. "SEQUENCE 526 AA; 59600 MW; 847E877A0A641725 CRC64;"^^ . "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. 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. ALTERNATIVE PRODUCTS: Event=Alternative splicing, Alternative initiation; Named isoforms=4; Name=1; Synonyms=p60-HCK, p61Hck; IsoId=P08631-1; Sequence=Displayed; Note=Initiates from a CTG codon; Name=2; Synonyms=p59-HCK, p59Hck; IsoId=P08631-2; Sequence=VSP_018858; Note=Met-1 is removed. Myristoylated at Gly-2. S-palmitoylated at Cys-3; Name=3; IsoId=P08631-3; Sequence=VSP_018858, VSP_041926; Name=4; IsoId=P08631-4; Sequence=VSP_041926; Note=Initiates from a CTG codon; 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 palmytoylation at position 2 requires prior myristoylation. Palmytoylation 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; GENE SYNONYMS:HCK. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License."^^ . . . . . . . . . . . . . . . . . . . . . "HCK_HUMAN"^^ . "2.7.10.2"^^ . "Hemopoietic cell kinase"^^ . "p59-HCK/p60-HCK"^^ . "HCK"^^ . "Hematopoietic cell kinase"^^ . "p59Hck"^^ . "p61Hck"^^ . . . . . . . . . . . . . "MGGRSSCEDPGCPRDEERAPRMGCMKSKFLQVGGNTFSKTETSASPHCPVYVPDPTSTIKPGPNSHNSNTPGIREAGSEDIIVVALYDYEAIHHEDLSFQKGDQMVVLEESGEWWKARSLATRKEGYIPSNYVARVDSLETEEWFFKGISRKDAERQLLAPGNMLGSFMIRDSETTKGSYSLSVRDYDPRQGDTVKHYKIRTLDNGGFYISPRSTFSTLQELVDHYKKGNDGLCQKLSVPCMSSKPQKPWEKDAWEIPRESLKLEKKLGAGQFGEVWMATYNKHTKVAVKTMKPGSMSVEAFLAEANVMKTLQHDKLVKLHAVVTKEPIYIITEFMAKGSLLDFLKSDEGSKQPLPKLIDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVIEDNEYTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPENCPEELYNIMMRCWKNRPEERPTFEYIQSVLDDFYTATESQYQQQP"^^ . "Tyrosine-protein kinase HCK"^^ .