P50545
Gene name |
Hck |
Protein name |
Tyrosine-protein kinase HCK |
Names |
Hematopoietic cell kinase, Hemopoietic cell kinase, p56-HCK, p56Hck, p59Hck |
Species |
Rattus norvegicus (Rat) |
KEGG Pathway |
rno:25734 |
EC number |
2.7.10.2: Protein-tyrosine kinases |
Protein Class |
|
Descriptions
Autoinhibitory domains (AIDs)
Target domain |
260-508 (Protein kinase domain) |
Relief mechanism |
Partner binding, Ligand binding |
Assay |
|
Target domain |
260-508 (Protein kinase domain) |
Relief mechanism |
PTM |
Assay |
|
Target domain |
260-508 (Protein kinase domain) |
Relief mechanism |
Ligand binding |
Assay |
|
Target domain |
260-508 (Protein kinase domain) |
Relief mechanism |
PTM |
Assay |
|
Accessory elements
No accessory elements
References
- Alvarado JJ et al. (2010) "Crystal structure of the Src family kinase Hck SH3-SH2 linker regulatory region supports an SH3-dominant activation mechanism", The Journal of biological chemistry, 285, 35455-61
- Engen JR et al. (2008) "Structure and dynamic regulation of Src-family kinases", Cellular and molecular life sciences : CMLS, 65, 3058-73
- Saharinen P et al. (2003) "Autoinhibition of Jak2 tyrosine kinase is dependent on specific regions in its pseudokinase domain", Molecular biology of the cell, 14, 1448-59
- Wang Q et al. (2010) "Multicolor monitoring of dysregulated protein kinases in chronic myelogenous leukemia", ACS chemical biology, 5, 887-95
- Sotirellis N et al. (1995) "Autophosphorylation induces autoactivation and a decrease in the Src homology 2 domain accessibility of the Lyn protein kinase", The Journal of biological chemistry, 270, 29773-80
- Williams NK et al. (2009) "Crystal structures of the Lyn protein tyrosine kinase domain in its Apo- and inhibitor-bound state", The Journal of biological chemistry, 284, 284-291
- Brian BF 4th et al. (2022) "SH3-domain mutations selectively disrupt Csk homodimerization or PTPN22 binding", Scientific reports, 12, 5875
- Register AC et al. (2014) "SH2-catalytic domain linker heterogeneity influences allosteric coupling across the SFK family", Biochemistry, 53, 6910-23
- Boggon TJ et al. (2004) "Structure and regulation of Src family kinases", Oncogene, 23, 7918-27
- Hong E et al. (2004) "Solution structure and backbone dynamics of the non-receptor protein-tyrosine kinase-6 Src homology 2 domain", The Journal of biological chemistry, 279, 29700-8
- Ko S et al. (2009) "Structural basis of the auto-inhibition mechanism of nonreceptor tyrosine kinase PTK6", Biochemical and biophysical research communications, 384, 236-42
- Qiu H et al. (2002) "Regulation of the nonreceptor tyrosine kinase Brk by autophosphorylation and by autoinhibition", The Journal of biological chemistry, 277, 34634-41
- Ma W et al. (2009) "Mutation profile of JAK2 transcripts in patients with chronic myeloproliferative neoplasias", The Journal of molecular diagnostics : JMD, 11, 49-53
- Laham LE et al. (2000) "The activation loop in Lck regulates oncogenic potential by inhibiting basal kinase activity and restricting substrate specificity", Oncogene, 19, 3961-70
- Furlan G et al. (2014) "Phosphatase CD45 both positively and negatively regulates T cell receptor phosphorylation in reconstituted membrane protein clusters", The Journal of biological chemistry, 289, 28514-25
- Williams JC et al. (1997) "The 2.35 A crystal structure of the inactivated form of chicken Src: a dynamic molecule with multiple regulatory interactions", Journal of molecular biology, 274, 757-75
- Meng Y et al. (2014) "Locking the active conformation of c-Src kinase through the phosphorylation of the activation loop", Journal of molecular biology, 426, 423-35
Autoinhibited structure
Activated structure
1 structures for P50545
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P50545-F1 | Predicted | AlphaFoldDB |
No variants for P50545
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for P50545 | |||||
No associated diseases with P50545
8 regional properties for P50545
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | AGC-kinase, C-terminal | 357 - 425 | IPR000961 |
| domain | Pleckstrin homology domain | 1150 - 1351 | IPR001849 |
| active_site | Serine/threonine-protein kinase, active site | 210 - 222 | IPR008271 |
| domain | HR1 rho-binding domain | 497 - 573 | IPR011072 |
| domain | ROCK, Rho binding domain | 978 - 1047 | IPR015008 |
| binding_site | Protein kinase, ATP binding site | 98 - 121 | IPR017441 |
| domain | Rho-associated protein kinase 2, catalytic domain | 39 - 417 | IPR029878 |
| domain | Rho-associated protein kinase 2, HR1 domain | 505 - 571 | IPR037311 |
Functions
| Description | ||
|---|---|---|
| EC Number | 2.7.10.2 | Protein-tyrosine kinases |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
10 GO annotations of cellular component
| Name | Definition |
|---|---|
| actin filament | A filamentous structure formed of a two-stranded helical polymer of the protein actin and associated proteins. Actin filaments are a major component of the contractile apparatus of skeletal muscle and the microfilaments of the cytoskeleton of eukaryotic cells. The filaments, comprising polymerized globular actin molecules, appear as flexible structures with a diameter of 5-9 nm. They are organized into a variety of linear bundles, two-dimensional networks, and three dimensional gels. In the cytoskeleton they are most highly concentrated in the cortex of the cell just beneath the plasma membrane. |
| caveola | A membrane raft that forms small pit, depression, or invagination that communicates with the outside of a cell and extends inward, indenting the cytoplasm and the cell membrane. Examples include flask-shaped invaginations of the plasma membrane in adipocytes associated with caveolin proteins, and minute pits or incuppings of the cell membrane formed during pinocytosis. Caveolae may be pinched off to form free vesicles within the cytoplasm. |
| cell projection | A prolongation or process extending from a cell, e.g. a flagellum or axon. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| extrinsic component of cytoplasmic side of plasma membrane | The component of a plasma membrane consisting of gene products and protein complexes that are loosely bound to its cytoplasmic surface, but not integrated into the hydrophobic region. |
| focal adhesion | A cell-substrate junction that anchors the cell to the extracellular matrix and that forms a point of termination of actin filaments. In insects focal adhesion has also been referred to as hemi-adherens junction (HAJ). |
| Golgi apparatus | A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways. |
| lysosome | A small lytic vacuole that has cell cycle-independent morphology found in most animal cells and that contains a variety of hydrolases, most of which have their maximal activities in the pH range 5-6. The contained enzymes display latency if properly isolated. About 40 different lysosomal hydrolases are known and lysosomes have a great variety of morphologies and functions. |
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
| transport vesicle | Any of the vesicles of the constitutive secretory pathway, which carry cargo from the endoplasmic reticulum to the Golgi, between Golgi cisternae, from the Golgi to the ER (retrograde transport) or to destinations within or outside the cell. |
6 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| non-membrane spanning protein tyrosine kinase activity | Catalysis of the reaction: ATP + protein L-tyrosine = ADP + protein L-tyrosine phosphate by a non-membrane spanning protein. |
| phosphotyrosine residue binding | Binding to a phosphorylated tyrosine residue within a protein. |
| protein serine/threonine/tyrosine kinase activity | Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate. |
| protein tyrosine kinase activity | Catalysis of the reaction: ATP + a protein tyrosine = ADP + protein tyrosine phosphate. |
| signaling receptor binding | Binding to one or more specific sites on a receptor molecule, a macromolecule that undergoes combination with a hormone, neurotransmitter, drug or intracellular messenger to initiate a change in cell function. |
16 GO annotations of biological process
| Name | Definition |
|---|---|
| cell differentiation | The process in which relatively unspecialized cells, e.g. embryonic or regenerative cells, acquire specialized structural and/or functional features that characterize the cells, tissues, or organs of the mature organism or some other relatively stable phase of the organism's life history. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state. |
| defense response to Gram-positive bacterium | Reactions triggered in response to the presence of a Gram-positive bacterium that act to protect the cell or organism. |
| exocytosis | A process of secretion by a cell that results in the release of intracellular molecules (e.g. hormones, matrix proteins) contained within a membrane-bounded vesicle. Exocytosis can occur either by full fusion, when the vesicle collapses into the plasma membrane, or by a kiss-and-run mechanism that involves the formation of a transient contact, a pore, between a granule (for exemple of chromaffin cells) and the plasma membrane. The latter process most of the time leads to only partial secretion of the granule content. Exocytosis begins with steps that prepare vesicles for fusion with the membrane (tethering and docking) and ends when molecules are secreted from the cell. |
| inflammatory response | The immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents. The process is characterized by local vasodilation, extravasation of plasma into intercellular spaces and accumulation of white blood cells and macrophages. |
| innate immune response | Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens. |
| negative regulation of apoptotic process | Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process. |
| peptidyl-tyrosine phosphorylation | The phosphorylation of peptidyl-tyrosine to form peptidyl-O4'-phospho-L-tyrosine. |
| phagocytosis | A vesicle-mediated transport process that results in the engulfment of external particulate material by phagocytes and their delivery to the lysosome. The particles are initially contained within phagocytic vacuoles (phagosomes), which then fuse with primary lysosomes to effect digestion of the particles. |
| positive regulation of actin cytoskeleton reorganization | Any process that activates or increases the frequency, rate or extent of actin cytoskeleton reorganization. |
| positive regulation of cell population proliferation | Any process that activates or increases the rate or extent of cell proliferation. |
| protein autophosphorylation | The phosphorylation by a protein of one or more of its own amino acid residues (cis-autophosphorylation), or residues on an identical protein (trans-autophosphorylation). |
| regulation of cell shape | Any process that modulates the surface configuration of a cell. |
| regulation of DNA-binding transcription factor activity | Any process that modulates the frequency, rate or extent of the activity of a transcription factor, any factor involved in the initiation or regulation of transcription. |
| regulation of phagocytosis | Any process that modulates the frequency, rate or extent of phagocytosis, the process in which phagocytes engulf external particulate material. |
| regulation of podosome assembly | Any process that modulates the frequency, rate or extent of podosome assembly. |
| transmembrane receptor protein tyrosine kinase signaling pathway | The series of molecular signals initiated by an extracellular ligand binding to a receptor on the surface of the target cell where the receptor possesses tyrosine kinase activity, and ending with the regulation of a downstream cellular process, e.g. transcription. |
84 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| A0JNB0 | FYN | Tyrosine-protein kinase Fyn | Bos taurus (Bovine) | SS |
| Q0VBZ0 | CSK | Tyrosine-protein kinase CSK | Bos taurus (Bovine) | SS |
| Q3ZC95 | BTK | Tyrosine-protein kinase | Bos taurus (Bovine) | EV SS |
| P42683 | LCK | Proto-oncogene tyrosine-protein kinase LCK | Gallus gallus (Chicken) | SS |
| P41239 | CSK | Tyrosine-protein kinase CSK | Gallus gallus (Chicken) | SS |
| P00523 | SRC | Proto-oncogene tyrosine-protein kinase Src | Gallus gallus (Chicken) | EV |
| Q02977 | YRK | Proto-oncogene tyrosine-protein kinase Yrk | Gallus gallus (Chicken) | SS |
| Q8JH64 | BTK | Tyrosine-protein kinase BTK | Gallus gallus (Chicken) | SS |
| P09324 | YES1 | Tyrosine-protein kinase Yes | Gallus gallus (Chicken) | SS |
| Q05876 | FYN | Tyrosine-protein kinase Fyn | Gallus gallus (Chicken) | SS |
| Q75R65 | JAK2 | Tyrosine-protein kinase JAK2 | Gallus gallus (Chicken) | SS |
| Q24592 | hop | Tyrosine-protein kinase hopscotch | Drosophila melanogaster (Fruit fly) | PR |
| P08630 | Btk | Tyrosine-protein kinase Btk | Drosophila melanogaster (Fruit fly) | SS |
| Q9V9J3 | Src42A | Tyrosine-protein kinase Src42A | Drosophila melanogaster (Fruit fly) | SS |
| P00528 | Src64B | Tyrosine-protein kinase Src64B | Drosophila melanogaster (Fruit fly) | SS |
| P41240 | CSK | Tyrosine-protein kinase CSK | Homo sapiens (Human) | SS |
| P51451 | BLK | Tyrosine-protein kinase Blk | Homo sapiens (Human) | SS |
| P06239 | LCK | Tyrosine-protein kinase Lck | Homo sapiens (Human) | EV |
| P23458 | JAK1 | Tyrosine-protein kinase JAK1 | Homo sapiens (Human) | SS |
| P06241 | FYN | Tyrosine-protein kinase Fyn | Homo sapiens (Human) | SS |
| P51813 | BMX | Cytoplasmic tyrosine-protein kinase BMX | Homo sapiens (Human) | SS |
| P12931 | SRC | Proto-oncogene tyrosine-protein kinase Src | Homo sapiens (Human) | EV |
| P09769 | FGR | Tyrosine-protein kinase Fgr | Homo sapiens (Human) | SS |
| P42680 | TEC | Tyrosine-protein kinase Tec | Homo sapiens (Human) | SS |
| O60674 | JAK2 | Tyrosine-protein kinase JAK2 | Homo sapiens (Human) | EV |
| P42679 | MATK | Megakaryocyte-associated tyrosine-protein kinase | Homo sapiens (Human) | SS |
| P52333 | JAK3 | Tyrosine-protein kinase JAK3 | Homo sapiens (Human) | SS |
| Q08881 | ITK | Tyrosine-protein kinase ITK/TSK | Homo sapiens (Human) | EV |
| P07948 | LYN | Tyrosine-protein kinase Lyn | Homo sapiens (Human) | SS |
| P29597 | TYK2 | Non-receptor tyrosine-protein kinase TYK2 | Homo sapiens (Human) | EV |
| Q13882 | PTK6 | Protein-tyrosine kinase 6 | Homo sapiens (Human) | EV |
| P07947 | YES1 | Tyrosine-protein kinase Yes | Homo sapiens (Human) | SS |
| P42685 | FRK | Tyrosine-protein kinase FRK | Homo sapiens (Human) | EV |
| Q06187 | BTK | Tyrosine-protein kinase BTK | Homo sapiens (Human) | EV |
| P08631 | HCK | Tyrosine-protein kinase HCK | Homo sapiens (Human) | EV |
| Q9R117 | Tyk2 | Non-receptor tyrosine-protein kinase TYK2 | Mus musculus (Mouse) | SS |
| P16277 | Blk | Tyrosine-protein kinase Blk | Mus musculus (Mouse) | SS |
| Q62270 | Srms | Tyrosine-protein kinase Srms | Mus musculus (Mouse) | SS |
| Q64434 | Ptk6 | Protein-tyrosine kinase 6 | Mus musculus (Mouse) | SS |
| P05480 | Src | Proto-oncogene tyrosine-protein kinase Src | Mus musculus (Mouse) | EV |
| P14234 | Fgr | Tyrosine-protein kinase Fgr | Mus musculus (Mouse) | SS |
| P35991 | Btk | Tyrosine-protein kinase BTK | Mus musculus (Mouse) | EV |
| P41241 | Csk | Tyrosine-protein kinase CSK | Mus musculus (Mouse) | EV |
| P25911 | Lyn | Tyrosine-protein kinase Lyn | Mus musculus (Mouse) | EV |
| Q62137 | Jak3 | Tyrosine-protein kinase JAK3 | Mus musculus (Mouse) | SS |
| Q62120 | Jak2 | Tyrosine-protein kinase JAK2 | Mus musculus (Mouse) | EV |
| P06240 | Lck | Proto-oncogene tyrosine-protein kinase LCK | Mus musculus (Mouse) | SS |
| P24604 | Tec | Tyrosine-protein kinase Tec | Mus musculus (Mouse) | SS |
| Q04736 | Yes1 | Tyrosine-protein kinase Yes | Mus musculus (Mouse) | SS |
| P39688 | Fyn | Tyrosine-protein kinase Fyn | Mus musculus (Mouse) | SS |
| P52332 | Jak1 | Tyrosine-protein kinase JAK1 | Mus musculus (Mouse) | SS |
| Q03526 | Itk | Tyrosine-protein kinase ITK/TSK | Mus musculus (Mouse) | SS |
| P41242 | Matk | Megakaryocyte-associated tyrosine-protein kinase | Mus musculus (Mouse) | SS |
| Q922K9 | Frk | Tyrosine-protein kinase FRK | Mus musculus (Mouse) | SS |
| P08103 | Hck | Tyrosine-protein kinase HCK | Mus musculus (Mouse) | SS |
| A1Y2K1 | FYN | Tyrosine-protein kinase Fyn | Sus scrofa (Pig) | SS |
| O19064 | JAK2 | Tyrosine-protein kinase JAK2 | Sus scrofa (Pig) | SS |
| Q62689 | Jak2 | Tyrosine-protein kinase JAK2 | Rattus norvegicus (Rat) | SS |
| Q63272 | Jak3 | Tyrosine-protein kinase JAK3 | Rattus norvegicus (Rat) | SS |
| Q64725 | Syk | Tyrosine-protein kinase SYK | Rattus norvegicus (Rat) | SS |
| Q6P6U0 | Fgr | Tyrosine-protein kinase Fgr | Rattus norvegicus (Rat) | SS |
| Q07014 | Lyn | Tyrosine-protein kinase Lyn | Rattus norvegicus (Rat) | SS |
| Q62844 | Fyn | Tyrosine-protein kinase Fyn | Rattus norvegicus (Rat) | SS |
| Q9WUD9 | Src | Proto-oncogene tyrosine-protein kinase Src | Rattus norvegicus (Rat) | SS |
| F1LM93 | Yes1 | Tyrosine-protein kinase Yes | Rattus norvegicus (Rat) | SS |
| Q62662 | Frk | Tyrosine-protein kinase FRK | Rattus norvegicus (Rat) | SS |
| P41243 | Matk | Megakaryocyte-associated tyrosine-protein kinase | Rattus norvegicus (Rat) | SS |
| P32577 | Csk | Tyrosine-protein kinase CSK | Rattus norvegicus (Rat) | SS |
| P70600 | Ptk2b | Protein-tyrosine kinase 2-beta | Rattus norvegicus (Rat) | PR |
| O35346 | Ptk2 | Focal adhesion kinase 1 | Rattus norvegicus (Rat) | SS |
| Q5U2X5 | Tnk2 | Activated CDC42 kinase 1 | Rattus norvegicus (Rat) | SS |
| Q01621 | Lck | Proto-oncogene tyrosine-protein kinase LCK | Rattus norvegicus (Rat) | SS |
| P09760 | Fer | Tyrosine-protein kinase Fer | Rattus norvegicus (Rat) | PR |
| G5ECJ6 | csk-1 | Tyrosine-protein kinase csk-1 | Caenorhabditis elegans | SS |
| O45539 | src-2 | Tyrosine protein-kinase src-2 | Caenorhabditis elegans | SS |
| G5EE56 | src-1 | Tyrosine protein-kinase src-1 | Caenorhabditis elegans | SS |
| F4JTP5 | STY46 | Serine/threonine-protein kinase STY46 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| O22558 | STY8 | Serine/threonine-protein kinase STY8 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q8RWL6 | STY17 | Serine/threonine-protein kinase STY17 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| A1A5H8 | yes1 | Tyrosine-protein kinase yes | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| F1RDG9 | fynb | Tyrosine-protein kinase fynb | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| O12990 | jak1 | Tyrosine-protein kinase JAK1 | Danio rerio (Zebrafish) (Brachydanio rerio) | PR |
| Q1JPZ3 | src | Proto-oncogene tyrosine-protein kinase Src | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| Q6EWH2 | fyna | Tyrosine-protein kinase fyna | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MGGRSSCEDP | GCPRGEGRVP | RMGCVKSRFL | REGSKASKIE | PNANQKGPVY | VPDPTSPKKL |
| 70 | 80 | 90 | 100 | 110 | 120 |
| GPNSINSLPP | GVVEGSEDTI | VVALYDYEAI | HREDLSFQKG | DQMVVLEESG | EWWKARSLAT |
| 130 | 140 | 150 | 160 | 170 | 180 |
| KKEGYIPSNY | VARVNSLETE | EWFFKGISRK | DAERHLLAPG | NMLGSFMIRD | SETTKGSYSL |
| 190 | 200 | 210 | 220 | 230 | 240 |
| SVRDFDPQHG | DTVKHYKIRT | LDSGGFYISP | RSTFSSLQEL | VVHYKKGKDG | LCQKLSVPCV |
| 250 | 260 | 270 | 280 | 290 | 300 |
| SPKPQKPWEK | DAWEIPRESL | QMEKKLGAGQ | FGEVWMATYN | KHTKVAVKTM | KPGSMSVEAF |
| 310 | 320 | 330 | 340 | 350 | 360 |
| LAEANLMKTL | QHDKLVKLHA | VVSQEPIFIV | TEFMAKGSLL | DFLKSEEGSK | QPLPKLIDFS |
| 370 | 380 | 390 | 400 | 410 | 420 |
| AQISEGMAFI | EQRNYIHRDL | RAANILVSAS | LVCKIADFGL | ARIIEDNEYT | AREGAKFPIK |
| 430 | 440 | 450 | 460 | 470 | 480 |
| WTAPEAINFG | SFTIKSDVWS | FGILLMEIVT | YGRIPYPGMS | NPEVIRALEH | GYRMPRPDNC |
| 490 | 500 | 510 | 520 | ||
| PEELYSIMIR | CWKNRPEERP | TFEYIQSVLD | DFYTATESQY | QQQP |