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ARAF A-Raf proto-oncogene, serine/threonine kinase [ Homo sapiens (human) ]

Gene ID: 369, updated on 7-Apr-2024

Summary

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Official Symbol
ARAFprovided by HGNC
Official Full Name
A-Raf proto-oncogene, serine/threonine kinaseprovided by HGNC
Primary source
HGNC:HGNC:646
See related
Ensembl:ENSG00000078061 MIM:311010; AllianceGenome:HGNC:646
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
PKS2; A-RAF; ARAF1; RAFA1
Summary
Enables protein serine/threonine kinase activity. Involved in negative regulation of apoptotic process; regulation of TOR signaling; and regulation of cellular protein metabolic process. Predicted to be active in cytosol and mitochondrion. Biomarker of high grade glioma. [provided by Alliance of Genome Resources, Apr 2022]
Expression
Ubiquitous expression in bone marrow (RPKM 16.5), spleen (RPKM 14.0) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
Xp11.3
Exon count:
16
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (47561205..47571908)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (46971095..46981798)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (47420604..47431307)

Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene zinc finger protein 41 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29593 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20804 Neighboring gene long intergenic non-protein coding RNA 1560 Neighboring gene uncharacterized LOC124905183 Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:47372169-47372670 Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:47372671-47373170 Neighboring gene MPRA-validated peak7378 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20805 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20806 Neighboring gene NUS1 pseudogene 1 Neighboring gene Sharpr-MPRA regulatory region 9461 Neighboring gene uncharacterized LOC124905184 Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:47415445-47415946 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20807 Neighboring gene Sharpr-MPRA regulatory region 4668 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:47434199-47434706 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:47434707-47435213 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:47435306-47435806 Neighboring gene Sharpr-MPRA regulatory region 5152 Neighboring gene CRISPRi-FlowFISH-validated HDAC6 regulatory element 2 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20808 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 20809 Neighboring gene Sharpr-MPRA regulatory region 5754 Neighboring gene synapsin I Neighboring gene TIMP metallopeptidase inhibitor 1 Neighboring gene microRNA 4769

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. ARAF mutations confer resistance to the RAF inhibitor belvarafenib in melanoma. Yen I, et al. Nature, 2021 Jun. PMID 33953400
  2. Differential localization of A-Raf regulates MST2-mediated apoptosis during epithelial differentiation. Rauch J, et al. Cell Death Differ, 2016 Aug. PMID 26891695, Free PMC Article
  3. A-Raf: A new star of the family of raf kinases. An S, et al. Crit Rev Biochem Mol Biol, 2015. PMID 26508523
  4. Dimerization of the kinase ARAF promotes MAPK pathway activation and cell migration. Mooz J, et al. Sci Signal, 2014 Aug 5. PMID 25097033
  5. Somatic activating ARAF mutations in Langerhans cell histiocytosis. Nelson DS, et al. Blood, 2014 May 15. PMID 24652991

See all (132) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Somatic ARAF mutations in pediatric Langerhans cell histiocytosis: clinicopathologic, genetic and functional profiling.
    Title: Somatic ARAF mutations in pediatric Langerhans cell histiocytosis: clinicopathologic, genetic and functional profiling.
  2. ARAF protein kinase activates RAS by antagonizing its binding to RASGAP NF1.
    Title: ARAF protein kinase activates RAS by antagonizing its binding to RASGAP NF1.
  3. ARAF suppresses ERBB3 expression and metastasis in a subset of lung cancers.
    Title: ARAF suppresses ERBB3 expression and metastasis in a subset of lung cancers.
  4. ARAF mutations confer resistance to the RAF inhibitor belvarafenib in melanoma.
    Title: ARAF mutations confer resistance to the RAF inhibitor belvarafenib in melanoma.
  5. Linc01232 promotes the metastasis of pancreatic cancer by suppressing the ubiquitin-mediated degradation of HNRNPA2B1 and activating the A-Raf-induced MAPK/ERK signaling pathway.
    Title: Linc01232 promotes the metastasis of pancreatic cancer by suppressing the ubiquitin-mediated degradation of HNRNPA2B1 and activating the A-Raf-induced MAPK/ERK signaling pathway.
  6. The constitutive or induced re-localization of A-Raf to the plasma membrane compromises its ability to efficiently sequester and inactivate MST2, thus rendering cells susceptible to apoptosis
    Title: Differential localization of A-Raf regulates MST2-mediated apoptosis during epithelial differentiation.
  7. This review discusses the regulation of A-Raf protein expression, and the roles of A-Raf in apoptosis and cancer, with a special focus on its role in resistance to Raf inhibitors. [review]
    Title: A-Raf: A new star of the family of raf kinases.
  8. analysis of FGFR2-PPHLN1 fusion and ARAF mutations in intrahepatic cholangiocarcinoma
    Title: Massive parallel sequencing uncovers actionable FGFR2-PPHLN1 fusion and ARAF mutations in intrahepatic cholangiocarcinoma.
  9. Aberrant expression of A-, B-, and C-RAF, and COT is frequent in PTC; increased expression of COT is correlated with recurrence of PTC.
    Title: Aberrant expression of COT is related to recurrence of papillary thyroid cancer.
  10. Dimerization of the kinase ARAF promotes MAPK pathway activation and cell migration.
    Title: Dimerization of the kinase ARAF promotes MAPK pathway activation and cell migration.
Submit: New GeneRIF Correction See all GeneRIFs (23)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Pr55(Gag) gag The amplified luminescent proximity homogeneous assay (AlphaScreen) identifies the interaction of HIV-1 Gag with ARAF PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables MAP kinase kinase kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein kinase activity TAS
Traceable Author Statement
more info
 PubMed 
enables protein serine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein serine/threonine kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in MAPK cascade IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in negative regulation of apoptotic process IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in phosphorylation IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of peptidyl-serine phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein modification process IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of TOR signaling IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of proteasomal ubiquitin-dependent protein catabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
is_active_in cellular_component ND
No biological Data available
more info
  
is_active_in cytosol IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
serine/threonine-protein kinase A-Raf
Names
A-Raf proto-oncogene serine/threonine-protein kinase
Oncogene ARAF1
Ras-binding protein DA-Raf
proto-oncogene A-Raf-1
proto-oncogene Pks
v-raf murine sarcoma 3611 viral oncogene homolog 1
v-raf murine sarcoma 3611 viral oncogene-like protein
NP_001243125.1
NP_001243126.1
NP_001645.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_016339.2 RefSeqGene

    Range
    5089..15792
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001256196.2 → NP_001243125.1  serine/threonine-protein kinase A-Raf isoform 2

    See identical proteins and their annotated locations for NP_001243125.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) has an alternate splice site in the coding region, which does not affect the reading frame, compared to variant 1. The resulting isoform (2) is 3 aa longer than isoform 1.
    Source sequence(s)
    BC002466, BC007514, DC362427
    UniProtKB/TrEMBL
    A0A0S2Z3F2, A6NIT1, Q96II5
    Conserved Domains (3) summary
    cd01816
    Location:20 → 91
    Raf_RBD; Ubiquitin domain of Raf serine/threonine kinases
    cd14150
    Location:312 → 576
    STKc_A-Raf; Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase
    pfam00130
    Location:99 → 146
    C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)

  2. NM_001256197.2 → NP_001243126.1  serine/threonine-protein kinase A-Raf isoform 3

    See identical proteins and their annotated locations for NP_001243126.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks several exons and its transcription extends past a splice site that is used in variant 1, resulting in an immediate translation termination and a novel 3' UTR compared to variant 1. The resulting isoform (3) has a shorter C-terminus, compared to isoform 1.
    Source sequence(s)
    AB158254, CA424869, DC362427
    Consensus CDS
    CCDS59164.1
    UniProtKB/TrEMBL
    Q59HC8
    Related
    ENSP00000366238.1, ENST00000377039.2
    Conserved Domains (2) summary
    cd01816
    Location:20 → 91
    Raf_RBD; Ubiquitin domain of Raf serine/threonine kinases
    pfam00130
    Location:99 → 146
    C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)

  3. NM_001654.5 → NP_001645.1  serine/threonine-protein kinase A-Raf isoform 1

    See identical proteins and their annotated locations for NP_001645.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the predominant isoform (1).
    Source sequence(s)
    BC002466, DC362427
    Consensus CDS
    CCDS35232.1
    UniProtKB/Swiss-Prot
    P07557, P10398, Q5H9B2, Q5H9B3
    UniProtKB/TrEMBL
    A0A024R178, A0A0S2Z3F2
    Related
    ENSP00000366244.4, ENST00000377045.9
    Conserved Domains (3) summary
    cd14150
    Location:309 → 573
    STKc_A-Raf; Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase
    cd17133
    Location:19 → 91
    RBD_ARAF; Ras-binding domain (RBD) found in serine/threonine-protein kinase ARAF
    pfam00130
    Location:99 → 144
    C1_1; Phorbol esters/diacylglycerol binding domain (C1 domain)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000023.11 Reference GRCh38.p14 Primary Assembly

    Range
    47561205..47571908
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060947.1 Alternate T2T-CHM13v2.0

    Range
    46971095..46981798
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P10398.2 GenPept UniProtKB/Swiss-Prot:P10398

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