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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

HCK Gene

protein-coding GIFtS: 73
GCID: GC20P030645

hemopoietic cell kinase

Explore 29 diseases affiliated with
HCK via

MalaCards

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Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Hemopoietic Cell Kinase¹ ² ³		P61Hck¹
JTK9¹ ²		EC 2.7.10.2³ ⁸
Hematopoietic Cell Kinase² ³		Tyrosine-Protein Kinase HCK²
P59-HCK/P60-HCK¹		EC 2.7.10⁸
P59Hck¹

External Ids:	HGNC: 4840¹	Entrez Gene: 3055²	Ensembl: ENSG00000101336⁷	OMIM: 142370⁵	UniProtKB: P08631³

Export aliases for HCK gene to outside databases

Previous GC identifers: GC20P030428 GC20P031338 GC20P031385 GC20P030103 GC20P030641 GC20P027428

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for HCK:

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)

UniProtKB/Swiss-Prot: HCK_HUMAN, P08631

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

Gene Wiki entry for HCK

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000020.10 NC_018931.1 NT_011362.10

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the HCK gene promoter:
p53 NF-kappaB2 STAT3 CUTL1 STAT5A NF-kappaB NF-kappaB1
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: HCK promoter sequence

Search SABiosciences Chromatin IP Primers for HCK

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat HCK

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 20q11-q12 Ensembl cytogenetic band: 20q11.21 HGNC cytogenetic band: 20q11-q12

HCK Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
HCK gene location

GeneLoc information about chromosome 20 GeneLoc Exon Structure

GeneLoc location for GC20P030645: view genomic region (about GC identifiers)

Start:	30,639,991 bp from pter	End:	30,689,659 bp from pter
Size:	49,669 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: HCK_HUMAN, P08631 (See protein sequence)

Recommended Name: Tyrosine-protein kinase HCK

Size: 526 amino acids; 59600 Da

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

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

Sequence caution: Sequence=AAA52643.1; Type=Frameshift; Positions=20; Sequence=BAF82585.1; Type=Erroneous initiation;

Note=Translation N-terminally extended;

6/17 PDB 3D structures from and Proteopedia for HCK (see all 17):

1AD5 (3D)

1BU1 (3D)

1QCF (3D)

2C0I (3D)

2C0O (3D)

2C0T (3D)

Secondary accessions: A8K1I1 B4DQB6 E1P5M2 Q29RX1 Q2VPE2 Q504R5 Q5T7K1 Q5T7K2 Q96CC0 Q9H5Y5 Q9NUA4

Q9UMJ5

Alternative splicing, Alternative initiation: 4 isoforms: P08631-1 P08631-2 P08631-3 P08631-4 (Initiates from a CTG codon)

Explore the universe of human proteins at neXtProt for HCK: NX_P08631

Post-translational modifications:

Phosphorylated on several 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 kinases¹

Ubiquitinated by CBL, leading to its degradation via the proteasome¹

Isoform 2 palmitoylation at position 2 requires prior myristoylation. Palmitoylation at position 3 is required for

caveolar localization of isoform 2¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P08631

4/28 DME Specific Peptides for HCK (P08631) (see all 28)

DAWEIPR

GQFGEVW

NCPEELY

KWTAPEA

HCK Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (6 alternative transcripts):

NP_001165600.1 NP_001165601.1 NP_001165602.1 NP_001165603.1 NP_001165604.1 NP_002101.2

ENSEMBL proteins:

ENSP00000365022 ENSP00000420457 ENSP00000262651 ENSP00000429848 ENSP00000427757

ENSP00000365012 ENSP00000444986 ENSP00000441169

Reactome Protein details: P08631
Human Recombinant Protein Products:

	EMD Millipore Purified and/or Recombinant HCK Protein
	Browse R&D Systems for human recombinant proteins
	Enzo Life Sciences proteins for HCK
	OriGene Purified Protein: HCK OriGene Protein Over-expression Lysate: HCK OriGene Custom Protein Services for HCK
	GenScript Custom Purified and Recombinant Proteins Services for HCK
	Novus Biologicals HCK Proteins Novus Biologicals HCK Lysates
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Uscn Proteins for HCK

Gene Ontology (GO): 5/10 cellular component terms (GO ID links to tree view) (see all 10): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005634	nucleus	IEA	--
GO:0005764	lysosome	IDA	15998323
GO:0005794	Golgi apparatus	IEA	--
GO:0005829	cytosol	TAS	--
GO:0005884	colocalizes with actin filament	IDA	15998323

HCK for ontologies About GeneDecksing

HCK Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of HCK
	R&D Systems Antibodies for HCK
	Cell Signaling Technology (CST) Antibodies for HCK
	OriGene Antibodies: HCK OriGene Custom Antibody Services for HCK
	GenScript Custom Superior Antibodies Services for HCK
	Novus Biologicals HCK Antibodies
	Abcam antibodies for HCK
	Uscn Antibodies for HCK
	ThermoFisher Antibody for HCK

Assay Products for HCK:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	R&D Systems Multiplex/Array Assay Kits & Reagents for HCK
	GenScript Custom Assay Services for HCK
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for HCK

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

HCK for domains About GeneDecksing

5/8 InterPro domains/families (see all 8):

IPR017441 Protein_kinase_ATP_BS

IPR011009 Kinase-like_dom

IPR001452 SH3_domain

IPR000719 Prot_kinase_cat_dom

IPR001245 Ser-Thr/Tyr_kinase_cat_dom

Graphical View of Domain Structure for InterPro Entry P08631

ProtoNet protein and cluster: P08631

3 Blocks protein families:

IPB000980 SH2 domain signature

IPB001452 SH3 domain signature

IPB008266 Tyrosine protein kinase

UniProtKB/Swiss-Prot: HCK_HUMAN, P08631

Domain: The SH3 domain mediates binding to HIV-1 Nef

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

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary: