MUSK_MOUSE
ID MUSK_MOUSE Reviewed; 868 AA.
AC Q61006; Q61005; Q61987; Q61988;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Muscle, skeletal receptor tyrosine-protein kinase;
DE EC=2.7.10.1;
DE AltName: Full=Muscle-specific tyrosine-protein kinase receptor;
DE Short=MuSK;
DE Short=Muscle-specific kinase receptor;
DE Flags: Precursor;
GN Name=Musk; Synonyms=Nsk2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RA Caruso A., Morris J.C., Neben S., Finnerty H., Beier D., Turner K.,
RA Wood C.R.;
RL Submitted (OCT-1995) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 3 AND 4), DEVELOPMENTAL
RP STAGE, AND TISSUE SPECIFICITY.
RC TISSUE=Myoblast;
RX PubMed=7624144;
RA Ganju P., Walls E., Brennan J., Reith A.D.;
RT "Cloning and developmental expression of Nsk2, a novel receptor tyrosine
RT kinase implicated in skeletal myogenesis.";
RL Oncogene 11:281-290(1995).
RN [3]
RP DISRUPTION PHENOTYPE, AND FUNCTION IN NEUROMUSCULAR JUNCTION DEVELOPMENT.
RX PubMed=8653786; DOI=10.1016/s0092-8674(00)81251-9;
RA DeChiara T.M., Bowen D.C., Valenzuela D.M., Simmons M.V., Poueymirou W.T.,
RA Thomas S., Kinetz E., Compton D.L., Rojas E., Park J.S., Smith C.,
RA DiStefano P.S., Glass D.J., Burden S.J., Yancopoulos G.D.;
RT "The receptor tyrosine kinase MuSK is required for neuromuscular junction
RT formation in vivo.";
RL Cell 85:501-512(1996).
RN [4]
RP IDENTIFICATION OF AGRIN AS LIGAND, IDENTIFICATION OF THE AGRIN RECEPTOR
RP COMPLEX, AND PHOSPHORYLATION.
RX PubMed=8653787; DOI=10.1016/s0092-8674(00)81252-0;
RA Glass D.J., Bowen D.C., Stitt T.N., Radziejewski C., Bruno J., Ryan T.E.,
RA Gies D.R., Shah S., Mattsson K., Burden S.J., DiStefano P.S.,
RA Valenzuela D.M., DeChiara T.M., Yancopoulos G.D.;
RT "Agrin acts via a MuSK receptor complex.";
RL Cell 85:513-523(1996).
RN [5]
RP FUNCTION IN ACETYLCHOLINE RECEPTOR CLUSTERING.
RX PubMed=11323662; DOI=10.1038/35074025;
RA Lin W., Burgess R.W., Dominguez B., Pfaff S.L., Sanes J.R., Lee K.F.;
RT "Distinct roles of nerve and muscle in postsynaptic differentiation of the
RT neuromuscular synapse.";
RL Nature 410:1057-1064(2001).
RN [6]
RP INTERACTION WITH DVL1 AND PAK1.
RX PubMed=12165471; DOI=10.1016/s0896-6273(02)00783-3;
RA Luo Z.G., Wang Q., Zhou J.Z., Wang J., Luo Z., Liu M., He X.,
RA Wynshaw-Boris A., Xiong W.C., Lu B., Mei L.;
RT "Regulation of AChR clustering by Dishevelled interacting with MuSK and
RT PAK1.";
RL Neuron 35:489-505(2002).
RN [7]
RP FUNCTION IN TRANSCRIPTION REGULATION.
RX PubMed=12756238; DOI=10.1083/jcb.200210156;
RA Lacazette E., Le Calvez S., Gajendran N., Brenner H.R.;
RT "A novel pathway for MuSK to induce key genes in neuromuscular synapse
RT formation.";
RL J. Cell Biol. 161:727-736(2003).
RN [8]
RP FUNCTION IN RAC1 ACTIVATION, FUNCTION IN PHOSPHORYLATION OF FNTA, AND
RP INTERACTION WITH FNTA.
RX PubMed=14622576; DOI=10.1016/s0896-6273(03)00695-0;
RA Luo Z.G., Je H.S., Wang Q., Yang F., Dobbins G.C., Yang Z.H., Xiong W.C.,
RA Lu B., Mei L.;
RT "Implication of geranylgeranyltransferase I in synapse formation.";
RL Neuron 40:703-717(2003).
RN [9]
RP INTERACTION WITH RNF31.
RX PubMed=14678832; DOI=10.1016/s1567-133x(03)00146-7;
RA Bromann P.A., Weiner J.A., Apel E.D., Lewis R.M., Sanes J.R.;
RT "A putative ariadne-like E3 ubiquitin ligase (PAUL) that interacts with the
RT muscle-specific kinase (MuSK).";
RL Gene Expr. Patterns 4:77-84(2004).
RN [10]
RP FUNCTION IN ACETYLCHOLINE RECEPTOR CLUSTERING.
RX PubMed=15340048; DOI=10.1128/mcb.24.18.7841-7854.2004;
RA Mittaud P., Camilleri A.A., Willmann R., Erb-Voegtli S., Burden S.J.,
RA Fuhrer C.;
RT "A single pulse of agrin triggers a pathway that acts to cluster
RT acetylcholine receptors.";
RL Mol. Cell. Biol. 24:7841-7854(2004).
RN [11]
RP ACTIVITY REGULATION, PHOSPHORYLATION AT SER-680 AND SER-697 BY CK2, AND
RP INTERACTION WITH CSNK2B.
RX PubMed=16818610; DOI=10.1101/gad.375206;
RA Cheusova T., Khan M.A., Schubert S.W., Gavin A.C., Buchou T., Jacob G.,
RA Sticht H., Allende J., Boldyreff B., Brenner H.R., Hashemolhosseini S.;
RT "Casein kinase 2-dependent serine phosphorylation of MuSK regulates
RT acetylcholine receptor aggregation at the neuromuscular junction.";
RL Genes Dev. 20:1800-1816(2006).
RN [12]
RP INTERACTION WITH DOK7, PHOSPHORYLATION AT TYR-553, AND MUTAGENESIS OF
RP TYR-553.
RX PubMed=16794080; DOI=10.1126/science.1127142;
RA Okada K., Inoue A., Okada M., Murata Y., Kakuta S., Jigami T., Kubo S.,
RA Shiraishi H., Eguchi K., Motomura M., Akiyama T., Iwakura Y., Higuchi O.,
RA Yamanashi Y.;
RT "The muscle protein Dok-7 is essential for neuromuscular synaptogenesis.";
RL Science 312:1802-1805(2006).
RN [13]
RP INTERACTION WITH PDZRN3, AND UBIQUITINATION.
RX PubMed=17576800; DOI=10.1083/jcb.200610060;
RA Lu Z., Je H.S., Young P., Gross J., Lu B., Feng G.;
RT "Regulation of synaptic growth and maturation by a synapse-associated E3
RT ubiquitin ligase at the neuromuscular junction.";
RL J. Cell Biol. 177:1077-1089(2007).
RN [14]
RP PHOSPHORYLATION, AND INTERACTION WITH LRP4.
RX PubMed=18848351; DOI=10.1016/j.cell.2008.10.002;
RA Kim N., Stiegler A.L., Cameron T.O., Hallock P.T., Gomez A.M., Huang J.H.,
RA Hubbard S.R., Dustin M.L., Burden S.J.;
RT "Lrp4 is a receptor for Agrin and forms a complex with MuSK.";
RL Cell 135:334-342(2008).
RN [15]
RP INTERACTION WITH NSF.
RX PubMed=18272689; DOI=10.1523/jneurosci.4130-07.2008;
RA Zhu D., Yang Z., Luo Z., Luo S., Xiong W.C., Mei L.;
RT "Muscle-specific receptor tyrosine kinase endocytosis in acetylcholine
RT receptor clustering in response to agrin.";
RL J. Neurosci. 28:1688-1696(2008).
RN [16]
RP INTERACTION WITH DNAJA3, AND SUBCELLULAR LOCATION.
RX PubMed=19038220; DOI=10.1016/j.neuron.2008.09.025;
RA Linnoila J., Wang Y., Yao Y., Wang Z.Z.;
RT "A mammalian homolog of Drosophila tumorous imaginal discs, Tid1, mediates
RT agrin signaling at the neuromuscular junction.";
RL Neuron 60:625-641(2008).
RN [17]
RP INTERACTION WITH CAV3.
RX PubMed=19940021; DOI=10.1091/mbc.e09-05-0381;
RA Hezel M., de Groat W.C., Galbiati F.;
RT "Caveolin-3 promotes nicotinic acetylcholine receptor clustering and
RT regulates neuromuscular junction activity.";
RL Mol. Biol. Cell 21:302-310(2010).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 544-556 IN COMPLEX WITH DOK7,
RP INTERACTION WITH DOK7, AND PHOSPHORYLATION AT TYR-553.
RX PubMed=20603078; DOI=10.1016/j.molcel.2010.06.007;
RA Bergamin E., Hallock P.T., Burden S.J., Hubbard S.R.;
RT "The cytoplasmic adaptor protein Dok7 activates the receptor tyrosine
RT kinase MuSK via dimerization.";
RL Mol. Cell 39:100-109(2010).
CC -!- FUNCTION: Receptor tyrosine kinase which plays a central role in the
CC formation and the maintenance of the neuromuscular junction (NMJ), the
CC synapse between the motor neuron and the skeletal muscle. Recruitment
CC of AGRIN by LRP4 to the MUSK signaling complex induces phosphorylation
CC and activation of MUSK, the kinase of the complex. The activation of
CC MUSK in myotubes regulates the formation of NMJs through the regulation
CC of different processes including the specific expression of genes in
CC subsynaptic nuclei, the reorganization of the actin cytoskeleton and
CC the clustering of the acetylcholine receptors (AChR) in the
CC postsynaptic membrane. May regulate AChR phosphorylation and clustering
CC through activation of ABL1 and Src family kinases which in turn
CC regulate MUSK. DVL1 and PAK1 that form a ternary complex with MUSK are
CC also important for MUSK-dependent regulation of AChR clustering. May
CC positively regulate Rho family GTPases through FNTA. Mediates the
CC phosphorylation of FNTA which promotes prenylation, recruitment to
CC membranes and activation of RAC1 a regulator of the actin cytoskeleton
CC and of gene expression. Other effectors of the MUSK signaling include
CC DNAJA3 which functions downstream of MUSK. May also play a role within
CC the central nervous system by mediating cholinergic responses, synaptic
CC plasticity and memory formation. {ECO:0000269|PubMed:11323662,
CC ECO:0000269|PubMed:12756238, ECO:0000269|PubMed:14622576,
CC ECO:0000269|PubMed:15340048, ECO:0000269|PubMed:8653786}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:O15146};
CC -!- ACTIVITY REGULATION: Positively regulated by CK2.
CC {ECO:0000269|PubMed:16818610}.
CC -!- SUBUNIT: Monomer. Homodimer (Probable). Interacts with LRP4; the
CC heterodimer forms an AGRIN receptor complex that binds AGRIN resulting
CC in activation of MUSK. Forms a heterotetramer composed of 2 DOK7 and 2
CC MUSK molecules which facilitates MUSK trans-autophosphorylation on
CC tyrosine residue and activation. Interacts (via cytoplasmic part) with
CC DOK7 (via IRS-type PTB domain); requires MUSK phosphorylation.
CC Interacts with DVL1 (via DEP domain); the interaction is direct and
CC mediates the formation of a DVL1, MUSK and PAK1 ternary complex
CC involved in AChR clustering. Interacts with PDZRN3; this interaction is
CC enhanced by agrin. Interacts with FNTA; the interaction is direct and
CC mediates AGRIN-induced phosphorylation and activation of FNTA.
CC Interacts with CSNK2B; mediates regulation by CK2. Interacts (via the
CC cytoplasmic domain) with DNAJA3. Interacts with NSF; may regulate MUSK
CC endocytosis and activity. Interacts with CAV3; may regulate MUSK
CC signaling. Interacts with RNF31. {ECO:0000269|PubMed:12165471,
CC ECO:0000269|PubMed:14622576, ECO:0000269|PubMed:14678832,
CC ECO:0000269|PubMed:16794080, ECO:0000269|PubMed:16818610,
CC ECO:0000269|PubMed:17576800, ECO:0000269|PubMed:18272689,
CC ECO:0000269|PubMed:18848351, ECO:0000269|PubMed:19038220,
CC ECO:0000269|PubMed:19940021, ECO:0000269|PubMed:20603078, ECO:0000305}.
CC -!- INTERACTION:
CC Q61006; Q18PE0: Dok7; NbExp=3; IntAct=EBI-3989087, EBI-3989091;
CC Q61006-3; P46460: Nsf; NbExp=5; IntAct=EBI-6308424, EBI-398006;
CC -!- SUBCELLULAR LOCATION: Postsynaptic cell membrane
CC {ECO:0000269|PubMed:19038220}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:19038220}. Note=Localizes to the postsynaptic cell
CC membrane of the neuromuscular junction.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=MLK2;
CC IsoId=Q61006-1; Sequence=Displayed;
CC Name=2; Synonyms=MLK1;
CC IsoId=Q61006-2; Sequence=VSP_010784;
CC Name=3;
CC IsoId=Q61006-3; Sequence=VSP_010785;
CC Name=4;
CC IsoId=Q61006-4; Sequence=VSP_010786;
CC -!- TISSUE SPECIFICITY: Expressed preferentially in skeletal muscle.
CC {ECO:0000269|PubMed:7624144}.
CC -!- DEVELOPMENTAL STAGE: Skeletal myogenesis is a major site of expression
CC during normal embryogenesis. In addition, the ganglia of the developing
CC peripheral nervous system and various embryonic epithelia, including
CC those of kidney, lung and gut are also sites of expression.
CC {ECO:0000269|PubMed:7624144}.
CC -!- PTM: Ubiquitinated by PDZRN3. Ubiquitination promotes endocytosis and
CC lysosomal degradation. {ECO:0000269|PubMed:17576800}.
CC -!- PTM: Phosphorylated (PubMed:16818610). Phosphorylation is induced by
CC AGRIN (PubMed:8653787, PubMed:18848351). Autophosphorylated.
CC Autophosphorylation at Tyr-553 is required for interaction with DOK7
CC which in turn stimulates the phosphorylation and the activation of MUSK
CC (PubMed:16794080, PubMed:20603078). {ECO:0000269|PubMed:16794080,
CC ECO:0000269|PubMed:16818610, ECO:0000269|PubMed:18848351,
CC ECO:0000269|PubMed:20603078, ECO:0000269|PubMed:8653787}.
CC -!- PTM: Neddylated. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice die perinatally being unable to take a
CC breath and to respond to tail or leg pinch. Despite the presence of
CC apparently normal skeletal muscle, the absence of differentiated nerve
CC terminals is sufficient to account for this phenotype. Every aspect of
CC NMJ formation examined is absent in these mice. Branches of the main
CC intramuscular nerve do not establish normal contacts with the muscle,
CC do not form correctly positioned or specialized nerve terminals, and
CC are apparently not given appropriate signals to stop their wandering
CC aimlessly across the muscle. Furthermore, postsynaptic differentiation
CC is absent, muscle-derived proteins normally localized to the synaptic
CC basal lamina or the postsynaptic membrane being uniformly distributed
CC in myofibers. {ECO:0000269|PubMed:8653786}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; U37708; AAA79203.1; -; mRNA.
DR EMBL; U37709; AAA79204.1; -; mRNA.
DR EMBL; X86444; CAA60165.1; -; mRNA.
DR EMBL; X86445; CAA60166.1; -; Genomic_DNA.
DR CCDS; CCDS18210.1; -. [Q61006-2]
DR CCDS; CCDS18211.1; -. [Q61006-1]
DR PIR; I48696; I48696.
DR PIR; I48697; I48697.
DR RefSeq; NP_001032205.1; NM_001037128.1.
DR RefSeq; NP_001032206.1; NM_001037129.1.
DR RefSeq; NP_001032207.1; NM_001037130.1. [Q61006-2]
DR RefSeq; NP_035074.2; NM_010944.2. [Q61006-1]
DR PDB; 3ML4; X-ray; 2.60 A; E/F/G/H=544-556.
DR PDBsum; 3ML4; -.
DR AlphaFoldDB; Q61006; -.
DR SMR; Q61006; -.
DR BioGRID; 201860; 5.
DR ELM; Q61006; -.
DR IntAct; Q61006; 4.
DR STRING; 10090.ENSMUSP00000081625; -.
DR GlyGen; Q61006; 3 sites.
DR iPTMnet; Q61006; -.
DR PhosphoSitePlus; Q61006; -.
DR jPOST; Q61006; -.
DR MaxQB; Q61006; -.
DR PaxDb; Q61006; -.
DR PRIDE; Q61006; -.
DR ProteomicsDB; 290077; -. [Q61006-1]
DR ProteomicsDB; 290078; -. [Q61006-2]
DR ProteomicsDB; 290079; -. [Q61006-3]
DR ProteomicsDB; 290080; -. [Q61006-4]
DR Antibodypedia; 29502; 487 antibodies from 34 providers.
DR DNASU; 18198; -.
DR Ensembl; ENSMUST00000084578; ENSMUSP00000081625; ENSMUSG00000057280. [Q61006-1]
DR Ensembl; ENSMUST00000102893; ENSMUSP00000099957; ENSMUSG00000057280. [Q61006-2]
DR GeneID; 18198; -.
DR KEGG; mmu:18198; -.
DR UCSC; uc033icg.1; mouse. [Q61006-1]
DR CTD; 4593; -.
DR MGI; MGI:103581; Musk.
DR VEuPathDB; HostDB:ENSMUSG00000057280; -.
DR eggNOG; KOG1026; Eukaryota.
DR GeneTree; ENSGT00940000158226; -.
DR HOGENOM; CLU_000288_30_5_1; -.
DR InParanoid; Q61006; -.
DR OMA; NERPWCY; -.
DR TreeFam; TF106465; -.
DR BRENDA; 2.7.10.1; 3474.
DR BioGRID-ORCS; 18198; 1 hit in 75 CRISPR screens.
DR ChiTaRS; Musk; mouse.
DR EvolutionaryTrace; Q61006; -.
DR PRO; PR:Q61006; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q61006; protein.
DR Bgee; ENSMUSG00000057280; Expressed in secondary oocyte and 90 other tissues.
DR ExpressionAtlas; Q61006; baseline and differential.
DR Genevisible; Q61006; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0042995; C:cell projection; ISO:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0031594; C:neuromuscular junction; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0045211; C:postsynaptic membrane; IDA:UniProtKB.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0045202; C:synapse; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005518; F:collagen binding; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0030165; F:PDZ domain binding; IPI:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0004713; F:protein tyrosine kinase activity; ISS:UniProtKB.
DR GO; GO:0038062; F:protein tyrosine kinase collagen receptor activity; IBA:GO_Central.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0060291; P:long-term synaptic potentiation; ISO:MGI.
DR GO; GO:0007613; P:memory; ISO:MGI.
DR GO; GO:0097049; P:motor neuron apoptotic process; IMP:MGI.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:MGI.
DR GO; GO:0007528; P:neuromuscular junction development; IGI:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:2000673; P:positive regulation of motor neuron apoptotic process; IMP:MGI.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:MGI.
DR GO; GO:2000541; P:positive regulation of protein geranylgeranylation; IMP:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IMP:UniProtKB.
DR GO; GO:1904395; P:positive regulation of skeletal muscle acetylcholine-gated channel clustering; IMP:UniProtKB.
DR GO; GO:0045887; P:positive regulation of synaptic assembly at neuromuscular junction; ISO:MGI.
DR GO; GO:0032224; P:positive regulation of synaptic transmission, cholinergic; ISO:MGI.
DR GO; GO:0046777; P:protein autophosphorylation; ISO:MGI.
DR GO; GO:0043113; P:receptor clustering; IMP:MGI.
DR GO; GO:0008582; P:regulation of synaptic assembly at neuromuscular junction; IMP:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IMP:MGI.
DR GO; GO:0051602; P:response to electrical stimulus; ISO:MGI.
DR GO; GO:0071340; P:skeletal muscle acetylcholine-gated channel clustering; IMP:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR Gene3D; 1.10.2000.10; -; 1.
DR Gene3D; 2.60.40.10; -; 3.
DR InterPro; IPR020067; Frizzled_dom.
DR InterPro; IPR036790; Frizzled_dom_sf.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR Pfam; PF01392; Fz; 1.
DR Pfam; PF07679; I-set; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00409; IG; 3.
DR SMART; SM00408; IGc2; 3.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 3.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50038; FZ; 1.
DR PROSITE; PS50835; IG_LIKE; 3.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane;
KW Developmental protein; Differentiation; Disulfide bond; Glycoprotein;
KW Immunoglobulin domain; Kinase; Magnesium; Membrane; Metal-binding;
KW Muscle protein; Nucleotide-binding; Phosphoprotein;
KW Postsynaptic cell membrane; Receptor; Reference proteome; Repeat; Signal;
KW Synapse; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase; Ubl conjugation.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..868
FT /note="Muscle, skeletal receptor tyrosine-protein kinase"
FT /id="PRO_0000024447"
FT TOPO_DOM 22..494
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 495..515
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 516..868
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 28..116
FT /note="Ig-like 1"
FT DOMAIN 121..205
FT /note="Ig-like 2"
FT DOMAIN 212..302
FT /note="Ig-like 3"
FT DOMAIN 312..450
FT /note="FZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DOMAIN 574..855
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 724
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 580..588
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 608
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 553
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:16794080,
FT ECO:0000269|PubMed:20603078"
FT MOD_RES 680
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000305|PubMed:16818610"
FT MOD_RES 697
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000305|PubMed:16818610"
FT MOD_RES 754
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q62838"
FT CARBOHYD 222
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 338
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000250"
FT CARBOHYD 459
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 49..99
FT /evidence="ECO:0000250"
FT DISULFID 98..112
FT /evidence="ECO:0000250"
FT DISULFID 142..190
FT /evidence="ECO:0000250"
FT DISULFID 233..282
FT /evidence="ECO:0000250"
FT DISULFID 317..382
FT /evidence="ECO:0000250"
FT DISULFID 325..375
FT /evidence="ECO:0000250"
FT DISULFID 366..406
FT /evidence="ECO:0000250"
FT DISULFID 394..447
FT /evidence="ECO:0000250"
FT DISULFID 398..434
FT /evidence="ECO:0000250"
FT VAR_SEQ 324..338
FT /note="VCDAVLAKDALVFFN -> GVLMQGPGEKMLLVFLPT (in isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:7624144"
FT /id="VSP_010785"
FT VAR_SEQ 454..462
FT /note="DYKKENITT -> A (in isoform 2)"
FT /evidence="ECO:0000303|Ref.1"
FT /id="VSP_010784"
FT VAR_SEQ 866..868
FT /note="VGV -> TDGRAHFFWPHQY (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:7624144"
FT /id="VSP_010786"
FT MUTAGEN 553
FT /note="Y->F: Loss of interaction with DOK7."
FT /evidence="ECO:0000269|PubMed:16794080"
FT CONFLICT 31
FT /note="T -> A (in Ref. 2; CAA60165/CAA60166)"
FT /evidence="ECO:0000305"
FT CONFLICT 169
FT /note="V -> A (in Ref. 2; CAA60165/CAA60166)"
FT /evidence="ECO:0000305"
FT CONFLICT 211..212
FT /note="FA -> LG (in Ref. 2; CAA60165/CAA60166)"
FT /evidence="ECO:0000305"
FT CONFLICT 235
FT /note="A -> E (in Ref. 2; CAA60165/CAA60166)"
FT /evidence="ECO:0000305"
FT CONFLICT 341
FT /note="Y -> H (in Ref. 2; CAA60165/CAA60166)"
FT /evidence="ECO:0000305"
FT CONFLICT 376
FT /note="N -> Y (in Ref. 2; CAA60165/CAA60166)"
FT /evidence="ECO:0000305"
FT CONFLICT 380
FT /note="Q -> L (in Ref. 2; CAA60165/CAA60166)"
FT /evidence="ECO:0000305"
FT CONFLICT 435
FT /note="S -> R (in Ref. 2; CAA60165/CAA60166)"
FT /evidence="ECO:0000305"
FT CONFLICT 503
FT /note="F -> L (in Ref. 2; CAA60165/CAA60166)"
FT /evidence="ECO:0000305"
FT CONFLICT 512
FT /note="A -> V (in Ref. 2; CAA60165/CAA60166)"
FT /evidence="ECO:0000305"
FT TURN 551..554
FT /evidence="ECO:0007829|PDB:3ML4"
SQ SEQUENCE 868 AA; 96693 MW; AFE4E644C6869933 CRC64;
MRELVNIPLL QMLTLVAFSG TEKLPKAPVI TTPLETVDAL VEEVATFMCA VESYPQPEIS
WTRNKILIKL FDTRYSIREN GQLLTILSVE DSDDGIYCCI ANNGVGGAVE SCGALQVKMK
PKITRPPINV KIIEGLKAVL PCTTMGNPKP SVSWIKGDNA LRENSRIAVL ESGSLRIHNV
QKEDAGQYRC VAKNSLGTAY SKLVKLEVEV FARILRAPES HNVTFGSFVT LRCTAIGIPV
PTISWIENGN AVSSGSIQES VKDRVIDSRL QLFITKPGLY TCIATNKHGE KFSTAKAAAT
VSIAEWSKSQ KDSQGYCAQY RGEVCDAVLA KDALVFFNTS YRDPEDAQEL LIHTAWNELK
AVSPLCRPAA EALLCNHLFQ ECSPGVVPTP MPICREYCLA VKELFCAKEW QAMEGKAHRG
LYRSGMHLLP VPECSKLPSM HRDPTACTRL PYLDYKKENI TTFPSITSSR PSADIPNLPA
STSSFAVSPA YSMTVIISIV SSFALFALLT IATLYCCRRR KEWKNKKRES TAVTLTTLPS
ELLLDRLHPN PMYQRMPLLL NPKLLSLEYP RNNIEYVRDI GEGAFGRVFQ ARAPGLLPYE
PFTMVAVKML KEEASADMQA DFQREAALMA EFDNPNIVKL LGVCAVGKPM CLLFEYMAYG
DLNEFLRSMS PHTVCSLSHS DLSTRARVSS PGPPPLSCAE QLCIARQVAA GMAYLSERKF
VHRDLATRNC LVGETMVVKI ADFGLSRNIY SADYYKADGN DAIPIRWMPP ESIFYNRYTT
ESDVWAYGVV LWEIFSYGLQ PYYGMAHEEV IYYVRDGNIL ACPENCPLEL YNLMRLCWSK
LPADRPSFCS IHRILQRMCE RAEGTVGV
