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 18420 |
15422 15422 |
16761 16761 |
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| PubChem |
888 888 |
5957 5957 |
6022 6022 |
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| 2iepA01 |
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Unbound | Unbound | Unbound | Unbound | Unbound | |
| 2iepB01 |
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Unbound | Unbound | Unbound | Unbound | Unbound | |
| 2iepA02 |
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Unbound | Unbound | Unbound | Unbound | Unbound | |
| 2iepB02 |
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Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3hklA |
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Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3hklB |
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Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1lufA01 |
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Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1lufA02 |
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Unbound | Unbound | Unbound | Unbound | Unbound | |
| Reference for Active-site residues | ||
|---|---|---|
| resource | references | E.C. |
| Literature [4] & Swiss-prot;Q62838 | ||
| Active-site residues | ||||||||||
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| PDB | Catalytic residues | Cofactor-binding residues | Modified residues | Main-chain involved in catalysis | Comment | |||||
| 2iepA01 |
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| 2iepB01 |
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| 2iepA02 |
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| 2iepB02 |
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| 3hklA |
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| 3hklB |
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| 1lufA01 |
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| 1lufA02 |
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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]
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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, |
| 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, |
| Related PDB | |
| Related UniProtKB | |
| [9] | |
| Resource | |
| Comments |
X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 313-494, |
| 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 |