OBSCN obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF [Homo sapiens] - Gene

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Summary

Official Symbol: OBSCNprovided by HGNC
Official Full Name: obscurin, cytoskeletal calmodulin and titin-interacting RhoGEFprovided by HGNC
Primary source: HGNC:15719
Locus tag: RP5-1139B12.1-10
See related: Ensembl:ENSG00000154358; HPRD:08594; HPRD:10551; MIM:608616; Vega:OTTHUMG00000039772
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: UNC89; ARHGEF30; FLJ14124; KIAA1556; KIAA1639; MGC120409; MGC120410; MGC120411; MGC120412; MGC138590; DKFZp666E245
Summary: The obscurin gene spans more than 150 kb, contains over 80 exons and encodes a protein of approximately 720 kDa. The encoded protein contains 68 Ig domains, 2 fibronectin domains, 1 calcium/calmodulin-binding domain, 1 RhoGEF domain with an associated PH domain, and 2 serine-threonine kinase domains. This protein belongs to the family of giant sacromeric signaling proteins that includes titin and nebulin, and may have a role in the organization of myofibrils during assembly and may mediate interactions between the sarcoplasmic reticulum and myofibrils. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

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Genomic context

Location :: 1q42.13

Sequence :: Chromosome: 1; NC_000001.10 (228395861..228566575)

See OBSCN in Epigenomics, MapViewer

Chromosome 1 - NC_000001.10 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?

Results describe the molecular basis for the head-to-tail interaction of the carboxyl terminus of titin and the amino-terminus of obscurin-like-1 by X-ray crystallography.
Title: Molecular basis of the head-to-tail assembly of giant muscle proteins obscurin-like 1 and titin.
Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
These findings reveal a novel signaling pathway in human skeletal muscle that involves obscurin and the Rho GTPase TC10 and implicate this pathway in new sarcomere formation.
Title: TC10 controls human myofibril organization and is activated by the sarcomeric RhoGEF obscurin.
Obscurin was never lacking in myofibrillar alterations, but was either preserved at the M-band level or diffusely spread over the sarcomeres.
Title: New aspects of obscurin in human striated muscles.
Structural and mutational studies of the binding region on small Ank1 for obscurin suggest that it consists of two ankyrin repeats with very similar structures.
Title: Mapping the binding site on small ankyrin 1 for obscurin.
Studies suggest that the obscurin abnormality may be involved in the pathogenesis of hypertrophic cardiomyopathy.
Title: Structural analysis of obscurin gene in hypertrophic cardiomyopathy.
The complete gene giant muscle protein obscurin was analysed. The fusion of the conventional obscurin A, containing only the GEF domain, and obscurin B, fusing into the 3' kinase exons, was experimentally confirmed and analysed.
Title: Complete human gene structure of obscurin: implications for isoform generation by differential splicing.
Results suggest that obscurin binds small ankyrin 1, and document a specific and direct interaction between proteins of the sarcomere and the sarcoplasmic reticulum.
Title: Obscurin is a ligand for small ankyrin 1 in skeletal muscle.
OBSCN and C9orf65 comprise a highly accurate two-gene classifier for differentiating gastrointestinal stromal tumors and leiomyosarcomas.
Title: Highly accurate two-gene classifier for differentiating gastrointestinal stromal tumors and leiomyosarcomas.

Submit: New GeneRIF Correction

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

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Products	Interactant	Other Gene	Source	Pubs	Description
Q5VST9	P16157	ANK1	HPRD	PubMed
Q5VST9	Q01484	ANK2	HPRD	PubMed
Q5VST9	Calmodulin 1	CALM1	HPRD	PubMed
Q5VST9	Q9UKX2	MYH2	HPRD	PubMed
Q5VST9	Q8WZ42	TTN	HPRD	PubMed
BioGRID:123847	BioGRID:106783	ANK1	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:123847	BioGRID:113188	SUMO1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:123847	BioGRID:113124	TTN	BioGRID	PubMed	Reconstituted Complex; Two-hybrid

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
Rho guanyl-nucleotide exchange factor activity	IEA Inferred from Electronic Annotation more info
calmodulin binding	IEA Inferred from Electronic Annotation more info
metal ion binding	IEA Inferred from Electronic Annotation more info
nucleotide binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info
structural constituent of muscle	NAS Non-traceable Author Statement more info	PubMed
titin binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
apoptotic process	TAS Traceable Author Statement more info
cell differentiation	IEA Inferred from Electronic Annotation more info
induction of apoptosis by extracellular signals	TAS Traceable Author Statement more info
multicellular organismal development	IEA Inferred from Electronic Annotation more info
nerve growth factor receptor signaling pathway	TAS Traceable Author Statement more info
regulation of Rho protein signal transduction	IEA Inferred from Electronic Annotation more info
regulation of small GTPase mediated signal transduction	TAS Traceable Author Statement more info
small GTPase mediated signal transduction	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
M band	ISS Inferred from Sequence or Structural Similarity more info	PubMed
Z disc	ISS Inferred from Sequence or Structural Similarity more info	PubMed
cytoplasm	IEA Inferred from Electronic Annotation more info
cytosol	TAS Traceable Author Statement more info
intracellular	IEA Inferred from Electronic Annotation more info
myofibril	NAS Non-traceable Author Statement more info	PubMed

General protein information

Preferred Names: obscurin

Names: obscurin; obscurin-MLCK; obscurin, myosin light chain kinase

NP_001092093.1

EC 2.7.11.1

NP_443075.2

EC 2.7.11.1

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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_032122.1 RefSeqGene

Range

5001..175715

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001098623.1 → NP_001092093.1 obscurin isoform b

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 3' UTR and the 3' coding region, compared to variant 1. The resulting isoform (b) contains a distinct C-terminus, compared to isoform a.

Source sequence(s)

AB046776, AB046859, AJ002535, AL353593, AL359510, AL670729, CN302348, DB163213, DB445363

UniProtKB/Swiss-Prot

Q5VST9

Related

ENSP00000409493, ENST00000422127

Conserved Domains (10) summary

cd00063
Location:4523 – 4608
Blast Score: 178

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cd00160
Location:5697 – 5873
Blast Score: 157

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.

cd00096
Location:5143 – 5213
Blast Score: 161

Ig; Immunoglobulin domain

cd04979
Location:3899 – 3975
Blast Score: 128

Ig_Semaphorin_C; Immunoglobulin (Ig)-like domain of semaphorin

cd00180
Location:6474 – 6652
Blast Score: 422

PKc; Catalytic domain of Protein Kinases

pfam07679
Location:10 – 99
Blast Score: 289

I-set; Immunoglobulin I-set domain

smart00220
Location:6468 – 6721
Blast Score: 593

S_TKc; Serine/Threonine protein kinases, catalytic domain

cl00065
Location:7557 – 7635
Blast Score: 105

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cl00273
Location:5894 – 5999
Blast Score: 174

PH-like; Pleckstrin homology-like domain

cl11960
Location:9 – 91
Blast Score: 164

Ig; Immunoglobulin domain
NM_052843.2 → NP_443075.2 obscurin isoform a

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the shorter transcript, and encodes the shorter isoform (a).

Source sequence(s)

AB046776, AJ002535, AL353593, AL359510, AL832357, BC034746, BU180714, CN302348

UniProtKB/Swiss-Prot

Q5VST9

Related

ENSP00000284548, OTTHUMP00000037764, ENST00000284548, OTTHUMT00000095986

Conserved Domains (7) summary

cd00063
Location:4523 – 4608
Blast Score: 179

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

cd00160
Location:5697 – 5873
Blast Score: 158

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.

cd00096
Location:5143 – 5213
Blast Score: 161

Ig; Immunoglobulin domain

cd04979
Location:3899 – 3975
Blast Score: 128

Ig_Semaphorin_C; Immunoglobulin (Ig)-like domain of semaphorin

pfam07679
Location:10 – 99
Blast Score: 287

I-set; Immunoglobulin I-set domain

cl00273
Location:5894 – 5999
Blast Score: 174

PH-like; Pleckstrin homology-like domain

cl11960
Location:9 – 91
Blast Score: 165

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_000001.10 Reference GRCh37.p5 Primary Assembly

Range

228395861..228566575

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000133.1 Alternate HuRef

Range

198910699..199081449

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AJ314896.1	CAC85745.1
genomic	AJ314898.1	CAC85746.1
genomic	AJ314900.1	CAC85747.1
genomic	AJ314903.1	CAC85750.1
genomic	AJ314904.1	CAC85751.1
genomic	AJ314905.1	CAC85752.1
genomic	AJ314906.1	CAC85753.1
genomic	AJ314907.1	CAC85754.1
genomic	AJ314908.1	CAC85755.1
genomic	AL353593.33	CAI19283.1
		CAI19284.1
		CAI19285.1
genomic	AL359510.24	CAI15072.1
genomic	AL670729.19	CAH71670.2
		CAH71673.1
genomic	AL670729.19	CAH71670.2
		CAH71673.1
genomic	CH471098.1	EAW69866.1
		EAW69867.1
mRNA	AB046776.1	BAB13382.1
mRNA	AB046859.2	BAB13465.2
mRNA	AJ002535.1	CAC44768.1
mRNA	AK024186.1	None
mRNA	AK097489.1	None
mRNA	AL832357.1	None
mRNA	AL833724.1	CAH56259.1
mRNA	AM231061.1	CAJ76912.1
mRNA	BC034746.1	None
mRNA	BC043916.1	None
mRNA	BC098118.1	AAH98118.1
mRNA	BC098262.1	AAH98262.1
mRNA	BC098292.1	AAH98292.1
mRNA	BC099731.1	AAH99731.1
mRNA	BC114382.1	AAI14383.1
mRNA	BC114461.1	AAI14462.1
mRNA	BU180714.1	None
mRNA	CN302348.1	None
mRNA	DB163213.1	None
mRNA	DB445363.1	None
mRNA	DQ400343.1	ABD63255.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
Q24JT4	GenPept	UniProtKB/TrEMBL:Q24JT4
Q5VST9.3	GenPept	UniProtKB/Swiss-Prot:Q5VST9
Q658N7	GenPept	UniProtKB/TrEMBL:Q658N7