EzCatDB: M00327
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DB codeM00327
RLCP classification3.103.130000.1162 : Transfer
CATH domainDomain 12.60.40.10 : Immunoglobulin-like
Domain 22.60.40.10 : Immunoglobulin-like
Domain 32.60.40.10 : Immunoglobulin-like
Domain 41.10.2000.10 : Frizzled cysteine-rich domain
Domain 5-.-.-.-
Domain 6-.-.-.-
Domain 73.30.200.20 : Phosphorylase Kinase; domain 1
Domain 81.10.510.10 : Transferase(Phosphotransferase); domain 1Catalytic domain
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,M00328,M00329,M00330,M00331,M00332,M00333,M00335,M00339,M00344
2.60.40.10 : Immunoglobulin-likeM00131,T00257,T00005,M00113,M00127,M00132,M00323,M00325,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,M00323,M00325,M00326,M00328,M00329,M00330,M00331,M00332,M00333,M00335,M00339,M00344,D00298

Enzyme Name
UniProtKBKEGG

Q62838
Protein nameMuscle, skeletal receptor tyrosine protein kinaseReceptor protein-tyrosine kinase
ATP:protein-tyrosine O-phosphotransferase (ambiguous)
MUSK
Protein-tyrosine kinase (ambiguous)
Protein tyrosine kinase (ambiguous)
Receptor protein tyrosine kinase
SynonymsEC 2.7.10.1
Muscle-specific tyrosine protein kinase receptor
MuSK
Muscle-specific kinase receptor
RefSeqNP_112323.1 (Protein)
NM_031061.1 (DNA/RNA sequence)
PfamPF01392 (Fz)
PF07679 (I-set)
PF07714 (Pkinase_Tyr)
[Graphical view]


UniProtKB:Accession NumberQ62838
Entry nameMUSK_RAT
ActivityATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
SubunitMonomer (By similarity). Homodimer (Probable). Interacts with LRP4, the heterodimer forms an AGRIN receptor complex that binds AGRIN resulting in activation of MUSK. Forms an heterotetramer composed of 2 DOK7 and 2 MUSK molecules which facilitates MUSK trans-autophosphorylation on tyrosine residue and activation. Interacts (via cytoplasmic part) with DOK7 (via IRS-type PTB domain), requires MUSK phosphorylation. Interacts with DVL1 (via DEP domain), the interaction is direct and mediates the formation of a DVL1, MUSK and PAK1 ternary complex involved in AChR clustering (By similarity). Interacts with PDZRN3, this interaction is enhanced by agrin (By similarity). Interacts with FNTA, the interaction is direct and mediates AGRIN-induced phosphorylation and activation of FNTA (By similarity). Interacts with CSNK2B, mediates regulation by CK2 (By similarity). Interacts (via the cytoplasmic domain) with DNAJA3. Interacts with NSF, may regulate MUSK endocytosis and activity (By similarity). Interacts with CAV3, may regulate MUSK signaling (By similarity). Interacts with RNF31 (By similarity).
Subcellular locationMembrane, Single-pass type I membrane protein (Potential).
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

             
2iepA01UnboundUnboundUnboundUnboundUnbound
2iepB01UnboundUnboundUnboundUnboundUnbound
2iepA02UnboundUnboundUnboundUnboundUnbound
2iepB02UnboundUnboundUnboundUnboundUnbound
3hklAUnboundUnboundUnboundUnboundUnbound
3hklBUnboundUnboundUnboundUnboundUnbound
1lufA01UnboundUnboundUnboundUnboundUnbound
1lufA02UnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Literature [4] & Swiss-prot;Q62838
pdbCatalytic residuesCofactor-binding residuesModified residuescomment
            
2iepA01               
 
 
 
2iepB01               
 
 
 
2iepA02               
 
 
 
2iepB02               
 
 
 
3hklA               
 
 
 
3hklB               
 
 
 
1lufA01               
 
 
 
1lufA02ASP 724;ARG 728
ASN 729;ASP 742 (Magnesium binding)
TYR 754 (auto-phosphorylation)
invisible 672-693, 757-760

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[11]Fig. 1

references
[1]
PubMed ID8653787
JournalCell
Year1996
Volume85
Pages513-23
AuthorsGlass DJ, Bowen DC, Stitt TN, Radziejewski C, Bruno J, Ryan TE, Gies DR, Shah S, Mattsson K, Burden SJ, DiStefano PS, Valenzuela DM, DeChiara TM, Yancopoulos GD
TitleAgrin acts via a MuSK receptor complex.
[2]
PubMed ID10619845
JournalEMBO J
Year2000
Volume19
Pages67-77
AuthorsHerbst R, Burden SJ
TitleThe juxtamembrane region of MuSK has a critical role in agrin-mediated signaling.
[3]
PubMed ID12165471
JournalNeuron
Year2002
Volume35
Pages489-505
AuthorsLuo ZG, Wang Q, Zhou JZ, Wang J, Luo Z, Liu M, He X, Wynshaw-Boris A, Xiong WC, Lu B, Mei L
TitleRegulation of AChR clustering by Dishevelled interacting with MuSK and PAK1.
[4]
CommentsX-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 560-860.
PubMed ID12220490
JournalStructure
Year2002
Volume10
Pages1187-96
AuthorsTill JH, Becerra M, Watty A, Lu Y, Ma Y, Neubert TA, Burden SJ, Hubbard SR
TitleCrystal structure of the MuSK tyrosine kinase: insights into receptor autoregulation.
Related PDB1luf
Related UniProtKBQ62838
[5]
PubMed ID15173825
JournalNat Rev Mol Cell Biol
Year2004
Volume5
Pages464-71
AuthorsHubbard SR
TitleJuxtamembrane autoinhibition in receptor tyrosine kinases.
[6]
CommentsX-RAY CRYSTALLOGRAPHY (2.21 ANGSTROMS) OF 22-212, FUNCTION, PHOSPHORYLATION, SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF MET-48; LEU-83 AND ILE-96, DISULFIDE BONDS.
PubMed ID17011580
JournalJ Mol Biol
Year2006
Volume364
Pages424-33
AuthorsStiegler AL, Burden SJ, Hubbard SR
TitleCrystal structure of the agrin-responsive immunoglobulin-like domains 1 and 2 of the receptor tyrosine kinase MuSK.
Related PDB2iep
Related UniProtKBQ62838
[7]
PubMed ID18848351
JournalCell
Year2008
Volume135
Pages334-42
AuthorsKim N, Stiegler AL, Cameron TO, Hallock PT, Gomez AM, Huang JH, Hubbard SR, Dustin ML, Burden SJ
TitleLrp4 is a receptor for Agrin and forms a complex with MuSK.
[8]
PubMed ID19038220
JournalNeuron
Year2008
Volume60
Pages625-41
AuthorsLinnoila J, Wang Y, Yao Y, Wang ZZ
TitleA mammalian homolog of Drosophila tumorous imaginal discs, Tid1, mediates agrin signaling at the neuromuscular junction.
[9]
CommentsX-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 313-494, SUBUNIT, DISULFIDE BONDS, GLYCOSYLATION AT ASN-338.
PubMed ID19664639
JournalJ Mol Biol
Year2009
Volume393
Pages1-9
AuthorsStiegler AL, Burden SJ, Hubbard SR
TitleCrystal structure of the frizzled-like cysteine-rich domain of the receptor tyrosine kinase MuSK.
Related PDB3hkl
Related UniProtKBQ62838
[10]
PubMed ID19244212
JournalSci Signal
Year2009
Volume2
Pagesra7
AuthorsInoue A, Setoguchi K, Matsubara Y, Okada K, Sato N, Iwakura Y, Higuchi O, Yamanashi Y
TitleDok-7 activates the muscle receptor kinase MuSK and shapes synapse formation.
[11]
PubMed ID20974278
JournalInt J Biochem Cell Biol
Year2011
Volume43
Pages295-8
AuthorsGhazanfari N, Fernandez KJ, Murata Y, Morsch M, Ngo ST, Reddel SW, Noakes PG, Phillips WD
TitleMuscle specific kinase: organiser of synaptic membrane domains.

comments
This enzyme belongs to Tyr protein kinase family.
The catalytic domain of this enzyme is homologous to that of vascular endothelial growth factor receptor (M00131 in EzCatDB).
The extracellular domains of this enzyme are composed of three immunoglobulin-like (Ig-like) repeats and a frizzled (FZ) cysteine-rich domain (see [2] and [9]).

createdupdated
2011-11-012012-12-12


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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