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

Gene ID: 3055, updated on 17-Mar-2015
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; HPRD:00796; MIM:142370; Vega:OTTHUMG00000032204
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]
Orthologs
See HCK in MapViewer
Location:
20q11-q12
Exon count:
15
Annotation release Status Assembly Chr Location
107 current GRCh38.p2 (GCF_000001405.28) 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 RNA, 5S ribosomal pseudogene 481 Neighboring gene cerebral cavernous malformation 2-like Neighboring gene transmembrane 9 superfamily protein member 4 Neighboring gene ribosomal L24 domain containing 1 pseudogene 6

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

NHGRI GWAS Catalog

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

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 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 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 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 Small molecule compounds, which inhibit the SH3 domain of HIV-1 Nef binding to Hck, significantly reduce Nef-mediated viral infectivity enhancement 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 Nef-induced aberrant molecular formation between Hck and M-CSF receptor inhibits M-CSF bioactivities in monocytes/macrophages 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 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 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 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 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 Mutations P72G, V74I, P75G, and R77K in the PXXPXR motif of HIV-1 Nef abolish the binding between Nef and Hck 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 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 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 HIV-1 Nef binds Hck and induces skewed Golgi-localization of Hck, which leads to Fms maturation arrest 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
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 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 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 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 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 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 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 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 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
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

Products Interactant Other Gene Complex Source Pubs Description

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
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein tyrosine kinase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
receptor binding IBA
Inferred from Biological aspect of Ancestor
more info
 
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
 
cellular response to peptide hormone stimulus IBA
Inferred from Biological aspect of Ancestor
more info
 
cytokine-mediated signaling pathway TAS
Traceable Author Statement
more info
PubMed 
inflammatory response IEA
Inferred from Electronic Annotation
more info
 
innate immune response IBA
Inferred from Biological aspect of Ancestor
more info
 
innate immune response TAS
Traceable Author Statement
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
 
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 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 
regulation of sequence-specific DNA binding transcription factor activity IMP
Inferred from Mutant Phenotype
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
 
viral process TAS
Traceable Author Statement
more info
 
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 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 
nucleus IEA
Inferred from Electronic Annotation
more info
 
transport vesicle IEA
Inferred from Electronic Annotation
more info
 
Preferred Names
tyrosine-protein kinase HCK
Names
tyrosine-protein kinase HCK
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

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 proteins identical to 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, OTTHUMP00000225030, ENST00000520553, OTTHUMT00000375751
    Conserved Domains (4) summary
    cd10363
    Location:119222
    SH2_Src_HCK; Src homology 2 (SH2) domain found in HCK
    pfam07714
    Location:241490
    Pkinase_Tyr; Protein tyrosine kinase
    cl17036
    Location:61116
    SH3; Src Homology 3 domain superfamily
    cl21453
    Location:233503
    PKc_like; Catalytic domain of the Protein Kinase superfamily
  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, OTTHUMP00000030579, ENST00000375862, OTTHUMT00000078604
    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; Catalytic domain of the Protein Kinase superfamily
  3. NM_001172131.1NP_001165602.1  tyrosine-protein kinase HCK isoform d

    See proteins identical to 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, OTTHUMP00000225031, ENST00000518730, OTTHUMT00000375752
    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; Catalytic domain of the Protein Kinase superfamily
  4. NM_001172132.1NP_001165603.1  tyrosine-protein kinase HCK isoform e

    See proteins identical to 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; Catalytic domain of the Protein Kinase superfamily
  5. NM_001172133.1NP_001165604.1  tyrosine-protein kinase HCK isoform b

    See proteins identical to 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, ENST00000538448
    Conserved Domains (4) summary
    cd10363
    Location:119222
    SH2_Src_HCK; Src homology 2 (SH2) domain found in HCK
    pfam07714
    Location:241490
    Pkinase_Tyr; Protein tyrosine kinase
    cl17036
    Location:61116
    SH3; Src Homology 3 domain superfamily
    cl21453
    Location:233503
    PKc_like; Catalytic domain of the Protein Kinase superfamily
  6. NM_002110.3NP_002101.2  tyrosine-protein kinase HCK isoform a

    See proteins identical to 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
    Related
    ENSP00000444986, ENST00000534862
    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; Catalytic domain of the Protein Kinase superfamily

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107

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

Reference GRCh38.p2 Primary Assembly

Genomic

  1. NC_000020.11 Reference GRCh38.p2 Primary Assembly

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

Alternate CHM1_1.1

Genomic

  1. NC_018931.2 Alternate CHM1_1.1

    Range
    30543895..30593543
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)