Monomer in the absence of bound KITLG/SCF. Homodimer in the presence of bound KITLG/SCF, forming a heterotetramer with two KITLG/SCF molecules. Interacts (via phosphorylated tyrosine residues) with the adapter proteins GRB2 and GRB7 (via SH2 domain), and SH2B2/APS. Interacts (via C-terminus) with MPDZ (via the tenth PDZ domain). Interacts (via phosphorylated tyrosine residues) with PIK3R1 and PIK3CD. Interacts (via phosphorylated tyrosine) with CRK (isoform Crk-II), FYN, SHC1 and MATK/CHK (via SH2 domain). Interacts with LYN and FES/FPS. Interacts (via phosphorylated tyrosine residues) with the protein phosphatases PTPN6/SHP-1 (via SH2 domain), PTPN11/SHP-2 (via SH2 domain) and PTPRU. Interacts with PLCG1.
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.
Subcellular Location:
Isoform 3
Cytoplasm
Detected in the cytoplasm of spermatozoa, especially in the equatorial and subacrosomal region of the sperm head.
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Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1);CATALYTIC ACTIVITY;AUTOPHOSPHORYLATION;SUBCELLULAR LOCATION;TISSUE SPECIFICITY
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Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA];ALTERNATIVE SPLICING (ISOFORMS 1 AND 2)
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Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2);SUBCELLULAR LOCATION;INDUCTION
6.
"Sequence of KIT mRNA from all-trans retinoic acid treated neuroblastoma cell lines." Staege M.S.
,
Neumann I.
,
Volkmer I.
Submitted (2010-03) to the EMBL/GenBank/DDBJ databases
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Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)
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Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2)
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Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)
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Cited for: FUNCTION IN PHOSPHORYLATION OF PIK3R1; RAF1 AND MAPK1;INTERACTION WITH GRB2; PIK3R1 AND PIK3 CATALYTIC SUBUNIT;ENZYME REGULATION;PHOSPHORYLATION
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Cited for: PHOSPHORYLATION AT SER-741; SER-746; SER-821 AND SER-959;ENZYME REGULATION;PARTIAL PROTEIN SEQUENCE;MUTAGENESIS OF SER-741 AND SER-746
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Cited for: INTERACTION WITH PIK3R1; MATK/CHK; FYN AND SHC1;PHOSPHORYLATION AT TYR-568; TYR-570 AND TYR-721
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Cited for: INTERACTION WITH PTPN6;AUTOPHOSPHORYLATION;FUNCTION IN PHOSPHORYLATION OF PTPN6
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Cited for: INTERACTION WITH GRB2 AND GRB7;PARTIAL PROTEIN SEQUENCE;AUTOPHOSPHORYLATION;PHOSPHORYLATION AT TYR-703 AND TYR-936
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Cited for: INTERACTION WITH PTPRU;FUNCTION IN PHOSPHORYLATION OF PTPRU
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Cited for: INTERACTION WITH MPDZ;CHARACTERIZATION OF VARIANT VAL-816;MUTAGENESIS OF LYS-623
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Cited for: INTERACTION WITH SH2B2/APS;FUNCTION IN PHOSPHORYLATION OF SH2B2/APS;MUTAGENESIS OF ILE-571 AND LEU-939
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Cited for: PHOSPHORYLATION AT SER-891 AND TYR-900;PARTIAL PROTEIN SEQUENCE;INTERACTION WITH CRK AND PIK3R1;FUNCTION IN PHOSPHORYLATION OF CRK; AKT1 AND MAP KINASES;IDENTIFICATION BY MASS SPECTROMETRY
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Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-130
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Cited for: INTERACTION WITH FES/FPS;CHARACTERIZATION OF VARIANT VAL-816
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Cited for: INTERACTION WITH GRB2 AND CBL;UBIQUITINATION;FUNCTION IN PHOSPHORYLATION OF CBL
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Cited for: FUNCTION IN ACTIVATION OF SIGNALING PATHWAYS AND CELL SURVIVAL;FUNCTION IN PHOSPHORYLATION OF CBL;PHOSPHORYLATION AT TYR-568; TYR-703; TYR-721 AND TYR-936;UBIQUITINATION;SUBCELLULAR LOCATION;CHARACTERIZATION OF VARIANT VAL-816
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Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-959;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
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Cited for: SUBCELLULAR LOCATION;ALTERNATIVE SPLICING;TISSUE SPECIFICITY
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Cited for: PHOSPHORYLATION AT TYR-547; TYR-553; TYR-703; TYR-721; TYR-730; TYR-823 AND TYR-900;IDENTIFICATION BY MASS SPECTROMETRY;MUTAGENESIS OF TYR-823;CHARACTERIZATION OF VARIANT HIS-816
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Cited for: FUNCTION;CATALYTIC ACTIVITY;ENZYME REGULATION;AUTOPHOSPHORYLATION;SUBUNIT;CHARACTERIZATION OF VARIANT VAL-816
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Cited for: FUNCTION IN ACTIVATION AND PHOSPHORYLATION OF STAT1; STAT3; STAT5A AND STAT5B
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Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 549-931 IN COMPLEX WITH ADP AND MAGNESIUM IONS;SUBUNIT;PHOSPHORYLATION AT TYR-568 AND TYR-570;IDENTIFICATION BY MASS SPECTROMETRY
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Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 565-935 IN COMPLEXES WITH INHIBITOR IMATINIB AND PHOSPHATE;ENZYME REGULATION
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Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 1-519 IN COMPLEX WITH KITLG/SCF;INTERACTION WITH KITLG/SCF;SUBUNIT;DISULFIDE BONDS;CATALYTIC ACTIVITY;AUTOPHOSPHORYLATION;MUTAGENESIS OF ARG-381 AND GLU-386;GLYCOSYLATION AT ASN-130; ASN-283; ASN-293; ASN-300; ASN-320; ASN-352 AND ASN-367
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Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 544-935 IN COMPLEX WITH SUNITINIB;CATALYTIC ACTIVITY;AUTOPHOSPHORYLATION;CHARACTERIZATION OF VARIANTS HIS-816 AND VAL-816;ENZYME REGULATION
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Cited for: X-RAY CRYSTALLOGRAPHY (1.45 ANGSTROMS) OF 564-574 IN COMPLEX WITH SOCS6;PHOSPHORYLATION AT TYR-568
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Cited for: VARIANTS GIST ILE-550; 550-LYS--LYS-558 DEL; 551-PRO--VAL-555 DEL; ASP-559 AND 559-VAL-VAL-560 DEL
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Cited for: VARIANT HIS-816;CHARACTERIZATION OF VARIANT HIS-816
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Cited for: VARIANTS MASTOCYTOSIS VAL-816; PHE-816; TYR-816 AND LYS-839;CHARACTERIZATION OF VARIANTS MASTOCYTOSIS VAL-816; PHE-816; TYR-816 AND LYS-839
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Cited for: VARIANTS [LARGE SCALE ANALYSIS] ILE-532; LEU-541; SER-691; ASN-715; ASN-737; TRP-804; TYR-816; LYS-822 AND PRO-829