NEB nebulin [Homo sapiens] - Gene

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Summary

Official Symbol: NEBprovided by HGNC
Official Full Name: nebulinprovided by HGNC
Primary source: HGNC:7720
See related: Ensembl:ENSG00000183091; HPRD:01196; MIM:161650; Vega:OTTHUMG00000153784
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: NEM2; NEB177D; FLJ11505; FLJ36536; FLJ39568; FLJ39584; DKFZp686C1456
Summary: This gene encodes nebulin, a giant protein component of the cytoskeletal matrix that coexists with the thick and thin filaments within the sarcomeres of skeletal muscle. In most vertebrates, nebulin accounts for 3 to 4% of the total myofibrillar protein. The encoded protein contains approximately 30-amino acid long modules that can be classified into 7 types and other repeated modules. Protein isoform sizes vary from 600 to 800 kD due to alternative splicing that is tissue-, species-,and developmental stage-specific. Of the 183 exons in the nebulin gene, at least 43 are alternatively spliced, although exons 143 and 144 are not found in the same transcript. Of the several thousand transcript variants predicted for nebulin, the RefSeq Project has decided to create three representative RefSeq records. Mutations in this gene are associated with recessive nemaline myopathy. [provided by RefSeq, Sep 2009]

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Genomic context

Location :: 2q22

Sequence :: Chromosome: 2; NC_000002.11 (152341853..152591001, complement)

See NEB in Epigenomics, MapViewer

Chromosome 2 - NC_000002.11 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?

distal nemaline myopathy caused by four different compound heterozygous nebulin mutations
Title: Nemaline myopathy caused by mutations in the nebulin gene may present as a distal myopathy.
The mechanics as well as the X-ray diffraction patterns of human membrane-permeabilized single muscle fibers expressing nebulin mutations are reported.
Title: Disrupted myosin cross-bridge cycling kinetics triggers muscle weakness in nebulin-related myopathy.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
Observational study of gene-disease association. (HuGE Navigator)
Title: Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
Data revealed markedly reduced nebulin protein levels in muscle from nemaline myopathy patients, whereas levels of other thin filament-based proteins were not significantly altered.
Title: Altered myofilament function depresses force generation in patients with nebulin-based nemaline myopathy (NEM2).
Nebulin regulates thin filament architecture by a mechanism that includes stabilizing the filaments and preventing actin depolymerization.
Title: Nebulin regulates actin filament lengths by a stabilization mechanism.
In all but two of eight homozygous patients with nebulin mutations, the clinical picture was more severe than in typical nemaline myopathy.
Title: The exon 55 deletion in the nebulin gene--one single founder mutation with world-wide occurrence.
These data suggest a model in which archvillin attaches directly to the Z-line of skeletal muscle through an interaction with the nebulin C-terminus.
Title: Archvillin anchors in the Z-line of skeletal muscle via the nebulin C-terminus.
Mutations caused absence of the C-terminal part of nebulin resulting in severe congenital form of nemaline myopathy.
Title: Mutations in the nebulin gene can cause severe congenital nemaline myopathy.
Nebulin is targeted and oriented through titin and myopalladin signaling during sarcomere assembly
Title: Interaction of nebulin SH3 domain with titin PEVK and myopalladin: implications for the signaling and assembly role of titin and nebulin.

Submit: New GeneRIF Correction See all (16)

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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

Nemaline myopathy 2, autosomal recessive

MIM: 256030

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_004534.1		TRIM55	BIND	PubMed	MURF-2 interacts with Nebulin.
P20929	Q8IZP0	ABI1	HPRD	PubMed
P20929	O43707	ACTN4	HPRD	PubMed
P20929	P17661	DES	HPRD	PubMed
P20929	Q86TC9	MYPN	HPRD	PubMed
P20929	P28289	TMOD1	HPRD	PubMed
P20929	Q8WZ42	TTN	HPRD	PubMed
BioGRID:110783	BioGRID:106821	APC	BioGRID	PubMed	Two-hybrid
BioGRID:110783	BioGRID:107252	CALM1	BioGRID	PubMed	Reconstituted Complex
BioGRID:110783	BioGRID:108038	DES	BioGRID	PubMed	Two-hybrid
BioGRID:110783	BioGRID:124185	MYPN	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:110783	BioGRID:112966	TMOD1	BioGRID	PubMed	Reconstituted Complex
BioGRID:110783	BioGRID:118898	TMOD4	BioGRID	PubMed	Reconstituted Complex
BioGRID:110783	BioGRID:124195	TRIM63	BioGRID	PubMed	Two-hybrid

Function	Evidence Code	Pubs
actin binding	IEA Inferred from Electronic Annotation more info
structural constituent of muscle	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
muscle filament sliding	TAS Traceable Author Statement more info
muscle organ development	TAS Traceable Author Statement more info	PubMed
regulation of actin filament length	NAS Non-traceable Author Statement more info	PubMed
somatic muscle development	NAS Non-traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
Z disc	IDA Inferred from Direct Assay more info	PubMed
actin cytoskeleton	TAS Traceable Author Statement more info	PubMed
cytoplasm	IEA Inferred from Electronic Annotation more info
cytosol	TAS Traceable Author Statement more info
sarcomere	IEA Inferred from Electronic Annotation more info

General protein information

Preferred Names: nebulin

Names: nebulin

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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_009382.2 RefSeqGene

Range

5001..254149

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001164507.1 → NP_001157979.1 nebulin isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents a transcript with all known exons of the nebulin gene except for exon 144. The RefSeq Project created this record to better support clinical studies but the combination of exons and splice sites still needs to be experimentally confirmed. The predicted protein (isoform 1) is 8525 aa long.

Source sequence(s)

AC009497, AC107052, AC116650, AH003593

Consensus CDS

CCDS54408.1

UniProtKB/TrEMBL

Q14214

Related

ENSP00000416578, ENST00000427231

Conserved Domains (2) summary

cd00174
Location:8484 – 8523
Blast Score: 109

SH3; Src homology 3 domains; SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of ...

cl11595
Location:1272 – 1302
Blast Score: 104

Nebulin; Nebulin repeat
NM_001164508.1 → NP_001157980.1 nebulin isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) represents a transcript with all known exons of the nebulin gene except for exon 143. The RefSeq Project created this record to better support clinical studies but the combination of exons and splice sites still needs to be experimentally confirmed. The predicted protein (isoform 2) is the same length as isoform 1 but has a different sequence due to the exchange of exon 143 for exon 144.

Source sequence(s)

AC009497, AC107052, AC116650, AH003593

Consensus CDS

CCDS54407.1

UniProtKB/TrEMBL

Q14214

Related

ENSP00000380505, ENST00000397345

Conserved Domains (2) summary

cd00174
Location:8484 – 8523
Blast Score: 109

SH3; Src homology 3 domains; SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of ...

cl11595
Location:1272 – 1302
Blast Score: 104

Nebulin; Nebulin repeat
NM_004543.4 → NP_004534.2 nebulin isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks many exons and uses different splice sites in its coding region, compared to variant 1. The combination of exons and splice sites has been experimentally confirmed as reported in accession X83957.1. The resulting protein (isoform 3, also known as the short form) is shorter when it is compared to isoform 1.

Source sequence(s)

AC107052, AH003593, AK056994, BC029384, BP232190, BP233123, BX283647, X83957

Consensus CDS

CCDS46424.1

UniProtKB/Swiss-Prot

P20929

UniProtKB/TrEMBL

Q05C45

UniProtKB/TrEMBL

Q14214

UniProtKB/TrEMBL

Q96MF8

Related

ENSP00000386259, OTTHUMP00000204401, ENST00000409198, OTTHUMT00000332406

Conserved Domains (2) summary

cd00174
Location:6628 – 6667
Blast Score: 109

SH3; Src homology 3 domains; SH3 domains bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs; they play a role in the regulation of enzymes by intramolecular interactions, changing the subcellular localization of ...

cl11595
Location:1272 – 1302
Blast Score: 104

Nebulin; Nebulin repeat

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_000002.11 Reference GRCh37.p5 Primary Assembly

Range

152341853..152591001, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000134.1

Range

144238157..144477212, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)
NW_001841344.1

Range

223..7407, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC009497.3	AAY14651.1
genomic	AC107052.4	AAY14977.1
genomic	AC116650.4	None
genomic	CH471058.2	EAX11499.1
		EAX11500.1
		EAX11501.1
		EAX11502.1
		EAX11503.1
		EAX11504.1
		EAX11505.1
		EAX11506.1
mRNA	AK021567.1	None
mRNA	AK056994.1	BAB71337.1
mRNA	AK093855.1	None
mRNA	AK096887.1	BAG53391.1
mRNA	AK096903.1	None
mRNA	AK129532.1	None
mRNA	AK300079.1	BAH13205.1
mRNA	AK300674.1	BAH13324.1
mRNA	AK300722.1	BAH13335.1
mRNA	AK307607.1	None
mRNA	BC012533.1	None
mRNA	BC022421.2	AAH22421.2
mRNA	BC029384.1	AAH29384.1
mRNA	BC050436.1	AAH50436.1
mRNA	BC056251.1	AAH56251.1
mRNA	BC063136.1	AAH63136.1
mRNA	BC105590.1	AAI05591.1
mRNA	BP232190.1	None
mRNA	BP233123.1	None
mRNA	BX283647.1	None
mRNA	BX648963.1	None
mRNA	M19669.1	AAA59917.1
mRNA	U35636.1	AAB02621.1
mRNA	U35637.1	AAB02622.1
mRNA	X58122.1	CAA41124.1
mRNA	X83957.1	CAA58788.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
P20929.4	GenPept	UniProtKB/Swiss-Prot:P20929
Q05C45	GenPept	UniProtKB/TrEMBL:Q05C45
Q14214	GenPept	UniProtKB/TrEMBL:Q14214
Q14215	GenPept	UniProtKB/TrEMBL:Q14215
Q14918	GenPept	UniProtKB/TrEMBL:Q14918
Q6P516	GenPept	UniProtKB/TrEMBL:Q6P516
Q6PJ54	GenPept	UniProtKB/TrEMBL:Q6PJ54
Q7Z2R0	GenPept	UniProtKB/TrEMBL:Q7Z2R0
Q86TG3	GenPept	UniProtKB/TrEMBL:Q86TG3
Q96MF8	GenPept	UniProtKB/TrEMBL:Q96MF8
Q9Y5Z1	GenPept	UniProtKB/TrEMBL:Q9Y5Z1