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Reviewed, UniProtKB/Swiss-Prot P10398 (ARAF_HUMAN)

Last modified February 9, 2010. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    A-Raf proto-oncogene serine/threonine-protein kinase
    EC=2.7.11.1
Alternative name(s):
    A-raf-1
    Proto-oncogene Pks
Gene names
Name: ARAF
Synonyms: ARAF1, PKS, PKS2
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length606 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Involved in the transduction of mitogenic signals from the cell membrane to the nucleus.

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Binds 2 zinc ions per subunit By similarity.

Subunit structure

Interacts with TH1L/NELFD. Ref.7

Tissue specificity

Predominantly in urogenital tissues By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily.

Contains 1 phorbol-ester/DAG-type zinc finger.

Contains 1 protein kinase domain.

Contains 1 RBD (Ras-binding) domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 606606A-Raf proto-oncogene serine/threonine-protein kinase
PRO_0000085622

Regions

Domain19 – 9173RBD
Domain310 – 570261Protein kinase
Zinc finger98 – 14447Phorbol-ester/DAG-type
Nucleotide binding316 – 3249ATP By similarity

Sites

Active site4291Proton acceptor By similarity
Metal binding991Zinc 1 By similarity
Metal binding1121Zinc 2 By similarity
Metal binding1151Zinc 2 By similarity
Metal binding1251Zinc 1 By similarity
Metal binding1281Zinc 1 By similarity
Metal binding1331Zinc 2 By similarity
Metal binding1361Zinc 2 By similarity
Metal binding1441Zinc 1 By similarity
Binding site3361ATP By similarity

Amino acid modifications

Modified residue1861Phosphoserine Ref.11
Modified residue2131Phosphothreonine Ref.10
Modified residue2151Phosphothreonine Ref.10
Modified residue2571Phosphoserine Ref.11 Ref.9
Modified residue3181Phosphothreonine Ref.13
Modified residue5801Phosphoserine Ref.11
Modified residue5821Phosphoserine Ref.11 Ref.8

Natural variations

Natural variant981M → T: dbSNP rs56197559. Ref.15
VAR_040375
Natural variant3311G → C in a colorectal adenocarcinoma sample; somatic mutation. Ref.15
VAR_040376
Natural variant5781E → D: dbSNP rs55852926. Ref.15
VAR_040377

Experimental info

Sequence conflict3681L → P in AAB08754. Ref.6
Sequence conflict3781F → V in AAB08754. Ref.6
Sequence conflict4691S → P in AAB08754. Ref.6
Sequence conflict4781I → T in AAB08754. Ref.6

Secondary structure

................. 606
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P10398-1 [UniParc].

Last modified October 1, 1996. Version 2.
Checksum: D23E5711304AA468

FASTA60667,585
        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 

« Hide

References

« Hide 'large scale' references
[1]"The complete coding sequence of the human A-raf-1 oncogene and transforming activity of a human A-raf carrying retrovirus."
Beck T.W., Huleihel M., Gunnell M., Bonner T.I., Rapp U.R.
Nucleic Acids Res. 15:595-609(1987) [PubMed: 3029685] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"The complete sequence and promoter activity of the human A-raf-1 gene (ARAF1)."
Lee J.-E., Beck T.W., Brennscheidt U., DeGennaro L.J., Rapp U.R.
Genomics 20:43-55(1994) [PubMed: 8020955] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Placenta.
[3]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
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.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"The DNA sequence of the human X chromosome."
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. expand/collapse author list , 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.
Nature 434:325-337(2005) [PubMed: 15772651] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Kidney.
[6]"Pks, a raf-related sequence in humans."
Mark G.E., Seeley T.W., Shows T.B., Mountz J.D.
Proc. Natl. Acad. Sci. U.S.A. 83:6312-6316(1986) [PubMed: 3529082] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 292-589.
[7]"Identification of TH1 as an interaction partner of A-Raf kinase."
Yin X.L., Chen S., Gu J.X.
Mol. Cell. Biochem. 231:69-74(2002) [PubMed: 11952167] [Abstract]
Cited for: INTERACTION WITH NELFD.
[8]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed: 17081983] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-582, MASS SPECTROMETRY.
Tissue: Epithelium.
[9]"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
Nat. Biotechnol. 24:1285-1292(2006) [PubMed: 16964243] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-257, MASS SPECTROMETRY.
Tissue: Epithelium.
[10]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-213 AND THR-215, MASS SPECTROMETRY.
[11]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-186; SER-257; SER-580 AND SER-582, MASS SPECTROMETRY.
[12]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[13]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed: 19690332] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-318, MASS SPECTROMETRY.
Tissue: T-cell.
[14]"Solution structure of the N-terminal RAS-binding domain (RBD) in human A-RAF kinase."
RIKEN structural genomics initiative (RSGI)
Submitted (JUL-2005) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 19-91.
[15]"Patterns of somatic mutation in human cancer genomes."
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. expand/collapse author list , 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.
Nature 446:153-158(2007) [PubMed: 17344846] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] THR-98; CYS-331 AND ASP-578.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X04790 mRNA. Translation: CAA28476.1.
L24038 Genomic DNA. Translation: AAA65219.1.
U01337 Genomic DNA. Translation: AAB03517.1.
BT019864 mRNA. Translation: AAV38667.1.
Z84466 Genomic DNA. Translation: CAI42468.1.
BC002466 mRNA. Translation: AAH02466.1.
M13829 mRNA. Translation: AAB08754.1.
IPIIPI00872240.
PIRTVHUAF. A53026.
RefSeqNP_001645.1.
UniGeneHs.446641

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1WXMNMR-A19-91[»]
SMRP10398. Positions 96-146, 303-576.
ModBaseSearch...

Protein-protein interaction databases

IntActP10398. 24 interactions.
STRINGP10398.

PTM databases

PhosphoSiteP10398.

Proteomic databases

PRIDEP10398.

Genome annotation databases

EnsemblENST00000377045; ENSP00000366244; ENSG00000078061; Homo sapiens. [Genome view]
GeneID369.
KEGGhsa:369.
UCSCuc010nhs.1. human.

Organism-specific databases

CTD369.
GeneCardsGC0XP047305.
H-InvDBHIX0016762.
HGNCHGNC:646. ARAF.
MIM311010. gene.
PharmGKBPA24928.
GenAtlasSearch...

Phylogenomic databases

HOVERGENP10398.

Enzyme and pathway databases

BRENDA2.7.10.2. 247.
2.7.11.1. 247.

Gene expression databases

ArrayExpressP10398.
BgeeP10398.
CleanExHS_ARAF.
GenevestigatorP10398.
GermOnlineENSG00000078061. Homo sapiens.

Family and domain databases

InterProIPR020454. DAG/PE_bd.
IPR011009. Kinase-like_dom.
IPR002219. Prot_Kinase_C-like_PE/DAG_bd.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR003116. Raf-like_ras_bd.
IPR008271. Ser/Thr_prot_kinase_AS.
[Graphical view]
PfamPF00130. C1_1. 1 hit.
PF02196. RBD. 1 hit.
[Graphical view]
PRINTSPR00008. DAGPEDOMAIN.
SMARTSM00109. C1. 1 hit.
SM00455. RBD. 1 hit.
[Graphical view]
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50898. RBD. 1 hit.
PS00479. ZF_DAG_PE_1. 1 hit.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00171. Adenosine triphosphate.
NextBio1545.
SOURCESearch...

Entry information

Entry nameARAF_HUMAN
AccessionPrimary (citable) accession number: P10398
Secondary accession number(s): P07557, Q5H9B3
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: October 1, 1996
Last modified: February 9, 2010
This is version 125 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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Index of Protein Data Bank (PDB) cross-references

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SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents