HCK
entrez
3055
canonical
uniprot
P08631
canonical
ensembl
ENSG00000101336
resolver
ensp
ENSP00000365012
resolver
ensp
ENSP00000365022
resolver
ensp
ENSP00000427757
resolver
ensp
ENSP00000429848
resolver
ensp
ENSP00000486627
resolver
genesymbol
HCK
resolver
hgnc
HGNC:4840
resolver
uniprot
A8K1I1
resolver
uniprot
A8K4G3
resolver
uniprot
B4DQB6
resolver
uniprot
E1P5M2
resolver
uniprot
Q29RX1
resolver
uniprot
Q2VPE2
resolver
uniprot
Q504R5
resolver
uniprot
Q5T7K1
resolver
uniprot
Q5T7K2
resolver
uniprot
Q96CC0
resolver
uniprot
Q9H5Y5
resolver
uniprot
Q9NUA4
resolver
uniprot
Q9UMJ5
resolver
uniprot_entry
A8K4G3_HUMAN
resolver
uniprot_entry
HCK_HUMAN
resolver
uniprot_sec
A8K1I1
resolver
uniprot_sec
B4DQB6
resolver
uniprot_sec
E1P5M2
resolver
uniprot_sec
Q29RX1
resolver
uniprot_sec
Q2VPE2
resolver
uniprot_sec
Q504R5
resolver
uniprot_sec
Q5T7K1
resolver
uniprot_sec
Q5T7K2
resolver
uniprot_sec
Q96CC0
resolver
uniprot_sec
Q9H5Y5
resolver
uniprot_sec
Q9NUA4
resolver
uniprot_sec
Q9UMJ5
resolver
activity_regulation
ACTIVITY 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. {ECO:0000269|PubMed:10644735, ECO:0000269|PubMed:10779760, ECO:0000269|PubMed:10973280, ECO:0000269|PubMed:16216497, ECO:0000269|PubMed:16849330, ECO:0000269|PubMed:20810664, ECO:0000269|PubMed:7535819, ECO:0000269|PubMed:9218412, ECO:0000269|PubMed:9406996}.
uniprot
proteins
amino_acid_sequence
MGGRSSCEDPGCPRDEERAPRMGCMKSKFLQVGGNTFSKTETSASPHCPVYVPDPTSTIKPGPNSHNSNTPGIREAGSEDIIVVALYDYEAIHHEDLSFQKGDQMVVLEESGEWWKARSLATRKEGYIPSNYVARVDSLETEEWFFKGISRKDAERQLLAPGNMLGSFMIRDSETTKGSYSLSVRDYDPRQGDTVKHYKIRTLDNGGFYISPRSTFSTLQELVDHYKKGNDGLCQKLSVPCMSSKPQKPWEKDAWEIPRESLKLEKKLGAGQFGEVWMATYNKHTKVAVKTMKPGSMSVEAFLAEANVMKTLQHDKLVKLHAVVTKEPIYIITEFMAKGSLLDFLKSDEGSKQPLPKLIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVIEDNEYTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPENCPEELYNIMMRCWKNRPEERPTFEYIQSVLDDFYTATESQYQQQP
uniprot
proteins
disease_involvement
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.; DISEASE: Autoinflammation with pulmonary and cutaneous vasculitis (AIPCV) [MIM:620296]: An autosomal dominant disorder characterized by cutaneous vasculitis and chronic pulmonary inflammation that evolves to fibrosis. AIPCV manifests soon after birth with petechial skin lesions, followed by progressive pulmonary involvement causing restrictive lung disease and respiratory insufficiency. {ECO:0000269|PubMed:34536415}. Note=The disease may be caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.10.2
uniprot
proteins
function
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. {ECO:0000269|PubMed:10092522, ECO:0000269|PubMed:10779760, ECO:0000269|PubMed:10973280, ECO:0000269|PubMed:11741929, ECO:0000269|PubMed:11896602, ECO:0000269|PubMed:12411494, ECO:0000269|PubMed:15010462, ECO:0000269|PubMed:15952790, ECO:0000269|PubMed:15998323, ECO:0000269|PubMed:17310994, ECO:0000269|PubMed:17535448, ECO:0000269|PubMed:19114024, ECO:0000269|PubMed:19903482, ECO:0000269|PubMed:20452982, ECO:0000269|PubMed:21338576, ECO:0000269|PubMed:7535819, ECO:0000269|PubMed:8132624, ECO:0000269|PubMed:9406996, ECO:0000269|PubMed:9407116}.
uniprot
proteins
mass_dalton
59600
uniprot
proteins
mutagenesis
MUTAGEN 3; /note="G->C: Slight palmitoylation, cytoplasmic and caveolar localization; in isoform 1;."; /evidence="ECO:0000269|PubMed:11904303, ECO:0000269|PubMed:7791757"; MUTAGEN 3; /note="G->S: Abolishes palmitoylation and localization at the cell membrane."; /evidence="ECO:0000269|PubMed:11904303, ECO:0000269|PubMed:7791757"; MUTAGEN 23; /note="G->A: Myristoylation and palmitoylation are abolished, leading to entirely cytoplasmic localization; in isoform 2."; /evidence="ECO:0000269|PubMed:7791757"; MUTAGEN 24; /note="C->S: Palmitoylation is abolished, some cytoplasmic and no calveolar localization; in isoform 2."; /evidence="ECO:0000269|PubMed:7791757"; MUTAGEN 290; /note="K->E: Loss of kinase activity."; /evidence="ECO:0000269|PubMed:11896602"; MUTAGEN 305; /note="E->A: Loss of kinase activity."; /evidence="ECO:0000269|PubMed:10644735"; MUTAGEN 381; /note="D->E: Loss of kinase activity."; /evidence="ECO:0000269|PubMed:15998323"; MUTAGEN 411; /note="Y->A: Reduced catalytic activity and higher affinity for target peptides."; /evidence="ECO:0000269|PubMed:10644735"; MUTAGEN 522; /note="Y->F: Constitutively activated kinase, leading to cellular transformation."; /evidence="ECO:0000269|PubMed:10092522, ECO:0000269|PubMed:11896602
uniprot
proteins
post_translational_modification
PTM: 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 kinases. {ECO:0000269|PubMed:10360180, ECO:0000269|PubMed:10644735, ECO:0000269|PubMed:10779760, ECO:0000269|PubMed:11896602, ECO:0000269|PubMed:12411494, ECO:0000269|PubMed:16216497, ECO:0000269|PubMed:8064233, ECO:0000269|PubMed:9024658, ECO:0000269|PubMed:9406996}.; PTM: Ubiquitinated by CBL, leading to its degradation via the proteasome. {ECO:0000269|PubMed:11896602}.; PTM: Isoform 2 palmitoylation at position 2 requires prior myristoylation. Palmitoylation at position 3 is required for caveolar localization of isoform 2. {ECO:0000269|PubMed:7791757}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
SRC subfamily
uniprot
proteins
protein_family
Tyr protein kinase family
uniprot
proteins
pubmed
10092522
uniprot
proteins
pubmed
10360180
uniprot
proteins
pubmed
10644735
uniprot
proteins
pubmed
10779760
uniprot
proteins
pubmed
10973280
uniprot
proteins
pubmed
11278465
uniprot
proteins
pubmed
11518702
uniprot
proteins
pubmed
11741929
uniprot
proteins
pubmed
11780052
uniprot
proteins
pubmed
11896602
uniprot
proteins
pubmed
11904303
uniprot
proteins
pubmed
12411494
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15010462
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
1572549
uniprot
proteins
pubmed
15952790
uniprot
proteins
pubmed
15998323
uniprot
proteins
pubmed
16216497
uniprot
proteins
pubmed
16849330
uniprot
proteins
pubmed
16997556
uniprot
proteins
pubmed
17141806
uniprot
proteins
pubmed
17310994
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17535448
uniprot
proteins
pubmed
18538446
uniprot
proteins
pubmed
1875927
uniprot
proteins
pubmed
19114024
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19718658
uniprot
proteins
pubmed
19807924
uniprot
proteins
pubmed
19903482
uniprot
proteins
pubmed
20452982
uniprot
proteins
pubmed
20810664
uniprot
proteins
pubmed
21338576
uniprot
proteins
pubmed
21477083
uniprot
proteins
pubmed
21625496
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
25469238
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
3453117
uniprot
proteins
pubmed
34536415
uniprot
proteins
pubmed
3496523
uniprot
proteins
pubmed
7535819
uniprot
proteins
pubmed
7791757
uniprot
proteins
pubmed
8064233
uniprot
proteins
pubmed
8132624
uniprot
proteins
pubmed
8995234
uniprot
proteins
pubmed
9024658
uniprot
proteins
pubmed
9109402
uniprot
proteins
pubmed
9218412
uniprot
proteins
pubmed
9406996
uniprot
proteins
pubmed
9407116
uniprot
proteins
pubmed
9571048
uniprot
proteins
pubmed
9778343
uniprot
proteins
sequence_length
526
uniprot
proteins
subcellular_location
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 {ECO:0000269|PubMed:11904303}; Lipid-anchor {ECO:0000269|PubMed:11904303}. Membrane, caveola {ECO:0000269|PubMed:11904303}; Lipid-anchor {ECO:0000269|PubMed:11904303}. Cell junction, focal adhesion {ECO:0000269|PubMed:11904303}. Cytoplasm, cytoskeleton {ECO:0000269|PubMed:11904303}. Golgi apparatus {ECO:0000269|PubMed:11904303}. Cytoplasmic vesicle {ECO:0000269|PubMed:11904303}. Lysosome {ECO:0000269|PubMed:11904303}. Nucleus {ECO:0000269|PubMed:11904303}. 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.
uniprot
proteins