specific kinase activity.
The RAF protooncogenes encode cytoplasmic protein serine/threonine
kinases that play a critical role in cell growth and development. Araf1
in the mouse is expressed predominantly in urogenital tissues (Lee et
al., 1994).
Pelkmans and Zerial (2005) explored the role of some kinases in caveolae
dynamics. Using RNAi, they identified functions at distinct steps of the
caveolar cycle. In the first step, the silencing of ARAF1, a
serine/threonine kinase involved in mitogenic signaling, resulted in
diffuse CAV1 (601047)-GFP staining that was laterally mobile, in
addition to the characteristic spot-like pattern. The authors suggested
that in the absence of ARAF1, the caveolar coat is less stable or
inefficiently assembled. Their observations revealed new principles in
caveolae trafficking and suggested that the dynamic properties of
caveolae and their transport competence are regulated by different
kinases operating at several levels.
Using yeast 2-hybrid analysis of HeLa cells, Yuryev et al. (2000) showed
that the N-terminal regulatory domain of ARAF interacted with the
putative mitochondrial proteins TOM (PPRF6; 613979) and TIM44 (TIMM44;
605058).
GENE STRUCTURE
Lee et al. (1994) demonstrated that the ARAF1 gene in the human
comprises 16 exons encoded by a minimum of 10,776 nucleotides.
MAPPING
Huebner et al. (1986) used a human ARAF cDNA to map the genes in mouse
and man. The mouse gene cosegregated with the X chromosome in Chinese
hamster-mouse hybrid cells. In humans, 2 independently segregating loci,
designated ARAF1 and ARAF2, were mapped to chromosomes X and 7,
respectively. (Huebner et al. (1986) had not conclusively shown that the
ARAF2 locus on chromosome 7 is transcribed, and indeed the ARAF2 locus,
now designated ARAF2P, has been shown to be a pseudogene (Lee et al.,
1994).) The single X-linked ARAF locus of the mouse and the ARAF1 locus
of man are actively transcribed in several mouse and human cell lines.
By in situ hybridization, Huebner et al. (1986) mapped the ARAF1 gene to
Xp21-q11, with most grains at Xp13-p11. Popescu and Mark (1989)
regionalized the gene to Xp11.4-p11.2 by in situ hybridization.
Avner et al. (1987) found that in the mouse the A-raf oncogene is on the
X chromosome, 10 to 17 cM proximal to the Hprt gene. The localization
was considered compatible with the presence of the ARAF oncogene on the
short arm of the X chromosome between the centromere and Xp21 in man.
*FIELD* RF
1. Avner, P.; Bucan, M.; Arnaud, D.; Lehrach, H.; Rapp, U.: A-raf
oncogene localizes on mouse X chromosome to region some 10-17 centimorgans
proximal to hypoxanthine phosphoribosyltransferase gene. Somat. Cell
Molec. Genet. 13: 267-272, 1987.
2. Beck, T. W.; Huleihel, M.; Gunnell, M.; Bonner, T. I.; Rapp, U.
R.: The complete coding sequence of the human A-raf-1 oncogene and
transforming activity of a human A-raf carrying retrovirus. Nucleic
Acids Res. 15: 595-609, 1987.
3. Huebner, K.; ar-Rushdi, A.; Griffin, C. A.; Isobe, M.; Kozak, C.;
Emanuel, B. S.; Nagarajan, L.; Cleveland, J. L.; Bonner, T. I.; Goldsborough,
M. D.; Croce, C. M.; Rapp, U.: Actively transcribed genes in the
raf oncogene group, located on the X chromosome in mouse and human. Proc.
Nat. Acad. Sci. 83: 3934-3938, 1986.
4. Lee, J.-E.; Beck, T. W.; Brennscheidt, U.; DeGennaro, L. J.; Rapp,
U. R.: The complete sequence and promoter activity of the human A-raf-1
gene (ARAF1). Genomics 20: 43-55, 1994.
5. Mark, G. E.; Seeley, T. W.; Shows, T. B.; Mountz, J. D.: Pks,
a raf-related sequence in humans. Proc. Nat. Acad. Sci. 83: 6312-6316,
1986.
6. Pelkmans, L.; Zerial, M.: Kinase-regulated quantal assemblies
and kiss-and-run recycling of caveolae. Nature 436: 128-133, 2005.
7. Popescu, N. C.; Mark, G. E.: Localization of the pKs gene, a raf
related sequence on human chromosomes X and 7. Oncogene 4: 517-519,
1989.
8. Yuryev, A.; Ono, M.; Goff, S. A.; Macaluso, F.; Wennogle, L. P.
: Isoform-specific localization of A-RAF in mitochondria. Molec.
Cell. Biol. 20: 4870-4878, 2000.
*FIELD* CN
Patricia A. Hartz - updated: 6/1/2011
Ada Hamosh - updated: 8/3/2005
*FIELD* CD
Victor A. McKusick: 6/25/1986
*FIELD* ED
mgross: 06/09/2011
terry: 6/1/2011
alopez: 8/4/2005
terry: 8/3/2005
carol: 3/14/2000
alopez: 8/21/1997
mark: 2/29/1996
carol: 5/31/1994
mimadm: 2/28/1994
supermim: 3/17/1992
carol: 10/21/1991
supermim: 3/20/1990
ddp: 10/26/1989