HCK (HCK proto-oncogene, Src family tyrosine kinase)

Gene

• Entrez ID: 3055
• Gene name: HCK proto-oncogene, Src family tyrosine kinase
• Gene symbol: HCK
• Synonyms (NCBI Gene): AIPCV, JTK9, p59Hck, p61Hck
• Chromosome: 20
• Chromosome location: 20q11.21
• 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 respirator

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs1600755957	G>T	Likely-pathogenic	Stop gained, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1042041	hsa-miR-1245b-3p	CLIP-seq
MIRT1042042	hsa-miR-3654	CLIP-seq
MIRT1042043	hsa-miR-3915	CLIP-seq
MIRT1042044	hsa-miR-3928	CLIP-seq
MIRT1042045	hsa-miR-4318	CLIP-seq
MIRT1042046	hsa-miR-4496	CLIP-seq
MIRT1042047	hsa-miR-4520a-3p	CLIP-seq
MIRT1042048	hsa-miR-4638-3p	CLIP-seq
MIRT1042049	hsa-miR-4738-3p	CLIP-seq
MIRT1042050	hsa-miR-548g	CLIP-seq

Transcription factors

Transcription factor	Regulation	Reference
PML	Unknown	21993313
RARA	Unknown	21993313
SPI1	Unknown	21993313

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000166	Function	Nucleotide binding	IEA
GO:0001784	Function	Phosphotyrosine residue binding	IPI	20624904
GO:0002376	Process	Immune system process	IEA
GO:0002522	Process	Leukocyte migration involved in immune response	TAS	18538446
GO:0002758	Process	Innate immune response-activating signaling pathway	IEA
GO:0002758	Process	Innate immune response-activating signaling pathway	TAS	18538446
GO:0002862	Process	Negative regulation of inflammatory response to antigenic stimulus	IEA
GO:0002862	Process	Negative regulation of inflammatory response to antigenic stimulus	TAS
GO:0004672	Function	Protein kinase activity	IEA
GO:0004713	Function	Protein tyrosine kinase activity	EXP	10861086, 16921024
GO:0004713	Function	Protein tyrosine kinase activity	IEA
GO:0004713	Function	Protein tyrosine kinase activity	IMP	10092522
GO:0004713	Function	Protein tyrosine kinase activity	TAS	3496523
GO:0004715	Function	Non-membrane spanning protein tyrosine kinase activity	IBA
GO:0004715	Function	Non-membrane spanning protein tyrosine kinase activity	IEA
GO:0005102	Function	Signaling receptor binding	IBA
GO:0005515	Function	Protein binding	IPI	7859737, 10092522, 11278465, 11741929, 12029088, 14993658, 15784897, 16273093, 16374509, 16636290, 17141806, 18042718, 19234535, 20670214, 22641034, 22939624, 23397142, 24658140, 24728074, 24860872, 25036101, 25416956, 25469238, 25814554, 25825872, 31980649, 32226298, 32296183, 3270
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IEA
GO:0005764	Component	Lysosome	IDA	15998323
GO:0005764	Component	Lysosome	IEA
GO:0005794	Component	Golgi apparatus	IEA
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	IEA
GO:0005829	Component	Cytosol	TAS
GO:0005856	Component	Cytoskeleton	IEA
GO:0005884	Component	Actin filament	IDA	15998323
GO:0005886	Component	Plasma membrane	IBA
GO:0005886	Component	Plasma membrane	IDA
GO:0005886	Component	Plasma membrane	IEA
GO:0005901	Component	Caveola	IDA	7791757
GO:0005901	Component	Caveola	IEA
GO:0005925	Component	Focal adhesion	IEA
GO:0005925	Component	Focal adhesion	IMP	11904303
GO:0006468	Process	Protein phosphorylation	TAS	3496523
GO:0006887	Process	Exocytosis	IEA
GO:0006909	Process	Phagocytosis	IEA
GO:0006909	Process	Phagocytosis	IEA
GO:0006950	Process	Response to stress	IEA
GO:0006954	Process	Inflammatory response	IEA
GO:0007155	Process	Cell adhesion	TAS	18538446
GO:0007169	Process	Cell surface receptor protein tyrosine kinase signaling pathway	IBA
GO:0007229	Process	Integrin-mediated signaling pathway	TAS	18538446
GO:0007498	Process	Mesoderm development	TAS	3453117
GO:0008284	Process	Positive regulation of cell population proliferation	IEA
GO:0008284	Process	Positive regulation of cell population proliferation	IMP	10092522
GO:0008289	Function	Lipid binding	EXP	31877324
GO:0008360	Process	Regulation of cell shape	IMP	10092522
GO:0009898	Component	Cytoplasmic side of plasma membrane	IEA
GO:0009898	Component	Cytoplasmic side of plasma membrane	IMP	11904303
GO:0016020	Component	Membrane	IEA
GO:0016301	Function	Kinase activity	IEA
GO:0016740	Function	Transferase activity	IEA
GO:0018108	Process	Peptidyl-tyrosine phosphorylation	IMP	10092522
GO:0019221	Process	Cytokine-mediated signaling pathway	TAS	18538446
GO:0030133	Component	Transport vesicle	IEA
GO:0030154	Process	Cell differentiation	IBA
GO:0030838	Process	Positive regulation of actin filament polymerization	TAS	18538446
GO:0031410	Component	Cytoplasmic vesicle	IEA
GO:0031663	Process	Lipopolysaccharide-mediated signaling pathway	TAS	18538446
GO:0032956	Process	Regulation of actin cytoskeleton organization	IMP	11904303
GO:0035556	Process	Intracellular signal transduction	IEA
GO:0035556	Process	Intracellular signal transduction	IMP	11904303
GO:0038096	Process	Fc-gamma receptor signaling pathway involved in phagocytosis	IEA
GO:0038096	Process	Fc-gamma receptor signaling pathway involved in phagocytosis	TAS
GO:0042995	Component	Cell projection	IEA
GO:0043066	Process	Negative regulation of apoptotic process	IMP	17535448
GO:0043299	Process	Leukocyte degranulation	TAS	18538446
GO:0045087	Process	Innate immune response	IEA
GO:0045121	Component	Membrane raft	IEA
GO:0045728	Process	Respiratory burst after phagocytosis	TAS	18538446
GO:0046777	Process	Protein autophosphorylation	IMP	10092522
GO:0050727	Process	Regulation of inflammatory response	TAS	18538446
GO:0050764	Process	Regulation of phagocytosis	IMP	11904303
GO:0050830	Process	Defense response to Gram-positive bacterium	IEA
GO:0050900	Process	Leukocyte migration	IEA
GO:0051090	Process	Regulation of DNA-binding transcription factor activity	IMP	17535448
GO:0060333	Process	Type II interferon-mediated signaling pathway	TAS	18538446
GO:0070161	Component	Anchoring junction	IEA
GO:0071396	Process	Cellular response to lipid	IEA
GO:0071801	Process	Regulation of podosome assembly	IDA	15998323

Other IDs

• MIM: 142370
• HGNC: 4840
• e!Ensembl: ENSG00000101336

Protein

• UniProt ID: P08631
• Protein name: Tyrosine-protein kinase HCK (EC 2.7.10.2) (Hematopoietic cell kinase) (Hemopoietic cell kinase) (p59-HCK/p60-HCK) (p59Hck) (p61Hck)
• Protein 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 ce
• PDB: 1AD5, 1BU1, 1QCF, 2C0I, 2C0O, 2C0T, 2HCK, 2HK5, 2OI3, 2OJ2, 3HCK, 3NHN, 3RBB, 3REA, 3REB, 3VRY, 3VRZ, 3VS0, 3VS1, 3VS2, 3VS3, 3VS4, 3VS5, 3VS6, 3VS7, 4HCK, 4LUD, 4LUE, 4ORZ, 4U5W, 5H09, 5H0B, 5H0E, 5H0G, 5H0H, 5HCK, 5NUH, 5ZJ6, 8F2P, 9BYJ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00018	SH3_1	84 → 130	SH3 domain	Domain
  PF00017	SH2	144 → 226	SH2 domain	Domain
  PF07714	PK_Tyr_Ser-Thr	262 → 511	Protein tyrosine and serine/threonine kinase	Domain

• Tissue specificity: 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. {ECO:0000269|PubMed:3453117, ECO:0000269|PubMed:80
• Sequence:

  MGGRSSCEDPGCPRDEERAPRMGCMKSKFLQVGGNTFSKTETSASPHCPVYVPDPTSTIK
  PGPNSHNSNTPGIREAGSEDIIVVALYDYEAIHHEDLSFQKGDQMVVLEESGEWWKARSL
  ATRKEGYIPSNYVARVDSLETEEWFFKGISRKDAERQLLAPGNMLGSFMIRDSETTKGSY
  SLSVRDYDPRQGDTVKHYKIRTLDNGGFYISPRSTFSTLQELVDHYKKGNDGLCQKLSVP
  CMSSKPQKPWEKDAWEIPRESLKLEKKLGAGQFGEVWMATYNKHTKVAVKTMKPGSMSVE
  AFLAEANVMKTLQHDKLVKLHAVVTKEPIYIITEFMAKGSLLDFLKSDEGSKQPLPKLID
  FSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVIEDNEYTAREGAKFP
  IKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPE
  NCPEELYNIMMRCWKNRPEERPTFEYIQSVLDDFYTATESQYQQQP

• Sequence length: 526

Pathways

KEGG:

Chemokine signaling pathway
Fc gamma R-mediated phagocytosis
Kaposi sarcoma-associated herpesvirus infection

Reactome:

Nef and signal transduction
FCGR activation
Regulation of signaling by CBL
FCGR3A-mediated IL10 synthesis
FCGR3A-mediated phagocytosis

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Autoinflammation with pulmonary and cutaneous vasculitis	Pathogenic	rs2046034449	RCV003158002	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ANKYLOSING SPONDYLITIS AND OTHER INFLAMMATORY SPONDYLOPATHIES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOIMMUNE DISEASES	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
INSOMNIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LIVER CIRRHOSIS, EXPERIMENTAL	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Acute Promyelocytic Leukemia	Promyelocytic Leukemia	BEFREE	21993313		★☆☆☆☆ Found in Text Mining only
Astrocytoma	Astrocytoma	Pubtator	24650279	Associate	★☆☆☆☆ Found in Text Mining only
Atherosclerosis	Atherosclerosis	Pubtator	34925641	Associate	★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial fibrillation	Pubtator	35919038	Associate	★☆☆☆☆ Found in Text Mining only
Breast Neoplasms	Breast neoplasm	Pubtator	33162805	Associate	★☆☆☆☆ Found in Text Mining only
Carcinogenesis	Carcinogenesis	Pubtator	37342066	Associate	★☆☆☆☆ Found in Text Mining only
Childhood Acute Lymphoblastic Leukemia	Lymphoblastic Leukemia	CTD_human_DG	17344919		★☆☆☆☆ Found in Text Mining only
Chronic Obstructive Airway Disease	Chronic Obstructive Pulmonary Disease	BEFREE	17024369, 22185326		★☆☆☆☆ Found in Text Mining only
Chronic Obstructive Airway Disease	Chronic Obstructive Pulmonary Disease	LHGDN	17024369		★☆☆☆☆ Found in Text Mining only
Colon Carcinoma	Colon Carcinoma	BEFREE	28399411		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	30684564, 35221332	Associate	★☆☆☆☆ Found in Text Mining only
Conventional (Clear Cell) Renal Cell Carcinoma	Renal Carcinoma	BEFREE	21969129		★☆☆☆☆ Found in Text Mining only
Diabetes Mellitus	Diabetes mellitus	Pubtator	37773841	Associate	★☆☆☆☆ Found in Text Mining only
Diabetic Nephropathies	Diabetic neuropathy	Pubtator	36568106	Stimulate	★☆☆☆☆ Found in Text Mining only
Diabetic Retinopathy	Diabetic retinopathy	Pubtator	37773794	Associate	★☆☆☆☆ Found in Text Mining only
Endometriosis	Endometriosis	BEFREE	29962266		★☆☆☆☆ Found in Text Mining only
Hematologic Neoplasms	Hematologic Neoplasms	BEFREE	27840303, 28399411		★☆☆☆☆ Found in Text Mining only
Hematologic Neoplasms	Hematologic neoplasm	Pubtator	27840303	Associate	★☆☆☆☆ Found in Text Mining only
Hurthle Cell Tumor	Tumor	BEFREE	21969129		★☆☆☆☆ Found in Text Mining only
L2 Acute Lymphoblastic Leukemia	Lymphoblastic Leukemia	CTD_human_DG	17344919		★☆☆☆☆ Found in Text Mining only
Leukemia	Leukemia	Pubtator	10658677, 27840303, 3496523	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid	Myeloid leukemia	Pubtator	31273084, 3496523	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	1825181, 26785729, 27840303, 31790499, 32226298, 3496523, 35280440	Associate	★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	23896410, 27323399, 27840303		★☆☆☆☆ Found in Text Mining only
Lymphoma	Lymphoma	Pubtator	35255496	Associate	★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	19734198		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	25774687		★☆☆☆☆ Found in Text Mining only
Malignant tumor of colon	Colonic Neoplasms	BEFREE	28399411		★☆☆☆☆ Found in Text Mining only
Melanoma	Melanoma	Pubtator	35135212	Associate	★☆☆☆☆ Found in Text Mining only
Mucocutaneous Lymph Node Syndrome	Kawasaki disease	Pubtator	36536067	Associate	★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	LHGDN	15010462		★☆☆☆☆ Found in Text Mining only
Multiple Myeloma	Multiple myeloma	Pubtator	15010462	Associate	★☆☆☆☆ Found in Text Mining only
MYELODYSPLASTIC SYNDROME	Myelodysplastic Syndrome	BEFREE	27840303		★☆☆☆☆ Found in Text Mining only
Myelodysplastic Syndromes	Myelodysplastic syndrome	Pubtator	27840303	Associate	★☆☆☆☆ Found in Text Mining only
Myeloproliferative Disorders	Myeloproliferative disorder	Pubtator	3496523	Associate	★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	19036015, 19114024, 19211505, 28399411		★☆☆☆☆ Found in Text Mining only
Ovarian Mucinous Adenocarcinoma	Ovarian adenocarcinoma	UNIPROT_DG			★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	35761259, 37342066	Associate	★☆☆☆☆ Found in Text Mining only
Oxyphilic Adenoma	Oxyphilic Adenoma	BEFREE	21969129		★☆☆☆☆ Found in Text Mining only
Pancreatic Neoplasms	Pancreatic neoplasm	Pubtator	17233815, 33213062	Associate	★☆☆☆☆ Found in Text Mining only
Polycythemia	Polycythemia	BEFREE	31065022		★☆☆☆☆ Found in Text Mining only
Precursor Cell Lymphoblastic Leukemia Lymphoma	Lymphoblastic Leukemia	CTD_human_DG	17344919		★☆☆☆☆ Found in Text Mining only
Pulmonary Disease Chronic Obstructive	Chronic obstructive pulmonary disease	Pubtator	22185326	Associate	★☆☆☆☆ Found in Text Mining only
Renal fibrosis	Renal fibrosis	BEFREE	27927780		★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	24192080	Associate	★☆☆☆☆ Found in Text Mining only
Squamous Cell Carcinoma of Head and Neck	Squamous cell carcinoma	Pubtator	37201466	Stimulate	★☆☆☆☆ Found in Text Mining only
Stomach Carcinoma	Stomach Carcinoma	BEFREE	19734198		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	38425243	Associate	★☆☆☆☆ Found in Text Mining only
Thyroid Cancer Papillary	Papillary thyroid cancer	Pubtator	35185791	Associate	★☆☆☆☆ Found in Text Mining only
Waldenstrom Macroglobulinemia	Waldenstrom`s Macroglobulinemia	BEFREE	27143257		★☆☆☆☆ Found in Text Mining only
Waldenstrom Macroglobulinemia	Waldenstrom macroglobulinemia	Pubtator	27143257, 33764527	Associate	★☆☆☆☆ Found in Text Mining only