Q95M30 (HCK_MACFA) Reviewed, UniProtKB/Swiss-Prot
Last modified October 16, 2013. Version 93. History...
Names and origin
|Protein names||Recommended name:|
Tyrosine-protein kinase HCK
Hematopoietic cell kinase
Hemopoietic cell kinase
|Organism||Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey)|
|Taxonomic identifier||9541 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Cercopithecidae › Cercopithecinae › Macaca|
|Sequence length||504 AA.|
|Sequence processing||The displayed sequence is further processed into a mature form.|
|Protein existence||Evidence at transcript level|
General annotation (Comments)
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 By similarity.
ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
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-389 is required for optimal activity. Phosphorylation at Tyr-500 inhibits kinase activity By similarity.
Interacts with ADAM15. Interacts with FASLG. Interacts with ARRB1 and ARRB2. 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. Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with CBL. Interacts with VAV1, WAS and RAPGEF1 By similarity.
Cytoplasmic vesicle › secretory vesicle By similarity. Cytoplasm › cytosol By similarity. Cell membrane; Lipid-anchor. Membrane › caveola; Lipid-anchor By similarity. Cell junction › focal adhesion By similarity. Cytoplasm › cytoskeleton By similarity. Golgi apparatus By similarity. Cytoplasmic vesicle By similarity. Lysosome By similarity. Nucleus By similarity. Note: A small fraction 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 By similarity.
Phosphorylated on several tyrosine residues. Autophosphorylated. Becomes rapidly phosphorylated upon activation of the immunoglobulin receptors FCGR1A and FCGR2A. Phosphorylation at Tyr-389 increases kinase activity. Phosphorylation at Tyr-500 inhibits kinase activity. Kinase activity is not required for phosphorylation at Tyr-500, suggesting that this site may be a target of other kinases By similarity.
Ubiquitinated by CBL, leading to its degradation via the proteasome By similarity.
Palmitoylation requires prior myristoylation. Palmitoylation is required for caveolar localization By similarity.
Contains 1 protein kinase domain.
Contains 1 SH2 domain.
Contains 1 SH3 domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Initiator methionine||1||1||Removed By similarity|
|Chain||2 – 504||503||Tyrosine-protein kinase HCK||PRO_0000088103|
|Domain||56 – 116||61||SH3|
|Domain||122 – 219||98||SH2|
|Domain||240 – 493||254||Protein kinase|
|Nucleotide binding||246 – 254||9||ATP By similarity|
|Active site||359||1||Proton acceptor By similarity|
|Binding site||268||1||ATP By similarity|
Amino acid modifications
|Modified residue||30||1||Phosphotyrosine By similarity|
|Modified residue||180||1||Phosphothreonine By similarity|
|Modified residue||187||1||Phosphotyrosine By similarity|
|Modified residue||389||1||Phosphotyrosine; by autocatalysis By similarity|
|Modified residue||440||1||Phosphoserine By similarity|
|Modified residue||500||1||Phosphotyrosine By similarity|
|Lipidation||2||1||N-myristoyl glycine By similarity|
|Lipidation||3||1||S-palmitoyl cysteine By similarity|
Thesis (2001), University of Marseille, France
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|AJ320181 mRNA. Translation: CAC44031.1.|
3D structure databases
|SMR||Q95M30. Positions 56-504. |
Protocols and materials databases
Enzyme and pathway databases
|BRENDA||126.96.36.199. 3121. |
Family and domain databases
|Gene3D||3.30.505.10. 1 hit. |
|InterPro||IPR011009. Kinase-like_dom. |
|Pfam||PF07714. Pkinase_Tyr. 1 hit. |
PF00017. SH2. 1 hit.
PF00018. SH3_1. 1 hit.
|PRINTS||PR00401. SH2DOMAIN. |
|SMART||SM00252. SH2. 1 hit. |
SM00326. SH3. 1 hit.
SM00219. TyrKc. 1 hit.
|SUPFAM||SSF50044. SSF50044. 1 hit. |
SSF56112. SSF56112. 1 hit.
|PROSITE||PS00107. PROTEIN_KINASE_ATP. 1 hit. |
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
PS50001. SH2. 1 hit.
PS50002. SH3. 1 hit.
|Accession||Primary (citable) accession number: Q95M30|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families