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UniProtKB/Swiss-Prot entry P10398


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name ARAF_HUMAN
Primary accession number P10398
Secondary accession numbers P07557 Q5H9B3
Integrated into Swiss-Prot on April 1, 1988
Sequence was last modified on October 1, 1996 (Sequence version 2)
Annotations were last modified on    December 16, 2008 (Entry version 109)
Name and origin of the protein
Protein name A-Raf proto-oncogene serine/threonine-protein kinase
Synonyms EC 2.7.11.1
A-raf-1
Proto-oncogene Pks
Gene name
Name: ARAF
Synonyms: ARAF1, PKS, PKS2
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA].
DOI=10.1093/nar/15.2.595; PubMed=3029685 [NCBI, ExPASy, EBI, Israel, Japan]
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).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
TISSUE=Placenta;
DOI=10.1006/geno.1994.1125; PubMed=8020955 [NCBI, ExPASy, EBI, Israel, Japan]
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).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.;
"Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
DOI=10.1038/nature03440; PubMed=15772651 [NCBI, ExPASy, EBI, Israel, Japan]
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C., Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.;
"The DNA sequence of the human X chromosome.";
Nature 434:325-337(2005).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Kidney;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[6]
NUCLEOTIDE SEQUENCE [MRNA] OF 292-589.
PubMed=3529082 [NCBI, ExPASy, EBI, Israel, Japan]
Mark G.E., Seeley T.W., Shows T.B., Mountz J.D.;
"Pks, a raf-related sequence in humans.";
Proc. Natl. Acad. Sci. U.S.A. 83:6312-6316(1986).
[7]
INTERACTION WITH NELFD.
DOI=10.1023/A:1014437024129; PubMed=11952167 [NCBI, ExPASy, EBI, Israel, Japan]
Yin X.L., Chen S., Gu J.X.;
"Identification of TH1 as an interaction partner of A-Raf kinase.";
Mol. Cell. Biochem. 231:69-74(2002).
[8]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-582, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1016/j.cell.2006.09.026; PubMed=17081983 [NCBI, ExPASy, EBI, Israel, Japan]
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.";
Cell 127:635-648(2006).
[9]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-257, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1038/nbt1240; PubMed=16964243 [NCBI, ExPASy, EBI, Israel, Japan]
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
"A probability-based approach for high-throughput protein phosphorylation analysis and site localization.";
Nat. Biotechnol. 24:1285-1292(2006).
[10]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-213 AND THR-215, AND MASS SPECTROMETRY.
DOI=10.1021/pr0705441; PubMed=18220336 [NCBI, ExPASy, EBI, Israel, Japan]
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.";
J. Proteome Res. 7:1346-1351(2008).
[11]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186; SER-257; SER-580 AND SER-582, AND MASS SPECTROMETRY.
DOI=10.1016/j.molcel.2008.07.007; PubMed=18691976 [NCBI, ExPASy, EBI, Israel, Japan]
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.;
"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.";
Mol. Cell 31:438-448(2008).
[12]
STRUCTURE BY NMR OF 19-91.
RIKEN structural genomics initiative (RSGI);
"Solution structure of the N-terminal RAS-binding domain (RBD) in human A-RAF kinase.";
Submitted (JUL-2005) to the PDB data bank.
[13]
VARIANTS [LARGE SCALE ANALYSIS] THR-98; CYS-331 AND ASP-578.
DOI=10.1038/nature05610; PubMed=17344846 [NCBI, ExPASy, EBI, Israel, Japan]
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
"Patterns of somatic mutation in human cancer genomes.";
Nature 446:153-158(2007).
Comments
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
X04790; CAA28476.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
L24038; AAA65219.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U01337; AAB03517.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BT019864; AAV38667.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
Z84466; CAI42468.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC002466; AAH02466.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M13829; AAB08754.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A53026; TVHUAF.
RefSeq NP_001645.1; -.
UniGene Hs.446641
3D structure databases
PDB
1WXM; NMR; -; A=19-91.[ExPASy / RCSB / EBI]
PDBsum 1WXM; -.
SMR P10398; 96-146, 303-576.
ModBase P10398.
Protein-protein interaction databases
IntAct P10398; 24.
PTM databases
PhosphoSite P10398; -.
Organism-specific databases
GeneCards GC0XP047305; -.
H-InvDB HIX0016762; -.
HGNC HGNC:646; ARAF.
GenAtlas ARAF.
MIM 311010; gene. [NCBI / EBI]
PharmGKB PA24928; -.
GeneCards P10398.
Gene expression databases
ArrayExpress P10398; -.
CleanEx HS_ARAF; -.
GermOnline ENSG00000078061; Homo sapiens.
Ontologies
GO
GO:0005524; Molecular function: ATP binding (non-traceable author statement from UniProtKB).
GO:0019992; Molecular function: diacylglycerol binding (inferred from electronic annotation from UniProtKB-KW).
GO:0005515; Molecular function: protein binding (inferred from physical interaction from IntAct).
GO:0004674; Molecular function: protein serine/threonine kinase activity (non-traceable author statement from UniProtKB).
GO:0005057; Molecular function: receptor signaling protein activity (inferred from electronic annotation from InterPro).
GO:0008270; Molecular function: zinc ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0007242; Biological process: intracellular signaling cascade (inferred from electronic annotation from InterPro).
GO:0006468; Biological process: protein amino acid phosphorylation (non-traceable author statement from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR002219; DAG_PE_bd.
IPR000719; Prot_kinase_core.
IPR017441; Protein_kinase_ATP_bd_CS.
IPR003116; Raf_like_ras_bd.
IPR017442; Se/Thr_pkinase-rel.
IPR008271; Ser_thr_pkin_AS.
Graphical view of domain structure.
Pfam PF00130; C1_1; 1.
PF00069; Pkinase; 1.
PF02196; RBD; 1.
Pfam graphical view of domain structure.
PRINTS PR00008; DAGPEDOMAIN.
ProDom PD000001; Prot_kinase; 1.
[Domain structure / List of seq. sharing at least 1 domain]
SMART SM00109; C1; 1.
SM00455; RBD; 1.
SMART graphical view of domain structure.
PROSITE PS00107; PROTEIN_KINASE_ATP; 1.
PS50011; PROTEIN_KINASE_DOM; 1.
PS00108; PROTEIN_KINASE_ST; 1.
PS50898; RBD; 1.
PS00479; ZF_DAG_PE_1; 1.
PS50081; ZF_DAG_PE_2; 1.
PROSITE graphical view of domain structure (profiles).
Proteomics databases
PRIDE P10398; -.
Genome annotation databases
Ensembl ENSG00000078061; Homo sapiens. [Contig view]
GeneID 369; -.
KEGG hsa:369; -.
Phylogenomic databases
HOVERGEN P10398; -.
Other
DrugBank DB00171; Adenosine triphosphate.
NextBio 1545; -.
SOURCE ARAF; Homo sapiens.
ProtoNet P10398.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; ATP-binding; Kinase; Metal-binding; Nucleotide-binding; Phorbol-ester binding; Phosphoprotein; Polymorphism; Proto-oncogene; Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   606  606     A-Raf proto-oncogene serine/threonine-protein kinase. PRO_0000085622
DOMAIN   19    91  73     RBD. 
DOMAIN   310   570  261     Protein kinase. 
ZN_FING   98   144  47     Phorbol-ester/DAG-type. 
NP_BIND   316   324  9     ATP (By similarity). 
ACT_SITE   429   429        Proton acceptor (By similarity). 
METAL   99    99        Zinc 1 (By similarity). 
METAL   112   112        Zinc 2 (By similarity). 
METAL   115   115        Zinc 2 (By similarity). 
METAL   125   125        Zinc 1 (By similarity). 
METAL   128   128        Zinc 1 (By similarity). 
METAL   133   133        Zinc 2 (By similarity). 
METAL   136   136        Zinc 2 (By similarity). 
METAL   144   144        Zinc 1 (By similarity). 
BINDING   336   336        ATP (By similarity). 
MOD_RES   186   186        Phosphoserine. 
MOD_RES   213   213        Phosphothreonine. 
MOD_RES   215   215        Phosphothreonine. 
MOD_RES   257   257        Phosphoserine. 
MOD_RES   580   580        Phosphoserine. 
MOD_RES   582   582        Phosphoserine. 
VARIANT   98    98  1     M -> T. VAR_040375 
VARIANT   331   331  1     G -> C (in a colorectal adenocarcinoma sample; somatic mutation). VAR_040376 
VARIANT   578   578  1     E -> D. VAR_040377 
CONFLICT   368   368        L -> P (in Ref. 6; AAB08754). 
CONFLICT   378   378        F -> V (in Ref. 6; AAB08754). 
CONFLICT   469   469        S -> P (in Ref. 6; AAB08754). 
CONFLICT   478   478        I -> T (in Ref. 6; AAB08754). 
STRAND   19    24  6      
STRAND   26    28  3      
STRAND   30    34  5      
HELIX   42    50  9      
STRAND   56    67  12      
STRAND   69    72  4      
STRAND   74    78  5      
STRAND   85    90  6      
Sequence information
Length: 606 AA [This is the length of the unprocessed precursor] Molecular weight: 67585 Da [This is the MW of the unprocessed precursor] CRC64: D23E5711304AA468 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MEPPRGPPAN GAEPSRAVGT VKVYLPNKQR TVVTVRDGMS VYDSLDKALK VRGLNQDCCV 

        70         80         90        100        110        120 
VYRLIKGRKT VTAWDTAIAP LDGEELIVEV LEDVPLTMHN FVRKTFFSLA FCDFCLKFLF 

       130        140        150        160        170        180 
HGFRCQTCGY KFHQHCSSKV PTVCVDMSTN RQQFYHSVQD LSGGSRQHEA PSNRPLNELL 

       190        200        210        220        230        240 
TPQGPSPRTQ HCDPEHFPFP APANAPLQRI RSTSTPNVHM VSTTAPMDSN LIQLTGQSFS 

       250        260        270        280        290        300 
TDAAGSRGGS DGTPRGSPSP ASVSSGRKSP HSKSPAEQRE RKSLADDKKK VKNLGYRDSG 

       310        320        330        340        350        360 
YYWEVPPSEV QLLKRIGTGS FGTVFRGRWH GDVAVKVLKV SQPTAEQAQA FKNEMQVLRK 

       370        380        390        400        410        420 
TRHVNILLFM GFMTRPGFAI ITQWCEGSSL YHHLHVADTR FDMVQLIDVA RQTAQGMDYL 

       430        440        450        460        470        480 
HAKNIIHRDL KSNNIFLHEG LTVKIGDFGL ATVKTRWSGA QPLEQPSGSV LWMAAEVIRM 

       490        500        510        520        530        540 
QDPNPYSFQS DVYAYGVVLY ELMTGSLPYS HIGCRDQIIF MVGRGYLSPD LSKISSNCPK 

       550        560        570        580        590        600 
AMRRLLSDCL KFQREERPLF PQILATIELL QRSLPKIERS ASEPSLHRTQ ADELPACLLS 


AARLVP 

P10398 in FASTA format

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