P10398 (ARAF_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine/threonine-protein kinase A-Raf
EC=2.7.11.1

Alternative name(s):
Proto-oncogene A-Raf
Proto-oncogene A-Raf-1
Proto-oncogene Pks

Gene names

Name:	ARAF
Synonyms:	ARAF1, PKS, PKS2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	606 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Disease	Proto-oncogene
Domain	Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	intracellular signal transduction Inferred from electronic annotation. Source: InterPro negative regulation of apoptotic process Inferred from direct assay. Source: UniProtKB positive regulation of peptidyl-serine phosphorylation Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Non-traceable author statement. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Inferred from direct assay. Source: UniProtKB receptor signaling protein activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ASS1	P00966	4	EBI-365961,EBI-536842
COPS3	Q9UNS2	3	EBI-365961,EBI-350590
CPS1	P31327	3	EBI-365961,EBI-536811
EFEMP1	Q12805	3	EBI-365961,EBI-536772
MAP2K2	P36507	4	EBI-365961,EBI-1056930
NUDT14	O95848	3	EBI-365961,EBI-536866
PBK	Q96KB5	3	EBI-365961,EBI-536853
PRPF6	O94906	4	EBI-365961,EBI-536755
RABGGTB	P53611	3	EBI-365961,EBI-536715
RRAS2	P62070	3	EBI-365961,EBI-491037
TH1L	Q8IXH7	5	EBI-365961,EBI-536725
TIMM44	O43615	3	EBI-365961,EBI-861737
TIMM50	Q3ZCQ8	3	EBI-365961,EBI-355175

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 606

606

Serine/threonine-protein kinase A-Raf

PRO_0000085622

Regions

Domain

19 – 91

73

RBD

Domain

310 – 570

261

Protein kinase

Zinc finger

98 – 144

47

Phorbol-ester/DAG-type

Nucleotide binding

316 – 324

9

ATP By similarity

Sites

Active site

429

1

Proton acceptor By similarity

Metal binding

99

1

Zinc 1 By similarity

Metal binding

112

1

Zinc 2 By similarity

Metal binding

115

1

Zinc 2 By similarity

Metal binding

125

1

Zinc 1 By similarity

Metal binding

128

1

Zinc 1 By similarity

Metal binding

133

1

Zinc 2 By similarity

Metal binding

136

1

Zinc 2 By similarity

Metal binding

144

1

Zinc 1 By similarity

Binding site

336

1

ATP By similarity

Amino acid modifications

Modified residue

186

1

Phosphoserine Ref.11

Modified residue

213

1

Phosphothreonine Ref.10

Modified residue

215

1

Phosphothreonine Ref.10

Modified residue

257

1

Phosphoserine Ref.9 Ref.11

Modified residue

318

1

Phosphothreonine Ref.12

Modified residue

580

1

Phosphoserine Ref.11

Modified residue

582

1

Phosphoserine Ref.8 Ref.11

Natural variations

Natural variant

98

1

M → T. Ref.15
Corresponds to variant rs56197559 [ dbSNP | Ensembl ].

VAR_040375

Natural variant

331

1

G → C in a colorectal adenocarcinoma sample; somatic mutation. Ref.15

VAR_040376

Natural variant

578

1

E → D. Ref.15
Corresponds to variant rs55852926 [ dbSNP | Ensembl ].

VAR_040377

Experimental info

Sequence conflict

368

1

L → P in AAB08754. Ref.6

Sequence conflict

378

1

F → V in AAB08754. Ref.6

Sequence conflict

469

1

S → P in AAB08754. Ref.6

Sequence conflict

478

1

I → T in AAB08754. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

606

Helix Strand Turn

Details...

Beta strand

19 – 24

6

Beta strand

26 – 28

3

Beta strand

30 – 34

5

Helix

42 – 50

9

Beta strand

56 – 67

12

Beta strand

69 – 72

4

Beta strand

74 – 78

5

Beta strand

85 – 90

6

Sequences

	Sequence		Length	Mass (Da)
	P10398 [UniParc]. Last modified October 1, 1996. Version 2. Checksum: D23E5711304AA468	FASTA	606	67,585
	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

References

	« Hide 'large scale' referencesShow '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. , 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: Cervix carcinoma.
[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: Cervix carcinoma.
[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. Tissue: Cervix carcinoma.
[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. Tissue: Cervix carcinoma.
[12]	"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: Leukemic T-cell.
[13]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[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. , 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.

IPI

IPI00020578.

PIR

TVHUAF. A53026.

RefSeq

NP_001645.1. NM_001654.3.

UniGene

Hs.446641.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WXM	NMR	-	A	19-91	[»]

ProteinModelPortal

P10398.

SMR

P10398. Positions 20-91, 96-146, 303-606.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-31374N.

IntAct

P10398. 30 interactions.

MINT

MINT-88835.

STRING

P10398.

PTM databases

PhosphoSite

P10398.

Polymorphism databases

DMDM

1730068.

Proteomic databases

PRIDE

P10398.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000377045; ENSP00000366244; ENSG00000078061.

GeneID

369.

KEGG

hsa:369.

UCSC

uc010nhs.1. human.

Organism-specific databases

CTD

369.

GeneCards

GC0XP047429.

H-InvDB

HIX0016762.

HGNC

HGNC:646. ARAF.

MIM

311010. gene.

neXtProt

NX_P10398.

PharmGKB

PA24928.

GenAtlas

Search...

Phylogenomic databases

GeneTree

ENSGT00600000084194.

HOVERGEN

HBG001886.

OrthoDB

EOG4CRKZT.

PhylomeDB

P10398.

Enzyme and pathway databases

BRENDA

2.7.10.2. 2681.

Gene expression databases

ArrayExpress

P10398.

Bgee

P10398.

CleanEx

HS_ARAF.

Genevestigator

P10398.

GermOnline

ENSG00000078061. Homo sapiens.

Family and domain databases

InterPro

IPR020454. 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.
IPR001245. Ser-Thr/Tyr_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

KO

K08845.

Pfam

PF00130. C1_1. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF02196. RBD. 1 hit.
[Graphical view]

PRINTS

PR00008. DAGPEDOMAIN.

SMART

SM00109. C1. 1 hit.
SM00455. RBD. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. 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]

ProtoNet

Search...

Other

DrugBank

DB00171. Adenosine triphosphate.

NextBio

1545.

SOURCE

Search...

Entry information

Entry name

ARAF_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 146 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.