DB code: M00323

RLCP classification 3.103.130000.1162 : Transfer
CATH domain -.-.-.- :
2.60.40.10 : Immunoglobulin-like
2.60.40.10 : Immunoglobulin-like
2.60.40.10 : Immunoglobulin-like
2.60.40.10 : Immunoglobulin-like
2.60.40.10 : Immunoglobulin-like
-.-.-.- :
-.-.-.- :
3.30.200.20 : Phosphorylase Kinase; domain 1
1.10.510.10 : Transferase(Phosphotransferase); domain 1 Catalytic domain
-.-.-.- :
E.C. 2.7.10.1
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
1.10.510.10 : Transferase(Phosphotransferase); domain 1 M00125 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-like M00131 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 1 M00125 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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P10721 Mast/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;
None NP_000213.1 (Protein)
NM_000222.2 (DNA/RNA sequence)
NP_001087241.1 (Protein)
NM_001093772.1 (DNA/RNA sequence)
PF00047 (ig)
PF07714 (Pkinase_Tyr)
[Graphical View]

KEGG enzyme name
Receptor protein-tyrosine kinase
ATP:protein-tyrosine O-phosphotransferase (ambiguous)
CKIT
KIT
Protein-tyrosine kinase (ambiguous)
Protein tyrosine kinase (ambiguous)
Receptor protein tyrosine kinase

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P10721 KIT_HUMAN ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. 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 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. Isoform 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.

KEGG Pathways
Map code Pathways E.C.

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C00002 C00585 C00008 C01167
E.C.
Compound Mg ATP [protein]-L-tyrosine ADP [protein]-L-tyrosine phosphate
Type divalent metal (Ca2+, Mg2+) amine group,nucleotide aromatic ring (only carbon atom),peptide/protein amine group,nucleotide aromatic ring (only carbon atom),peptide/protein,phosphate group/phosphate ion
ChEBI 18420
 18420
 		15422
 15422
 		16761
 16761
PubChem 888
 888
 		5957
 5957
 		6022
 6022
2e9wA01 Unbound Unbound Unbound Unbound Unbound
2e9wB01 Unbound Unbound Unbound Unbound Unbound
2ec8A01 Unbound Unbound Unbound Unbound Unbound
2e9wA02 Unbound Unbound Unbound Unbound Unbound
2e9wB02 Unbound Unbound Unbound Unbound Unbound
2ec8A02 Unbound Unbound Unbound Unbound Unbound
2e9wA03 Unbound Unbound Unbound Unbound Unbound
2e9wB03 Unbound Unbound Unbound Unbound Unbound
2ec8A03 Unbound Unbound Unbound Unbound Unbound
2e9wA04 Unbound Unbound Unbound Unbound Unbound
2e9wB04 Unbound Unbound Unbound Unbound Unbound
2ec8A04 Unbound Unbound Unbound Unbound Unbound
2e9wA05 Unbound Unbound Unbound Unbound Unbound
2e9wB05 Unbound Unbound Unbound Unbound Unbound
2ec8A05 Unbound Unbound Unbound Unbound Unbound
1pkgA Unbound Unbound Unbound Unbound Unbound
1pkgB Unbound Unbound Unbound Unbound Unbound
1pkgA01 Unbound Unbound Unbound Bound:ADP Unbound
1pkgB01 Unbound Unbound Unbound Bound:ADP Unbound
1t45A01 Unbound Unbound Unbound Unbound Unbound
1t46A01 Unbound Unbound Unbound Unbound Unbound
3g0eA01 Unbound Unbound Unbound Unbound Unbound
3g0fA01 Unbound Unbound Unbound Unbound Unbound
3g0fB01 Unbound Unbound Unbound Unbound Unbound
1pkgA02 Bound:_MG Unbound Unbound Unbound Bound:PTR_568 (chain B)
1pkgB02 Bound:_MG Unbound Unbound Unbound Unbound
1t45A02 Unbound Unbound Unbound Unbound Unbound
1t46A02 Unbound Unbound Unbound Unbound Unbound
3g0eA02 Unbound Unbound Unbound Unbound Unbound
3g0fA02 Unbound Unbound Unbound Unbound Unbound
3g0fB02 Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Literature [3] & Swiss-prot;P10721

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
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
1pkgA02 ASP 792;ARG 796 ASN 797;ASP 810 (Magnesium binding)
1pkgB02 ASP 792;ARG 796 ASN 797;ASP 810 (Magnesium binding) invisible 817-829
1t45A02 ASP 792;ARG 796 ASN 797;ASP 810 (Magnesium binding)
1t46A02 ASP 792;ARG 796 ASN 797;ASP 810 (Magnesium binding)
3g0eA02 ASP 792;ARG 796 ASN 797;ASP 810 (Magnesium binding)
3g0fA02 ASP 792;ARG 796 ASN 797;ASP 810 (Magnesium binding)
3g0fB02 ASP 792;ARG 796 ASN 797;ASP 810 (Magnesium binding)

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[3]
FIG. 4
[6]
p.1309

References
[1]
Resource
Comments
Medline ID
PubMed ID 9045650
Journal J Biol Chem
Year 1997
Volume 272
Pages 6311-7
Authors Lemmon MA, Pinchasi D, Zhou M, Lax I, Schlessinger J
Title Kit receptor dimerization is driven by bivalent binding of stem cell factor.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 10224103
Journal J Biol Chem
Year 1999
Volume 274
Pages 13399-402
Authors Ma Y, Cunningham ME, Wang X, Ghosh I, Regan L, Longley BJ
Title Inhibition of spontaneous receptor phosphorylation by residues in a putative alpha-helix in the KIT intracellular juxtamembrane region.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 12824176
Journal J Biol Chem
Year 2003
Volume 278
Pages 31461-4
Authors Mol CD, Lim KB, Sridhar V, Zou H, Chien EY, Sang BC, Nowakowski J, Kassel DB, Cronin CN, McRee DE
Title Structure of a c-kit product complex reveals the basis for kinase transactivation.
Related PDB 1pkg
Related UniProtKB P10721
[4]
Resource
Comments
Medline ID
PubMed ID 12697809
Journal Mol Cell Biol
Year 2003
Volume 23
Pages 3067-78
Authors Chan PM, Ilangumaran S, La Rose J, Chakrabartty A, Rottapel R
Title Autoinhibition of the kit receptor tyrosine kinase by the cytosolic juxtamembrane region.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 15123710
Journal J Biol Chem
Year 2004
Volume 279
Pages 31655-63
Authors Mol CD, Dougan DR, Schneider TR, Skene RJ, Kraus ML, Scheibe DN, Snell GP, Zou H, Sang BC, Wilson KP
Title Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase.
Related PDB 1t45 1t46
Related UniProtKB P10721
[6]
Resource
Comments
Medline ID
PubMed ID 16226710
Journal Biochem Biophys Res Commun
Year 2005
Volume 338
Pages 1307-15
Authors Roskoski R Jr
Title Structure and regulation of Kit protein-tyrosine kinase--the stem cell factor receptor.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 16483568
Journal Eur J Pharmacol
Year 2006
Volume 533
Pages 327-40
Authors Reber L, Da Silva CA, Frossard N
Title Stem cell factor and its receptor c-Kit as targets for inflammatory diseases.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 17662946
Journal Cell
Year 2007
Volume 130
Pages 323-34
Authors Yuzawa S, Opatowsky Y, Zhang Z, Mandiyan V, Lax I, Schlessinger J
Title Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor.
Related PDB 2e9w 2ec8
Related UniProtKB P10721
[9]
Resource
Comments
Medline ID
PubMed ID 18214972
Journal Proteins
Year 2008
Volume 72
Pages 323-32
Authors Zou J, Wang YD, Ma FX, Xiang ML, Shi B, Wei YQ, Yang SY
Title Detailed conformational dynamics of juxtamembrane region and activation loop in c-Kit kinase activation process.
Related PDB
Related UniProtKB
[10]
Resource
Comments
Medline ID
PubMed ID 19164557
Journal Proc Natl Acad Sci U S A
Year 2009
Volume 106
Pages 1542-7
Authors Gajiwala 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
Title KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients.
Related PDB 3g0e 3g0f
Related UniProtKB P10721

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).

Created Updated
2011-10-04 2012-12-06