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

Summary

Official Symbol: OBSCNprovided by HGNC
Official Full Name: obscurin, cytoskeletal calmodulin and titin-interacting RhoGEFprovided by HGNC
Primary source: HGNC:HGNC:15719
See related: Ensembl:ENSG00000154358 MIM:608616; AllianceGenome:HGNC:15719
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; RHABDO1; ARHGEF30
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]
Expression: Broad expression in heart (RPKM 8.6), prostate (RPKM 2.9) and 15 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q42.13

Exon count:: 118

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (228208044..228378876)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (227396836..227567714)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (228395745..228566577)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Essential role of obscurin kinase-1 in cardiomyocyte coupling via N-cadherin phosphorylation.
Title: Essential role of obscurin kinase-1 in cardiomyocyte coupling via N-cadherin phosphorylation.
Novel OBSCN variants associated with a risk to exercise-intolerance and rhabdomyolysis.
Title: Novel OBSCN variants associated with a risk to exercise-intolerance and rhabdomyolysis.
Bi-allelic loss-of-function OBSCN variants predispose individuals to severe recurrent rhabdomyolysis.
Title: Bi-allelic loss-of-function OBSCN variants predispose individuals to severe recurrent rhabdomyolysis.
When is an obscurin variant pathogenic? The impact of Arg4344Gln and Arg4444Trp variants on protein-protein interactions and protein stability.
Title: When is an obscurin variant pathogenic? The impact of Arg4344Gln and Arg4444Trp variants on protein-protein interactions and protein stability.
Truncating Variants in OBSCN Gene Associated With Disease-Onset and Outcomes of Hypertrophic Cardiomyopathy.
Title: Truncating Variants in OBSCN Gene Associated With Disease-Onset and Outcomes of Hypertrophic Cardiomyopathy.
Giant obscurin regulates migration and metastasis via RhoA-dependent cytoskeletal remodeling in pancreatic cancer.
Title: Giant obscurin regulates migration and metastasis via RhoA-dependent cytoskeletal remodeling in pancreatic cancer.
Intracellular calcium current disorder and disease phenotype in OBSCN mutant iPSC-based cardiomyocytes in arrhythmogenic right ventricular cardiomyopathy.
Title: Intracellular calcium current disorder and disease phenotype in OBSCN mutant iPSC-based cardiomyocytes in arrhythmogenic right ventricular cardiomyopathy.
This study finds in all cases tested that tandem obscurin Ig domains interact at the poles of each domain and tend to stay relatively extended in solution. NMR, SAXS, and MD simulations reveal that while tandem domains are elongated, they also bend and flex significantly.
Title: Obscurin is a semi-flexible molecule in solution.
association of frameshift and splicing variants, all clustering to the C terminus of the same isoform group, with occurrence of rare left ventricular noncompaction phenotype
Title: Obscurin Variants in Patients With Left Ventricular Noncompaction.
demonstrate that loss of giant obscurins from breast epithelial cells is associated with significantly increased phosphorylation and subsequent activation of the PI3K signaling cascade
Title: Giant obscurins regulate the PI3K cascade in breast epithelial cells via direct binding to the PI3K/p85 regulatory subunit.

Submit: New GeneRIF Correction See all GeneRIFs (29)

Phenotypes

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

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Rhabdomyolysis, susceptibility to, 1 MedGen: C5774307 OMIM: 620235 GeneReviews: Not available	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-76459 (e-PCR)
- UniSTS:23192

SHGC-76456 (e-PCR)
- UniSTS:13508

NoName (e-PCR)
- UniSTS:487117

SHGC-146605 (e-PCR)
- UniSTS:175321

Clone Names

FLJ14124, KIAA1556, KIAA1639, MGC120409, MGC120410, MGC120411, MGC120412, MGC138590, DKFZp666E245

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ankyrin binding	IPI Inferred from Physical Interaction more info	PubMed
enables calmodulin binding	IEA Inferred from Electronic Annotation more info
enables guanyl-nucleotide exchange factor activity	TAS Traceable Author Statement more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables phosphatidylinositol-3,4,5-trisphosphate binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidylinositol-3,4-bisphosphate binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidylinositol-3-phosphate binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidylinositol-4,5-bisphosphate binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidylinositol-4-phosphate binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidylinositol-5-phosphate binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables structural constituent of muscle	NAS Non-traceable Author Statement more info	PubMed
enables titin binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in protein localization to M-band	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in regulation of small GTPase mediated signal transduction	TAS Traceable Author Statement more info
involved_in sarcomere organization	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in M band	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in Z disc	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in myofibril	NAS Non-traceable Author Statement more info	PubMed
located_in nuclear body	IDA Inferred from Direct Assay more info
located_in plasma membrane	IDA Inferred from Direct Assay more info
located_in sarcolemma	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: obscurin

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

NP_001092093.2

EC 2.7.11.1

NP_001258152.2

EC 2.7.11.1

NP_001373054.1

EC 2.7.11.1

NP_443075.3

EC 2.7.11.1

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.

Genomic

NG_032122.1 RefSeqGene

Range

4885..175717

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_412

mRNA and Protein(s)

NM_001098623.2 → NP_001092093.2 obscurin isoform b

See identical proteins and their annotated locations for NP_001092093.2

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)

AL353593, AL359510, AL670729

Consensus CDS

CCDS58065.1

UniProtKB/Swiss-Prot

Q2A664, Q5T7G8, Q5T7G9, Q5VST9, Q5VSU2, Q86YC7, Q8NHN0, Q8NHN1, Q8NHN2, Q8NHN3, Q8NHN4, Q8NHN5, Q8NHN6, Q8NHN7, Q8NHN8, Q8NHN9, Q96AA2, Q9HCD3, Q9HCL6

Related

ENSP00000409493.1, ENST00000422127.5

Conserved Domains (15) summary

cd00096
Location:5143 → 5213

Ig; Immunoglobulin domain

smart00408
Location:7477 → 7543

IGc2; Immunoglobulin C-2 Type

cd12025
Location:5602 → 5664

SH3_Obscurin_like; Src homology 3 domain of Obscurin and similar proteins

smart00060
Location:7557 → 7635

FN3; Fibronectin type 3 domain

smart00220
Location:6468 → 6721

S_TKc; Serine/Threonine protein kinases, catalytic domain

smart00410
Location:248 → 328

IG_like; Immunoglobulin like

cd00063
Location:4523 → 4608

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 ...

pfam07679
Location:10 → 99

I-set; Immunoglobulin I-set domain

cd13239
Location:5882 → 6006

PH_Obscurin; Obscurin pleckstrin homology (PH) domain

cd14107
Location:6465 → 6721

STKc_obscurin_rpt1; Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin

cd14110
Location:7668 → 7924

STKc_obscurin_rpt2; Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin

pfam00047
Location:811 → 872

ig; Immunoglobulin domain

pfam13895
Location:3101 → 3181

Ig_2; Immunoglobulin domain

cl02571
Location:5697 → 5873

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.

cl11960
Location:9 → 91

Ig; Immunoglobulin domain
NM_001271223.3 → NP_001258152.2 obscurin isoform IC

Status: REVIEWED

Description

Transcript Variant: This variant (IC) represents an inferred complete model that includes additional in-frame coding exons with consensus splice sites. The exons included in this inferred variant are supported by a combination of available cDNA data and sequence analysis of repetitive exons. This transcript represents a predicted protein (isoform IC) of 8,923 amino acids.

Source sequence(s)

AL353593, AL359510, AL670729

Consensus CDS

CCDS59204.1

UniProtKB/TrEMBL

A6NGQ3, H3BPX2

Related

ENSP00000455507.2, ENST00000570156.7

Conserved Domains (14) summary

cd12025
Location:6559 → 6621

SH3_Obscurin_like; Src homology 3 domain of Obscurin and similar proteins

smart00060
Location:8514 → 8592

FN3; Fibronectin type 3 domain

smart00325
Location:6654 → 6832

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases

smart00410
Location:3263 → 3340

IG_like; Immunoglobulin like

cd00063
Location:5480 → 5565

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 ...

cd13239
Location:6839 → 6963

PH_Obscurin; Obscurin pleckstrin homology (PH) domain

cd14107
Location:7422 → 7678

STKc_obscurin_rpt1; Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin

cd14110
Location:8625 → 8879

STKc_obscurin_rpt2; Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin

pfam15822
Location:7760 → 8033

MISS; MAPK-interacting and spindle-stabilizing protein-like

pfam07679
Location:10 → 99

I-set; Immunoglobulin I-set domain

cd00096
Location:1927 → 1931

Ig; Ig strand B [structural motif]

cd20967
Location:1722 → 1803

IgI_C2_MyBP-C-like; Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains

cd20971
Location:6971 → 7061

IgI_1_Titin-A168_like; First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains

cl11960
Location:1913 → 1994

Ig; Immunoglobulin domain
NM_001386125.1 → NP_001373054.1 obscurin isoform c

Status: REVIEWED

Source sequence(s)

AL353593, AL359510, AL670729

Consensus CDS

CCDS91171.1

UniProtKB/TrEMBL

A0A7P0Z489

Related

ENSP00000505517.1, ENST00000680850.1

Conserved Domains (16) summary

cd12025
Location:6559 → 6621

SH3_Obscurin_like; Src homology 3 domain of Obscurin and similar proteins

smart00060
Location:8514 → 8592

FN3; Fibronectin type 3 domain

smart00325
Location:6654 → 6832

RhoGEF; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases

smart00409
Location:3263 → 3340

IG; Immunoglobulin

smart00410
Location:4679 → 4754

IG_like; Immunoglobulin like

cd00063
Location:5480 → 5565

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 ...

cd13239
Location:6839 → 6963

PH_Obscurin; Obscurin pleckstrin homology (PH) domain

cd14107
Location:7422 → 7678

STKc_obscurin_rpt1; Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin

cd14110
Location:8625 → 8881

STKc_obscurin_rpt2; Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin

pfam15822
Location:7760 → 8033

MISS; MAPK-interacting and spindle-stabilizing protein-like

pfam07679
Location:10 → 99

I-set; Immunoglobulin I-set domain

pfam13927
Location:5390 → 5466

Ig_3; Immunoglobulin domain

cd00096
Location:1913 → 1915

Ig; Ig strand A [structural motif]

cd20967
Location:1722 → 1803

IgI_C2_MyBP-C-like; Domain C2 of human cardiac Myosin Binding Protein C and similar domains; a member of the I-set of IgSF domains

cd20971
Location:6971 → 7061

IgI_1_Titin-A168_like; First immunoglobulin-like domains A168 within the A-band segment of human cardiac titin, and similar domains; a member of the I-set of IgSF domains

cl11960
Location:1913 → 1994

Ig; Immunoglobulin domain
NM_052843.4 → NP_443075.3 obscurin isoform a

Status: REVIEWED

Description

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

Source sequence(s)

AL353593, AL359510, AL670729

Consensus CDS

CCDS1570.2

UniProtKB/Swiss-Prot

Q5VST9

Related

ENSP00000284548.11, ENST00000284548.16

Conserved Domains (14) summary

cd00096
Location:5143 → 5213

Ig; Immunoglobulin domain

smart00015
Location:4872 → 4893

IQ; Calmodulin-binding motif

smart00408
Location:6121 → 6189

IGc2; Immunoglobulin C-2 Type

cd12025
Location:5602 → 5664

SH3_Obscurin_like; Src homology 3 domain of Obscurin and similar proteins

smart00409
Location:2834 → 2911

IG; Immunoglobulin

smart00410
Location:248 → 328

IG_like; Immunoglobulin like

cd00063
Location:4523 → 4608

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 ...

pfam07679
Location:10 → 99

I-set; Immunoglobulin I-set domain

cd13239
Location:5882 → 6006

PH_Obscurin; Obscurin pleckstrin homology (PH) domain

pfam00047
Location:811 → 872

ig; Immunoglobulin domain

pfam00169
Location:5896 → 6000

PH; PH domain

pfam13895
Location:3101 → 3181

Ig_2; Immunoglobulin domain

cl02571
Location:5697 → 5873

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.

cl11960
Location:9 → 91

Ig; Immunoglobulin domain