MUSK muscle, skeletal, receptor tyrosine kinase [Homo sapiens] - Gene

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Summary

Official Symbol: MUSKprovided by HGNC
Official Full Name: muscle, skeletal, receptor tyrosine kinaseprovided by HGNC
Primary source: HGNC:7525
Locus tag: RP11-104M22.1
See related: Ensembl:ENSG00000030304; HPRD:03190; MIM:601296; Vega:OTTHUMG00000020485
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MGC126323; MGC126324
Summary: This gene encodes a muscle-specific tyrosine kinase receptor. The encoded protein may play a role in clustering of the acetylcholine receptor in the postsynaptic neuromuscular junction. Mutations in this gene have been associated with congenital myasthenic syndrome. Alternatively spliced transcript variants have been described.[provided by RefSeq, Oct 2009]

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Genomic context

Location :: 9q31.3-q32

Sequence :: Chromosome: 9; NC_000009.11 (113431051..113563278)

See MUSK in Epigenomics, MapViewer

Chromosome 9 - NC_000009.11 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Two family cases are reported that transmit MuSK antibody myasthenia gravis to the offspring by different maternal mechanisms.
Title: Transmission of maternal muscle-specific tyrosine kinase (MuSK) to offspring: report of two cases.
The ability of immobilized MuSK extracellular domain to remove practically all anti-MuSK antibodies from patients' sera should prove invaluable for development of an antigen-specific therapeutic approach for MuSK myasthenia gravis.
Title: Development of a highly sensitive diagnostic assay for muscle-specific tyrosine kinase (MuSK) autoantibodies in myasthenia gravis.
Lrp4 is a cis-acting ligand for MuSK
Title: Agrin binds to the N-terminal region of Lrp4 protein and stimulates association between Lrp4 and the first immunoglobulin-like domain in muscle-specific kinase (MuSK).
The importance of MuSK as a synapse organiser is highlighted by cases of autoimmune myasthenia gravis in which MuSK autoantibodies can deplete MuSK from the postsynaptic membrane, leading to complete disassembly of the adult neuromuscular junction.
Title: Muscle specific kinase: organiser of synaptic membrane domains.
these findings demonstrate that missense mutations in MUSK can result in a severe form of congenital myasthenic syndrome and indicate that the inability of MuSK mutants to interact with Dok-7.
Title: Mutations in MUSK causing congenital myasthenic syndrome impair MuSK-Dok-7 interaction.
Anti-MuSK protein positive patients have more predominantly bulbar involvement and had more severe myasthenia gravis.
Title: [Seronegative myasthenia and myasthenia gravis with anti-MuSK antibody: a retrospective study of 20 cases].
This study report a family known so far with a congenital myasthenic syndromes due to a mutation in the MUSK gene.
Title: Refinement of the clinical phenotype in musk-related congenital myasthenic syndromes.
Anti-MuSK antibodies influence the activity of MuSK molecules without reducing their number, thereby diminishing the size of the endplate and affecting the functioning of acetylcholine receptors.
Title: The effect of plasma from muscle-specific tyrosine kinase myasthenia patients on regenerating endplates.
Thymectomy is mostly considered scarcely effective; however, at present, no firm conclusions can be drawn on its role in the treatment of this form of myasthenia gravis
Title: Response to therapy in myasthenia gravis with anti-MuSK antibodies.
single-fiber electromyography of distal limb muscles tends to have a lower yield of abnormality in MuSK-antibody-positive patients than either acetylcholine receptor-antibody-positive or seronegative myasthenia gravis
Title: Clinical phenotype of muscle-specific tyrosine kinase-antibody-positive myasthenia gravis.

Submit: New GeneRIF Correction See all (22)

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Myasthenic syndrome, congenital, associated with acetylcholine receptor deficiency

MIM: 608931

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Products	Interactant	Other Gene	Source	Pubs	Description
O15146	Q9Y215	COLQ	HPRD	PubMed
O15146	Q18PE1	DOK7	HPRD	PubMed
O15146	Q13702	RAPSN	HPRD	PubMed
O15146	Q8NF91	SYNE1	HPRD	PubMed
BioGRID:110679	BioGRID:110815	NEDD8	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110679	BioGRID:116664	PDZRN3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110679	BioGRID:116928	SYNE1	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:110679	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-Western

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
PDZ domain binding	IEA Inferred from Electronic Annotation more info
nucleotide binding	IEA Inferred from Electronic Annotation more info
protein tyrosine kinase activity	ISS Inferred from Sequence or Structural Similarity more info
receptor activity	IEA Inferred from Electronic Annotation more info
transmembrane receptor protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
cell differentiation	IEA Inferred from Electronic Annotation more info
memory	ISS Inferred from Sequence or Structural Similarity more info
multicellular organismal development	IEA Inferred from Electronic Annotation more info
neuromuscular junction development	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of gene expression	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of neuron apoptosis	IEA Inferred from Electronic Annotation more info
positive regulation of protein geranylgeranylation	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of protein phosphorylation	ISS Inferred from Sequence or Structural Similarity more info
protein autophosphorylation	ISS Inferred from Sequence or Structural Similarity more info
regulation of synaptic growth at neuromuscular junction	ISS Inferred from Sequence or Structural Similarity more info
regulation of transcription, DNA-dependent	IEA Inferred from Electronic Annotation more info
skeletal muscle acetylcholine-gated channel clustering	ISS Inferred from Sequence or Structural Similarity more info
transmembrane receptor protein tyrosine kinase signaling pathway	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
cell junction	IEA Inferred from Electronic Annotation more info
integral to plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
neuromuscular junction	ISS Inferred from Sequence or Structural Similarity more info
plasma membrane	IEA Inferred from Electronic Annotation more info
postsynaptic membrane	ISS Inferred from Sequence or Structural Similarity more info

General protein information

Preferred Names: muscle, skeletal receptor tyrosine-protein kinase

Names: muscle, skeletal receptor tyrosine-protein kinase; muscle-specific kinase receptor; muscle-specific tyrosine-protein kinase receptor

NP_001159752.1

EC 2.7.10.1

NP_001159753.1

EC 2.7.10.1

NP_005583.1

EC 2.7.10.1

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NCBI Reference Sequences (RefSeq)

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.

Genomic

NG_016016.1 RefSeqGene

Range

5001..137228

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001166280.1 → NP_001159752.1 muscle, skeletal receptor tyrosine-protein kinase isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains an alternate in-frame exon and lacks an alternate in-frame exon in the middle portion of the coding region compared to variant 1. The encoded isoform (2) is shorter than isoform 1.

Source sequence(s)

AF006464, BC109098, BG825304

UniProtKB/Swiss-Prot

O15146

Related

ENSP00000363570, ENST00000374447

Conserved Domains (6) summary

cd05050
Location:483 – 772
Blast Score: 1571

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

cd00096
Location:239 – 300
Blast Score: 129

Ig; Immunoglobulin domain

pfam07679
Location:121 – 199
Blast Score: 275

I-set; Immunoglobulin I-set domain

pfam07714
Location:489 – 770
Blast Score: 1009

Pkinase_Tyr; Protein tyrosine kinase

cl02447
Location:317 – 379
Blast Score: 249

CRD_FZ; CRD_domain cysteine-rich domain, also known as Fz (frizzled) domain

cl11960
Location:135 – 199
Blast Score: 192

Ig; Immunoglobulin domain
NM_001166281.1 → NP_001159753.1 muscle, skeletal receptor tyrosine-protein kinase isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate in-frame exon in the middle portion of the coding region compared to variant 1. The encoded isoform (3) is shorter than isoform 1.

Source sequence(s)

AF006464, BC109099, BG825304

UniProtKB/Swiss-Prot

O15146

Conserved Domains (6) summary

cd05050
Location:473 – 762
Blast Score: 1571

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

cd00096
Location:229 – 290
Blast Score: 129

Ig; Immunoglobulin domain

pfam07679
Location:121 – 208
Blast Score: 282

I-set; Immunoglobulin I-set domain

pfam07714
Location:479 – 760
Blast Score: 1008

Pkinase_Tyr; Protein tyrosine kinase

cl02447
Location:307 – 369
Blast Score: 249

CRD_FZ; CRD_domain cysteine-rich domain, also known as Fz (frizzled) domain

cl11960
Location:135 – 201
Blast Score: 194

Ig; Immunoglobulin domain
NM_005592.3 → NP_005583.1 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)

AF006464, BC109099, BG825304

Consensus CDS

CCDS48005.1

UniProtKB/Swiss-Prot

O15146

Related

ENSP00000363571, ENST00000374448

Conserved Domains (6) summary

cd05050
Location:569 – 858
Blast Score: 1570

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

cd00096
Location:229 – 290
Blast Score: 128

Ig; Immunoglobulin domain

pfam07679
Location:121 – 208
Blast Score: 281

I-set; Immunoglobulin I-set domain

pfam07714
Location:575 – 856
Blast Score: 1010

Pkinase_Tyr; Protein tyrosine kinase

cl02447
Location:315 – 457
Blast Score: 596

CRD_FZ; CRD_domain cysteine-rich domain, also known as Fz (frizzled) domain

cl11960
Location:135 – 201
Blast Score: 193

Ig; Immunoglobulin domain

RefSeqs of Annotated Genomes: Build 37.3

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

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000009.11 Reference GRCh37.p5 Primary Assembly

Range

113431051..113563278

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000141.1 Alternate HuRef

Range

83032852..83161644

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AL157881.14	CAH69976.1
		CAH69977.1
		CAH69978.1
genomic	AL513328.12	CAI17349.1
		CAI17350.1
		CAI17351.1
genomic	CH471105.1	EAW59065.1
		EAW59066.1
		EAW59067.1
mRNA	AA448972.1	None
mRNA	AF006464.1	AAB63044.1
mRNA	BC109098.1	AAI09099.1
mRNA	BC109099.1	AAI09100.1
mRNA	BG825304.1	None
mRNA	Z25436.1	CAA80923.1
other-genetic	EU832778.1	ACE87789.1
other-genetic	EU832779.1	ACE87790.1
other-genetic	GQ129313.1	ACT64447.1