| IED ID | IndEnz0002015881 |
| Enzyme Type ID | protease015881 |
| Protein Name |
Mast/stem cell growth factor receptor Kit SCFR EC 2.7.10.1 Proto-oncogene c-Kit Tyrosine-protein kinase Kit CD antigen CD117 |
| Gene Name | KIT |
| Organism | Canis lupus familiaris (Dog) (Canis familiaris) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Laurasiatheria Carnivora Caniformia Canidae (dog coyote wolf fox) Canis Canis lupus (Gray wolf) Canis lupus familiaris (Dog) (Canis familiaris) |
| Enzyme Sequence | MRGARGAWDFLCVLLLLLLLGVQTGSSQPSVSPGEPSLPSIHPAKSELIVSVGDELRLSCTDPGFVKWTFETLGQLNENTHNEWITEKAEAGHTGNYTCTNRDGLSRSIYVFVRDPAKLFLVDLPLYGKEGNDTLVRCPLTDPEVTNYSLRGCEGKPLPKDLTFVADPKAGITIRNVKREYHRLCLHCSADQKGRTVLSKKFTLKVRAAIRAVPVVSVSKTSSLLKEGEAFSVMCFIKDVSSFVDSMWIKENSQQTNAQTQSNSWHHGDFNFERQEKLIISSARVNDSGVFMCYANNTFGSANVTTTLEVVDKGFINIFPMMSTTIFVNDGENVDLIVEYEAYPKPEHQQWIYMNRTFTDKWEDYPKSDNESNIRYVSELHLTRLKGNEGGTYTFQVSNSDVNSSVTFNVYVNTKPEILTHESLTNGMLQCVVAGFPEPAVDWYFCPGAEQRCSVPIGPMDVQMQNSSLSPSGKLVVQSSIDYSAFKHNGTVECRAYNNVGRSSAFFNFAFKGNSKEQIHPHTLFTPLLIGFVIAAGMMCIIVMILTYKYLQKPMYEVQWKVVEEINGNNYVYIDPTQLPYDHKWEFPRNRLSFGKTLGAGAFGKVVEATAYGLIKSDAAMTVAVKMLKPSAHLTEREALMSELKVLSYLGNHMNIVNLLGACTVGGPTLVITEYCCYGDLLNFLRRKRDSFICSKQEDHGEVALYKNLLHSKESSCSDSTNEYMDMKPGVSYVVPTKADKRRSARIGSYIERDVTPAIMEDDELALDLEDLLSFSYQVAKGMAFLASKNCIHRDLAARNILLTHGRITKICDFGLARDIKNDSNYVVKGNARLPVKWMAPESIFNCVYTFESDVWSYGIFLWELFSLGSSPYPGMPVDSKFYKMIKEGFRMLSPEHAPAEMYDIMKTCWDADPLKRPTFKQIVQLIEKQISDSTNHIYSNLANCSPNPERPVVDHSVRINSVGSSASSTQPLLVHEDV |
| Enzyme Length | 979 |
| Uniprot Accession Number | O97799 |
| Absorption | |
| Active Site | ACT_SITE 795; /note="Proton acceptor"; /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-ProRule:PRU10028" |
| Activity Regulation | ACTIVITY REGULATION: Present in an inactive conformation in the absence of bound ligand. KITLG/SCF binding leads to dimerization and activation by autophosphorylation on tyrosine residues. Activity is down-regulated by PRKCA-mediated phosphorylation on serine residues (By similarity). {ECO:0000250}. |
| Binding Site | BINDING 626; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00159; BINDING 799; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-[protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858, ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1; Evidence={ECO:0000255|PROSITE-ProRule:PRU10028}; |
| DNA Binding | |
| EC Number | 2.7.10.1 |
| Enzyme Function | FUNCTION: Tyrosine-protein kinase that acts as cell-surface receptor for the cytokine KITLG/SCF and plays an essential role in the regulation of cell survival and proliferation, hematopoiesis, stem cell maintenance, gametogenesis, mast cell development, migration and function, and in melanogenesis. In response to KITLG/SCF binding, KIT can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the AKT1 signaling pathway by phosphorylation of PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT also transmits signals via GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT signaling is modulated by protein phosphatases, and by rapid internalization and degradation of the receptor. Activated KIT promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1 (By similarity). {ECO:0000250}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | NP_BIND 599..606; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00159; NP_BIND 674..680; /note=ATP; /evidence=ECO:0000255|PROSITE-ProRule:PRU00159 |
| Features | Active site (1); Alternative sequence (1); Binding site (2); Chain (1); Disulfide bond (5); Domain (6); Glycosylation (11); Metal binding (3); Modified residue (15); Nucleotide binding (2); Region (1); Sequence conflict (3); Signal peptide (1); Site (3); Topological domain (2); Transmembrane (1) |
| Keywords | ATP-binding;Alternative splicing;Cell membrane;Disulfide bond;Glycoprotein;Immunoglobulin domain;Kinase;Magnesium;Membrane;Metal-binding;Nucleotide-binding;Phosphoprotein;Proto-oncogene;Receptor;Reference proteome;Repeat;Signal;Transferase;Transmembrane;Transmembrane helix;Tyrosine-protein kinase;Ubl conjugation |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein. |
| Modified Residue | MOD_RES 550; /note=Phosphotyrosine; by autocatalysis; /evidence=ECO:0000250|UniProtKB:P10721; MOD_RES 556; /note=Phosphotyrosine; by autocatalysis; /evidence=ECO:0000250|UniProtKB:P10721; MOD_RES 571; /note=Phosphotyrosine; by autocatalysis; /evidence=ECO:0000250|UniProtKB:P10721; MOD_RES 573; /note=Phosphotyrosine; by autocatalysis; /evidence=ECO:0000250|UniProtKB:P10721; MOD_RES 706; /note=Phosphotyrosine; by autocatalysis; /evidence=ECO:0000250|UniProtKB:P10721; MOD_RES 724; /note=Phosphotyrosine; by autocatalysis; /evidence=ECO:0000250|UniProtKB:P10721; MOD_RES 733; /note=Phosphotyrosine; by autocatalysis; /evidence=ECO:0000250|UniProtKB:P10721; MOD_RES 744; /note=Phosphoserine; by PKC/PRKCA; /evidence=ECO:0000250|UniProtKB:P10721; MOD_RES 749; /note=Phosphoserine; by PKC/PRKCA; /evidence=ECO:0000250|UniProtKB:P10721; MOD_RES 824; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P10721; MOD_RES 826; /note=Phosphotyrosine; by autocatalysis; /evidence=ECO:0000250|UniProtKB:P10721; MOD_RES 894; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P10721; MOD_RES 903; /note=Phosphotyrosine; by autocatalysis; /evidence=ECO:0000250|UniProtKB:P10721; MOD_RES 939; /note=Phosphotyrosine; by autocatalysis; /evidence=ECO:0000250|UniProtKB:P10721; MOD_RES 962; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P10721 |
| Post Translational Modification | PTM: Ubiquitinated by SOCS6. KIT is rapidly ubiquitinated after autophosphorylation induced by KITLG/SCF binding, leading to internalization and degradation. {ECO:0000250}.; PTM: Autophosphorylated on tyrosine residues. KITLG/SCF binding promotes autophosphorylation. Phosphorylated tyrosine residues are important for interaction with specific binding partners (By similarity). {ECO:0000250}. |
| Signal Peptide | SIGNAL 1..27; /evidence=ECO:0000255 |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | |
| Gene Encoded By | |
| Mass | 109,753 |
| Kinetics | |
| Metal Binding | METAL 571; /note=Magnesium; /evidence=ECO:0000250; METAL 800; /note=Magnesium; /evidence=ECO:0000250; METAL 813; /note=Magnesium; /evidence=ECO:0000250 |
| Rhea ID | RHEA:10596 |
| Cross Reference Brenda | 2.7.10.1; |