EzCatDB: M00323
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DB codeM00323
RLCP classification3.103.130000.1162 : Transfer
CATH domainDomain 1-.-.-.-
Domain 22.60.40.10 : Immunoglobulin-like
Domain 32.60.40.10 : Immunoglobulin-like
Domain 42.60.40.10 : Immunoglobulin-like
Domain 52.60.40.10 : Immunoglobulin-like
Domain 62.60.40.10 : Immunoglobulin-like
Domain 7-.-.-.-
Domain 8-.-.-.-
Domain 93.30.200.20 : Phosphorylase Kinase; domain 1
Domain 101.10.510.10 : Transferase(Phosphotransferase); domain 1Catalytic domain
Domain 11-.-.-.-
E.C.2.7.10.1

CATH domainRelated DB codes (homologues)
1.10.510.10 : Transferase(Phosphotransferase); domain 1M00125,M00124,M00131,T00224,M00127,M00129,M00130,M00132,M00136,M00196,M00197,M00198,M00304,M00325,M00326,M00327,M00328,M00329,M00330,M00331,M00332,M00333,M00335,M00339,M00344
2.60.40.10 : Immunoglobulin-likeM00131,T00257,T00005,M00113,M00127,M00132,M00325,M00327,M00329,M00330,M00331,M00332,T00307,D00166,D00500,M00112,M00193,T00063,T00065,T00067,T00245
3.30.200.20 : Phosphorylase Kinase; domain 1M00125,M00124,M00131,T00224,M00127,M00129,M00130,M00132,M00136,M00196,M00197,M00198,M00304,M00325,M00326,M00327,M00328,M00329,M00330,M00331,M00332,M00333,M00335,M00339,M00344,D00298

Enzyme Name
UniProtKBKEGG

P10721
Protein nameMast/stem cell growth factor receptor Kit (SCFR) (EC 2.7.10.1) (Piebald trait protein) (PBT) (Proto-oncogene c-Kit) (Tyrosine-protein kinase Kit) (p145 c-kit) (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog)AltName: CD_antigen=CD117;Receptor protein-tyrosine kinase
ATP:protein-tyrosine O-phosphotransferase (ambiguous)
CKIT
KIT
Protein-tyrosine kinase (ambiguous)
Protein tyrosine kinase (ambiguous)
Receptor protein tyrosine kinase
SynonymsNone
RefSeqNP_000213.1 (Protein)
NM_000222.2 (DNA/RNA sequence)
NP_001087241.1 (Protein)
NM_001093772.1 (DNA/RNA sequence)
PfamPF00047 (ig)
PF07714 (Pkinase_Tyr)
[Graphical view]


UniProtKB:Accession NumberP10721
Entry nameKIT_HUMAN
ActivityATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
SubunitMonomer 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 PIK3 catalytic subunit. 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. Interacts with DOK1 and TEC.
Subcellular locationIsoform 1: Cell membrane, Single-pass type I membrane protein.,Isoform 2: Cell membrane, Single-pass type I membrane protein.,Isoform 3: Cytoplasm. Note=Detected in the cytoplasm of spermatozoa, especially in the equatorial and subacrosomal region of the sperm head.
Cofactor

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00305C00002C00585C00008C01167
CompoundMgATP[protein]-L-tyrosineADP[protein]-L-tyrosine phosphate
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotidearomatic ring (only carbon atom),peptide/proteinamine group,nucleotidearomatic ring (only carbon atom),peptide/protein,phosphate group/phosphate ion
ChEBI18420
15422

16761

PubChem888
5957

6022

             
2e9wA01UnboundUnboundUnboundUnboundUnbound
2e9wB01UnboundUnboundUnboundUnboundUnbound
2ec8A01UnboundUnboundUnboundUnboundUnbound
2e9wA02UnboundUnboundUnboundUnboundUnbound
2e9wB02UnboundUnboundUnboundUnboundUnbound
2ec8A02UnboundUnboundUnboundUnboundUnbound
2e9wA03UnboundUnboundUnboundUnboundUnbound
2e9wB03UnboundUnboundUnboundUnboundUnbound
2ec8A03UnboundUnboundUnboundUnboundUnbound
2e9wA04UnboundUnboundUnboundUnboundUnbound
2e9wB04UnboundUnboundUnboundUnboundUnbound
2ec8A04UnboundUnboundUnboundUnboundUnbound
2e9wA05UnboundUnboundUnboundUnboundUnbound
2e9wB05UnboundUnboundUnboundUnboundUnbound
2ec8A05UnboundUnboundUnboundUnboundUnbound
1pkgAUnboundUnboundUnboundUnboundUnbound
1pkgBUnboundUnboundUnboundUnboundUnbound
1pkgA01UnboundUnboundUnboundBound:ADPUnbound
1pkgB01UnboundUnboundUnboundBound:ADPUnbound
1t45A01UnboundUnboundUnboundUnboundUnbound
1t46A01UnboundUnboundUnboundUnboundUnbound
3g0eA01UnboundUnboundUnboundUnboundUnbound
3g0fA01UnboundUnboundUnboundUnboundUnbound
3g0fB01UnboundUnboundUnboundUnboundUnbound
1pkgA02Bound:_MGUnboundUnboundUnboundBound:PTR 568(chain B)
1pkgB02Bound:_MGUnboundUnboundUnboundUnbound
1t45A02UnboundUnboundUnboundUnboundUnbound
1t46A02UnboundUnboundUnboundUnboundUnbound
3g0eA02UnboundUnboundUnboundUnboundUnbound
3g0fA02UnboundUnboundUnboundUnboundUnbound
3g0fB02UnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Literature [3] & Swiss-prot;P10721
pdbCatalytic residuesCofactor-binding residuesModified residuescomment
            
2e9wA01               
 
 
 
2e9wB01               
 
 
 
2ec8A01               
 
 
 
2e9wA02               
 
 
 
2e9wB02               
 
 
 
2ec8A02               
 
 
 
2e9wA03               
 
 
 
2e9wB03               
 
 
 
2ec8A03               
 
 
 
2e9wA04               
 
 
 
2e9wB04               
 
 
 
2ec8A04               
 
 
 
2e9wA05               
 
 
 
2e9wB05               
 
 
 
2ec8A05               
 
 
 
1pkgA               
 
PTR 568;PTR 570 (auto-phosphorylation)
 
1pkgB               
 
PTR 568;PTR 570 (auto-phosphorylation)
 
1pkgA01               
 
 
 
1pkgB01               
 
 
 
1t45A01               
 
 
 
1t46A01               
 
 
 
3g0eA01               
 
 
 
3g0fA01               
 
 
 
3g0fB01               
 
 
 
1pkgA02ASP 792;ARG 796
ASN 797;ASP 810 (Magnesium binding)
 
 
1pkgB02ASP 792;ARG 796
ASN 797;ASP 810 (Magnesium binding)
 
invisible 817-829
1t45A02ASP 792;ARG 796
ASN 797;ASP 810 (Magnesium binding)
 
 
1t46A02ASP 792;ARG 796
ASN 797;ASP 810 (Magnesium binding)
 
 
3g0eA02ASP 792;ARG 796
ASN 797;ASP 810 (Magnesium binding)
 
 
3g0fA02ASP 792;ARG 796
ASN 797;ASP 810 (Magnesium binding)
 
 
3g0fB02ASP 792;ARG 796
ASN 797;ASP 810 (Magnesium binding)
 
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[3]FIG. 4
[6]p.1309

references
[1]
PubMed ID9045650
JournalJ Biol Chem
Year1997
Volume272
Pages6311-7
AuthorsLemmon MA, Pinchasi D, Zhou M, Lax I, Schlessinger J
TitleKit receptor dimerization is driven by bivalent binding of stem cell factor.
[2]
PubMed ID10224103
JournalJ Biol Chem
Year1999
Volume274
Pages13399-402
AuthorsMa Y, Cunningham ME, Wang X, Ghosh I, Regan L, Longley BJ
TitleInhibition of spontaneous receptor phosphorylation by residues in a putative alpha-helix in the KIT intracellular juxtamembrane region.
[3]
PubMed ID12824176
JournalJ Biol Chem
Year2003
Volume278
Pages31461-4
AuthorsMol CD, Lim KB, Sridhar V, Zou H, Chien EY, Sang BC, Nowakowski J, Kassel DB, Cronin CN, McRee DE
TitleStructure of a c-kit product complex reveals the basis for kinase transactivation.
Related PDB1pkg
Related UniProtKBP10721
[4]
PubMed ID12697809
JournalMol Cell Biol
Year2003
Volume23
Pages3067-78
AuthorsChan PM, Ilangumaran S, La Rose J, Chakrabartty A, Rottapel R
TitleAutoinhibition of the kit receptor tyrosine kinase by the cytosolic juxtamembrane region.
[5]
PubMed ID15123710
JournalJ Biol Chem
Year2004
Volume279
Pages31655-63
AuthorsMol CD, Dougan DR, Schneider TR, Skene RJ, Kraus ML, Scheibe DN, Snell GP, Zou H, Sang BC, Wilson KP
TitleStructural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase.
Related PDB1t45,1t46
Related UniProtKBP10721
[6]
PubMed ID16226710
JournalBiochem Biophys Res Commun
Year2005
Volume338
Pages1307-15
AuthorsRoskoski R Jr
TitleStructure and regulation of Kit protein-tyrosine kinase--the stem cell factor receptor.
[7]
PubMed ID16483568
JournalEur J Pharmacol
Year2006
Volume533
Pages327-40
AuthorsReber L, Da Silva CA, Frossard N
TitleStem cell factor and its receptor c-Kit as targets for inflammatory diseases.
[8]
PubMed ID17662946
JournalCell
Year2007
Volume130
Pages323-34
AuthorsYuzawa S, Opatowsky Y, Zhang Z, Mandiyan V, Lax I, Schlessinger J
TitleStructural basis for activation of the receptor tyrosine kinase KIT by stem cell factor.
Related PDB2e9w,2ec8
Related UniProtKBP10721
[9]
PubMed ID18214972
JournalProteins
Year2008
Volume72
Pages323-32
AuthorsZou J, Wang YD, Ma FX, Xiang ML, Shi B, Wei YQ, Yang SY
TitleDetailed conformational dynamics of juxtamembrane region and activation loop in c-Kit kinase activation process.
[10]
PubMed ID19164557
JournalProc Natl Acad Sci U S A
Year2009
Volume106
Pages1542-7
AuthorsGajiwala KS, Wu JC, Christensen J, Deshmukh GD, Diehl W, DiNitto JP, English JM, Greig MJ, He YA, Jacques SL, Lunney EA, McTigue M, Molina D, Quenzer T, Wells PA, Yu X, Zhang Y, Zou A, Emmett MR, Marshall AG, Zhang HM, Demetri GD
TitleKIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients.
Related PDB3g0e,3g0f
Related UniProtKBP10721

comments
This enzyme belongs to platelet-derived growth factor (PDGF) receptor family, along with homologous enzymes, such as colony-stimulating factor-1 receptor (CSF-1-R, cFMS) (M00330 in EzCatDB) and Receptor-type tyrosine-protein kinase FLT3 (M00331 in EzCatDB). This enzyme seems to interact with different proteins from those proteins which are interacted with the homologous enzymes.
The catalytic domain of this enzyme is homologous to that of vascular endothelial growth factor receptor (M00131 in EzCatDB).

createdupdated
2011-10-042012-12-06


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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