Protein detail

ARAF

Serine/threonine-protein kinase A-Raf (EC 2.7.11.1) (Proto-oncogene A-Raf) (Proto-oncogene A-Raf-1) (Proto-oncogene Pks)

Entry name ARAF	UniProt ID P10398	EVMP confidence score 0.63
Supporting publications (n) 8	Transmembrane count	Protein classification EnzymesHuman disease related genesPlasma proteinsPredicted intracellular proteins

Basic Information

Protein Names

Serine/threonine-protein kinase A-Raf (EC 2.7.11.1) (Proto-oncogene A-Raf) (Proto-oncogene A-Raf-1) (Proto-oncogene Pks)

Protein Class (4)

EnzymesHuman disease related genesPlasma proteinsPredicted intracellular proteins

Protein Function (5)

Predicted intracellular proteins
ENZYME proteins:Transferases
Enzymes
Human disease related genes:Cancers:Cancers of haematopoietic and lymphoid tissues
Kinases:TKL Ser/Thr protein kinases

Ensembl

ENSG00000078061

Entrez Gene Symbol

ARAF

Gene Synonym

ARAF1

Gene Description

A-Raf proto-oncogene, serine/threonine kinase

Chromosome

Position

47561205-47571908

Supporting publications (n)

EVMP confidence score

0.63

Fluorescence & Localization

Function & Pathway

Protein Function (5)

Predicted intracellular proteins
ENZYME proteins:Transferases
Enzymes
Human disease related genes:Cancers:Cancers of haematopoietic and lymphoid tissues
Kinases:TKL Ser/Thr protein kinases

Cellular Component (3)

Molecular Function (8)

Biological Process (3)

KEGG (36)

Page 1 of 4

Reactome (10)

Mediation Categories (2)

Clinical-translation mediationReceptor-signaling mediation

Relations & Evidence42

Enzyme-Mediated Modification (18)

18 records.

Substrate Gene Symbol	Enzyme Gene Symbol	Enzyme UniProt ID	Residue Type	Residue Offset	Modification	Database
ARAF	JAK2	O60674	Y	302	phosphorylation	Reactome_ProtMapperProtMapper
ARAF	JAK2	O60674	T	455	phosphorylation	Reactome_ProtMapperProtMapper
ARAF	JAK2	O60674	T	452	phosphorylation	Reactome_ProtMapperProtMapper
ARAF	JAK2	O60674	S	299	phosphorylation	Reactome_ProtMapperProtMapper
ARAF	BRAF	P15056	Y	302	phosphorylation	Reactome_ProtMapperProtMapper
ARAF	BRAF	P15056	T	455	phosphorylation	Reactome_ProtMapperProtMapper
ARAF	BRAF	P15056	T	452	phosphorylation	Reactome_ProtMapperProtMapper
ARAF	BRAF	P15056	S	299	phosphorylation	Reactome_ProtMapperProtMapper

Page 2 of 2Previous

Ligand-Receptor Signaling (6)

6 records.

Category	Parent	Database	Receiver
receptor	receptor	OmniPath	Yes
intracellular	intracellular	LOCATE
intracellular	intracellular	ComPPI
intracellular	intracellular	GO_Intercell
intracellular	intracellular	OmniPath
receptor	receptor	scConnect	Yes

Regulatory Interaction Network (10)

10 records.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
ARAF	P10398	MP2K2	P36507	Yes	Yes		WangKEGG-MEDICUSSIGNORHPRDCui2007HINTIntActSPIKE_LCLit-BM-17SPIKE	HINT:35271311 Lit-BM-17:24746704 HINT:24746704 Lit-BM-17:21988832 SIGNOR:21779497 IntAct:11909642 HINT:25852190 IntAct:21988832 SPIKE:18039929 HINT:32707033 HPRD:11909642 SPIKE_LC:11909642 SPIKE_LC:16189514 SPIKE_LC:18039929 HINT:11909642 Lit-BM-17:25852190 Lit-BM-17:11909642
ARAF	P10398	MP2K1	Q02750	Yes	Yes		KEGG-MEDICUSHPRD_MIMPSIGNORProtMapperHINTPhosphoSite_KEAHPRDCui2007CancerCellMapWangPhosphoSite_ProtMapperphosphoELM_MIMPPhosphoSite_MIMPMIMPiPTMnetPhosphoPointKEAHPRD_KEASIGNOR_ProtMapperSPIKE_LCSPIKE	KEA:7873542 HINT:24746704 SPIKE_LC:8621729 HPRD:8621729 SPIKE:18039929 HINT:32707033 SIGNOR:8621729 KEA:15466476 KEA:8039496 SPIKE_LC:18039929 KEA:7936666 HINT:35271311 HINT:8621729 ProtMapper:8394352 KEA:15175348 KEA:8621729 KEA:8131746 KEA:7731720 SPIKE:8621729 HPRD:8394352 HINT:26496610 ProtMapper:8157000 KEA:7624324 KEA:8394352 HINT:24114843 ProtMapper:8621729 KEA:8157000 ProtMapper:7731720 CancerCellMap:8621729 HPRD:8157000 HPRD:7731720 KEA:94178255
SRC	P12931	ARAF	P10398	Yes	Yes		phosphoELM_MIMPPhosphoSite_MIMPMIMPPhosphoSite_norefSIGNORiPTMnetProtMapperReactome_ProtMapperPhosphoSite_KEAKEAphosphoELM_KEAphosphoELMSIGNOR_ProtMapperPhosphoSitePhosphoSite_ProtMapper	KEA:9020159 SIGNOR:9020159 PhosphoSite:9020159 phosphoELM:9020159 ProtMapper:9020159
ARAF	P10398	SMAD2	Q15796	Yes		Yes	SIGNOR	SIGNOR:23591895
RASH	P01112	ARAF	P10398	Yes	Yes		WangKEGG-MEDICUSSIGNORHPRDHINTIntActInnateDBDIPSPIKE_LC	HINT:12620389 HINT:24441586 SPIKE_LC:17145710 DIP:24441586 HINT:34591642 HPRD:12620389 InnateDB:10545207 IntAct:12620389 SIGNOR:21779497 IntAct:24441586 HINT:10545207 HINT:34591612
RASN	P01111	ARAF	P10398	Yes	Yes		KEGG-MEDICUSWangHINTSIGNOR	SIGNOR:21779497 HINT:34591642
KSR2	Q6VAB6	ARAF	P10398	Yes	Yes		SIGNOR	SIGNOR:29433126
KSR1	Q8IVT5	ARAF	P10398	Yes	Yes		SIGNOR	SIGNOR:29433126
PAK1	Q13153	ARAF	P10398	Yes	Yes		KEGG-MEDICUSiPTMnetSIGNORProtMapperSIGNOR_ProtMapper	SIGNOR:15710605 ProtMapper:15710605
ARAF	P10398	NHRF2	Q15599	Yes	Yes		iPTMnetSIGNORProtMapperPhosphoSitePhosphoSite_ProtMapper	PhosphoSite:26251448 SIGNOR:26310448 PhosphoSite:26310448

Protein Complex Composition (7)

7 records.

Component Name	Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs	References
ARAF-PIK3R1 complex	ARAF PIK3R1	P10398 P27986	0:0	CORUM	CORUM:7361	10967104
	CAPN7 CHMP5 PIP4P1 SARAF SPAST VPS4B VPS9D1 VTA1	O75351 Q86T03 Q96BY9 Q9NP79 Q9NZZ3 Q9UBP0 Q9Y2B5 Q9Y6W3	0:0:0:0:0:0:0:0	hu.MAP
	CAPN7 CHMP2B CHMP5 SARAF VPS4B VTA1	O75351 Q96BY9 Q9NP79 Q9NZZ3 Q9UQN3 Q9Y6W3	0:0:0:0:0:0	hu.MAP
	APOA1 ARAF KRAS	P01116 P02647 P10398	1:2:1	PDB	PDB:2mse
	ARAF SFN	P10398 P31947	1:1	PDB	PDB:8vsmPDB:8vslPDB:8vsn
	ARL14EP FAF2 SARAF SETDB1	Q15047 Q8N8R7 Q96BY9 Q96CS3	0:0:0:0	hu.MAP
	SARAF	Q96BY9	2	PDB	PDB:6o2wPDB:6o2vPDB:6o2u

Isolation & Detection Technology (1)

1 record.

EV Isolation Method	Detection Method	Number of References	References
Differential UltracentrifugationUltrafiltration / Tangential Flow FiltrationSize Exclusion Chromatography	Mass spectrometryMass spectrometry [LTQ-FT Ultra]Small R sequencing (Illumi HiSeq 2000 (Solexa)	10	28211531 33169421 31414377 29441425 28914500 25776846 28240915 31718609 32331267 34202855

Sequence, Structure & Domains

Sequences

Length

606

Mass

67,585

Sequence

MEPPRGPPANGAEPSRAVGTVKVYLPNKQRTVVTVRDGMSVYDSLDKALKVRGLNQDCCVVYRLIKGRKTVTAWDTAIAPLDGEELIVEVLEDVPLTMHNFVRKTFFSLAFCDFCLKFLFHGFRCQTCGYKFHQHCSSKVPTVCVDMSTNRQQFYHSVQDLSGGSRQHEAPSNRPLNELLTPQGPSPRTQHCDPEHFPFPAPANAPLQRIRSTSTPNVHMVSTTAPMDSNLIQLTGQSFSTDAAGSRGGSDGTPRGSPSPASVSSGRKSPHSKSPAEQRERKSLADDKKKVKNLGYRDSGYYWEVPPSEVQLLKRIGTGSFGTVFRGRWHGDVAVKVLKVSQPTAEQAQAFKNEMQVLRKTRHVNILLFMGFMTRPGFAIITQWCEGSSLYHHLHVADTRFDMVQLIDVARQTAQGMDYLHAKNIIHRDLKSNNIFLHEGLTVKIGDFGLATVKTRWSGAQPLEQPSGSVLWMAAEVIRMQDPNPYSFQSDVYAYGVVLYELMTGSLPYSHIGCRDQIIFMVGRGYLSPDLSKISSNCPKAMRRLLSDCLKFQREERPLFPQILATIELLQRSLPKIERSASEPSLHRTQADELPACLLSAARLVP

Alternative Products

Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=P10398-1; Sequence=Displayed; Name=2; Synonyms=DA-Raf1; IsoId=P10398-2; Sequence=VSP_045609, VSP_045610

Alternative Sequence

186; S -> R (in isoform 2); 187..606; Missing (in isoform 2)

3D Structural Models

Turn

51..53

Helix

42..50; 79..81

Beta Strand

19..24; 26..28; 30..34; 56..67; 69..72; 74..78; 82..84; 85..90

3D Structure

NMR spectroscopy (2); X-ray crystallography (4)

Domain & Motif Annotations

Compositional Bias

274..289; Basic and acidic residues

Zinc Finger

98..144; Phorbol-ester/DAG-type

Domain (FT)

19..91; RBD; 310..570; Protein kinase

Region

160..207; Disordered; 240..290; Disordered

Protein Families (3)

Protein kinase superfamily
TKL Ser/Thr protein kinase family
RAF subfamily

Sequence Similarities

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily.

Clinical Relevance

Disease Involvement

Proto-oncogene

Drugs (55)

TRAMETINIB DIMETHYL SULFOXIDE L-372662 ARGIPRESSIN D(CH2)5[TYR(ME)2,THR4,TYR-NH29]OVT RO5028442 D(CH2)5[TYR(ME)2,THR4,TYR(3125I)-NH29]OVT REGORAFENIB COBIMETINIB L-366,948 L-369,020 D(CH2)5[TYR(ME)2]AVP SORAFENIB DESMOPRESSIN TOVORAFENIB RETOSIBAN XL281 COMPOUND 37 [PMID: 16250654]SSR126768A ENCORAFENIB [PHE3]OT L-368,930 D(CH2)5[TYR(ME)2,THR4,PHE(3125I,4N3)-NH29]OVT DESGLYNH2-D(CH2)5[TYR(ME)2,THR4,ORN8]OT LIT-001 [3H]AVP (HUMAN, MOUSE, RAT)BELVARAFENIB ARGIPRESTOCIN LS-192629 [MPA1,D-TYR(ET)2,D-TIC7,AIB9]OT NELIVAPTAN L-365,209 L-366,682 [MPA1,D-TYR(ET)2,D-TIC7]OT LY-3009120 CARBETOCIN [THR4,GLY7]OT L023103 [MPA1,D-TYR(ET)2,D-TIC7,D-TIC9]OT [125I]D(CH2)5[TYR(ME)2,THR4,ORN8,TYR-NH29]OVT RELCOVAPTAN ATOSIBAN L-368,228 BALOVAPTAN D[CHA4]AVP L-368,899 D(CH2)5[TYR(ME)2,THR4,PHE(3I,4N3)-NH29]OVT D[LEU4]AVP OPC-21268 L-371,257 [35S]NON-PEPTIDE OT ANTAGONIST L-367,773 [111IN]DOTA-DLVT L-366,875 L-366,509 L-367,938

Antibody (3)

HPA066326 CAB080050 CAB080051

Interaction Protein (19)

ENSG00000096384ENSG00000101158ENSG00000105197ENSG00000105401ENSG00000108953ENSG00000126934ENSG00000128245ENSG00000132155ENSG00000134070ENSG00000134308ENSG00000150455ENSG00000157764ENSG00000164924ENSG00000166913ENSG00000169032ENSG00000170027ENSG00000174775ENSG00000175793ENSG00000185507

Interaction Count

Interaction Dataset (4)

intact_biogridbiogrid_opencell_bioplexintact_biogrid_opencellbiogrid_opencell

Supporting Publications8

PMID	Title	Related sentences
27487081	Comparative Proteomic Analysis of Extracellular Vesicles Isolated by Acoustic Trapping or Differential Centrifugation.	No related sentences available
36064647	Systemic proteomics and miRNA profile analysis of exosomes derived from human pluripotent stem cells.	No related sentences available
36146834	Human Cytomegalovirus Modifies Placental Small Extracellular Vesicle Composition to Enhance Infection of Fetal Neural Cells In Vitro.	No related sentences available
36982312	Saliva and Saliva Extracellular Vesicles for Biomarker Candidate Identification-Assay Development and Pilot Study in Amyotrophic Lateral Sclerosis.	No related sentences available
37322475	Comprehensive profiling of extracellular vesicles in uveitis and scleritis enables biomarker discovery and mechanism exploration.	No related sentences available
38113368	In-Depth Proteome Profiling of Small Extracellular Vesicles Isolated from Cancer Cell Lines and Patient Serum.	No related sentences available
38207106	Proteomic, Metabolomic, and Fatty Acid Profiling of Small Extracellular Vesicles from Glioblastoma Stem-Like Cells and Their Role in Tumor Heterogeneity.	No related sentences available
40189497	Small extracellular vesicle-based one-step high-throughput microfluidic platform for epithelial ovarian cancer diagnosis.	No related sentences available