Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
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)DescriptionActionsGraphical viewLength
Metal bindingi99Zinc 1By similarity1
Metal bindingi112Zinc 2By similarity1
Metal bindingi115Zinc 2By similarity1
Metal bindingi125Zinc 1By similarity1
Metal bindingi128Zinc 1By similarity1
Metal bindingi133Zinc 2By similarity1
Metal bindingi136Zinc 2By similarity1
Metal bindingi144Zinc 1By similarity1
Binding sitei336ATPPROSITE-ProRule annotation1
Active sitei429Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri98 – 144Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST47
Nucleotide bindingi316 – 324ATPPROSITE-ProRule annotation9

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
  • signal transducer activity, downstream of receptor 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

BioCyciZFISH:HS01268-MONOMER.
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.
R-HSA-6802946. Signaling by moderate kinase activity BRAF mutants.
R-HSA-6802948. Signaling by high-kinase activity BRAF mutants.
R-HSA-6802949. Signaling by RAS mutants.
R-HSA-6802952. Signaling by BRAF and RAF fusions.
R-HSA-6802955. Paradoxical activation of RAF signaling by kinase inactive BRAF.
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

DisGeNETi369.
OpenTargetsiENSG00000078061.
PharmGKBiPA24928.

Chemistry databases

ChEMBLiCHEMBL1169596.
DrugBankiDB00171. Adenosine triphosphate.
GuidetoPHARMACOLOGYi1933.

Polymorphism and mutation databases

BioMutaiARAF.
DMDMi1730068.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000856221 – 606Serine/threonine-protein kinase A-RafAdd BLAST606

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei157PhosphoserineCombined sources1
Modified residuei162PhosphoserineCombined sources1
Modified residuei181PhosphothreonineCombined sources1
Modified residuei186PhosphoserineCombined sources1
Modified residuei253PhosphothreonineCombined sources1
Modified residuei257PhosphoserineCombined sources1
Modified residuei269PhosphoserineCombined sources1
Modified residuei318PhosphothreonineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

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

PTM databases

iPTMnetiP10398.
PhosphoSitePlusiP10398.

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 interactors.
DIPiDIP-31374N.
IntActiP10398. 81 interactors.
MINTiMINT-88835.
STRINGi9606.ENSP00000366244.

Chemistry databases

BindingDBiP10398.

Structurei

Secondary structure

1606
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi19 – 24Combined sources6
Beta strandi26 – 28Combined sources3
Beta strandi30 – 34Combined sources5
Helixi42 – 50Combined sources9
Turni51 – 53Combined sources3
Beta strandi56 – 67Combined sources12
Beta strandi69 – 72Combined sources4
Beta strandi74 – 78Combined sources5
Helixi79 – 81Combined sources3
Beta strandi82 – 84Combined sources3
Beta strandi85 – 90Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WXMNMR-A19-91[»]
2MSENMR-D19-91[»]
ProteinModelPortaliP10398.
SMRiP10398.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10398.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini19 – 91RBDPROSITE-ProRule annotationAdd BLAST73
Domaini310 – 570Protein kinasePROSITE-ProRule annotationAdd BLAST261

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)DescriptionActionsGraphical viewLength
Zinc fingeri98 – 144Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST47

Keywords - Domaini

Zinc-finger

Phylogenomic databases

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

Family and domain databases

CDDicd00029. C1. 1 hit.
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)DescriptionActionsGraphical viewLength
Sequence conflicti368L → P in AAB08754 (PubMed:3529082).Curated1
Sequence conflicti378F → V in AAB08754 (PubMed:3529082).Curated1
Sequence conflicti469S → P in AAB08754 (PubMed:3529082).Curated1
Sequence conflicti478I → T in AAB08754 (PubMed:3529082).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04037598M → T.1 PublicationCorresponds to variant rs56197559dbSNPEnsembl.1
Natural variantiVAR_040376331G → C in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_040377578E → D.1 PublicationCorresponds to variant rs55852926dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_045609186S → R in isoform 2. 2 Publications1
Alternative sequenceiVSP_045610187 – 606Missing in isoform 2. 2 PublicationsAdd BLAST420

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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1WXMNMR-A19-91[»]
2MSENMR-D19-91[»]
ProteinModelPortaliP10398.
SMRiP10398.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106864. 91 interactors.
DIPiDIP-31374N.
IntActiP10398. 81 interactors.
MINTiMINT-88835.
STRINGi9606.ENSP00000366244.

Chemistry databases

BindingDBiP10398.
ChEMBLiCHEMBL1169596.
DrugBankiDB00171. Adenosine triphosphate.
GuidetoPHARMACOLOGYi1933.

PTM databases

iPTMnetiP10398.
PhosphoSitePlusiP10398.

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.
DisGeNETi369.
GeneCardsiARAF.
HGNCiHGNC:646. ARAF.
HPAiHPA046188.
HPA066326.
MIMi311010. gene.
neXtProtiNX_P10398.
OpenTargetsiENSG00000078061.
PharmGKBiPA24928.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:HS01268-MONOMER.
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.
R-HSA-6802946. Signaling by moderate kinase activity BRAF mutants.
R-HSA-6802948. Signaling by high-kinase activity BRAF mutants.
R-HSA-6802949. Signaling by RAS mutants.
R-HSA-6802952. Signaling by BRAF and RAF fusions.
R-HSA-6802955. Paradoxical activation of RAF signaling by kinase inactive BRAF.
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

CDDicd00029. C1. 1 hit.
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: November 30, 2016
This is version 199 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.