ID KIT_BOVIN Reviewed; 977 AA.
AC P43481;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 01-MAY-2013, entry version 121.
DE RecName: Full=Mast/stem cell growth factor receptor Kit;
DE Short=SCFR;
DE EC=2.7.10.1;
DE AltName: Full=Proto-oncogene c-Kit;
DE AltName: Full=Tyrosine-protein kinase Kit;
DE AltName: CD_antigen=CD117;
DE Flags: Precursor;
GN Name=KIT;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Laurasiatheria; Cetartiodactyla; Ruminantia;
OC Pecora; Bovidae; Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7512939; DOI=10.1016/0378-1119(94)90592-4;
RA Kubota T., Hikono H., Sasaki E., Sakurai M.;
RT "Sequence of a bovine c-kit proto-oncogene cDNA.";
RL Gene 141:305-306(1994).
CC -!- FUNCTION: Tyrosine-protein kinase that acts as cell-surface
CC receptor for the cytokine KITLG/SCF and plays an essential role in
CC the regulation of cell survival and proliferation, hematopoiesis,
CC stem cell maintenance, gametogenesis, mast cell development,
CC migration and function, and in melanogenesis. In response to
CC KITLG/SCF binding, KIT can activate several signaling pathways.
CC Phosphorylates PIK3R1, PLCG1, SH2B2/APS and CBL. Activates the
CC AKT1 signaling pathway by phosphorylation of PIK3R1, the
CC regulatory subunit of phosphatidylinositol 3-kinase. Activated KIT
CC also transmits signals via GRB2 and activation of RAS, RAF1 and
CC the MAP kinases MAPK1/ERK2 and/or MAPK3/ERK1. Promotes activation
CC of STAT family members STAT1, STAT3, STAT5A and STAT5B. Activation
CC of PLCG1 leads to the production of the cellular signaling
CC molecules diacylglycerol and inositol 1,4,5-trisphosphate. KIT
CC signaling is modulated by protein phosphatases, and by rapid
CC internalization and degradation of the receptor. Activated KIT
CC promotes phosphorylation of the protein phosphatases PTPN6/SHP-1
CC and PTPRU, and of the transcription factors STAT1, STAT3, STAT5A
CC and STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform
CC Crk-II), LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1
CC (By similarity).
CC -!- CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a
CC [protein]-L-tyrosine phosphate.
CC -!- ENZYME REGULATION: Present in an inactive conformation in the
CC absence of bound ligand. KITLG/SCF binding leads to dimerization
CC and activation by autophosphorylation on tyrosine residues.
CC Activity is down-regulated by PRKCA-mediated phosphorylation on
CC serine residues (By similarity).
CC -!- SUBUNIT: Monomer in the absence of bound KITLG/SCF. Homodimer in
CC the presence of bound KITLG/SCF, forming a heterotetramer with two
CC KITLG/SCF molecules. Interacts (via phosphorylated tyrosine
CC residues) with the adapter proteins GRB2 and GRB7 (via SH2
CC domain), and SH2B2/APS. Interacts (via C-terminus) with MPDZ (via
CC the tenth PDZ domain). Interacts (via phosphorylated tyrosine
CC residues) with PIK3R1 and PIK3CD. Interacts (via phosphorylated
CC tyrosine) with CRK (isoform Crk-II), FYN, SHC1 and MATK/CHK (via
CC SH2 domain). Interacts with LYN and FES/FPS. Interacts (via
CC phosphorylated tyrosine residues) with the protein phosphatases
CC PTPN6/SHP-1 (via SH2 domain), PTPN11/SHP-2 (via SH2 domain) and
CC PTPRU. Interacts with PLCG1. Interacts with DOK1 and TEC (By
CC similarity).
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein.
CC -!- PTM: Ubiquitinated by SOCS6. KIT is rapidly ubiquitinated after
CC autophosphorylation induced by KITLG/SCF binding, leading to
CC internalization and degradation (By similarity).
CC -!- PTM: Autophosphorylated on tyrosine residues. KITLG/SCF binding
CC promotes autophosphorylation. Phosphorylated tyrosine residues are
CC important for interaction with specific binding partners (By
CC similarity).
CC -!- MISCELLANEOUS: Numerous proteins are phosphorylated in response to
CC KIT signaling, but it is not evident to determine which are
CC directly phosphorylated by KIT under in vivo conditions (By
CC similarity).
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. CSF-1/PDGF receptor subfamily.
CC -!- SIMILARITY: Contains 5 Ig-like C2-type (immunoglobulin-like)
CC domains.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; D16680; BAA04084.1; -; mRNA.
DR IPI; IPI00714791; -.
DR UniGene; Bt.91791; -.
DR ProteinModelPortal; P43481; -.
DR SMR; P43481; 33-508, 548-928.
DR STRING; 9913.ENSBTAP00000003498; -.
DR MEROPS; I43.001; -.
DR PRIDE; P43481; -.
DR Ensembl; ENSBTAT00000003498; ENSBTAP00000003498; ENSBTAG00000002699.
DR eggNOG; COG0515; -.
DR GeneTree; ENSGT00660000095142; -.
DR HOGENOM; HOG000112008; -.
DR HOVERGEN; HBG004335; -.
DR InParanoid; P43481; -.
DR OMA; DSGVFMC; -.
DR OrthoDB; EOG4W0XCD; -.
DR BRENDA; 2.7.10.1; 908.
DR ArrayExpress; P43481; -.
DR GO; GO:0005737; C:cytoplasm; IEA:Compara.
DR GO; GO:0009897; C:external side of plasma membrane; IEA:Compara.
DR GO; GO:0005615; C:extracellular space; IEA:Compara.
DR GO; GO:0016021; C:integral to membrane; IEA:UniProtKB-KW.
DR GO; GO:0005634; C:nucleus; IEA:Compara.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0019955; F:cytokine binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004716; F:receptor signaling protein tyrosine kinase activity; IEA:InterPro.
DR GO; GO:0005020; F:stem cell factor receptor activity; IEA:Compara.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISS:UniProtKB.
DR GO; GO:0000187; P:activation of MAPK activity; ISS:UniProtKB.
DR GO; GO:0060326; P:cell chemotaxis; ISS:UniProtKB.
DR GO; GO:0097067; P:cellular response to thyroid hormone stimulus; IEA:Compara.
DR GO; GO:0002371; P:dendritic cell cytokine production; ISS:UniProtKB.
DR GO; GO:0050910; P:detection of mechanical stimulus involved in sensory perception of sound; ISS:UniProtKB.
DR GO; GO:0048565; P:digestive tract development; ISS:UniProtKB.
DR GO; GO:0035162; P:embryonic hemopoiesis; ISS:UniProtKB.
DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0038162; P:erythropoietin-mediated signaling pathway; ISS:UniProtKB.
DR GO; GO:0038093; P:Fc receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0035234; P:germ cell programmed cell death; IEA:Compara.
DR GO; GO:0006687; P:glycosphingolipid metabolic process; IEA:Compara.
DR GO; GO:0002327; P:immature B cell differentiation; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; ISS:UniProtKB.
DR GO; GO:0007243; P:intracellular protein kinase cascade; IEA:Compara.
DR GO; GO:0038109; P:Kit signaling pathway; ISS:UniProtKB.
DR GO; GO:0030032; P:lamellipodium assembly; ISS:UniProtKB.
DR GO; GO:0002320; P:lymphoid progenitor cell differentiation; IEA:Compara.
DR GO; GO:0008584; P:male gonad development; IEA:Compara.
DR GO; GO:0002551; P:mast cell chemotaxis; IEA:Compara.
DR GO; GO:0032762; P:mast cell cytokine production; ISS:UniProtKB.
DR GO; GO:0043303; P:mast cell degranulation; ISS:UniProtKB.
DR GO; GO:0060374; P:mast cell differentiation; ISS:UniProtKB.
DR GO; GO:0035855; P:megakaryocyte development; ISS:UniProtKB.
DR GO; GO:0097326; P:melanocyte adhesion; ISS:UniProtKB.
DR GO; GO:0030318; P:melanocyte differentiation; ISS:UniProtKB.
DR GO; GO:0097324; P:melanocyte migration; ISS:UniProtKB.
DR GO; GO:0002318; P:myeloid progenitor cell differentiation; IEA:Compara.
DR GO; GO:0043069; P:negative regulation of programmed cell death; IEA:Compara.
DR GO; GO:0001541; P:ovarian follicle development; ISS:UniProtKB.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell proliferation; IEA:Compara.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Compara.
DR GO; GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; IEA:Compara.
DR GO; GO:0042511; P:positive regulation of tyrosine phosphorylation of Stat1 protein; IEA:Compara.
DR GO; GO:0042517; P:positive regulation of tyrosine phosphorylation of Stat3 protein; IEA:Compara.
DR GO; GO:0042523; P:positive regulation of tyrosine phosphorylation of Stat5 protein; IEA:Compara.
DR GO; GO:0046777; P:protein autophosphorylation; IEA:Compara.
DR GO; GO:0008360; P:regulation of cell shape; ISS:UniProtKB.
DR GO; GO:0048070; P:regulation of developmental pigmentation; IEA:Compara.
DR GO; GO:0009314; P:response to radiation; IEA:Compara.
DR GO; GO:0023014; P:signal transduction by phosphorylation; IEA:GOC.
DR GO; GO:0007286; P:spermatid development; IEA:Compara.
DR GO; GO:0007283; P:spermatogenesis; ISS:UniProtKB.
DR GO; GO:0048863; P:stem cell differentiation; ISS:UniProtKB.
DR GO; GO:0030217; P:T cell differentiation; ISS:UniProtKB.
DR Gene3D; 2.60.40.10; -; 5.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR000719; Prot_kinase_cat_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR027263; SCGF_receptor.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR016243; Tyr_kinase_CSF1/PDGF_rcpt.
DR InterPro; IPR001824; Tyr_kinase_rcpt_3_CS.
DR Pfam; PF07679; I-set; 1.
DR Pfam; PF07714; Pkinase_Tyr; 1.
DR PIRSF; PIRSF500951; SCGF_recepter; 1.
DR PIRSF; PIRSF000615; TyrPK_CSF1-R; 1.
DR SMART; SM00409; IG; 2.
DR SMART; SM00408; IGc2; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF56112; Kinase_like; 1.
DR PROSITE; PS50835; IG_LIKE; 2.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS00240; RECEPTOR_TYR_KIN_III; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell membrane; Complete proteome; Disulfide bond;
KW Glycoprotein; Immunoglobulin domain; Kinase; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Phosphoprotein; Proto-oncogene;
KW Receptor; Reference proteome; Repeat; Signal; Transferase;
KW Transmembrane; Transmembrane helix; Tyrosine-protein kinase;
KW Ubl conjugation.
FT SIGNAL 1 25 Potential.
FT CHAIN 26 977 Mast/stem cell growth factor receptor
FT Kit.
FT /FTId=PRO_0000016750.
FT TOPO_DOM 26 525 Extracellular (Potential).
FT TRANSMEM 526 546 Helical; (Potential).
FT TOPO_DOM 547 977 Cytoplasmic (Potential).
FT DOMAIN 27 112 Ig-like C2-type 1.
FT DOMAIN 121 205 Ig-like C2-type 2.
FT DOMAIN 212 309 Ig-like C2-type 3.
FT DOMAIN 318 411 Ig-like C2-type 4.
FT DOMAIN 414 508 Ig-like C2-type 5.
FT DOMAIN 590 938 Protein kinase.
FT NP_BIND 597 604 ATP (By similarity).
FT NP_BIND 672 678 ATP (By similarity).
FT REGION 569 571 Important for interaction with
FT phosphotyrosine-binding proteins (By
FT similarity).
FT ACT_SITE 793 793 Proton acceptor (By similarity).
FT METAL 569 569 Magnesium (By similarity).
FT METAL 798 798 Magnesium (By similarity).
FT METAL 811 811 Magnesium (By similarity).
FT BINDING 624 624 ATP (By similarity).
FT BINDING 797 797 ATP (By similarity).
FT SITE 569 569 Interaction with SH2B2/APS (By
FT similarity).
FT SITE 937 937 Important for interaction with
FT phosphotyrosine-binding proteins (By
FT similarity).
FT SITE 937 937 Interaction with SH2B2/APS (By
FT similarity).
FT MOD_RES 569 569 Phosphotyrosine; by autocatalysis (By
FT similarity).
FT MOD_RES 571 571 Phosphotyrosine; by autocatalysis (By
FT similarity).
FT MOD_RES 704 704 Phosphotyrosine; by autocatalysis (By
FT similarity).
FT MOD_RES 722 722 Phosphotyrosine; by autocatalysis (By
FT similarity).
FT MOD_RES 742 742 Phosphoserine; by PKC/PRKCA (By
FT similarity).
FT MOD_RES 747 747 Phosphoserine; by PKC/PRKCA (By
FT similarity).
FT MOD_RES 822 822 Phosphoserine (By similarity).
FT MOD_RES 824 824 Phosphotyrosine; by autocatalysis (By
FT similarity).
FT MOD_RES 892 892 Phosphoserine (By similarity).
FT MOD_RES 901 901 Phosphotyrosine (By similarity).
FT MOD_RES 937 937 Phosphotyrosine; by autocatalysis (By
FT similarity).
FT MOD_RES 960 960 Phosphoserine (By similarity).
FT CARBOHYD 94 94 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 130 130 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 145 145 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 284 284 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 294 294 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 301 301 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 321 321 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 353 353 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 368 368 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 401 401 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 464 464 N-linked (GlcNAc...) (Potential).
FT CARBOHYD 487 487 N-linked (GlcNAc...) (Potential).
FT DISULFID 58 97 By similarity.
FT DISULFID 136 186 By similarity.
FT DISULFID 151 183 By similarity.
FT DISULFID 233 291 By similarity.
FT DISULFID 429 492 By similarity.
SQ SEQUENCE 977 AA; 109685 MW; 4B2719050883B7EF CRC64;
MRGARGAWDF LFVLLLLLLV QTGSSQPSVS PGELSLPSIH PAKSELIVSV GDEIRLLCTD
PGFVKWTFEI LGQLSEKTNP EWITEKAEAT NTGNYTCTNK GGLSSSIYVF VRDPEKLFLI
DLPLYGKEEN DTLVRCPLTD PEVTNYSLTG CEGKPLPKDL TFVADPKAGI TIRNVKREYH
RLCLHCSANQ RGKSMLSKKF TLKVRAAIKA VPVVSVSKTS YLLREGEEFA VTCLIKDVSS
SVDSMWIKEN SQQTKAQTKK NSWHQGDFSY LRQERLTISS ARVNDSGVFM CYANNTFGSA
NVTTTLEVVD KGFINIFPMM NTTVFVNDGE NVDLVVEYEA YPKPVHRQWI YMNRTSTDKW
DDYPKSENES NIRYVNELHL TRLKGTEGGT YTFHVSNSDV NSSVTFNVYV NTKPEILTHD
RLVNGMLQCV AAGFPEPTID WYFCPGTEQR CSVPVGPVDV QIQNSSVSPF GKLVVYSTID
DSTFKHNGTV ECRAYNDVGK SSASFNFAFK GNSKEQIHAH TLFTPLLIGF VIAAGLMCIF
VMILTYKYLQ KPMYEVQWKV VEEINGNNYV YIDPTQLPYD HKWEFPRNRL SFGKTLGAGA
FGKVVEATAY GLIKSDAAMT VAVKMLKPSA HLTEREALMS ELKVLSYLGN HMNIVNLLGA
CTIGGPTLVI TEYCCYGDLL NFLRRKRDSF ICSKQEDHAE VALYKNLLHS KESSCNDSTN
EYMDMKPGVS YVVPTKADKR RSARIGSYIE RDVTPAIMED DELALDLEDL LSFSYQVAKG
MAFLASKNCI HRDLAARNIL LTHGRITKIC DFGLARDIKN DSNYVVKGNA RLPVKWMAPE
SIFNCVYTFE SDVWSYGIFL WELFSLGSSP YPGMPVDSKF YKMIKEGFRM LSPEHAPAEM
YDIMKTCWDA DPLKRPTFKQ IVQLIEKQIS ESTNHIYSNL ANCSPHRENP AVDHSVRINS
VGSSASSTQP LLVHEDV
//
