M00323
type: Enzyme
rlcp: p1162
cath: http://ezcatdb.cbrc.jp/EzCatDB/cath/-.-.-.-
cath: Immunoglobulin-like
cath: Phosphorylase Kinase; domain 1
cath: Transferase(Phosphotransferase); domain 1
ec: https://purl.uniprot.org/enzyme/2.7.10.1
uniprot: P10721
kegg enzyme: Receptor protein-tyrosine kinase
kegg enzyme: ATP:protein-tyrosine O-phosphotransferase (ambiguous)
kegg enzyme: CKIT
kegg enzyme: KIT
kegg enzyme: Protein-tyrosine kinase (ambiguous)
kegg enzyme: Protein tyrosine kinase (ambiguous)
kegg enzyme: Receptor protein tyrosine kinase
kegg cofactor: Mg
kegg substrate: ATP
kegg substrate: [protein]-L-tyrosine
kegg product: ADP
kegg product: [protein]-L-tyrosine phosphate
pdb: 2e9wA01
pdb: 2e9wB01
pdb: 2ec8A01
pdb: 2e9wA02
pdb: 2e9wB02
pdb: 2ec8A02
pdb: 2e9wA03
pdb: 2e9wB03
pdb: 2ec8A03
pdb: 2e9wA04
pdb: 2e9wB04
pdb: 2ec8A04
pdb: 2e9wA05
pdb: 2e9wB05
pdb: 2ec8A05
pdb: 1pkgA
pdb: 1pkgB
pdb: 1pkgA01
pdb: 1pkgB01
pdb: 1t45A01
pdb: 1t46A01
pdb: 3g0eA01
pdb: 3g0fA01
pdb: 3g0fB01
pdb: 1pkgA02
pdb: 1pkgB02
pdb: 1t45A02
pdb: 1t46A02
pdb: 3g0eA02
pdb: 3g0fA02
pdb: 3g0fB02
pdb bound state: Unbound
  compound: ATP
  pdb: 2e9wA01
pdb bound state: Unbound
  compound: ATP
  pdb: 2e9wB01
pdb bound state: Unbound
  compound: ATP
  pdb: 2ec8A01
pdb bound state: Unbound
  compound: ATP
  pdb: 2e9wA02
pdb bound state: Unbound
  compound: ATP
  pdb: 2e9wB02
pdb bound state: Unbound
  compound: ATP
  pdb: 2ec8A02
pdb bound state: Unbound
  compound: ATP
  pdb: 2e9wA03
pdb bound state: Unbound
  compound: ATP
  pdb: 2e9wB03
pdb bound state: Unbound
  compound: ATP
  pdb: 2ec8A03
pdb bound state: Unbound
  compound: ATP
  pdb: 2e9wA04
pdb bound state: Unbound
  compound: ATP
  pdb: 2e9wB04
pdb bound state: Unbound
  compound: ATP
  pdb: 2ec8A04
pdb bound state: Unbound
  compound: ATP
  pdb: 2e9wA05
pdb bound state: Unbound
  compound: ATP
  pdb: 2e9wB05
pdb bound state: Unbound
  compound: ATP
  pdb: 2ec8A05
pdb bound state: Unbound
  compound: ATP
  pdb: 1pkgA
active site residues resources: Autoinhibition of the kit receptor tyrosine kinase by the cytosolic juxtamembrane region.
active site residues resources: P10721
references: Kit receptor dimerization is driven by bivalent binding of stem cell factor.
references: Inhibition of spontaneous receptor phosphorylation by residues in a putative alpha-helix in the KIT intracellular juxtamembrane region.
references: Structure of a c-kit product complex reveals the basis for kinase transactivation.
references: Autoinhibition of the kit receptor tyrosine kinase by the cytosolic juxtamembrane region.
references: Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase.
references: Structure and regulation of Kit protein-tyrosine kinase--the stem cell factor receptor.
references: Stem cell factor and its receptor c-Kit as targets for inflammatory diseases.
references: Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor.
references: Detailed conformational dynamics of juxtamembrane region and activation loop in c-Kit kinase activation process.
references: KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients.
comment: 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).

Immunoglobulin-like
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/2.60.40.10

Phosphorylase Kinase; domain 1
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.30.200.20

Transferase(Phosphotransferase); domain 1
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/1.10.510.10
catalytic domain: index.html

Mg
type: KeggCofactor
references: KEGG:C00305
compound type: divalent metal (Ca2+, Mg2+)
references: CHEBI:18420
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

ATP
type: KeggSubstrate
references: KEGG:C00002
compound type: amine group
compound type: nucleotide
references: CHEBI:15422
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

[protein]-L-tyrosine
type: KeggSubstrate
references: KEGG:C00585
compound type: aromatic ring (only carbon atom)
compound type: peptide/protein

ADP
type: KeggProduct
references: KEGG:C00008
compound type: amine group
compound type: nucleotide
references: CHEBI:16761
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

[protein]-L-tyrosine phosphate
type: KeggProduct
references: KEGG:C01167
compound type: aromatic ring (only carbon atom)
compound type: peptide/protein
compound type: phosphate group/phosphate ion

1pkgA
type: Pdb
references: 1pkg
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1pkg
modified residue: PTR 568;PTR 570 (auto-phosphorylation)

1pkgB
type: Pdb
references: 1pkg
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1pkg
modified residue: PTR 568;PTR 570 (auto-phosphorylation)

1pkgA02
type: Pdb
references: 1pkg
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1pkg
catalytic residue: ASP 792;ARG 796
cofactor binding residue: ASN 797;ASP 810 (Magnesium binding)

1pkgB02
type: Pdb
references: 1pkg
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1pkg
catalytic residue: ASP 792;ARG 796
cofactor binding residue: ASN 797;ASP 810 (Magnesium binding)
comment: invisible 817-829

1t45A02
type: Pdb
references: 1t45
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1t45
catalytic residue: ASP 792;ARG 796
cofactor binding residue: ASN 797;ASP 810 (Magnesium binding)

1t46A02
type: Pdb
references: 1t46
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1t46
catalytic residue: ASP 792;ARG 796
cofactor binding residue: ASN 797;ASP 810 (Magnesium binding)

3g0eA02
type: Pdb
references: 3g0e
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3g0e
catalytic residue: ASP 792;ARG 796
cofactor binding residue: ASN 797;ASP 810 (Magnesium binding)

3g0fA02
type: Pdb
references: 3g0f
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3g0f
catalytic residue: ASP 792;ARG 796
cofactor binding residue: ASN 797;ASP 810 (Magnesium binding)

3g0fB02
type: Pdb
references: 3g0f
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3g0f
catalytic residue: ASP 792;ARG 796
cofactor binding residue: ASN 797;ASP 810 (Magnesium binding)

Kit receptor dimerization is driven by bivalent binding of stem cell factor.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9045650
journal: J Biol Chem
volume: 272
pages: 6311-7
published year: 1997
authors:
  item: Lemmon MA
  item: Pinchasi D
  item: Zhou M
  item: Lax I
  item: Schlessinger J

Inhibition of spontaneous receptor phosphorylation by residues in a putative alpha-helix in the KIT intracellular juxtamembrane region.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10224103
journal: J Biol Chem
volume: 274
pages: 13399-402
published year: 1999
authors:
  item: Ma Y
  item: Cunningham ME
  item: Wang X
  item: Ghosh I
  item: Regan L
  item: Longley BJ

Structure of a c-kit product complex reveals the basis for kinase transactivation.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12824176
journal: J Biol Chem
volume: 278
pages: 31461-4
published year: 2003
authors:
  item: Mol CD
  item: Lim KB
  item: Sridhar V
  item: Zou H
  item: Chien EY
  item: Sang BC
  item: Nowakowski J
  item: Kassel DB
  item: Cronin CN
  item: McRee DE
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P10721

Autoinhibition of the kit receptor tyrosine kinase by the cytosolic juxtamembrane region.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12697809
journal: Mol Cell Biol
volume: 23
pages: 3067-78
published year: 2003
authors:
  item: Chan PM
  item: Ilangumaran S
  item: La Rose J
  item: Chakrabartty A
  item: Rottapel R

Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/15123710
journal: J Biol Chem
volume: 279
pages: 31655-63
published year: 2004
authors:
  item: Mol CD
  item: Dougan DR
  item: Schneider TR
  item: Skene RJ
  item: Kraus ML
  item: Scheibe DN
  item: Snell GP
  item: Zou H
  item: Sang BC
  item: Wilson KP
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P10721

Structure and regulation of Kit protein-tyrosine kinase--the stem cell factor receptor.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/16226710
journal: Biochem Biophys Res Commun
volume: 338
pages: 1307-15
published year: 2005
authors:
  item: Roskoski R Jr

Stem cell factor and its receptor c-Kit as targets for inflammatory diseases.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/16483568
journal: Eur J Pharmacol
volume: 533
pages: 327-40
published year: 2006
authors:
  item: Reber L
  item: Da Silva CA
  item: Frossard N

Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/17662946
journal: Cell
volume: 130
pages: 323-34
published year: 2007
authors:
  item: Yuzawa S
  item: Opatowsky Y
  item: Zhang Z
  item: Mandiyan V
  item: Lax I
  item: Schlessinger J
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P10721

Detailed conformational dynamics of juxtamembrane region and activation loop in c-Kit kinase activation process.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/18214972
journal: Proteins
volume: 72
pages: 323-32
published year: 2008
authors:
  item: Zou J
  item: Wang YD
  item: Ma FX
  item: Xiang ML
  item: Shi B
  item: Wei YQ
  item: Yang SY

KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/19164557
journal: Proc Natl Acad Sci U S A
volume: 106
pages: 1542-7
published year: 2009
authors:
  item: Gajiwala KS
  item: Wu JC
  item: Christensen J
  item: Deshmukh GD
  item: Diehl W
  item: DiNitto JP
  item: English JM
  item: Greig MJ
  item: He YA
  item: Jacques SL
  item: Lunney EA
  item: McTigue M
  item: Molina D
  item: Quenzer T
  item: Wells PA
  item: Yu X
  item: Zhang Y
  item: Zou A
  item: Emmett MR
  item: Marshall AG
  item: Zhang HM
  item: Demetri GD
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: P10721

ReferenceForCatalyticMechanism
reference index: 3
reference section: FIG. 4

ReferenceForCatalyticMechanism
reference index: 6
reference section: p.1309