Human Gene HCK (ENST00000375852.5_15) from GENCODE V47lift37
  Description: HCK proto-oncogene, Src family tyrosine kinase, transcript variant 1 (from RefSeq NM_002110.5)
Gencode Transcript: ENST00000375852.5_15
Gencode Gene: ENSG00000101336.18_17
Transcript (Including UTRs)
   Position: hg19 chr20:30,640,045-30,689,659 Size: 49,615 Total Exon Count: 13 Strand: +
Coding Region
   Position: hg19 chr20:30,640,228-30,689,322 Size: 49,095 Coding Exon Count: 13 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr20:30,640,045-30,689,659)mRNA (may differ from genome)Protein (526 aa)
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-  Comments and Description Text from UniProtKB
  ID: HCK_HUMAN
DESCRIPTION: RecName: Full=Tyrosine-protein kinase HCK; EC=2.7.10.2; AltName: Full=Hematopoietic cell kinase; AltName: Full=Hemopoietic cell kinase; AltName: Full=p59-HCK/p60-HCK; AltName: Full=p59Hck; AltName: Full=p61Hck;
FUNCTION: Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS.
CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
ENZYME REGULATION: Subject to autoinhibition, mediated by intramolecular interactions involving the SH2 and SH3 domains. Kinase activity is also regulated by phosphorylation at regulatory tyrosine residues. Phosphorylation at Tyr-411 is required for optimal activity. Phosphorylation at Tyr-522 inhibits kinase activity. Inhibited by PP1 and A-770041.
SUBUNIT: Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with VAV1, WAS and RAPGEF1 (By similarity). Interacts (via SH3 domain) with HIV-1 Nef and Vif. This interaction stimulates its tyrosine-kinase activity. Interacts (via SH3 domain) with HEV ORF3 protein. Interacts with ARRB1 and ARRB2. Interacts with ADAM15. Interacts with FASLG. Interacts with CBL. Interacts with FCGR1A; the interaction may be indirect. Interacts with IL6ST. Interacts (via SH3 domain) with ELMO1. Interacts (via SH3 domain) with TP73. Interacts with YAP1. Interacts with ABL1 and ITGB1, and thereby recruits ABL1 to activated ITGB1.
INTERACTION: O92972:- (xeno); NbExp=2; IntAct=EBI-346340, EBI-710506; P27958:- (xeno); NbExp=5; IntAct=EBI-346340, EBI-706378; Q92556:ELMO1; NbExp=4; IntAct=EBI-346340, EBI-346417; Q07666:KHDRBS1; NbExp=2; IntAct=EBI-346340, EBI-1364; P12504:vif (xeno); NbExp=3; IntAct=EBI-346340, EBI-779991; P42768:WAS; NbExp=9; IntAct=EBI-346340, EBI-346375; O43516:WIPF1; NbExp=3; IntAct=EBI-346340, EBI-346356;
SUBCELLULAR LOCATION: Isoform 1: Lysosome. Membrane; Lipid-anchor. Cell projection, podosome membrane; Lipid-anchor. Cytoplasm, cytosol. Note=Associated with specialized secretory lysosomes called azurophil granules. At least half of this isoform is found in the cytoplasm, some of this fraction is myristoylated.
SUBCELLULAR LOCATION: Isoform 2: Cell membrane; Lipid-anchor. Membrane, caveola; Lipid-anchor. Cell junction, focal adhesion. Cytoplasm, cytoskeleton. Golgi apparatus. Cytoplasmic vesicle. Lysosome. Nucleus. Note=20% of this isoform is associated with caveolae. Localization at the cell membrane and at caveolae requires palmitoylation at Cys-3. Colocalizes with the actin cytoskeleton at focal adhesions.
SUBCELLULAR LOCATION: Cytoplasmic vesicle, secretory vesicle. Cytoplasm, cytosol.
TISSUE SPECIFICITY: Detected in monocytes and neutrophils (at protein level). Expressed predominantly in cells of the myeloid and B-lymphoid lineages. Highly expressed in granulocytes. Detected in tonsil.
INDUCTION: Up-regulated during myeloid cell differentiation. The highest levels are detected in fully differentiated phagocytes. Up-regulated by IL2.
DOMAIN: The SH3 domain mediates binding to HIV-1 Nef.
PTM: Phosphorylated on serveral tyrosine residues. Autophosphorylated. Becomes rapidly phosphorylated upon activation of the immunoglobulin receptors FCGR1A and FCGR2A. Phosphorylation by the BCR-ABL fusion protein mediates activation of HCK. Phosphorylation at Tyr-411 increases kinase activity. Phosphorylation at Tyr-522 inhibits kinase activity. Kinase activity is not required for phosphorylation at Tyr-522, suggesting that this site is a target of other kinases.
PTM: Ubiquitinated by CBL, leading to its degradation via the proteasome.
PTM: Isoform 2 palmitoylation at position 2 requires prior myristoylation. Palmitoylation at position 3 is required for caveolar localization of isoform 2.
DISEASE: Note=Aberrant activation of HCK by HIV-1 protein Nef enhances HIV-1 replication and contributes to HIV-1 pathogenicity.
DISEASE: Note=Aberrant activation of HCK, e.g. by the BCR-ABL fusion protein, promotes cancer cell proliferation.
SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.
SIMILARITY: Contains 1 protein kinase domain.
SIMILARITY: Contains 1 SH2 domain.
SIMILARITY: Contains 1 SH3 domain.
SEQUENCE CAUTION: Sequence=AAA52643.1; Type=Frameshift; Positions=20; Sequence=BAF82585.1; Type=Erroneous initiation; Note=Translation N-terminally extended;

-  Primer design for this transcript
 

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-  MalaCards Disease Associations
  MalaCards Gene Search: HCK
Diseases sorted by gene-association score: hiv-1 (14), flying phobia (11), pylorospasm (10), fourth cranial nerve palsy (9), frey syndrome (8), de quervain disease (7), malignant anus melanoma (7), median arcuate ligament syndrome (7), cecal disease (6), mitral valve insufficiency (6), mitral valve stenosis (6), cervical adenosquamous carcinoma (6), splenic artery aneurysm (5), hemometra (5), aortic valve disease 1 (4), extratemporal epilepsy (4), paralytic squint (4), lung lymphoma (4), transverse colon cancer (3), leukemia, chronic myeloid, somatic (2), aortic valve disease 2 (1)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 287.18 RPKM in Whole Blood
Total median expression: 544.04 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -62.40183-0.341 Picture PostScript Text
3' UTR -102.70337-0.305 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011009 - Kinase-like_dom
IPR000719 - Prot_kinase_cat_dom
IPR017441 - Protein_kinase_ATP_BS
IPR001245 - Ser-Thr/Tyr_kinase_cat_dom
IPR000980 - SH2
IPR001452 - SH3_domain
IPR008266 - Tyr_kinase_AS
IPR020635 - Tyr_kinase_cat_dom

Pfam Domains:
PF00017 - SH2 domain
PF00018 - SH3 domain
PF00069 - Protein kinase domain
PF07653 - Variant SH3 domain
PF07714 - Protein tyrosine and serine/threonine kinase
PF14604 - Variant SH3 domain

SCOP Domains:
50044 - SH3-domain
56112 - Protein kinase-like (PK-like)
55550 - SH2 domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1AD5 - X-ray MuPIT 1BU1 - X-ray MuPIT 1QCF - X-ray MuPIT 2C0I - X-ray MuPIT 2C0O - X-ray MuPIT 2C0T - X-ray MuPIT 2HCK - X-ray MuPIT 2HK5 - X-ray MuPIT 2OI3 - NMR MuPIT 2OJ2 - NMR MuPIT 3HCK - NMR MuPIT 3NHN - X-ray MuPIT 3RBB - X-ray MuPIT 3REA - X-ray MuPIT 3REB - X-ray MuPIT 4HCK - NMR MuPIT 5HCK - NMR MuPIT


ModBase Predicted Comparative 3D Structure on P08631
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
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-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0001784 phosphotyrosine binding
GO:0004672 protein kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0004715 non-membrane spanning protein tyrosine kinase activity
GO:0005102 receptor binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity

Biological Process:
GO:0002376 immune system process
GO:0002522 leukocyte migration involved in immune response
GO:0002758 innate immune response-activating signal transduction
GO:0006468 protein phosphorylation
GO:0006887 exocytosis
GO:0006909 phagocytosis
GO:0006954 inflammatory response
GO:0007155 cell adhesion
GO:0007169 transmembrane receptor protein tyrosine kinase signaling pathway
GO:0007229 integrin-mediated signaling pathway
GO:0007498 mesoderm development
GO:0008284 positive regulation of cell proliferation
GO:0008360 regulation of cell shape
GO:0016032 viral process
GO:0016310 phosphorylation
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0019221 cytokine-mediated signaling pathway
GO:0030154 cell differentiation
GO:0030838 positive regulation of actin filament polymerization
GO:0031663 lipopolysaccharide-mediated signaling pathway
GO:0038083 peptidyl-tyrosine autophosphorylation
GO:0038096 Fc-gamma receptor signaling pathway involved in phagocytosis
GO:0043066 negative regulation of apoptotic process
GO:0043299 leukocyte degranulation
GO:0045087 innate immune response
GO:0045728 respiratory burst after phagocytosis
GO:0046777 protein autophosphorylation
GO:0050690 regulation of defense response to virus by virus
GO:0050727 regulation of inflammatory response
GO:0050764 regulation of phagocytosis
GO:0051090 regulation of sequence-specific DNA binding transcription factor activity
GO:0060333 interferon-gamma-mediated signaling pathway
GO:0071801 regulation of podosome assembly
GO:2000251 positive regulation of actin cytoskeleton reorganization

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005764 lysosome
GO:0005794 Golgi apparatus
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0005886 plasma membrane
GO:0005901 caveola
GO:0005925 focal adhesion
GO:0016020 membrane
GO:0030054 cell junction
GO:0030133 transport vesicle
GO:0031234 extrinsic component of cytoplasmic side of plasma membrane
GO:0031410 cytoplasmic vesicle
GO:0042995 cell projection
GO:0005884 actin filament


-  Descriptions from all associated GenBank mRNAs
  AK289896 - Homo sapiens cDNA FLJ77650 complete cds.
AK298726 - Homo sapiens cDNA FLJ60326 complete cds, highly similar to Tyrosine-protein kinase HCK (EC 2.7.10.2).
AK225819 - Homo sapiens mRNA for hemopoietic cell kinase isoform p61HCK variant, clone: FCC128H06.
AK290928 - Homo sapiens cDNA FLJ78472 complete cds, highly similar to Human hemopoietic cell protein-tyrosine kinase (HCK) gene.
AK026432 - Homo sapiens cDNA: FLJ22779 fis, clone KAIA1741.
BC108930 - Homo sapiens hemopoietic cell kinase, mRNA (cDNA clone MGC:120509 IMAGE:40025497), complete cds.
BC108931 - Homo sapiens hemopoietic cell kinase, mRNA (cDNA clone MGC:120510 IMAGE:40025500), complete cds.
BC113854 - Homo sapiens hemopoietic cell kinase, mRNA (cDNA clone MGC:120512 IMAGE:40025503), complete cds.
BC114463 - Homo sapiens hemopoietic cell kinase, mRNA (cDNA clone MGC:120511 IMAGE:40025502), complete cds.
AK314335 - Homo sapiens cDNA, FLJ95095.
BC094847 - Homo sapiens hemopoietic cell kinase, mRNA (cDNA clone MGC:104866 IMAGE:5923744), complete cds.
BC014435 - Homo sapiens hemopoietic cell kinase, mRNA (cDNA clone MGC:22922 IMAGE:4855747), complete cds.
M16591 - Human hemopoietic cell protein-tyrosine kinase (HCK) gene, complete cds, clone lambda-a2/1a.
M16592 - Human hemopoietic cell protein-tyrosine kinase (HCK) gene, complete cds, clone HK24.
CU676991 - Synthetic construct Homo sapiens gateway clone IMAGE:100019717 5' read HCK mRNA.
KJ891339 - Synthetic construct Homo sapiens clone ccsbBroadEn_00733 HCK gene, encodes complete protein.
JD065986 - Sequence 47010 from Patent EP1572962.
BC073748 - Homo sapiens cDNA clone IMAGE:6301005, partial cds.
JD535703 - Sequence 516727 from Patent EP1572962.
JD506843 - Sequence 487867 from Patent EP1572962.
JD367959 - Sequence 348983 from Patent EP1572962.
JD456202 - Sequence 437226 from Patent EP1572962.
JD280746 - Sequence 261770 from Patent EP1572962.
JD077577 - Sequence 58601 from Patent EP1572962.
JD478745 - Sequence 459769 from Patent EP1572962.
JD382166 - Sequence 363190 from Patent EP1572962.
JD152019 - Sequence 133043 from Patent EP1572962.
JD086659 - Sequence 67683 from Patent EP1572962.
JD184525 - Sequence 165549 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_vifPathway - HIV-1 defeats host-mediated resistance by CEM15
h_bArrestin-srcPathway - Roles of ¿-arrestin-dependent Recruitment of Src Kinases in GPCR Signaling

Reactome (by CSHL, EBI, and GO)

Protein P08631 (Reactome details) participates in the following event(s):

R-HSA-200858 Nef Binds and activates the Src-family tyrosine kinase Hck
R-HSA-879917 CBL, GRB2, FYN and PI3K p85 subunit are constitutively associated
R-HSA-912629 CBL is tyrosine phosphorylated
R-HSA-164944 Nef and signal transduction
R-HSA-912631 Regulation of signaling by CBL
R-HSA-164952 The role of Nef in HIV-1 replication and disease pathogenesis
R-HSA-2029481 FCGR activation
R-HSA-512988 Interleukin-3, 5 and GM-CSF signaling
R-HSA-162909 Host Interactions of HIV factors
R-HSA-2029480 Fcgamma receptor (FCGR) dependent phagocytosis
R-HSA-449147 Signaling by Interleukins
R-HSA-162906 HIV Infection
R-HSA-168249 Innate Immune System
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-5663205 Infectious disease
R-HSA-168256 Immune System
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: A8K1I1, B4DQB6, E1P5M2, ENST00000375852.1, ENST00000375852.2, ENST00000375852.3, ENST00000375852.4, HCK_HUMAN, NM_002110, P08631, Q29RX1, Q2VPE2, Q504R5, Q5T7K1, Q5T7K2, Q96CC0, Q9H5Y5, Q9NUA4, Q9UMJ5, uc318moe.1, uc318moe.2
UCSC ID: ENST00000375852.5_15
RefSeq Accession: NM_001172129.3
Protein: P08631 (aka HCK_HUMAN)

-  Gene Model Information
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-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.