P42683
Gene name |
LCK |
Protein name |
Proto-oncogene tyrosine-protein kinase LCK |
Names |
EC 2.7.10.2 , Protein-tyrosine kinase C-TKL , p56tk1 |
Species |
Gallus gallus (Chicken) |
KEGG Pathway |
|
EC number |
2.7.10.2: Protein-tyrosine kinases |
Protein Class |
|
Descriptions
Autoinhibitory domains (AIDs)
Target domain |
244-497 (Protein kinase domain) |
Relief mechanism |
Partner binding, Ligand binding |
Assay |
|
Target domain |
244-497 (Protein kinase domain) |
Relief mechanism |
PTM |
Assay |
|
Target domain |
244-497 (Protein kinase domain) |
Relief mechanism |
Ligand binding |
Assay |
|
Target domain |
244-497 (Protein kinase domain) |
Relief mechanism |
PTM |
Assay |
|
Accessory elements
380-404 (Activation loop from InterPro)
Target domain |
244-497 (Protein kinase domain) |
Relief mechanism |
|
Assay |
|
References
- 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
- Engen JR et al. (2008) "Structure and dynamic regulation of Src-family kinases", Cellular and molecular life sciences : CMLS, 65, 3058-73
- 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
- Schindler T et al. (1999) "Crystal structure of Hck in complex with a Src family-selective tyrosine kinase inhibitor", Molecular cell, 3, 639-48
- 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
- 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
- Kükenshöner T et al. (2017) "Selective Targeting of SH2 Domain-Phosphotyrosine Interactions of Src Family Tyrosine Kinases with Monobodies", Journal of molecular biology, 429, 1364-1380
- 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
Autoinhibited structure
Activated structure
1 structures for P42683
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P42683-F1 | Predicted | AlphaFoldDB |
No variants for P42683
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for P42683 | |||||
No associated diseases with P42683
9 regional properties for P42683
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Protein kinase domain | 244 - 497 | IPR000719 |
| domain | SH2 domain | 124 - 223 | IPR000980 |
| domain | Serine-threonine/tyrosine-protein kinase, catalytic domain | 244 - 492 | IPR001245 |
| domain | SH3 domain | 60 - 120 | IPR001452 |
| active_site | Tyrosine-protein kinase, active site | 359 - 371 | IPR008266 |
| binding_site | Protein kinase, ATP binding site | 250 - 272 | IPR017441 |
| domain | Tyrosine-protein kinase, catalytic domain | 244 - 493 | IPR020635 |
| domain | Lck, SH3 domain | 64 - 117 | IPR035749 |
| domain | Tyrosine-protein kinase Lck, SH2 domain | 122 - 222 | IPR035850 |
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 | |
4 GO annotations of cellular component
| Name | Definition |
|---|---|
| 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. |
| membrane raft | Any of the small (10-200 nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched membrane domains that compartmentalize cellular processes. Small rafts can sometimes be stabilized to form larger platforms through protein-protein and protein-lipid interactions. |
| pericentriolar material | A network of small fibers that surrounds the centrioles in cells; contains the microtubule nucleating activity of the centrosome. |
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 |
| protein serine/threonine phosphatase activity | Catalysis of the reaction |
| protein tyrosine kinase activity | Catalysis of the reaction |
| SH2 domain binding | Binding to a SH2 domain (Src homology 2) of a protein, a protein domain of about 100 amino-acid residues and belonging to the alpha + beta domain class. |
| 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. |
10 GO annotations of biological process
| Name | Definition |
|---|---|
| activation of cysteine-type endopeptidase activity involved in apoptotic process | Any process that initiates the activity of the inactive enzyme cysteine-type endopeptidase in the context of an apoptotic process. |
| B cell receptor signaling pathway | The series of molecular signals initiated by the cross-linking of an antigen receptor on a B cell. |
| innate immune response | Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens. |
| intracellular zinc ion homeostasis | A homeostatic process involved in the maintenance of a steady state level of zinc ions within a cell. |
| phosphorylation | The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide. |
| positive regulation of intrinsic apoptotic signaling pathway | Any process that activates or increases the frequency, rate or extent of intrinsic apoptotic signaling pathway. |
| positive regulation of T cell activation | Any process that activates or increases the frequency, rate or extent of T cell activation. |
| response to xenobiotic stimulus | Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a xenobiotic, a compound foreign to the organim exposed to it. It may be synthesized by another organism (like ampicilin) or it can be a synthetic chemical. |
| T cell differentiation | The process in which a precursor cell type acquires characteristics of a more mature T-cell. A T cell is a type of lymphocyte whose definin characteristic is the expression of a T cell receptor complex. |
| 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. |
79 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 |
| Q75R65 | JAK2 | Tyrosine-protein kinase JAK2 | Gallus gallus (Chicken) | SS |
| P00523 | SRC | Proto-oncogene tyrosine-protein kinase Src | Gallus gallus (Chicken) | EV |
| P09324 | YES1 | Tyrosine-protein kinase Yes | Gallus gallus (Chicken) | SS |
| P41239 | CSK | Tyrosine-protein kinase CSK | Gallus gallus (Chicken) | SS |
| Q02977 | YRK | Proto-oncogene tyrosine-protein kinase Yrk | Gallus gallus (Chicken) | SS |
| Q05876 | FYN | Tyrosine-protein kinase Fyn | Gallus gallus (Chicken) | SS |
| Q8JH64 | BTK | Tyrosine-protein kinase BTK | Gallus gallus (Chicken) | SS |
| F1N9Y5 | SYK | Tyrosine-protein kinase SYK | Gallus gallus (Chicken) | SS |
| Q00944 | PTK2 | Focal adhesion kinase 1 | Gallus gallus (Chicken) | EV |
| Q24592 | hop | Tyrosine-protein kinase hopscotch | Drosophila melanogaster (Fruit fly) | PR |
| P08630 | Btk | Tyrosine-protein kinase Btk | Drosophila melanogaster (Fruit fly) | SS |
| P00528 | Src64B | Tyrosine-protein kinase Src64B | Drosophila melanogaster (Fruit fly) | SS |
| Q9V9J3 | Src42A | Tyrosine-protein kinase Src42A | 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 |
| 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 |
| P08631 | HCK | Tyrosine-protein kinase HCK | 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 |
| P06239 | LCK | Tyrosine-protein kinase Lck | Homo sapiens (Human) | EV |
| Q9R117 | Tyk2 | Non-receptor tyrosine-protein kinase TYK2 | Mus musculus (Mouse) | SS |
| P08103 | Hck | Tyrosine-protein kinase HCK | 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 |
| 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 |
| P06240 | Lck | Proto-oncogene tyrosine-protein kinase LCK | Mus musculus (Mouse) | SS |
| A1Y2K1 | FYN | Tyrosine-protein kinase Fyn | Sus scrofa (Pig) | SS |
| O19064 | JAK2 | Tyrosine-protein kinase JAK2 | Sus scrofa (Pig) | SS |
| Q62662 | Frk | Tyrosine-protein kinase FRK | Rattus norvegicus (Rat) | SS |
| Q62844 | Fyn | Tyrosine-protein kinase Fyn | Rattus norvegicus (Rat) | SS |
| Q07014 | Lyn | Tyrosine-protein kinase Lyn | Rattus norvegicus (Rat) | SS |
| P50545 | Hck | Tyrosine-protein kinase HCK | Rattus norvegicus (Rat) | SS |
| Q9WUD9 | Src | Proto-oncogene tyrosine-protein kinase Src | Rattus norvegicus (Rat) | SS |
| Q6P6U0 | Fgr | Tyrosine-protein kinase Fgr | Rattus norvegicus (Rat) | SS |
| Q62689 | Jak2 | Tyrosine-protein kinase JAK2 | Rattus norvegicus (Rat) | SS |
| Q63272 | Jak3 | Tyrosine-protein kinase JAK3 | Rattus norvegicus (Rat) | SS |
| P32577 | Csk | Tyrosine-protein kinase CSK | Rattus norvegicus (Rat) | SS |
| P41243 | Matk | Megakaryocyte-associated tyrosine-protein kinase | Rattus norvegicus (Rat) | SS |
| F1LM93 | Yes1 | Tyrosine-protein kinase Yes | Rattus norvegicus (Rat) | SS |
| Q01621 | Lck | Proto-oncogene tyrosine-protein kinase LCK | Rattus norvegicus (Rat) | SS |
| G5ECJ6 | csk-1 | Tyrosine-protein kinase csk-1 | Caenorhabditis elegans | SS |
| G5EE56 | src-1 | Tyrosine protein-kinase src-1 | Caenorhabditis elegans | SS |
| O45539 | src-2 | Tyrosine protein-kinase src-2 | Caenorhabditis elegans | SS |
| Q2MHE4 | HT1 | Serine/threonine/tyrosine-protein kinase HT1 | 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 |
| MGCCCSSDYD | EDWIENIDIC | EHCNYPIDPD | SKRQQLIRNV | SEVRDPLVSY | EAMSPPCSPL |
| 70 | 80 | 90 | 100 | 110 | 120 |
| QDKLVVALYD | YEPTHDGDLG | LKQGEKLRVL | EESGEWWRAQ | SLTTGQEGLI | PHNFVAMVNS |
| 130 | 140 | 150 | 160 | 170 | 180 |
| LEPEPWFFKN | LSRKNAEARL | LASGNTHGSF | LIRESETSKG | SYSLSVRDFD | QNQGETVKHY |
| 190 | 200 | 210 | 220 | 230 | 240 |
| KIRNMDNGGY | YISPRVTFSS | LHELVEYYSS | SSDGLCTRLG | KPCRTQKPQK | PWWQDEWEVP |
| 250 | 260 | 270 | 280 | 290 | 300 |
| RESLKLVEKL | GAGQFGEVWM | GFYNGHTKVA | IKNLKQGSMS | PSAFLAEANL | MKNLQHPRLV |
| 310 | 320 | 330 | 340 | 350 | 360 |
| RLYAVVTKEP | IYIITEYMEK | GSLVDFLKTS | EGIKLSINKL | LDMAAQIAEG | MAFIEAKNYI |
| 370 | 380 | 390 | 400 | 410 | 420 |
| HRDLRAANIL | VSEALCCKIA | DFGLARLIED | NEYTAREGAK | FPIKWTAPEA | INYGTFTIKS |
| 430 | 440 | 450 | 460 | 470 | 480 |
| DVWSFGILLT | EIVTYGRIPY | PGMTNPEVIQ | NLERGYRMPQ | PDNCPQELYE | LMMQCWKEQP |
| 490 | 500 | ||||
| EERPTFEYMK | SVLEDFFTAT | EGQYQQQP |