KIT_CALJA
ID KIT_CALJA Reviewed; 972 AA.
AC Q76II0;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 111.
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 Callithrix jacchus (White-tufted-ear marmoset).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Platyrrhini; Cebidae;
OC Callitrichinae; Callithrix; Callithrix.
OX NCBI_TaxID=9483;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Izawa K.;
RT "Cloning of c-kit cDNA of common marmoset.";
RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
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; AB097502; BAD04018.1; -; mRNA.
DR RefSeq; NP_001171967.1; NM_001185038.1.
DR AlphaFoldDB; Q76II0; -.
DR SMR; Q76II0; -.
DR STRING; 9483.ENSCJAP00000034112; -.
DR GeneID; 100411615; -.
DR KEGG; cjc:100411615; -.
DR CTD; 3815; -.
DR eggNOG; KOG0200; Eukaryota.
DR InParanoid; Q76II0; -.
DR OrthoDB; 236292at2759; -.
DR Proteomes; UP000008225; Unplaced.
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:0033674; P:positive regulation of kinase activity; IEA:UniProt.
DR GO; GO:0032765; P:positive regulation of mast cell cytokine production; ISS:UniProtKB.
DR GO; GO:0031401; P:positive regulation of protein modification process; IEA:UniProt.
DR GO; GO:0048584; P:positive regulation of response to stimulus; IEA:UniProt.
DR GO; GO:0046777; P:protein autophosphorylation; IEA:UniProt.
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; 3.
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; 1.
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..972
FT /note="Mast/stem cell growth factor receptor Kit"
FT /id="PRO_0000248275"
FT TOPO_DOM 26..520
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 521..541
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 542..972
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..308
FT /note="Ig-like C2-type 3"
FT DOMAIN 317..410
FT /note="Ig-like C2-type 4"
FT DOMAIN 413..507
FT /note="Ig-like C2-type 5"
FT DOMAIN 585..933
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 564..566
FT /note="Important for interaction with phosphotyrosine-
FT binding proteins"
FT /evidence="ECO:0000250"
FT ACT_SITE 788
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 564
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 592..599
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 619
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 667..673
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 792
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 793
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT BINDING 806
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250"
FT SITE 564
FT /note="Interaction with SH2B2/APS"
FT /evidence="ECO:0000250"
FT SITE 932
FT /note="Important for interaction with phosphotyrosine-
FT binding proteins"
FT /evidence="ECO:0000250"
FT SITE 932
FT /note="Interaction with SH2B2/APS"
FT /evidence="ECO:0000250"
FT MOD_RES 543
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 549
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 564
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 566
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 699
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 717
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 726
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 737
FT /note="Phosphoserine; by PKC/PRKCA"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 742
FT /note="Phosphoserine; by PKC/PRKCA"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 817
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 819
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 887
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 896
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 932
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P10721"
FT MOD_RES 955
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10721"
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 283
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 300
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 320
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 352
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 367
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 463
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 486
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..290
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 428..491
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 972 AA; 109680 MW; 5BC959312C3BB1FA CRC64;
MRGARGAWDF LCVLLLLLRV QTGSSQPSVS PEEASPPFID PAKSELIVSV GDEIRLFCND
PGFVKWTFEV LDQMNENKQK EWIMQKAEAT NTGKYTCTNK HGLSSSIYVF VRDPDKLFLV
DRSLYGKEDN DTLVRCPLTD PEVTNYSLKG CQGKPIPKDL RFVPDPKAGI TIKNVKRAYH
RLCLHCSADR KGQSKLSEKF ILKVRPAFKA VPVVSVSKAS YLLREGEEFT VTCTIKDVSS
SVYSSWKKEN SPTKLQEKYN SWHQGDFNYE RQATLTISSV RVNDSGVFMC YASNTFGSAN
VTTTLEVVDK GFINIFPMIN TTVFVNDGEN VDLIVEYEAF PRPEHQQWIY MNRTFTDKWE
DYPKSENESN IRYVSELHLT RLKDTEGGTY TFLVSNSDVS SSIAFTVYVN TKPEILTYDR
LMNGMLQCVA AGFPEPTIDW YFCPGTEQRC SAPVLPVDVQ IQNTSGPPFG KLVVQSSIDS
SAFKHNGTVE CKAYNDVGKT SAYFNFAFKE QIQPHTLFTP LLIGFVVVAG MMCIIVMILT
YKYLQKPMYE VQWKVVEEIN GNNYVYIDPT QLPYDHKWEF PRNRLSFGKT LGAGAFGKVV
EATAYGLIKS DTAMTVAVKM LKPSAHLTER EALMSELKVL SYLGNHMNIV NLLGACTIGG
PTLVITEYCC YGDLLNFLRR KRDSFICSKQ EDHAEAALYK NLLHSKESSC SDSTNEYMDM
KPGVSYVVPT KAEKRRSARV GSYIERDVTP AIMEDDELAL DLEDLLSFSY QVAKGMAFLA
SKNCIHRDLA ARNILLTHGR ITKICDFGLA RDIKNDSNYV VKGNARLPVK WMAPESIFNC
VYTFESDVWS YGIFLWELFS LGSSPYPGMP VDSKFYKMIK EGFRMLSPEH APAEMYDIMK
TCWDADPLKR PTFKQIVQLI EKQISESTNH IYSNLTNCSP SQQKPVVDHS VRINSVGSTA
SSSQPLLVRD DV
