Musk muscle, skeletal, receptor tyrosine kinase [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Muskprovided by MGI
Official Full Name: muscle, skeletal, receptor tyrosine kinaseprovided by MGI
Primary source: MGI:MGI:103581
See related: Ensembl:ENSMUSG00000057280 AllianceGenome:MGI:103581
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Mlk; Mdk4; Nsk1; Nsk2; Nsk3
Summary: This gene encodes a member of the protein tyrosine kinase family. The encoded protein is a type 1 receptor-like protein located in muscle membrane that is activated by the heparan sulfate proteoglycan agrin released by nerve cells. The encoded protein activates signaling cascades responsible for multiple aspects of motor neuron and muscle development, including organization of the postsynaptic membrane, synaptic gene transcription, patterning of skeletal muscle, anchoring of acetylcholinesterase, and guidance of motor axons. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
Expression: Broad expression in limb E14.5 (RPKM 1.2), colon adult (RPKM 0.4) and 16 other tissues See more
Orthologs: human all
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Genomic context

Location:: 4 B3; 4 31.87 cM

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	4	NC_000070.7 (58285742..58377848)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	4	NC_000070.6 (58285729..58377848)

Chromosome 4 - NC_000070.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Proteolytic ectodomain shedding of muscle-specific tyrosine kinase in myasthenia gravis.
Title: Proteolytic ectodomain shedding of muscle-specific tyrosine kinase in myasthenia gravis.
Activation of Muscle-Specific Kinase (MuSK) Reduces Neuromuscular Defects in the Delta7 Mouse Model of Spinal Muscular Atrophy (SMA).
Title: Activation of Muscle-Specific Kinase (MuSK) Reduces Neuromuscular Defects in the Delta7 Mouse Model of Spinal Muscular Atrophy (SMA).
Muscle specific kinase protects dystrophic mdx mouse muscles from eccentric contraction-induced loss of force-producing capacity.
Title: Muscle specific kinase protects dystrophic mdx mouse muscles from eccentric contraction-induced loss of force-producing capacity.
During development, MuSK serves as a signaling hub, coordinating the alignment of the pre- and postsynaptic components of the synapse. Adult mice that received repeated daily injections of IgG from anti-MuSK(+) myasthenia gravis patients developed muscle weakness, associated with neuromuscular transmission failure. Review.
Title: The mouse passive-transfer model of MuSK myasthenia gravis: disrupted MuSK signaling causes synapse failure.
Agrin induced an Lrp4-independent increase in dendritic branch complexity, an Lrp4-dependent increase of excitatory synaptic puncta and an Lrp4- and MuSK-independent decrease in the density of puncta containing inhibitory synapse-associated proteins. Results establish selective roles for agrin, Lrp4 and MuSK during dendritogenesis and synaptogenesis in cultured CNS neurons.
Title: The role of agrin, Lrp4 and MuSK during dendritic arborization and synaptogenesis in cultured embryonic CNS neurons.
Gene expression profiling showed that MuSK was required for the BMP4-induced expression of a subset of genes in myoblasts, including regulator of G protein signaling 4 (Rgs4).
Title: MuSK is a BMP co-receptor that shapes BMP responses and calcium signaling in muscle cells.
These mice showed only marginal activation of MuSK and died by 3 weeks of age apparently due to an abnormally small number and size of neuromuscular junction (NMJs).
Title: The carboxyl-terminal region of Dok-7 plays a key, but not essential, role in activation of muscle-specific receptor kinase MuSK and neuromuscular synapse formation.
data reveal that muscle skeletal receptor tyrosine kinase cysteine-rich domain is critical for neuromuscular junction formation and plays an unsuspected role in NMJ maintenance in adulthood.
Title: MuSK frizzled-like domain is critical for mammalian neuromuscular junction formation and maintenance.
Forced expression of Dok-7 in muscle enhanced MuSK activation in mice lacking agrin or Lrp4 and restored midmuscle NMJ formation in agrin-deficient mice, but not in Lrp4-deficient mice.
Title: The MuSK activator agrin has a separate role essential for postnatal maintenance of neuromuscular synapses.
pathogenic IgG4 antibodies to MuSK bind to a structural epitope in the first Ig-like domain of MuSK, prevent binding between MuSK and Lrp4, and inhibit Agrin-stimulated MuSK phosphorylation.
Title: MuSK IgG4 autoantibodies cause myasthenia gravis by inhibiting binding between MuSK and Lrp4.

Submit: New GeneRIF Correction See all GeneRIFs (33)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (3) 1 citation
Spontaneous (1) 1 citation
Targeted (6) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables PDZ domain binding	IPI Inferred from Physical Interaction more info	PubMed
enables Wnt-protein binding	IBA Inferred from Biological aspect of Ancestor more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	ISO Inferred from Sequence Orthology more info
enables protein tyrosine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein tyrosine kinase activity	IGI Inferred from Genetic Interaction more info	PubMed
enables protein tyrosine kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables protein tyrosine kinase activity	ISO Inferred from Sequence Orthology more info
enables protein tyrosine kinase activity	ISS Inferred from Sequence or Structural Similarity more info
enables transmembrane receptor protein tyrosine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables transmembrane receptor protein tyrosine kinase activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in cell surface receptor protein tyrosine kinase signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in enzyme-linked receptor protein signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in enzyme-linked receptor protein signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in enzyme-linked receptor protein signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in long-term synaptic potentiation	ISO Inferred from Sequence Orthology more info
involved_in memory	ISO Inferred from Sequence Orthology more info
acts_upstream_of motor neuron apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in multicellular organism development	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of gene expression	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within neuromuscular junction development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in neuromuscular junction development	ISO Inferred from Sequence Orthology more info
involved_in neuromuscular junction development	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of Rac protein signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of Rac protein signal transduction	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of Rac protein signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of gene expression	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within positive regulation of motor neuron apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of neuron projection development	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of peptidyl-tyrosine phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of protein geranylgeranylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein phosphorylation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of skeletal muscle acetylcholine-gated channel clustering	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of skeletal muscle acetylcholine-gated channel clustering	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of skeletal muscle acetylcholine-gated channel clustering	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of synaptic assembly at neuromuscular junction	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of synaptic transmission, cholinergic	ISO Inferred from Sequence Orthology more info
involved_in protein phosphorylation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within receptor clustering	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within receptor clustering	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in receptor clustering	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of synaptic assembly at neuromuscular junction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to electrical stimulus	ISO Inferred from Sequence Orthology more info
involved_in skeletal muscle acetylcholine-gated channel clustering	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in cell projection	ISO Inferred from Sequence Orthology more info
located_in external side of plasma membrane	ISO Inferred from Sequence Orthology more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in neuromuscular junction	IDA Inferred from Direct Assay more info	PubMed
located_in neuromuscular junction	IDA Inferred from Direct Assay more info	PubMed
located_in neuromuscular junction	ISO Inferred from Sequence Orthology more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info	PubMed
is_active_in postsynaptic membrane	IDA Inferred from Direct Assay more info	PubMed
located_in postsynaptic membrane	IDA Inferred from Direct Assay more info	PubMed
part_of receptor complex	IBA Inferred from Biological aspect of Ancestor more info
part_of receptor complex	ISO Inferred from Sequence Orthology more info	PubMed
located_in synapse	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: muscle, skeletal receptor tyrosine-protein kinase

Names: muscle localized kinase 2; muscle-specific kinase receptor; muscle-specific tyrosine-protein kinase receptor

NP_001032204.2

EC 2.7.10.1

NP_001032205.1

EC 2.7.10.1

NP_001032206.1

EC 2.7.10.1

NP_001032207.1

EC 2.7.10.1

NP_001159468.1

EC 2.7.10.1

NP_035074.2

EC 2.7.10.1

XP_006537722.1

EC 2.7.10.1

XP_006537724.1

EC 2.7.10.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001037127.2 → NP_001032204.2 muscle, skeletal receptor tyrosine-protein kinase isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

AL805969, AL807748

Consensus CDS

CCDS51182.1

UniProtKB/TrEMBL

Q32SD4

Conserved Domains (6) summary

cd05050
Location:593 → 882

PTKc_Musk; Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase

cd00096
Location:239 → 306

Ig; Immunoglobulin domain

cd07469
Location:338 → 482

CRD_TK_ROR_related; Cysteine-rich domain of proteins similar to tyrosine kinase-like orphan receptors

pfam07679
Location:121 → 208

I-set; Immunoglobulin I-set domain

pfam07714
Location:599 → 880

Pkinase_Tyr; Protein tyrosine kinase

cl11960
Location:135 → 201

Ig; Immunoglobulin domain
NM_001037128.1 → NP_001032205.1 muscle, skeletal receptor tyrosine-protein kinase isoform 2

See identical proteins and their annotated locations for NP_001032205.1

Status: REVIEWED

Description

Transcript Variant: This variant lacks an alternate, in-frame segment in the coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.

Source sequence(s)

AY955297, BC100342, U37709

UniProtKB/TrEMBL

Q32SD3, Q32SD4

Conserved Domains (6) summary

cd05050
Location:578 → 867

PTKc_Musk; Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase

cd00096
Location:239 → 306

Ig; Immunoglobulin domain

cd07469
Location:323 → 467

CRD_TK_ROR_related; Cysteine-rich domain of proteins similar to tyrosine kinase-like orphan receptors

pfam07679
Location:121 → 208

I-set; Immunoglobulin I-set domain

pfam07714
Location:584 → 865

Pkinase_Tyr; Protein tyrosine kinase

cl11960
Location:135 → 201

Ig; Immunoglobulin domain
NM_001037129.1 → NP_001032206.1 muscle, skeletal receptor tyrosine-protein kinase isoform 3

See identical proteins and their annotated locations for NP_001032206.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks two alternate, in-frame segments in the coding region, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.

Source sequence(s)

BC100342, U37709

Consensus CDS

CCDS38770.1

UniProtKB/TrEMBL

I7GSQ5, Q497X0

Related

ENSMUSP00000136696.2, ENSMUST00000177951.8

Conserved Domains (6) summary

cd05050
Location:570 → 859

PTKc_Musk; Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase

cd00096
Location:239 → 306

Ig; Immunoglobulin domain

cd07469
Location:323 → 466

CRD_TK_ROR_related; Cysteine-rich domain of proteins similar to tyrosine kinase-like orphan receptors

pfam07679
Location:121 → 208

I-set; Immunoglobulin I-set domain

pfam07714
Location:576 → 857

Pkinase_Tyr; Protein tyrosine kinase

cl11960
Location:135 → 201

Ig; Immunoglobulin domain
NM_001037130.1 → NP_001032207.1 muscle, skeletal receptor tyrosine-protein kinase isoform 5

See identical proteins and their annotated locations for NP_001032207.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks three alternate, in-frame segments in the coding region, compared to variant 1. The encoded isoform (5) is shorter than isoform 1.

Source sequence(s)

BC100342, U37708

Consensus CDS

CCDS18210.1

UniProtKB/TrEMBL

I7GSQ5, Q32S49

Related

ENSMUSP00000099957.4, ENSMUST00000102893.10

Conserved Domains (6) summary

cd05050
Location:560 → 849

PTKc_Musk; Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase

cd00096
Location:229 → 296

Ig; Immunoglobulin domain

cd07469
Location:313 → 456

CRD_TK_ROR_related; Cysteine-rich domain of proteins similar to tyrosine kinase-like orphan receptors

pfam07679
Location:121 → 208

I-set; Immunoglobulin I-set domain

pfam07714
Location:566 → 847

Pkinase_Tyr; Protein tyrosine kinase

cl11960
Location:135 → 201

Ig; Immunoglobulin domain
NM_001165996.1 → NP_001159468.1 muscle, skeletal receptor tyrosine-protein kinase isoform 6

See identical proteins and their annotated locations for NP_001159468.1

Status: REVIEWED

Description

Transcript Variant: This variant (6) lacks an alternate in-frame exon and uses an alternate in-frame splice site in the central coding region, and differs in the presence and absence of exons in the 3' coding region and 3' UTR, compared to variant 1. The resulting isoform (6) has a distinct C-terminus and is shorter than isoform 1.

Source sequence(s)

AL805969, AL807748

UniProtKB/TrEMBL

Q1XD56

Conserved Domains (4) summary

cd00096
Location:229 → 296

Ig; Immunoglobulin domain

cd07469
Location:313 → 457

CRD_TK_ROR_related; Cysteine-rich domain of proteins similar to tyrosine kinase-like orphan receptors

pfam07679
Location:121 → 208

I-set; Immunoglobulin I-set domain

cl11960
Location:135 → 201

Ig; Immunoglobulin domain
NM_010944.2 → NP_035074.2 muscle, skeletal receptor tyrosine-protein kinase isoform 4

See identical proteins and their annotated locations for NP_035074.2

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks two alternate, in-frame segments in the coding region, compared to variant 1. The encoded isoform (4) is shorter than isoform 1.

Source sequence(s)

BC100342, U37709

Consensus CDS

CCDS18211.1

UniProtKB/Swiss-Prot

Q61005, Q61006, Q61987, Q61988

UniProtKB/TrEMBL

I7GSQ5, Q32S50

Related

ENSMUSP00000081625.6, ENSMUST00000084578.12

Conserved Domains (6) summary

cd05050
Location:568 → 857

PTKc_Musk; Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase

cd00096
Location:229 → 296

Ig; Immunoglobulin domain

cd07469
Location:313 → 457

CRD_TK_ROR_related; Cysteine-rich domain of proteins similar to tyrosine kinase-like orphan receptors

pfam07679
Location:121 → 208

I-set; Immunoglobulin I-set domain

pfam07714
Location:574 → 855

Pkinase_Tyr; Protein tyrosine kinase

cl11960
Location:135 → 201

Ig; Immunoglobulin domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000070.7 Reference GRCm39 C57BL/6J

Range

58285742..58377848

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006537659.4 → XP_006537722.1 muscle, skeletal receptor tyrosine-protein kinase isoform X1

See identical proteins and their annotated locations for XP_006537722.1

UniProtKB/TrEMBL

Q32SD4

Conserved Domains (4) summary

cd05050
Location:588 → 877

PTKc_Musk; Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase

cd07469
Location:333 → 477

CRD_TK_ROR_related; Cysteine-rich domain of proteins similar to tyrosine kinase-like orphan receptors

pfam07679
Location:121 → 208

I-set; Immunoglobulin I-set domain

pfam13927
Location:246 → 306

Ig_3; Immunoglobulin domain
XM_006537661.4 → XP_006537724.1 muscle, skeletal receptor tyrosine-protein kinase isoform X2

UniProtKB/TrEMBL

I7GSQ5

Conserved Domains (4) summary

cd05050
Location:580 → 869

PTKc_Musk; Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase

cd07469
Location:333 → 476

CRD_TK_ROR_related; Cysteine-rich domain of proteins similar to tyrosine kinase-like orphan receptors

pfam07679
Location:121 → 208

I-set; Immunoglobulin I-set domain

cl11960
Location:233 → 316

Ig; Immunoglobulin domain