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

    Gene ID: 369, updated on 3-Nov-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 protein metabolic process. Predicted to be active in cytosol and mitochondrion. Biomarker of high grade glioma. [provided by Alliance of Genome Resources, Nov 2024]
    Expression
    Ubiquitous expression in bone marrow (RPKM 16.5), spleen (RPKM 14.0) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ARAF in Genome Data Viewer
    Location:
    Xp11.3
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (47561205..47571908)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (46971095..46981798)
    RS_2024_09 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 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. Identification of key residues in the A-Raf kinase important for phosphoinositide lipid binding specificity. Johnson LM, et al. Biochemistry, 2005 Mar 8. PMID 15736953
    2. ARAF mutations confer resistance to the RAF inhibitor belvarafenib in melanoma. Yen I, et al. Nature, 2021 Jun. PMID 33953400
    3. 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
    4. A-Raf: A new star of the family of raf kinases. An S, et al. Crit Rev Biochem Mol Biol, 2015. PMID 26508523
    5. Dimerization of the kinase ARAF promotes MAPK pathway activation and cell migration. Mooz J, et al. Sci Signal, 2014 Aug 5. PMID 25097033

    See all (143) 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 histone H2AS1 kinase activity IEA
    Inferred from Electronic Annotation
    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 chromatin remodeling IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of peptidyl-serine phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein modification process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in protein phosphorylation 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_2024_08

    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

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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