Protein: Tyrosine-protein kinase HCK (EC 2.7.10.2) (Hematopoietic cell kinase) (Hemopoietic cell kinase) (p59-HCK/p60-HCK) (p59Hck) (p61Hck) (P08631)
Organism: Homo sapiens (Human)
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.
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.
Interaction partners:
- Tyrosine-protein kinase Lyn
- Engulfment and cell motility protein 1
- Receptor-type tyrosine-protein phosphatase C
- High affinity immunoglobulin gamma Fc receptor I
- SHC-transforming protein 1
- Low affinity immunoglobulin gamma Fc region receptor II-a
- Focal adhesion kinase 1
- Low affinity immunoglobulin gamma Fc region receptor III-A
- Tyrosine-protein kinase ITK/TSK
- Low affinity immunoglobulin gamma Fc region receptor III-B
Sequence:
MGGRSSCEDPGCPRDEERAPRMGCMKSKFLQVGGNTFSKTETSASPHCPVYVPDPTSTIKPGPNSHNSNTPGIREAGSEDIIVVALYDYEAIHHEDLSFQKGDQMVVLEESGEWWKARSLATRKEGYIPSNYVARVDSLETEEWFFKGISRKDAERQLLAPGNMLGSFMIRDSETTKGSYSLSVRDYDPRQGDTVKHYKIRTLDNGGFYISPRSTFSTLQELVDHYKKGNDGLCQKLSVPCMSSKPQKPWEKDAWEIPRESLKLEKKLGAGQFGEVWMATYNKHTKVAVKTMKPGSMSVEAFLAEANVMKTLQHDKLVKLHAVVTKEPIYIITEFMAKGSLLDFLKSDEGSKQPLPKLIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVIEDNEYTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPENCPEELYNIMMRCWKNRPEERPTFEYIQSVLDDFYTATESQYQQQP