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    HCK HCK proto-oncogene, Src family tyrosine kinase [ Homo sapiens (human) ]

    Gene ID: 3055, updated on 15-Apr-2019

    Summary

    Official Symbol
    HCKprovided by HGNC
    Official Full Name
    HCK proto-oncogene, Src family tyrosine kinaseprovided by HGNC
    Primary source
    HGNC:HGNC:4840
    See related
    Ensembl:ENSG00000101336 MIM:142370
    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
    JTK9; p59Hck; p61Hck
    Summary
    The protein encoded by this gene is a member of the Src family of tyrosine kinases. This protein is primarily hemopoietic, particularly in cells of the myeloid and B-lymphoid lineages. It may help couple the Fc receptor to the activation of the respiratory burst. In addition, it may play a role in neutrophil migration and in the degranulation of neutrophils. Multiple isoforms with different subcellular distributions are produced due to both alternative splicing and the use of alternative translation initiation codons, including a non-AUG (CUG) codon. [provided by RefSeq, Feb 2010]
    Expression
    Broad expression in appendix (RPKM 55.1), spleen (RPKM 40.9) and 14 other tissues See more
    Orthologs

    Genomic context

    See HCK in Genome Data Viewer
    Location:
    20q11.21
    Exon count:
    15
    Annotation release Status Assembly Chr Location
    109 current GRCh38.p12 (GCF_000001405.38) 20 NC_000020.11 (32052188..32101856)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (30639991..30689659)

    Chromosome 20 - NC_000020.11Genomic Context describing neighboring genes Neighboring gene CCM2 like scaffold protein Neighboring gene RNA, 5S ribosomal pseudogene 482 Neighboring gene transmembrane 9 superfamily member 4 Neighboring gene uncharacterized LOC107985403 Neighboring gene ribosomal L24 domain containing 1 pseudogene 6

    Genomic regions, transcripts, and products

    Expression

    • 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

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Phenotypes

    NHGRI GWAS Catalog

    Description
    Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
    NHGRI GWA Catalog

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120 downregulates the expression of HCK proto-oncogene, Src family tyrosine kinase (HCK) in human B cells PubMed
    Nef nef HIV-1 Nef binds HCK without affecting SH2-tail interaction and impacts local dynamics near the HCK active site; these changes are reversed in the presence of a selective inhibitor of the Nef-HCK complex PubMed
    nef HIV-1 Nef activates HCK via HCK SH3 domain displacement NOT via dephosphorylation or release from the SH2 domain PubMed
    nef The PXXP motif (65-82) and C-terminal proline residues 147 and 150 of HIV-1 Nef interacts with the SH3 domain of Hck; the single amino acid residue 96 in the Hck SH3 domain determines its high affinity in binding to Nef PubMed
    nef HIV-1-mediated effects on podosomes and migration involve Nef-HCK interaction, and HCK-mediated phosphorylation of WASP at podosomes PubMed
    nef The HIV-1 Nef EEEE(65) targeting motif enables the Nef PXXP(75) motif to bind and activate a trans-Golgi network-localized tyrosine kinase Hck PubMed
    nef Mutations P72G, V74I, P75G, and R77K in the PXXPXR motif of HIV-1 Nef abolish the binding between Nef and Hck PubMed
    nef Small molecule compounds, which inhibit the SH3 domain of HIV-1 Nef binding to Hck, significantly reduce Nef-mediated viral infectivity enhancement PubMed
    nef Mutation of the PXXP motif in HIV-1 Nef abolishes the interaction of Nef with Hck in transgenic mice, resulting in the delayed development of an AIDS-like disease in the mice PubMed
    nef SH3-dependent activation of Hck by HIV-1 Nef binding or by SH2-kinase linker mutation does not modulate tail tyrosine phosphorylation in vivo PubMed
    nef The Interaction of HIV-1 Nef with the SH3 domain of Hck regulates the effects of Nef on Hck tyrosine kinase activation PubMed
    nef Structure analyses reveal that an RT loop region (residues 90-108) in the Hck SH3 domain binds to the PXXP motif (residues 69-78) of HIV-1 Nef; proline residues substituted by alanine in the PXXP motif abolish its binding to Hck PubMed
    nef HIV-1 Nef induces accumulation of Hck at the recycling endosomes and the trans-Golgi network by blocking the anterograde transport of Hck to the plasma membrane PubMed
    nef HIV-1 Nef associates with Hck in HIV-1 virions derived from 293T cells and primary monocyte-derived macrophages PubMed
    nef Molecular modeling has identified three residues in the core region of Nef from HIV-1 SF2 (Ala83, His116, and Tyr120) that are required for Hck recruitment and activation PubMed
    nef HIV-1 Nef activates endogenous Hck in the granulocyte-macrophage colony-stimulating factor-dependent human myeloid cell line, TF-1, resulting in TF-1 cytokine-independence and Stat 3 activation PubMed
    nef The Nef-HCK complex involves the Nef PXXPXR motif intercalating with the HCK SH3 surface residues Tyr-90, Tyr-92, Trp-118, Pro-133, and Tyr-136 PubMed
    nef HCK SH2 kinase linker residues Pro250 and Pro253 make stable hydrophobic contacts with SH3 domain residues Tyr90, Trp118, and Tyr136 to stabilize the HIV-1 Nef dimer interface PubMed
    nef The binding of HIV-1 Nef to the SH3 domain of Hck is required for Nef/activated PAK2 complex formation. A new locus GFP/F (G67, F68, P69 and F90) of Nef is involved in the Nef/activated PAK2 complex formation PubMed
    nef Diaminoquinoxaline benzenesulfonamide (DQBS) treatment reduces the amount of both HCK and the p85 regulatory subunit of PI3K associated with HIV-1 Nef and completely blocks Nef-dependent activation of ZAP-70 PubMed
    nef The Nef/hnRNPK/PKC-delta/Hck protein complex activates Pak2 activity but inhibits Pak1 activity, which induces paxillin phosphorylation on Ser272/274 and regulates paxillin/TACE association and secretion PubMed
    nef The Nef/hnRNPK/PKC-delta/Hck protein complex increases paxillin phosphorylation at position Y118 and activates and secrets TACE through Erk1/2 activation PubMed
    nef The first 18 amino acids (SH4 domain) of Hck, including the myristoylation site (G2), are required for the HIV-1 Nef-induced accumulation of Hck at the recycling endosomes and the trans-Golgi network PubMed
    nef The HIV-1 Nef highly conserved valine-glycine-phenylalanine amino acid triplet (VGF) motif is required for the physical interaction of the adjacent proline-rich motif with Hck PubMed
    nef In promonocytic cells, Nef/Hck complex recruits the ZAP-70 homolog Syk to downregulate MHC-I PubMed
    nef Nef/Hck complex recruits and phosphorylates the tyrosine kinase ZAP-70, which binds class I PI3K to trigger MHC-I downregulation in primary CD4+ T cells PubMed
    nef PACS-1S278A mutant blocks the association of Nef with Hck on the cell membrane, while wild-type PACS-1 has no effect PubMed
    nef HIV-1 Nef binds Hck and induces skewed Golgi-localization of Hck, which leads to Fms maturation arrest PubMed
    nef HIV-1 Nef-induced activation of p61Hck is required for the formation of multinucleated giant cells (MGCs), which is dependent on lysosomal proteins including vacuolar adenosine triphosphatase and proteases participated in Nef-induced MGCs PubMed
    nef The primary M-group HIV-1 Nef proteins (from A, B, C, F, G, H, J, and K subtypes) strongly activate HCK in cells PubMed
    nef HIV-1 Nef causes the FMS N-glycosylation defect and induces relocalization of the GM130 by activating the p56Hck/MEK/ERK/GRASP65 phosphorylation cascade in the Golgi PubMed
    nef The interaction of SIV Nef with human Hck is not mediated via conserved proline-rich motifs, which are known to mediate HIV-1 Nef binding to the Hck SH3 domain; instead, SIV Nef binds the Hck SH2 domain PubMed
    nef Hck binds to HIV-1 subtype B and E Nef proteins with equal affinity, but has weaker binding to HIV-2 subtype A Nef and no binding to HIV-2 subtype B Nef PubMed
    nef Peptides derived from the Hck SH3 domain with high affinity binding to HIV-1 Nef inhibit SH3-dependent Nef functions, such as association with PAK2 and induction of NFAT PubMed
    nef A dominant-negative mutant protein derived from Hck, (composed of the N-terminal region, SH2, and SH3 domains) interacts with HIV-1 Nef and inhibits Nef-induced downregulation of MHC class I PubMed
    nef HIV-1 Nef increases the amount of intracellular stored Ca2+ in myelomonocytic cells through binding to Hck PubMed
    nef HIV-1 Nef-induced aberrant molecular formation between Hck and M-CSF receptor inhibits M-CSF bioactivities in monocytes/macrophages PubMed
    nef In Rat-2 fibroblasts co-expressing Hck and a Nef fusion protein with the hormone-binding domain of estrogen receptor (Nef-ER), 4-hydroxytamoxifen treatment induces Nef-ER oligomerization, leading to Hck kinase activation and cellular transformation PubMed
    nef HIV-1 Nef alleles (HIV-1 SF2, LAI and Consensus) bind and activate Hck, while HIV-1 ELI Nef fails to bind to the Hck SH3 domain in vitro and does not cooperate with Hck in fibroblast transformation PubMed
    nef Induction of AP-1 by HIV-1 Nef is a specific feature of human and murine macrophage cell lines that requires signal transduction events involving Hck and MAPK PubMed
    Vif vif The interaction of Hck with HIV-1 Vif affects Vif oligomerization in living cells PubMed
    vif Vif binds specifically to the Src homology 3 domain of Hck, represses the kinase activity of Hck, and suppresses negative effects of Hck on HIV-1 replication PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from BioSystems

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    non-membrane spanning protein tyrosine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    phosphotyrosine residue binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein tyrosine kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    signaling receptor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    Process Evidence Code Pubs
    Fc-gamma receptor signaling pathway involved in phagocytosis TAS
    Traceable Author Statement
    more info
     
    cell adhesion TAS
    Traceable Author Statement
    more info
    PubMed 
    cell differentiation IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    cytokine-mediated signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    inflammatory response IEA
    Inferred from Electronic Annotation
    more info
     
    innate immune response-activating signal transduction TAS
    Traceable Author Statement
    more info
    PubMed 
    integrin-mediated signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    interferon-gamma-mediated signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    leukocyte degranulation TAS
    Traceable Author Statement
    more info
    PubMed 
    leukocyte migration involved in immune response TAS
    Traceable Author Statement
    more info
    PubMed 
    lipopolysaccharide-mediated signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    mesoderm development TAS
    Traceable Author Statement
    more info
    PubMed 
    negative regulation of apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    peptidyl-tyrosine autophosphorylation IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    peptidyl-tyrosine phosphorylation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of actin cytoskeleton reorganization IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of actin cytoskeleton reorganization IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of actin filament polymerization TAS
    Traceable Author Statement
    more info
    PubMed 
    positive regulation of cell proliferation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    protein autophosphorylation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    protein phosphorylation TAS
    Traceable Author Statement
    more info
    PubMed 
    regulation of DNA-binding transcription factor activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    regulation of cell shape IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    regulation of defense response to virus by virus TAS
    Traceable Author Statement
    more info
     
    regulation of inflammatory response TAS
    Traceable Author Statement
    more info
    PubMed 
    regulation of phagocytosis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    regulation of podosome assembly IDA
    Inferred from Direct Assay
    more info
    PubMed 
    respiratory burst after phagocytosis TAS
    Traceable Author Statement
    more info
    PubMed 
    transmembrane receptor protein tyrosine kinase signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    Component Evidence Code Pubs
    Golgi apparatus IEA
    Inferred from Electronic Annotation
    more info
     
    colocalizes_with actin filament IDA
    Inferred from Direct Assay
    more info
    PubMed 
    caveola IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cell projection IEA
    Inferred from Electronic Annotation
    more info
     
    cytosol TAS
    Traceable Author Statement
    more info
     
    extrinsic component of cytoplasmic side of plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    extrinsic component of cytoplasmic side of plasma membrane IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    focal adhesion IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    lysosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    plasma membrane IDA
    Inferred from Direct Assay
    more info
     
    transport vesicle IEA
    Inferred from Electronic Annotation
    more info
     

    General protein information

    Preferred Names
    tyrosine-protein kinase HCK
    Names
    hematopoietic cell kinase
    hemopoietic cell kinase
    p59-HCK/p60-HCK
    NP_001165600.1
    NP_001165601.1
    NP_001165602.1
    NP_001165603.1
    NP_001165604.1
    NP_002101.2

    NCBI Reference Sequences (RefSeq)

    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_029471.1 RefSeqGene

      Range
      5001..54669
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001172129.1NP_001165600.1  tyrosine-protein kinase HCK isoform b

      See identical proteins and their annotated locations for NP_001165600.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes two isoforms due to the use of alternative translation initiation codons, as demonstrated in PMIDs 1875927 and 7791757. The longer isoform (a, also known as p61HCK) is derived from an upstream non-AUG (CUG) start codon, while the shorter isoform (b, also known as p59HCK) is derived from a downstream AUG start codon. The shorter isoform (b) is represented in this RefSeq. Both variants 1 and 4 encode isoform b.
      Source sequence(s)
      AW139272, BC114463, DA465978
      Consensus CDS
      CCDS54455.1
      UniProtKB/Swiss-Prot
      P08631
      Related
      ENSP00000429848.1, ENST00000520553.5
      Conserved Domains (3) summary
      cd10363
      Location:119222
      SH2_Src_HCK; Src homology 2 (SH2) domain found in HCK
      cl17036
      Location:61116
      SH3; Src Homology 3 domain superfamily
      cl21453
      Location:233503
      PKc_like; Protein Kinases, catalytic domain
    2. NM_001172130.1NP_001165601.1  tyrosine-protein kinase HCK isoform c

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1. This variant encodes two isoforms due to the use of alternative translation initiation codons, as demonstrated in PMIDs 1875927 and 7791757. The longer isoform (c) is derived from an upstream non-AUG (CUG) start codon, while the shorter isoform (d) is derived from a downstream AUG start codon. The longer isoform (c) is represented in this RefSeq, but it is overall shorter, compared to isoform a.
      Source sequence(s)
      AK289896, AW139272, BC113854, DA465978
      Consensus CDS
      CCDS54453.1
      UniProtKB/Swiss-Prot
      P08631
      Related
      ENSP00000365022.2, ENST00000375862.6
      Conserved Domains (4) summary
      cd10363
      Location:139242
      SH2_Src_HCK; Src homology 2 (SH2) domain found in HCK
      pfam07714
      Location:261510
      Pkinase_Tyr; Protein tyrosine kinase
      cl17036
      Location:81136
      SH3; Src Homology 3 domain superfamily
      cl21453
      Location:253523
      PKc_like; Protein Kinases, catalytic domain
    3. NM_001172131.1NP_001165602.1  tyrosine-protein kinase HCK isoform d

      See identical proteins and their annotated locations for NP_001165602.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1. This variant encodes two isoforms due to the use of alternative translation initiation codons, as demonstrated in PMIDs 1875927 and 7791757. The longer isoform (c) is derived from an upstream non-AUG (CUG) start codon, while the shorter isoform (d) is derived from a downstream AUG start codon. The shorter isoform (d) is represented in this RefSeq, and is overall shorter, compared to isoform a.
      Source sequence(s)
      AK289896, AW139272, BC113854, DA465978
      Consensus CDS
      CCDS54456.1
      UniProtKB/Swiss-Prot
      P08631
      Related
      ENSP00000427757.1, ENST00000518730.5
      Conserved Domains (4) summary
      cd10363
      Location:118221
      SH2_Src_HCK; Src homology 2 (SH2) domain found in HCK
      pfam07714
      Location:240489
      Pkinase_Tyr; Protein tyrosine kinase
      cl17036
      Location:60115
      SH3; Src Homology 3 domain superfamily
      cl21453
      Location:232502
      PKc_like; Protein Kinases, catalytic domain
    4. NM_001172132.1NP_001165603.1  tyrosine-protein kinase HCK isoform e

      See identical proteins and their annotated locations for NP_001165603.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in its 5' UTR and uses an alternate AUG translation start codon, compared to variant 1. The encoded isoform (e) has a distinct and shorter N-terminus, compared to isoform a.
      Source sequence(s)
      AK290928, AW139272, DA465978
      UniProtKB/TrEMBL
      A8K4G3
      Conserved Domains (4) summary
      cd10363
      Location:120223
      SH2_Src_HCK; Src homology 2 (SH2) domain found in HCK
      pfam07714
      Location:242491
      Pkinase_Tyr; Protein tyrosine kinase
      cl17036
      Location:62117
      SH3; Src Homology 3 domain superfamily
      cl21453
      Location:234504
      PKc_like; Protein Kinases, catalytic domain
    5. NM_001172133.1NP_001165604.1  tyrosine-protein kinase HCK isoform b

      See identical proteins and their annotated locations for NP_001165604.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) differs in its 5' UTR and uses the downstream AUG start codon, compared to variant 1, resulting in an isoform (b) that is shorter at the N-terminus, compared to isoform a. Both variants 1 and 4 encode isoform b.
      Source sequence(s)
      AK298726, AW139272, DA465978
      Consensus CDS
      CCDS54455.1
      UniProtKB/Swiss-Prot
      P08631
      Related
      ENSP00000441169.1, ENST00000538448.5
      Conserved Domains (3) summary
      cd10363
      Location:119222
      SH2_Src_HCK; Src homology 2 (SH2) domain found in HCK
      cl17036
      Location:61116
      SH3; Src Homology 3 domain superfamily
      cl21453
      Location:233503
      PKc_like; Protein Kinases, catalytic domain
    6. NM_002110.4NP_002101.2  tyrosine-protein kinase HCK isoform a

      See identical proteins and their annotated locations for NP_002101.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes two isoforms due to the use of alternative translation initiation codons, as demonstrated in PMIDs 1875927 and 7791757. The longer isoform (a, also known as p61HCK) is derived from an upstream non-AUG (CUG) start codon, while the shorter isoform (b, also known as p59HCK) is derived from a downstream AUG start codon. The longer isoform (a) is represented in this RefSeq.
      Source sequence(s)
      AW139272, BC114463, DA465978
      Consensus CDS
      CCDS33460.1
      UniProtKB/Swiss-Prot
      P08631
      UniProtKB/TrEMBL
      F6SF04
      Related
      ENSP00000365012.2, ENST00000375852.3
      Conserved Domains (4) summary
      cd10363
      Location:140243
      SH2_Src_HCK; Src homology 2 (SH2) domain found in HCK
      pfam07714
      Location:262511
      Pkinase_Tyr; Protein tyrosine kinase
      cl17036
      Location:82137
      SH3; Src Homology 3 domain superfamily
      cl21453
      Location:254524
      PKc_like; Protein Kinases, catalytic domain

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

    Reference GRCh38.p12 Primary Assembly

    Genomic

    1. NC_000020.11 Reference GRCh38.p12 Primary Assembly

      Range
      32052188..32101856
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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