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Protein

Serine/threonine-protein kinase A-Raf

Gene

ARAF

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May also regulate the TOR signaling cascade.1 Publication
Isoform 2: Serves as a positive regulator of myogenic differentiation by inducing cell cycle arrest, the expression of myogenin and other muscle-specific proteins, and myotube formation.1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Zn2+By similarityNote: Binds 2 Zn2+ ions per subunit.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi99 – 991Zinc 1By similarity
Metal bindingi112 – 1121Zinc 2By similarity
Metal bindingi115 – 1151Zinc 2By similarity
Metal bindingi125 – 1251Zinc 1By similarity
Metal bindingi128 – 1281Zinc 1By similarity
Metal bindingi133 – 1331Zinc 2By similarity
Metal bindingi136 – 1361Zinc 2By similarity
Metal bindingi144 – 1441Zinc 1By similarity
Binding sitei336 – 3361ATPPROSITE-ProRule annotation
Active sitei429 – 4291Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri98 – 14447Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd
BLAST
Nucleotide bindingi316 – 3249ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • metal ion binding Source: UniProtKB-KW
  • protein kinase activity Source: ProtInc
  • protein serine/threonine kinase activity Source: UniProtKB
  • receptor signaling protein activity Source: InterPro

GO - Biological processi

  • cellular protein modification process Source: ProtInc
  • MAPK cascade Source: Reactome
  • negative regulation of apoptotic process Source: UniProtKB
  • positive regulation of peptidyl-serine phosphorylation Source: UniProtKB
  • regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
  • regulation of TOR signaling Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Metal-binding, Nucleotide-binding, Zinc

Enzyme and pathway databases

BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-5673000. RAF activation.
R-HSA-5674135. MAP2K and MAPK activation.
R-HSA-5675221. Negative regulation of MAPK pathway.
SignaLinkiP10398.
SIGNORiP10398.

Names & Taxonomyi

Protein namesi
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 namesi
Name:ARAF
Synonyms:ARAF1, PKS, PKS2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:646. ARAF.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

PharmGKBiPA24928.

Chemistry

ChEMBLiCHEMBL3559685.
DrugBankiDB00171. Adenosine triphosphate.
GuidetoPHARMACOLOGYi1933.

Polymorphism and mutation databases

BioMutaiARAF.
DMDMi1730068.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 606606Serine/threonine-protein kinase A-RafPRO_0000085622Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei157 – 1571PhosphoserineCombined sources
Modified residuei162 – 1621PhosphoserineCombined sources
Modified residuei181 – 1811PhosphothreonineCombined sources
Modified residuei186 – 1861PhosphoserineCombined sources
Modified residuei253 – 2531PhosphothreonineCombined sources
Modified residuei257 – 2571PhosphoserineCombined sources
Modified residuei269 – 2691PhosphoserineCombined sources
Modified residuei318 – 3181PhosphothreonineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP10398.
MaxQBiP10398.
PaxDbiP10398.
PeptideAtlasiP10398.
PRIDEiP10398.
TopDownProteomicsiP10398-1. [P10398-1]

PTM databases

iPTMnetiP10398.
PhosphoSiteiP10398.

Expressioni

Tissue specificityi

Predominantly in urogenital tissues.

Gene expression databases

BgeeiENSG00000078061.
CleanExiHS_ARAF.
ExpressionAtlasiP10398. baseline and differential.
GenevisibleiP10398. HS.

Organism-specific databases

HPAiHPA046188.
HPA066326.

Interactioni

Subunit structurei

Interacts with TH1L/NELFD.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
ASS1P009664EBI-365961,EBI-536842
BRAFP150562EBI-365961,EBI-365980
COPS3Q9UNS23EBI-365961,EBI-350590
CPS1P313273EBI-365961,EBI-536811
EFEMP1Q128053EBI-365961,EBI-536772
HSP90AB1P082386EBI-365961,EBI-352572
IRAK2O431872EBI-365961,EBI-447733
IRF7Q929852EBI-365961,EBI-968267
MAP2K2P365076EBI-365961,EBI-1056930
NELFCDQ8IXH75EBI-365961,EBI-536725
NUDT14O958483EBI-365961,EBI-536866
PBKQ96KB53EBI-365961,EBI-536853
PKMP146182EBI-365961,EBI-353408
PRPF6O949064EBI-365961,EBI-536755
RABGGTBP536113EBI-365961,EBI-536715
RRAS2P620703EBI-365961,EBI-491037
SFNP319472EBI-365961,EBI-476295
TIMM44O436153EBI-365961,EBI-861737
TIMM50Q3ZCQ84EBI-365961,EBI-355175
TIRAPP587532EBI-365961,EBI-528644
YWHAEP622583EBI-365961,EBI-356498
YWHAZP631045EBI-365961,EBI-347088

Protein-protein interaction databases

BioGridi106864. 91 interactions.
DIPiDIP-31374N.
IntActiP10398. 80 interactions.
MINTiMINT-88835.
STRINGi9606.ENSP00000366244.

Chemistry

BindingDBiP10398.

Structurei

Secondary structure

1
606
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi19 – 246Combined sources
Beta strandi26 – 283Combined sources
Beta strandi30 – 345Combined sources
Helixi42 – 509Combined sources
Turni51 – 533Combined sources
Beta strandi56 – 6712Combined sources
Beta strandi69 – 724Combined sources
Beta strandi74 – 785Combined sources
Helixi79 – 813Combined sources
Beta strandi82 – 843Combined sources
Beta strandi85 – 906Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1WXMNMR-A19-91[»]
2MSENMR-D19-91[»]
ProteinModelPortaliP10398.
SMRiP10398. Positions 19-91, 96-146, 273-576.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10398.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini19 – 9173RBDPROSITE-ProRule annotationAdd
BLAST
Domaini310 – 570261Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 phorbol-ester/DAG-type zinc finger.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 RBD (Ras-binding) domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri98 – 14447Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd
BLAST

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG0193. Eukaryota.
ENOG410Y4UP. LUCA.
GeneTreeiENSGT00760000118807.
HOGENOMiHOG000252972.
HOVERGENiHBG001886.
InParanoidiP10398.
KOiK08845.
PhylomeDBiP10398.
TreeFamiTF317006.

Family and domain databases

InterProiIPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR002219. PE/DAG-bd.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR003116. RBD_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PfamiPF00130. C1_1. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF02196. RBD. 1 hit.
[Graphical view]
PRINTSiPR00008. DAGPEDOMAIN.
SMARTiSM00109. C1. 1 hit.
SM00455. RBD. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. 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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P10398-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEPPRGPPAN GAEPSRAVGT VKVYLPNKQR TVVTVRDGMS VYDSLDKALK
60 70 80 90 100
VRGLNQDCCV VYRLIKGRKT VTAWDTAIAP LDGEELIVEV LEDVPLTMHN
110 120 130 140 150
FVRKTFFSLA FCDFCLKFLF HGFRCQTCGY KFHQHCSSKV PTVCVDMSTN
160 170 180 190 200
RQQFYHSVQD LSGGSRQHEA PSNRPLNELL TPQGPSPRTQ HCDPEHFPFP
210 220 230 240 250
APANAPLQRI RSTSTPNVHM VSTTAPMDSN LIQLTGQSFS TDAAGSRGGS
260 270 280 290 300
DGTPRGSPSP ASVSSGRKSP HSKSPAEQRE RKSLADDKKK VKNLGYRDSG
310 320 330 340 350
YYWEVPPSEV QLLKRIGTGS FGTVFRGRWH GDVAVKVLKV SQPTAEQAQA
360 370 380 390 400
FKNEMQVLRK TRHVNILLFM GFMTRPGFAI ITQWCEGSSL YHHLHVADTR
410 420 430 440 450
FDMVQLIDVA RQTAQGMDYL HAKNIIHRDL KSNNIFLHEG LTVKIGDFGL
460 470 480 490 500
ATVKTRWSGA QPLEQPSGSV LWMAAEVIRM QDPNPYSFQS DVYAYGVVLY
510 520 530 540 550
ELMTGSLPYS HIGCRDQIIF MVGRGYLSPD LSKISSNCPK AMRRLLSDCL
560 570 580 590 600
KFQREERPLF PQILATIELL QRSLPKIERS ASEPSLHRTQ ADELPACLLS

AARLVP
Length:606
Mass (Da):67,585
Last modified:October 1, 1996 - v2
Checksum:iD23E5711304AA468
GO
Isoform 2 (identifier: P10398-2) [UniParc]FASTAAdd to basket
Also known as: DA-Raf1

The sequence of this isoform differs from the canonical sequence as follows:
     186-186: S → R
     187-606: Missing.

Note: Has a wider tissue distribution than isoform 1, and acts as dominant-negative antagonist.
Show »
Length:186
Mass (Da):20,904
Checksum:i22710574E5D8A1B3
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti368 – 3681L → P in AAB08754 (PubMed:3529082).Curated
Sequence conflicti378 – 3781F → V in AAB08754 (PubMed:3529082).Curated
Sequence conflicti469 – 4691S → P in AAB08754 (PubMed:3529082).Curated
Sequence conflicti478 – 4781I → T in AAB08754 (PubMed:3529082).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti98 – 981M → T.1 Publication
Corresponds to variant rs56197559 [ dbSNP | Ensembl ].
VAR_040375
Natural varianti331 – 3311G → C in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication
VAR_040376
Natural varianti578 – 5781E → D.1 Publication
Corresponds to variant rs55852926 [ dbSNP | Ensembl ].
VAR_040377

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei186 – 1861S → R in isoform 2. 2 PublicationsVSP_045609
Alternative sequencei187 – 606420Missing in isoform 2. 2 PublicationsVSP_045610Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X04790 mRNA. Translation: CAA28476.1.
L24038 Genomic DNA. Translation: AAA65219.1.
U01337 Genomic DNA. Translation: AAB03517.1.
AB158254 mRNA. Translation: BAE66645.1.
BT019864 mRNA. Translation: AAV38667.1.
AL542736 mRNA. No translation available.
Z84466 Genomic DNA. Translation: CAI42468.1.
Z84466 Genomic DNA. Translation: CAI42469.1.
BC002466 mRNA. Translation: AAH02466.1.
M13829 mRNA. Translation: AAB08754.1.
CCDSiCCDS35232.1. [P10398-1]
CCDS59164.1. [P10398-2]
PIRiA53026. TVHUAF.
RefSeqiNP_001243125.1. NM_001256196.1.
NP_001243126.1. NM_001256197.1. [P10398-2]
NP_001645.1. NM_001654.4. [P10398-1]
XP_011542210.1. XM_011543908.2. [P10398-1]
UniGeneiHs.446641.

Genome annotation databases

EnsembliENST00000377039; ENSP00000366238; ENSG00000078061. [P10398-2]
ENST00000377045; ENSP00000366244; ENSG00000078061. [P10398-1]
GeneIDi369.
KEGGihsa:369.
UCSCiuc031tjj.2. human. [P10398-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X04790 mRNA. Translation: CAA28476.1.
L24038 Genomic DNA. Translation: AAA65219.1.
U01337 Genomic DNA. Translation: AAB03517.1.
AB158254 mRNA. Translation: BAE66645.1.
BT019864 mRNA. Translation: AAV38667.1.
AL542736 mRNA. No translation available.
Z84466 Genomic DNA. Translation: CAI42468.1.
Z84466 Genomic DNA. Translation: CAI42469.1.
BC002466 mRNA. Translation: AAH02466.1.
M13829 mRNA. Translation: AAB08754.1.
CCDSiCCDS35232.1. [P10398-1]
CCDS59164.1. [P10398-2]
PIRiA53026. TVHUAF.
RefSeqiNP_001243125.1. NM_001256196.1.
NP_001243126.1. NM_001256197.1. [P10398-2]
NP_001645.1. NM_001654.4. [P10398-1]
XP_011542210.1. XM_011543908.2. [P10398-1]
UniGeneiHs.446641.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1WXMNMR-A19-91[»]
2MSENMR-D19-91[»]
ProteinModelPortaliP10398.
SMRiP10398. Positions 19-91, 96-146, 273-576.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106864. 91 interactions.
DIPiDIP-31374N.
IntActiP10398. 80 interactions.
MINTiMINT-88835.
STRINGi9606.ENSP00000366244.

Chemistry

BindingDBiP10398.
ChEMBLiCHEMBL3559685.
DrugBankiDB00171. Adenosine triphosphate.
GuidetoPHARMACOLOGYi1933.

PTM databases

iPTMnetiP10398.
PhosphoSiteiP10398.

Polymorphism and mutation databases

BioMutaiARAF.
DMDMi1730068.

Proteomic databases

EPDiP10398.
MaxQBiP10398.
PaxDbiP10398.
PeptideAtlasiP10398.
PRIDEiP10398.
TopDownProteomicsiP10398-1. [P10398-1]

Protocols and materials databases

DNASUi369.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000377039; ENSP00000366238; ENSG00000078061. [P10398-2]
ENST00000377045; ENSP00000366244; ENSG00000078061. [P10398-1]
GeneIDi369.
KEGGihsa:369.
UCSCiuc031tjj.2. human. [P10398-1]

Organism-specific databases

CTDi369.
GeneCardsiARAF.
HGNCiHGNC:646. ARAF.
HPAiHPA046188.
HPA066326.
MIMi311010. gene.
neXtProtiNX_P10398.
PharmGKBiPA24928.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0193. Eukaryota.
ENOG410Y4UP. LUCA.
GeneTreeiENSGT00760000118807.
HOGENOMiHOG000252972.
HOVERGENiHBG001886.
InParanoidiP10398.
KOiK08845.
PhylomeDBiP10398.
TreeFamiTF317006.

Enzyme and pathway databases

BRENDAi2.7.10.2. 2681.
ReactomeiR-HSA-5673000. RAF activation.
R-HSA-5674135. MAP2K and MAPK activation.
R-HSA-5675221. Negative regulation of MAPK pathway.
SignaLinkiP10398.
SIGNORiP10398.

Miscellaneous databases

ChiTaRSiARAF. human.
EvolutionaryTraceiP10398.
GeneWikiiARAF.
GenomeRNAii369.
PROiP10398.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000078061.
CleanExiHS_ARAF.
ExpressionAtlasiP10398. baseline and differential.
GenevisibleiP10398. HS.

Family and domain databases

InterProiIPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR002219. PE/DAG-bd.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR003116. RBD_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PfamiPF00130. C1_1. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF02196. RBD. 1 hit.
[Graphical view]
PRINTSiPR00008. DAGPEDOMAIN.
SMARTiSM00109. C1. 1 hit.
SM00455. RBD. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00107. 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]
ProtoNetiSearch...

Entry informationi

Entry nameiARAF_HUMAN
AccessioniPrimary (citable) accession number: P10398
Secondary accession number(s): P07557, Q5H9B2, Q5H9B3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: October 1, 1996
Last modified: September 7, 2016
This is version 196 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.