DB code: M00327

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
1.10.2000.10 : Frizzled cysteine-rich domain
-.-.-.- :
-.-.-.- :
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 M00323 M00325 M00326 M00328 M00329 M00330 M00331 M00332 M00333 M00335 M00339 M00344
2.60.40.10 : Immunoglobulin-like M00131 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 1 M00125 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

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q62838 Muscle, skeletal receptor tyrosine protein kinase
EC 2.7.10.1
Muscle-specific tyrosine protein kinase receptor
MuSK
Muscle-specific kinase receptor
NP_112323.1 (Protein)
NM_031061.1 (DNA/RNA sequence)
PF01392 (Fz)
PF07679 (I-set)
PF07714 (Pkinase_Tyr)
[Graphical View]

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

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q62838 MUSK_RAT ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Monomer (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). Membrane, Single-pass type I membrane protein (Potential).

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
15422
16761
PubChem 888
5957
6022
2iepA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
2iepB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
2iepA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
2iepB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
3hklA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
3hklB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1lufA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound
1lufA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Literature [4] & Swiss-prot;Q62838

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
2iepA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2iepB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2iepA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
2iepB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
3hklA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
3hklB Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1lufA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1lufA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ASP 724;ARG 728 ASN 729;ASP 742 (Magnesium binding) TYR 754 (auto-phosphorylation) invisible 672-693, 757-760

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[11]
Fig. 1

References
[1]
Resource
Comments
Medline ID
PubMed ID 8653787
Journal Cell
Year 1996
Volume 85
Pages 513-23
Authors Glass 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
Title Agrin acts via a MuSK receptor complex.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 10619845
Journal EMBO J
Year 2000
Volume 19
Pages 67-77
Authors Herbst R, Burden SJ
Title The juxtamembrane region of MuSK has a critical role in agrin-mediated signaling.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 12165471
Journal Neuron
Year 2002
Volume 35
Pages 489-505
Authors Luo ZG, Wang Q, Zhou JZ, Wang J, Luo Z, Liu M, He X, Wynshaw-Boris A, Xiong WC, Lu B, Mei L
Title Regulation of AChR clustering by Dishevelled interacting with MuSK and PAK1.
Related PDB
Related UniProtKB
[4]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 560-860.
Medline ID
PubMed ID 12220490
Journal Structure
Year 2002
Volume 10
Pages 1187-96
Authors Till JH, Becerra M, Watty A, Lu Y, Ma Y, Neubert TA, Burden SJ, Hubbard SR
Title Crystal structure of the MuSK tyrosine kinase: insights into receptor autoregulation.
Related PDB 1luf
Related UniProtKB Q62838
[5]
Resource
Comments
Medline ID
PubMed ID 15173825
Journal Nat Rev Mol Cell Biol
Year 2004
Volume 5
Pages 464-71
Authors Hubbard SR
Title Juxtamembrane autoinhibition in receptor tyrosine kinases.
Related PDB
Related UniProtKB
[6]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.21 ANGSTROMS) OF 22-212, FUNCTION, PHOSPHORYLATION, SUBUNIT, SUBCELLULAR LOCATION, MUTAGENESIS OF MET-48; LEU-83 AND ILE-96, DISULFIDE BONDS.
Medline ID
PubMed ID 17011580
Journal J Mol Biol
Year 2006
Volume 364
Pages 424-33
Authors Stiegler AL, Burden SJ, Hubbard SR
Title Crystal structure of the agrin-responsive immunoglobulin-like domains 1 and 2 of the receptor tyrosine kinase MuSK.
Related PDB 2iep
Related UniProtKB Q62838
[7]
Resource
Comments
Medline ID
PubMed ID 18848351
Journal Cell
Year 2008
Volume 135
Pages 334-42
Authors Kim N, Stiegler AL, Cameron TO, Hallock PT, Gomez AM, Huang JH, Hubbard SR, Dustin ML, Burden SJ
Title Lrp4 is a receptor for Agrin and forms a complex with MuSK.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 19038220
Journal Neuron
Year 2008
Volume 60
Pages 625-41
Authors Linnoila J, Wang Y, Yao Y, Wang ZZ
Title A mammalian homolog of Drosophila tumorous imaginal discs, Tid1, mediates agrin signaling at the neuromuscular junction.
Related PDB
Related UniProtKB
[9]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 313-494, SUBUNIT, DISULFIDE BONDS, GLYCOSYLATION AT ASN-338.
Medline ID
PubMed ID 19664639
Journal J Mol Biol
Year 2009
Volume 393
Pages 1-9
Authors Stiegler AL, Burden SJ, Hubbard SR
Title Crystal structure of the frizzled-like cysteine-rich domain of the receptor tyrosine kinase MuSK.
Related PDB 3hkl
Related UniProtKB Q62838
[10]
Resource
Comments
Medline ID
PubMed ID 19244212
Journal Sci Signal
Year 2009
Volume 2
Pages ra7
Authors Inoue A, Setoguchi K, Matsubara Y, Okada K, Sato N, Iwakura Y, Higuchi O, Yamanashi Y
Title Dok-7 activates the muscle receptor kinase MuSK and shapes synapse formation.
Related PDB
Related UniProtKB
[11]
Resource
Comments
Medline ID
PubMed ID 20974278
Journal Int J Biochem Cell Biol
Year 2011
Volume 43
Pages 295-8
Authors Ghazanfari N, Fernandez KJ, Murata Y, Morsch M, Ngo ST, Reddel SW, Noakes PG, Phillips WD
Title Muscle specific kinase: organiser of synaptic membrane domains.
Related PDB
Related UniProtKB

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]).

Created Updated
2011-11-01 2012-12-12