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Protein

Serine/threonine-protein kinase A-Raf

Gene

ARAF

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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
  • MAP kinase kinase kinase activity Source: GO_Central
  • metal ion binding Source: UniProtKB-KW
  • mitogen-activated protein kinase kinase binding Source: GO_Central
  • protein kinase activity Source: ProtInc
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
LigandATP-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
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

EuPathDBiHostDB:ENSG00000078061.12
HGNCiHGNC:646 ARAF
MIMi311010 gene
neXtProtiNX_P10398

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

DisGeNETi369
MalaCardsiARAF
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
ProteomicsDBi52601
TopDownProteomicsiP10398-1 [P10398-1]

PTM databases

iPTMnetiP10398
PhosphoSitePlusiP10398

Expressioni

Tissue specificityi

Predominantly in urogenital tissues.

Gene expression databases

BgeeiENSG00000078061 Expressed in 214 organ(s), highest expression level in muscle of leg
CleanExiHS_ARAF
ExpressionAtlasiP10398 baseline and differential
GenevisibleiP10398 HS

Organism-specific databases

HPAiHPA046188
HPA066326

Interactioni

Subunit structurei

Interacts with TH1L/NELFD.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi106864, 93 interactors
DIPiDIP-31374N
IntActiP10398, 87 interactors
MINTiP10398
STRINGi9606.ENSP00000366244

Chemistry databases

BindingDBiP10398

Structurei

Secondary structure

1606
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

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
GeneTreeiENSGT00900000140880
HOGENOMiHOG000252972
HOVERGENiHBG055881
InParanoidiP10398
KOiK08845
PhylomeDBiP10398
TreeFamiTF317006

Family and domain databases

CDDicd00029 C1, 1 hit
InterProiView protein in InterPro
IPR020454 DAG/PE-bd
IPR011009 Kinase-like_dom_sf
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-like_domsf
PfamiView protein in Pfam
PF00130 C1_1, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PF02196 RBD, 1 hit
PRINTSiPR00008 DAGPEDOMAIN
SMARTiView protein in SMART
SM00109 C1, 1 hit
SM00455 RBD, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF54236 SSF54236, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in 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

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q96II5Q96II5_HUMAN
ARAF protein
ARAF
609Annotation score:

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 → T1 PublicationCorresponds to variant dbSNP:rs56197559Ensembl.1
Natural variantiVAR_040376331G → C in a colorectal adenocarcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_040377578E → D1 PublicationCorresponds to variant dbSNP:rs55852926Ensembl.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 No translation available.
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

Similar proteinsi

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 No translation available.
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, 93 interactors
DIPiDIP-31374N
IntActiP10398, 87 interactors
MINTiP10398
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
ProteomicsDBi52601
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
EuPathDBiHostDB:ENSG00000078061.12
GeneCardsiARAF
HGNCiHGNC:646 ARAF
HPAiHPA046188
HPA066326
MalaCardsiARAF
MIMi311010 gene
neXtProtiNX_P10398
OpenTargetsiENSG00000078061
PharmGKBiPA24928
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0193 Eukaryota
ENOG410Y4UP LUCA
GeneTreeiENSGT00900000140880
HOGENOMiHOG000252972
HOVERGENiHBG055881
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
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
PROiPR:P10398
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000078061 Expressed in 214 organ(s), highest expression level in muscle of leg
CleanExiHS_ARAF
ExpressionAtlasiP10398 baseline and differential
GenevisibleiP10398 HS

Family and domain databases

CDDicd00029 C1, 1 hit
InterProiView protein in InterPro
IPR020454 DAG/PE-bd
IPR011009 Kinase-like_dom_sf
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-like_domsf
PfamiView protein in Pfam
PF00130 C1_1, 1 hit
PF07714 Pkinase_Tyr, 1 hit
PF02196 RBD, 1 hit
PRINTSiPR00008 DAGPEDOMAIN
SMARTiView protein in SMART
SM00109 C1, 1 hit
SM00455 RBD, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF54236 SSF54236, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in 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
ProtoNetiSearch...

Entry informationi

Entry nameiARAF_HUMAN
AccessioniPrimary (citable) accession number: P10398
Secondary accession number(s): P07557, Q5H9B2, Q5H9B3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: October 1, 1996
Last modified: October 10, 2018
This is version 210 of the entry and version 2 of the sequence. See 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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  6. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  7. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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