MUSK_HUMAN
Evidence for PS localization
Functions
Receptor tyrosine kinase which plays a central role in the formation and the maintenance of the neuromuscular junction (NMJ), the synapse between the motor neuron and the skeletal muscle (PubMed). Recruitment of AGRIN by LRP4 to the MUSK signaling complex induces phosphorylation and activation of MUSK, the kinase of the complex. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. May regulate AChR phosphorylation and clustering through activation of ABL1 and Src family kinases which in turn regulate MUSK. DVL1 and PAK1 that form a ternary complex with MUSK are also important for MUSK-dependent regulation of AChR clustering. May positively regulate Rho family GTPases through FNTA. Mediates the phosphorylation of FNTA which promotes prenylation, recruitment to membranes and activation of RAC1 a regulator of the actin cytoskeleton and of gene expression. Other effectors of the MUSK signaling include DNAJA3 which functions downstream of MUSK. May also play a role within the central nervous system by mediating cholinergic responses, synaptic plasticity and memory formation . [View more on UniProt]
Protein features
Binary interactions with known binding regions
Interacting region for partners were not defined.
Network
Isoforms
Disease-causing germline mutations
| Position | Amino acid | Mutation | Disease | Overlap with binding region |
|---|---|---|---|---|
| 790 | Val | Met | Myasthenicsyndrome,congenital,9,associatedwithacetylcholinereceptordeficiency(CMS9) | - |
| 605 | Met | Ile | Myasthenicsyndrome,congenital,9,associatedwithacetylcholinereceptordeficiency(CMS9) | - |
| 727 | Ala | Val | Myasthenicsyndrome,congenital,9,associatedwithacetylcholinereceptordeficiency(CMS9) | - |
| 38 | Asp | Glu | Myasthenicsyndrome,congenital,9,associatedwithacetylcholinereceptordeficiency(CMS9) | - |
| 344 | Pro | Arg | Myasthenicsyndrome,congenital,9,associatedwithacetylcholinereceptordeficiency(CMS9) | - |
| 575 | Ile | Thr | Fetalakinesiadeformationsequence1(FADS1) | - |
| 835 | Met | Val | Myasthenicsyndrome,congenital,9,associatedwithacetylcholinereceptordeficiency(CMS9) | - |
Linear motifs
No annotated instance was found. To search for linear motifs, use the ELM prediction server.
Fingerprint
Molecular function
| Term | Name | % | Distance from the top of the tree | Annotated in MUSK_HUMAN |
|---|---|---|---|---|
| GO:0017076 | purine nucleotide binding | 35.5556 | 4 | yes |
| GO:0032555 | purine ribonucleotide binding | 35.5556 | 4 | yes |
| GO:0035639 | purine ribonucleoside triphosphate binding | 35.5556 | 4 | yes |
| GO:0019900 | kinase binding | 35.5556 | 4 | no |
| GO:0019901 | protein kinase binding | 35.5556 | 5 | no |
| GO:0046872 | metal ion binding | 31.1111 | 4 | yes |
| GO:0005524 | ATP binding | 26.6667 | 5 | yes |
| GO:0030554 | adenyl nucleotide binding | 26.6667 | 5 | yes |
| GO:0032559 | adenyl ribonucleotide binding | 26.6667 | 5 | yes |
| GO:0004712 | protein serine/threonine/tyrosine kinase activity | 17.7778 | 4 | yes |
| GO:0016301 | kinase activity | 17.7778 | 4 | yes |
| GO:0016773 | phosphotransferase activity, alcohol group as acceptor | 17.7778 | 4 | yes |
| GO:0004713 | protein tyrosine kinase activity | 11.1111 | 4 | yes |
| GO:0004714 | transmembrane receptor protein tyrosine kinase activity | 4.4444 | 5 | yes |
| GO:0019199 | transmembrane receptor protein kinase activity | 4.4444 | 4 | yes |
| GO:0038062 | protein tyrosine kinase collagen receptor activity | 4.4444 | 5 | yes |
| GO:0038064 | collagen receptor activity | 4.4444 | 4 | yes |
Biological process
| Term | Name | % | Distance from top the of the tree | Annotated in MUSK_HUMAN |
|---|---|---|---|---|
| GO:0008104 | protein localization | 62.2222 | 4 | yes |
| GO:0048522 | positive regulation of cellular process | 57.7778 | 4 | yes |
| GO:0031323 | regulation of cellular metabolic process | 55.5556 | 4 | yes |
| GO:0060255 | regulation of macromolecule metabolic process | 53.3333 | 4 | yes |
| GO:0051171 | regulation of nitrogen compound metabolic process | 51.1111 | 4 | yes |
| GO:0080090 | regulation of primary metabolic process | 51.1111 | 4 | yes |
| GO:0006996 | organelle organization | 51.1111 | 4 | no |
| GO:0010646 | regulation of cell communication | 48.8889 | 4 | no |
| GO:0009893 | positive regulation of metabolic process | 48.8889 | 4 | yes |
| GO:0010604 | positive regulation of macromolecule metabolic process | 48.8889 | 5 | yes |
| GO:0051128 | regulation of cellular component organization | 46.6667 | 4 | yes |
| GO:0051173 | positive regulation of nitrogen compound metabolic process | 46.6667 | 5 | yes |
| GO:0009966 | regulation of signal transduction | 46.6667 | 4 | no |
| GO:0048523 | negative regulation of cellular process | 44.4444 | 4 | no |
| GO:0031325 | positive regulation of cellular metabolic process | 44.4444 | 5 | yes |
| GO:0051246 | regulation of protein metabolic process | 42.2222 | 5 | yes |
| GO:0042325 | regulation of phosphorylation | 40.0000 | 7 | yes |
| GO:0051174 | regulation of phosphorus metabolic process | 40.0000 | 5 | yes |
| GO:0051247 | positive regulation of protein metabolic process | 40.0000 | 6 | yes |
| GO:0016192 | vesicle-mediated transport | 40.0000 | 4 | no |
| GO:0071702 | organic substance transport | 40.0000 | 4 | no |
| GO:0071705 | nitrogen compound transport | 40.0000 | 4 | no |
| GO:1902531 | regulation of intracellular signal transduction | 40.0000 | 5 | no |
| GO:0019220 | regulation of phosphate metabolic process | 40.0000 | 6 | yes |
| GO:0015031 | protein transport | 37.7778 | 4 | no |
| GO:0001932 | regulation of protein phosphorylation | 37.7778 | 7 | yes |
| GO:0031399 | regulation of protein modification process | 37.7778 | 6 | yes |
| GO:0042327 | positive regulation of phosphorylation | 35.5556 | 8 | yes |
| GO:0043549 | regulation of kinase activity | 35.5556 | 5 | yes |
| GO:0045937 | positive regulation of phosphate metabolic process | 35.5556 | 7 | yes |
| GO:0051338 | regulation of transferase activity | 35.5556 | 4 | yes |
| GO:0010562 | positive regulation of phosphorus metabolic process | 35.5556 | 6 | yes |
| GO:0031401 | positive regulation of protein modification process | 35.5556 | 7 | yes |
| GO:0043085 | positive regulation of catalytic activity | 33.3333 | 4 | yes |
| GO:0044087 | regulation of cellular component biogenesis | 33.3333 | 4 | yes |
| GO:0051049 | regulation of transport | 33.3333 | 4 | no |
| GO:0023056 | positive regulation of signaling | 33.3333 | 4 | no |
| GO:0001934 | positive regulation of protein phosphorylation | 33.3333 | 8 | yes |
| GO:0006886 | intracellular protein transport | 31.1111 | 4 | no |
| GO:0030030 | cell projection organization | 31.1111 | 4 | no |
| GO:0072657 | protein localization to membrane | 28.8889 | 4 | yes |
| GO:0009892 | negative regulation of metabolic process | 28.8889 | 4 | no |
| GO:0045859 | regulation of protein kinase activity | 28.8889 | 6 | no |
| GO:0010647 | positive regulation of cell communication | 28.8889 | 5 | no |
| GO:0048584 | positive regulation of response to stimulus | 28.8889 | 4 | no |
| GO:0051347 | positive regulation of transferase activity | 26.6667 | 5 | yes |
| GO:0022607 | cellular component assembly | 26.6667 | 4 | no |
| GO:0031344 | regulation of cell projection organization | 26.6667 | 5 | no |
| GO:0051130 | positive regulation of cellular component organization | 26.6667 | 5 | no |
| GO:0061024 | membrane organization | 26.6667 | 4 | no |
| GO:0120035 | regulation of plasma membrane bounded cell projection organization | 26.6667 | 6 | no |
| GO:0009967 | positive regulation of signal transduction | 26.6667 | 5 | no |
| GO:0010941 | regulation of cell death | 26.6667 | 4 | no |
| GO:0042981 | regulation of apoptotic process | 26.6667 | 6 | no |
| GO:0043067 | regulation of programmed cell death | 26.6667 | 5 | no |
| GO:0009889 | regulation of biosynthetic process | 26.6667 | 4 | yes |
| GO:0010468 | regulation of gene expression | 26.6667 | 5 | yes |
| GO:0031326 | regulation of cellular biosynthetic process | 26.6667 | 5 | yes |
| GO:0033674 | positive regulation of kinase activity | 26.6667 | 6 | yes |
| GO:0034330 | cell junction organization | 26.6667 | 4 | yes |
| GO:0031324 | negative regulation of cellular metabolic process | 24.4444 | 5 | no |
| GO:0033043 | regulation of organelle organization | 24.4444 | 5 | no |
| GO:0060627 | regulation of vesicle-mediated transport | 24.4444 | 4 | no |
| GO:0022603 | regulation of anatomical structure morphogenesis | 24.4444 | 4 | no |
| GO:0010605 | negative regulation of macromolecule metabolic process | 24.4444 | 5 | no |
| GO:0051336 | regulation of hydrolase activity | 24.4444 | 4 | no |
| GO:0032101 | regulation of response to external stimulus | 24.4444 | 4 | no |
| GO:0006796 | phosphate-containing compound metabolic process | 24.4444 | 4 | yes |
| GO:0010556 | regulation of macromolecule biosynthetic process | 24.4444 | 5 | yes |
| GO:0036211 | protein modification process | 22.2222 | 4 | yes |
| GO:0043412 | macromolecule modification | 22.2222 | 4 | yes |
| GO:0019219 | regulation of nucleobase-containing compound metabolic process | 22.2222 | 5 | no |
| GO:0080134 | regulation of response to stress | 22.2222 | 4 | no |
| GO:1902533 | positive regulation of intracellular signal transduction | 22.2222 | 6 | no |
| GO:0007010 | cytoskeleton organization | 22.2222 | 5 | no |
| GO:0120036 | plasma membrane bounded cell projection organization | 22.2222 | 5 | no |
| GO:0006468 | protein phosphorylation | 22.2222 | 5 | yes |
| GO:0007167 | enzyme-linked receptor protein signaling pathway | 22.2222 | 4 | yes |
| GO:0007169 | transmembrane receptor protein tyrosine kinase signaling pathway | 22.2222 | 5 | yes |
| GO:0016310 | phosphorylation | 22.2222 | 5 | yes |
| GO:0050808 | synapse organization | 20.0000 | 5 | yes |
| GO:0046777 | protein autophosphorylation | 17.7778 | 6 | yes |
| GO:0043113 | receptor clustering | 15.5556 | 5 | yes |
| GO:0050807 | regulation of synapse organization | 15.5556 | 5 | yes |
| GO:1901888 | regulation of cell junction assembly | 15.5556 | 5 | yes |
| GO:0007528 | neuromuscular junction development | 13.3333 | 6 | yes |
| GO:0010628 | positive regulation of gene expression | 13.3333 | 6 | yes |
| GO:0071340 | skeletal muscle acetylcholine-gated channel clustering | 11.1111 | 6 | yes |
| GO:0048638 | regulation of developmental growth | 8.8889 | 4 | yes |
| GO:0051963 | regulation of synapse assembly | 8.8889 | 6 | yes |
| GO:1904396 | regulation of neuromuscular junction development | 6.6667 | 6 | yes |
| GO:2000112 | regulation of cellular macromolecule biosynthetic process | 6.6667 | 6 | yes |
| GO:0008582 | regulation of synaptic assembly at neuromuscular junction | 6.6667 | 5 | yes |
| GO:0050890 | cognition | 4.4444 | 4 | yes |
| GO:2000539 | regulation of protein geranylgeranylation | 4.4444 | 7 | yes |
| GO:2000541 | positive regulation of protein geranylgeranylation | 4.4444 | 6 | yes |
| GO:0007613 | memory | 4.4444 | 4 | yes |
Disease
| Term | Name | % | Distance from top the of the tree | Annotated in MUSK_HUMAN |
|---|---|---|---|---|
| DOID:3635 | congenital myasthenic syndrome | 8.8889 | 7 | yes |
| DOID:439 | neuromuscular junction disease | 8.8889 | 6 | yes |
| DOID:440 | neuromuscular disease | 8.8889 | 5 | yes |
| DOID:574 | peripheral nervous system disease | 8.8889 | 3 | yes |
| DOID:870 | neuropathy | 8.8889 | 4 | yes |
| DOID:0110670 | congenital myasthenic syndrome 9 | 4.4444 | 8 | yes |
| DOID:0111377 | fetal akinesia deformation sequence syndrome 1 | 4.4444 | 3 | yes |
| DOID:0050700 | cardiomyopathy | 4.4444 | 4 | no |
| DOID:0060036 | intrinsic cardiomyopathy | 4.4444 | 5 | no |
| DOID:114 | heart disease | 4.4444 | 3 | no |
| DOID:2843 | long QT syndrome | 4.4444 | 6 | no |
| DOID:0060038 | specific developmental disorder | 4.4444 | 3 | no |
| DOID:1059 | intellectual disability | 4.4444 | 4 | no |
All partners
| Uniprot ID | Details | Highest evidence | Localizing into PSD | HPA (protein expression in neurons) |
|---|---|---|---|---|
| LRP4_HUMAN | [view entry] [view interactions] | Low throughput | yes | yes |
| AGRIN_HUMAN | [view entry] [view interactions] | Low throughput | yes | yes |
| DOK7_HUMAN | [view interactions] | Low throughput | no | yes |
| DNJA3_HUMAN | [view entry] [view interactions] | Low throughput | yes | yes |
| NSF_HUMAN | [view entry] [view interactions] | Low throughput | yes | yes |
| ARF6_HUMAN | [view entry] [view interactions] | Low throughput | yes | yes |
| RB11A_HUMAN | [view entry] [view interactions] | Low throughput | yes | yes |
| ACHB_HUMAN | [view entry] [view interactions] | Low throughput | yes | yes |
| SYNE1_HUMAN | [view entry] [view interactions] | Low throughput | yes | yes |
| DVL1_HUMAN | [view entry] [view interactions] | Low throughput | yes | yes |
| ERBIN_HUMAN | [view entry] [view interactions] | Low throughput | yes | yes |
| PZRN3_HUMAN | [view interactions] | Low throughput | no | yes |
| RNF31_HUMAN | [view interactions] | Low throughput | no | yes |
| LRRC1_HUMAN | [view interactions] | Low throughput | no | yes |
| SCRIB_HUMAN | [view entry] [view interactions] | Low throughput | yes | no |
| MUSK_HUMAN | [view entry] [view interactions] | Low throughput | yes | no |
| HS90B_HUMAN | [view entry] [view interactions] | High throughput | yes | yes |
| ERP44_HUMAN | [view interactions] | High throughput | no | yes |
| LG3BP_HUMAN | [view interactions] | High throughput | no | no |
| HLAB_HUMAN | [view interactions] | High throughput | no | yes |
| HLAC_HUMAN | [view interactions] | High throughput | no | no |
| CDC37_HUMAN | [view interactions] | High throughput | no | yes |
| CALM2_HUMAN | [view entry] [view interactions] | High throughput | yes | yes |
| CALM3_HUMAN | [view entry] [view interactions] | High throughput | yes | yes |
| CALM1_HUMAN | [view entry] [view interactions] | High throughput | yes | yes |
| ILKAP_HUMAN | [view interactions] | High throughput | no | yes |
| STYX_HUMAN | [view interactions] | High throughput | no | yes |
| FKBP5_HUMAN | [view interactions] | High throughput | no | yes |
| HS90A_HUMAN | [view entry] [view interactions] | High throughput | yes | yes |
| COPB2_HUMAN | [view entry] [view interactions] | High throughput | yes | yes |
| GCP60_HUMAN | [view interactions] | High throughput | no | yes |
| SC24B_HUMAN | [view interactions] | High throughput | no | yes |
| COPD_HUMAN | [view entry] [view interactions] | High throughput | yes | yes |
| COPE_HUMAN | [view interactions] | High throughput | no | yes |
| SC23A_HUMAN | [view entry] [view interactions] | High throughput | yes | yes |
| S23IP_HUMAN | [view interactions] | High throughput | no | yes |
| CEP85_HUMAN | [view interactions] | High throughput | no | no |
| TNR6B_HUMAN | [view interactions] | High throughput | no | yes |
| SC23B_HUMAN | [view interactions] | High throughput | no | yes |
| SC31A_HUMAN | [view entry] [view interactions] | High throughput | yes | yes |
| ZN512_HUMAN | [view interactions] | High throughput | no | yes |
| CKAP4_HUMAN | [view entry] [view interactions] | High throughput | yes | yes |
| TFG_HUMAN | [view interactions] | High throughput | no | yes |
| SC24A_HUMAN | [view interactions] | High throughput | no | no |
| TACC1_HUMAN | [view entry] [view interactions] | High throughput | yes | yes |
| EMD_HUMAN | [view interactions] | High throughput | no | yes |
| RACK1_HUMAN | [view interactions] | High throughput | no | yes |
| TM209_HUMAN | [view interactions] | High throughput | no | no |
| ARFG3_HUMAN | [view entry] [view interactions] | High throughput | yes | no |
| NUD19_HUMAN | [view interactions] | High throughput | no | no |
| AL3A2_HUMAN | [view entry] [view interactions] | High throughput | yes | yes |
| CLCC1_HUMAN | [view interactions] | High throughput | no | yes |
| STIM1_HUMAN | [view interactions] | High throughput | no | yes |
| CDKAL_HUMAN | [view interactions] | High throughput | no | no |
| RHG32_HUMAN | [view entry] [view interactions] | High throughput | yes | yes |
| TM201_HUMAN | [view interactions] | High throughput | no | no |
| ANKL2_HUMAN | [view interactions] | High throughput | no | yes |
| USO1_HUMAN | [view entry] [view interactions] | High throughput | yes | yes |
| APMAP_HUMAN | [view interactions] | High throughput | no | yes |
| KRI1_HUMAN | [view interactions] | High throughput | no | yes |
| VAPA_HUMAN | [view entry] [view interactions] | High throughput | yes | yes |
| NSMA3_HUMAN | [view interactions] | High throughput | no | yes |
| DJB11_HUMAN | [view interactions] | High throughput | no | yes |
| NDC1_HUMAN | [view interactions] | High throughput | no | yes |
| STX5_HUMAN | [view interactions] | High throughput | no | yes |
| UBP54_HUMAN | [view interactions] | High throughput | no | yes |
| SCFD1_HUMAN | [view entry] [view interactions] | High throughput | yes | yes |
| PTN1_HUMAN | [view interactions] | High throughput | no | yes |
| TTC17_HUMAN | [view interactions] | High throughput | no | yes |
| VRK2_HUMAN | [view interactions] | High throughput | no | no |
| GORS2_HUMAN | [view interactions] | High throughput | no | yes |
| ARFG2_HUMAN | [view entry] [view interactions] | High throughput | yes | yes |
| JPH1_HUMAN | [view interactions] | High throughput | no | no |
| SRPRA_HUMAN | [view interactions] | High throughput | no | no |
| SC22B_HUMAN | [view entry] [view interactions] | High throughput | yes | no |
| VAPB_HUMAN | [view entry] [view interactions] | High throughput | yes | yes |
| ASTRA_HUMAN | [view interactions] | High throughput | no | no |
| AAAS_HUMAN | [view interactions] | High throughput | no | yes |
| ADA30_HUMAN | [view interactions] | High throughput | no | no |
| DJC13_HUMAN | [view entry] [view interactions] | High throughput | yes | yes |
| RBNS5_HUMAN | [view interactions] | High throughput | no | yes |
| PAK4_HUMAN | [view interactions] | Computational | no | yes |
| SRC_HUMAN | [view entry] [view interactions] | Computational | yes | no |
| PAK3_HUMAN | [view entry] [view interactions] | Computational | yes | no |
| PAK2_HUMAN | [view entry] [view interactions] | Computational | yes | no |
| 1433G_HUMAN | [view entry] [view interactions] | Computational | yes | yes |
| COLQ_HUMAN | [view interactions] | Computational | no | no |
| PAK1_HUMAN | [view entry] [view interactions] | Computational | yes | yes |
| PAK5_HUMAN | [view interactions] | Computational | no | yes |
| RAC1_HUMAN | [view entry] [view interactions] | Computational | yes | no |
| ACHD_HUMAN | [view entry] [view interactions] | Computational | yes | no |
| CDC42_HUMAN | [view entry] [view interactions] | Computational | yes | yes |
| FAK2_HUMAN | [view entry] [view interactions] | Computational | yes | yes |
| RAPSN_HUMAN | [view entry] [view interactions] | Computational | yes | no |
| FAK1_HUMAN | [view entry] [view interactions] | Computational | yes | yes |
| ACES_HUMAN | [view interactions] | Computational | no | no |
| WNT4_HUMAN | [view interactions] | Computational | no | no |