KIT_CAPHI
ID KIT_CAPHI Reviewed; 978 AA.
AC Q28317;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 152.
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 Capra hircus (Goat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Capra.
OX NCBI_TaxID=9925;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Shiba; TISSUE=Cerebellum;
RX PubMed=9199245; DOI=10.1016/s0167-4781(97)00055-9;
RA Tanaka S., Yanagisawa N., Tojo H., Kim Y.-J., Tsujimura T., Kitamura Y.,
RA Sawasaki T., Tachi C.;
RT "Molecular cloning of cDNA encoding the c-kit receptor of Shiba goats and a
RT novel alanine insertion specific to goats and sheep in the kinase insert
RT region.";
RL Biochim. Biophys. Acta 1352:151-155(1997).
CC -!- FUNCTION: Tyrosine-protein kinase that acts as cell-surface receptor
CC for the cytokine KITLG/SCF and plays an essential role in the
CC regulation of cell survival and proliferation, hematopoiesis, stem cell
CC maintenance, gametogenesis, mast cell development, migration and
CC function, and in melanogenesis. In response to KITLG/SCF binding, KIT
CC can activate several signaling pathways. Phosphorylates PIK3R1, PLCG1,
CC SH2B2/APS and CBL. Activates the AKT1 signaling pathway by
CC phosphorylation of PIK3R1, the regulatory subunit of
CC phosphatidylinositol 3-kinase. Activated KIT also transmits signals via
CC GRB2 and activation of RAS, RAF1 and the MAP kinases MAPK1/ERK2 and/or
CC MAPK3/ERK1. Promotes activation of STAT family members STAT1, STAT3,
CC STAT5A and STAT5B. Activation of PLCG1 leads to the production of the
CC cellular signaling molecules diacylglycerol and inositol 1,4,5-
CC trisphosphate. KIT signaling is modulated by protein phosphatases, and
CC by rapid internalization and degradation of the receptor. Activated KIT
CC promotes phosphorylation of the protein phosphatases PTPN6/SHP-1 and
CC PTPRU, and of the transcription factors STAT1, STAT3, STAT5A and
CC STAT5B. Promotes phosphorylation of PIK3R1, CBL, CRK (isoform Crk-II),
CC LYN, MAPK1/ERK2 and/or MAPK3/ERK1, PLCG1, SRC and SHC1 (By similarity).
CC {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- ACTIVITY REGULATION: Present in an inactive conformation in the absence
CC of bound ligand. KITLG/SCF binding leads to dimerization and activation
CC by autophosphorylation on tyrosine residues. Activity is down-regulated
CC by PRKCA-mediated phosphorylation on serine residues (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Monomer in the absence of bound KITLG/SCF. Homodimer in the
CC presence of bound KITLG/SCF, forming a heterotetramer with two
CC KITLG/SCF molecules. Interacts (via phosphorylated tyrosine residues)
CC with the adapter proteins GRB2 and GRB7 (via SH2 domain), and
CC SH2B2/APS. Interacts (via C-terminus) with MPDZ (via the tenth PDZ
CC domain). Interacts (via phosphorylated tyrosine residues) with PIK3R1
CC and PIK3CD. Interacts (via phosphorylated tyrosine) with CRK (isoform
CC Crk-II), FYN, SHC1 and MATK/CHK (via SH2 domain). Interacts with LYN
CC and FES/FPS. Interacts (via phosphorylated tyrosine residues) with the
CC protein phosphatases PTPN6/SHP-1 (via SH2 domain), PTPN11/SHP-2 (via
CC SH2 domain) and PTPRU. Interacts with PLCG1. Interacts with DOK1 and
CC TEC. Interacts with IL1RAP (independent of stimulation with KITLG/SCF).
CC A mast cell-specific KITLG/SCF-induced interleukin-33 signaling complex
CC contains IL1RL1, IL1RAP, KIT and MYD88 (By similarity).
CC {ECO:0000250|UniProtKB:P05532, ECO:0000250|UniProtKB:P10721}.
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. {ECO:0000250}.
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). {ECO:0000250}.
CC -!- MISCELLANEOUS: Numerous proteins are phosphorylated in response to KIT
CC signaling, but it is not evident to determine which are directly
CC phosphorylated by KIT under in vivo conditions. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. CSF-1/PDGF receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; D45168; BAA08116.1; -; mRNA.
DR RefSeq; NP_001272653.1; NM_001285724.1.
DR AlphaFoldDB; Q28317; -.
DR SMR; Q28317; -.
DR STRING; 9925.ENSCHIP00000025751; -.
DR GeneID; 100861386; -.
DR KEGG; chx:100861386; -.
DR CTD; 3815; -.
DR OrthoDB; 236292at2759; -.
DR BRENDA; 2.7.10.1; 1166.
DR Proteomes; UP000291000; Unassembled WGS sequence.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
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:0004714; F:transmembrane receptor protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0031532; P:actin cytoskeleton reorganization; ISS:UniProtKB.
DR GO; GO:0060326; P:cell chemotaxis; ISS:UniProtKB.
DR GO; GO:0019221; P:cytokine-mediated signaling pathway; 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:0002327; P:immature B cell differentiation; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; ISS:UniProtKB.
DR GO; GO:0038109; P:Kit signaling pathway; ISS:UniProtKB.
DR GO; GO:0030032; P:lamellipodium assembly; 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:0001541; P:ovarian follicle development; ISS:UniProtKB.
DR GO; GO:0043473; P:pigmentation; ISS:UniProtKB.
DR GO; GO:0002732; P:positive regulation of dendritic cell cytokine production; ISS:UniProtKB.
DR GO; GO:0032765; P:positive regulation of mast cell cytokine production; ISS:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IEA:UniProt.
DR GO; GO:0008360; P:regulation of cell shape; ISS:UniProtKB.
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; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR013151; Immunoglobulin.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_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; IPR001824; Tyr_kinase_rcpt_3_CS.
DR Pfam; PF00047; ig; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PIRSF; PIRSF500951; SCGF_recepter; 1.
DR SMART; SM00409; IG; 4.
DR SMART; SM00408; IGc2; 2.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 3.
DR SUPFAM; SSF56112; SSF56112; 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; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Kinase; Magnesium; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Proto-oncogene; Receptor;
KW Reference proteome; Repeat; Signal; Transferase; Transmembrane;
KW Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..978
FT /note="Mast/stem cell growth factor receptor Kit"
FT /id="PRO_0000016752"
FT TOPO_DOM 26..525
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 526..546
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 547..978
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 27..112
FT /note="Ig-like C2-type 1"
FT DOMAIN 121..205
FT /note="Ig-like C2-type 2"
FT DOMAIN 212..309
FT /note="Ig-like C2-type 3"
FT DOMAIN 318..411
FT /note="Ig-like C2-type 4"
FT DOMAIN 414..508
FT /note="Ig-like C2-type 5"
FT DOMAIN 590..939
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 569..571
FT /note="Important for interaction with phosphotyrosine-
FT binding proteins"
FT /evidence="ECO:0000250"
FT ACT_SITE 794
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 569
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 597..604
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 624
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 672..678
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 798
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 799
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 812
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT SITE 569
FT /note="Interaction with SH2B2/APS"
FT /evidence="ECO:0000250"
FT SITE 938
FT /note="Important for interaction with phosphotyrosine-
FT binding proteins"
FT /evidence="ECO:0000250"
FT SITE 938
FT /note="Interaction with SH2B2/APS"
FT /evidence="ECO:0000250"
FT MOD_RES 548
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 554
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 569
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 571
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 704
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 722
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 731
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 743
FT /note="Phosphoserine; by PKC/PRKCA"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 748
FT /note="Phosphoserine; by PKC/PRKCA"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 823
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 825
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 893
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 902
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 938
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 961
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT CARBOHYD 94
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 130
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 145
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 284
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 294
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 301
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 321
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 353
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 368
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 401
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 464
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 487
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 58..97
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 136..186
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 151..183
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 233..291
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 429..492
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 978 AA; 109722 MW; CA4D663F98205CA9 CRC64;
MRGARGAWDF LFVLLLLLLV QTGSSQPSVS PGELSLPSIH PAKSELIVSV GDEIRLLCTD
PGFVKWTFEI LGQLSEKTNP EWITEKAEAT NTGNYTCTNK GGLSSSIYVF VRDPEKLFLI
DLPLYGKEEN DTLVRCPLTD PEVTNYSLTG CEGKPLPKDL TFVADPKAGI TIRNVKREYH
RLCLHCSANQ KGKSMLSKKF TLKVRAAIKA VPVVSVSKTS YLLREGEEFA VTCLIKDVSS
SVDSMWIKEN SQQSKAQTKK NSWHQGDFSY LRQERLTISS ARVNDSGVFM CYANNTFGSA
NVTTTLEVVD KGFINIFPMM NTTVFVNDGE NVDLVVEYEA YPKPEHRQWI YMNRTSTDKW
DDYPKSENES NIRYVNELHL TRLKGTEGGT YTFHVSNSDV NSSVTFNVNV NTKPEILTHD
RLVNGMLQCV AAGFPEPTID WYFCPGTEQR CSVPVGPVDV QIQNSSVSPF GKLVVYSTID
DSTFKHNGTV ECRAYNDVGK SSASFNFAFK GNNKEQIHAH TLFTPLLIGF VIAAGLMCIF
VMILTYKYLQ KPMYEVQWKV VEEINGNNYV YIDPTQLPYD HKWEFPRNRL SFGKTLGAGA
FGKVVEATAY GLIKSDAAMT VAVKMLKPSA HLTEREALMS ELKVLSYLGN HMNIVNLLGA
CTIGGPTLVI TEYCCYGDLL NFLRRKRDSF ICSKQEDHAE VALYKNLLHS KESSCNDSTN
EYMDMKPGVS YVVPTKAADK RRSARIGSYI ERDVTPAIME DDELALDLED LLSFSYQVAK
GMAFLASKNC IHRDLAARNI LLTHGRITKI CDFGLARDIK NDSNYVVKGN ARLPVKWMAP
ESIFNCVYTF ESDVWSYGIF LWELFSLGSS PYPGMPVDSK FYKMIKEGFR MLSPEHAPAE
MYDIMKTCWD ADPLKRPTFK QIVQLIEKQI SESTNHIYSN LANCSPHREN PAVDHSVRIN
SVGSSASSTQ PLLVHEDV
