EzCatDB: M00329
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DB codeM00329
RLCP classification3.103.130000.1162 : Transfer
CATH domainDomain 12.130.10.10 : Methylamine Dehydrogenase; Chain H
Domain 23.30.1680.10 : ligand-binding face of the semaphorins, domain 2
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,M00323,M00325,M00326,M00327,M00328,M00330,M00331,M00332,M00333,M00335,M00339,M00344
2.130.10.10 : Methylamine Dehydrogenase; Chain HS00852,D00039
2.60.40.10 : Immunoglobulin-likeM00131,T00257,T00005,M00113,M00127,M00132,M00323,M00325,M00327,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,M00323,M00325,M00326,M00327,M00328,M00330,M00331,M00332,M00333,M00335,M00339,M00344,D00298

Enzyme Name
UniProtKBKEGG

Q04912
Protein nameMacrophage-stimulating protein receptor (MSP receptor) (EC 2.7.10.1) (CDw136) (Protein-tyrosine kinase 8) (p185-Ron)AltName: CD_antigen=CD136;Receptor protein-tyrosine kinase
ATP:protein-tyrosine O-phosphotransferase (ambiguous)
MST1R
Protein-tyrosine kinase (ambiguous)
Protein tyrosine kinase (ambiguous)
PTK
Receptor protein tyrosine kinase
RON
SynonymsNone
ContainsMacrophage-stimulating protein receptor alpha chain
Macrophage-stimulating protein receptor beta chain
RefSeqNP_001231866.1 (Protein)
NM_001244937.1 (DNA/RNA sequence)
NP_002438.2 (Protein)
NM_002447.2 (DNA/RNA sequence)
PfamPF07714 (Pkinase_Tyr)
PF01403 (Sema)
PF01833 (TIG)
[Graphical view]


UniProtKB:Accession NumberQ04912
Entry nameRON_HUMAN
ActivityATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
SubunitHeterodimer of an alpha chain and a beta chain which are disulfide linked. Binds PLXNB1. Associates with and is negatively regulated by HYAL2. Interacts when phosphorylated with downstream effectors including PIK3R1, PCLG1, GRB2 and GAB1. Interacts with integrin beta1/ITGB1 in a ligand-independent fashion.
Subcellular locationMembrane, Single-pass type I membrane protein.
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

             
4fwwA01UnboundUnboundUnboundUnboundUnbound
4fwwA02UnboundUnboundUnboundUnboundUnbound
3plsA01UnboundUnboundUnboundAnalogue:ANPUnbound
3plsA02Bound:_MGUnboundUnboundUnboundUnbound

Active-site residues
resource
Literature [7] & Swiss-prot;Q04912
pdbCatalytic residuesCofactor-binding residuesModified residues
           
4fwwA01 
 
 
4fwwA02 
 
 
3plsA01                 
 
 
3plsA02ASP 1208;ARG 1212
ASN 1213;ASP 1226(Magnesium binding)
TYR 1238;TYR 1239;TYR 1358 (auto-phosphorylation)

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[7]FIGURE 1

references
[1]
PubMed ID8062829
JournalEMBO J
Year1994
Volume13
Pages3524-32
AuthorsGaudino G, Follenzi A, Naldini L, Collesi C, Santoro M, Gallo KA, Godowski PJ, Comoglio PM
TitleRON is a heterodimeric tyrosine kinase receptor activated by the HGF homologue MSP.
[2]
PubMed ID7939629
JournalScience
Year1994
Volume266
Pages117-9
AuthorsWang MH, Ronsin C, Gesnel MC, Coupey L, Skeel A, Leonard EJ, Breathnach R
TitleIdentification of the ron gene product as the receptor for the human macrophage stimulating protein.
[3]
PubMed ID10631120
JournalBiochem Biophys Res Commun
Year2000
Volume267
Pages669-75
AuthorsXiao ZQ, Chen YQ, Wang MH
TitleRequirement of both tyrosine residues 1330 and 1337 in the C-terminal tail of the RON receptor tyrosine kinase for epithelial cell scattering and migration.
[4]
PubMed ID14597639
JournalJ Biol Chem
Year2004
Volume279
Pages3726-32
AuthorsAngeloni D, Danilkovitch-Miagkova A, Miagkov A, Leonard EJ, Lerman MI
TitleThe soluble sema domain of the RON receptor inhibits macrophage-stimulating protein-induced receptor activation.
[5]
PubMed ID15632155
JournalJ Biol Chem
Year2005
Volume280
Pages8893-900
AuthorsYokoyama N, Ischenko I, Hayman MJ, Miller WT
TitleThe C terminus of RON tyrosine kinase plays an autoinhibitory role.
[6]
PubMed ID18950514
JournalJ Exp Clin Cancer Res
Year2008
Volume27
Pages55
AuthorsLu Y, Yao HP, Wang MH
TitleSignificance of the entire C-terminus in biological activities mediated by the RON receptor tyrosine kinase and its oncogenic variant RON160.
[7]
CommentsX-RAY CRYSTALLOGRAPHY (2.24 ANGSTROMS) OF 1060-1357 IN COMPLEX WITH AMP-PNP AND MAGNESIUM, ACTIVE SITE, PHOSPHORYLATION AT TYR-1238.
PubMed ID20726546
JournalBiochemistry
Year2010
Volume49
Pages7972-4
AuthorsWang J, Steinbacher S, Augustin M, Schreiner P, Epstein D, Mulvihill MJ, Crew AP
TitleThe crystal structure of a constitutively active mutant RON kinase suggests an intramolecular autophosphorylation hypothesis.
Related PDB3pls
Related UniProtKBQ04912
[8]
PubMed ID22848655
JournalPLoS One
Year2012
Volume7
Pagese41912
AuthorsChao KL, Tsai IW, Chen C, Herzberg O
TitleCrystal structure of the Sema-PSI extracellular domain of human RON receptor tyrosine kinase.
Related PDB4fww

comments
This enzyme is homologous to c-MET (M00322 in EzCatDB).
The catalytic domain of this enzyme is homologous to that of vascular endothelial growth factor receptor (M00131 in EzCatDB).

createdupdated
2011-11-092012-12-11


Copyright: Nozomi Nagano, JST & CBRC-AIST
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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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