P08103 · HCK_MOUSE
- ProteinTyrosine-protein kinase HCK
- GeneHck
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids524 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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 (By similarity).
Catalytic activity
- ATP + L-tyrosyl-[protein] = ADP + H+ + O-phospho-L-tyrosyl-[protein]
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-409 is required for optimal activity. Phosphorylation at Tyr-520 inhibits kinase activity. Inhibited by PP1.
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTyrosine-protein kinase HCK
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP08103
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Isoform 1
Membrane ; Lipid-anchor
Cell projection, podosome membrane ; Lipid-anchor
Note: Associated with specialized secretory lysosomes called azurophil granules. A fraction of this isoform is found in the cytoplasm, some of this fraction is myristoylated (By similarity).
Isoform 2
Cell membrane ; Lipid-anchor
Membrane, caveola ; Lipid-anchor
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 (By similarity).
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
No visible phenotype, but macrophages have impaired phagocytosis. Mice lacking both HCK and FGR are extremely sensitive to infections by L.monocytogenes.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 409 | Reduced autophosphorylation. | ||||
Sequence: Y → F |
Keywords
- Disease
PTM/Processing
Features
Showing features for initiator methionine, lipidation, chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Initiator methionine | 1 | In isoform P08103-2; Removed | ||||
Sequence: M | ||||||
Lipidation | 2 | N-myristoyl glycine | ||||
Sequence: G | ||||||
Lipidation | 2 | In isoform P08103-2; N-myristoyl glycine | ||||
Sequence: G | ||||||
Chain | PRO_0000024435 | 2-524 | Tyrosine-protein kinase HCK | |||
Sequence: GGRSSCEDPGCPRSEGRAPRMGCVKSRFLRDGSKASKTEPSANQKGPVYVPDPTSSSKLGPNNSNSMPPGFVEGSEDTIVVALYDYEAIHREDLSFQKGDQMVVLEEAGEWWKARSLATKKEGYIPSNYVARVNSLETEEWFFKGISRKDAERHLLAPGNMLGSFMIRDSETTKGSYSLSVRDFDPQHGDTVKHYKIRTLDSGGFYISPRSTFSSLQELVLHYKKGKDGLCQKLSVPCVSPKPQKPWEKDAWEIPRESLQMEKKLGAGQFGEVWMATYNKHTKVAVKTMKPGSMSVEAFLAEANLMKSLQHDKLVKLHAVVSQEPIFIVTEFMAKGSLLDFLKSEEGSKQPLPKLIDFSAQISEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARIIEDNEYTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALEHGYRMPRPDNCPEELYNIMIRCWKNRPEERPTFEYIQSVLDDFYTATESQYQQQP | ||||||
Lipidation | 3 | In isoform P08103-2; S-palmitoyl cysteine | ||||
Sequence: G | ||||||
Modified residue | 50 | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | ||||||
Modified residue | 200 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 207 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 409 | Phosphotyrosine; by autocatalysis | ||||
Sequence: Y | ||||||
Modified residue | 460 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 520 | Phosphotyrosine | ||||
Sequence: Y |
Post-translational modification
Phosphorylated on several tyrosine residues. Autophosphorylated. Becomes rapidly phosphorylated upon activation of the immunoglobulin receptors FCGR1A and FCGR2A. Phosphorylation at Tyr-409 increases kinase activity. Phosphorylation at Tyr-520 inhibits kinase activity. Kinase activity is not required for phosphorylation at Tyr-520, suggesting that this site may be a target of other kinases.
Ubiquitinated by CBL, leading to its degradation via the proteasome.
Isoform 2 palmitoylation at position 2 requires prior myristoylation. Palmitoylation at position 3 is required for caveolar localization of isoform 2.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed predominantly in cells of the myeloid and B-lymphoid lineages.
Gene expression databases
Interaction
Subunit
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 (By similarity).
Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with CBL. Interacts with VAV1, WAS and RAPGEF1. Interacts (via SH3 domain) with WDCP (By similarity).
Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with CBL. Interacts with VAV1, WAS and RAPGEF1. Interacts (via SH3 domain) with WDCP (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
XENO | P08103 | WAS P42768 | 3 | EBI-6248894, EBI-346375 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-72 | Disordered | ||||
Sequence: MGGRSSCEDPGCPRSEGRAPRMGCVKSRFLRDGSKASKTEPSANQKGPVYVPDPTSSSKLGPNNSNSMPPGF | ||||||
Compositional bias | 37-72 | Polar residues | ||||
Sequence: SKTEPSANQKGPVYVPDPTSSSKLGPNNSNSMPPGF | ||||||
Domain | 76-136 | SH3 | ||||
Sequence: SEDTIVVALYDYEAIHREDLSFQKGDQMVVLEEAGEWWKARSLATKKEGYIPSNYVARVNS | ||||||
Domain | 142-239 | SH2 | ||||
Sequence: WFFKGISRKDAERHLLAPGNMLGSFMIRDSETTKGSYSLSVRDFDPQHGDTVKHYKIRTLDSGGFYISPRSTFSSLQELVLHYKKGKDGLCQKLSVPC | ||||||
Domain | 260-513 | Protein kinase | ||||
Sequence: LQMEKKLGAGQFGEVWMATYNKHTKVAVKTMKPGSMSVEAFLAEANLMKSLQHDKLVKLHAVVSQEPIFIVTEFMAKGSLLDFLKSEEGSKQPLPKLIDFSAQISEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARIIEDNEYTAREGAKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALEHGYRMPRPDNCPEELYNIMIRCWKNRPEERPTFEYIQSVLDDFY |
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative initiation.
P08103-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Synonymsp59-HCK
- NoteInitiates from a CTG codon.
- Length524
- Mass (Da)59,129
- Last updated2007-01-23 v4
- ChecksumDF72FD69B38C9706
P08103-2
- Name2
- Synonymsp56-HCK
- Differences from canonical
- 1-21: Missing
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
F6UND7 | F6UND7_MOUSE | Hck | 524 |
Sequence caution
Features
Showing features for alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_018859 | 1-21 | in isoform 2 | |||
Sequence: Missing | ||||||
Compositional bias | 37-72 | Polar residues | ||||
Sequence: SKTEPSANQKGPVYVPDPTSSSKLGPNNSNSMPPGF |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
Y00487 EMBL· GenBank· DDBJ | CAA68544.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
J03023 EMBL· GenBank· DDBJ | AAA37305.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
AK149736 EMBL· GenBank· DDBJ | BAE29054.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
AK150290 EMBL· GenBank· DDBJ | BAE29445.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
AK150709 EMBL· GenBank· DDBJ | BAE29787.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
AK155975 EMBL· GenBank· DDBJ | BAE33532.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
AK165315 EMBL· GenBank· DDBJ | BAE38133.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
BC010478 EMBL· GenBank· DDBJ | AAH10478.2 EMBL· GenBank· DDBJ | mRNA |