Reviewed, UniProtKB/Swiss-Prot P10398 (ARAF_HUMAN)

Names and origin

Protein names

Recommended 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

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.
Sequence processing	The displayed sequence is not processed.
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.
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	Phorbol-ester binding Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	protein amino acid phosphorylation Non-traceable author statement. Source: UniProtKB
Molecular function	ATP binding Non-traceable author statement. Source: UniProtKB protein binding Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Non-traceable author statement. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ASS1	P00966	3	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	3	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	4	EBI-365961,EBI-536725
TIMM44	O43615	3	EBI-365961,EBI-861737
TIMM50	Q3ZCQ8	2	EBI-365961,EBI-355175
YWHAG	P61981	1	EBI-365961,EBI-359832

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Chain

1 – 606

606

A-Raf proto-oncogene serine/threonine-protein kinase

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

213

1

Phosphothreonine

Modified residue

215

1

Phosphothreonine

Modified residue

257

1

Phosphoserine

Modified residue

582

1

Phosphoserine

Natural variations

Natural variant

98

1

M → T

Natural variant

331

1

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

Natural variant

578

1

E → D

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)
	P10398-1 [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: 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]	"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.
[12]	"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

EMBLGenBankDDBJ

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.

PIR

TVHUAF. A53026.

RefSeq

NP_001645.1.

UniGene

Hs.446641

3D structure databases

PDBMSD

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

SMR

P10398. Positions 96-146, 303-576.

ModBase

Search...

Protein-protein interaction databases

IntAct

P10398.

PTM databases

PhosphoSite

P10398.

Genome annotation databases

Ensembl

ENSG00000078061. Homo sapiens. [Contig view]

GeneID

369.

KEGG

hsa:369.

Organism-specific databases

H-InvDB

HIX0016762.

HGNC

HGNC:646. ARAF.