Obscn obscurin, cytoskeletal calmodulin and titin-interacting RhoGEF [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Obscnprovided by MGI
Official Full Name: obscurin, cytoskeletal calmodulin and titin-interacting RhoGEFprovided by MGI
Primary source: MGI:MGI:2681862
See related: Ensembl:ENSMUSG00000061462 AllianceGenome:MGI:2681862
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Gm878; UNC89
Summary: The obscurin gene spans more than 150 kb, contains over 80 exons and encodes a protein of approximately 800 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 is one of three giant sacromeric signaling proteins that includes titin and nebulin. It may have a role in the organization of myofibrils during assembly and also may mediate interactions between the sarcoplasmic reticulum and myofibrils. Alternatively spliced transcript variants encoding different isoforms have been described although the full-length nature is not known for all splicing variants. [provided by RefSeq, Jan 2010]
Expression: Biased expression in heart adult (RPKM 40.7), mammary gland adult (RPKM 7.2) and 1 other tissue See more
Orthologs: human all
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Genomic context

Location:: 11 B1.3; 11 36.4 cM

Exon count:: 114

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	11	NC_000077.7 (58885082..59027201, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	11	NC_000077.6 (58994256..59136375, complement)

Chromosome 11 - NC_000077.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: 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?

Impaired Intracellular Ca(2+) Dynamics, M-Band and Sarcomere Fragility in Skeletal Muscles of Obscurin KO Mice.
Title: Impaired Intracellular Ca(2+) Dynamics, M-Band and Sarcomere Fragility in Skeletal Muscles of Obscurin KO Mice.
Deletion of obscurin immunoglobulin domains Ig58/59 leads to age-dependent cardiac remodeling and arrhythmia.
Title: Deletion of obscurin immunoglobulin domains Ig58/59 leads to age-dependent cardiac remodeling and arrhythmia.
Skeletal muscle-specific Obsl1 knockouts show a benign phenotype similar to obscurin knockouts. Only deletion of both proteins and removal of their functional redundancy revealed their roles for sarcolemmal stability and sarcoplasmic reticulum organization.
Title: Murine obscurin and Obsl1 have functionally redundant roles in sarcolemmal integrity, sarcoplasmic reticulum organization, and muscle metabolism.
These findings implicate small obscurins in the maintenance of cardiomyocyte size and coupling.
Title: Novel obscurins mediate cardiomyocyte adhesion and size via the PI3K/AKT/mTOR signaling pathway.
Altogether, these results suggest that obscurin is required for the maintenance of morphological and ultrastructural integrity of skeletal muscle fibers against damage induced by intense mechanical stress and point to the diaphragm as the skeletal muscle most severely affected in obscurin-deficient mice.
Title: Exercise-induced alterations and loss of sarcomeric M-line organization in the diaphragm muscle of obscurin knockout mice.
obscurins are not restricted to striated muscles, but are abundantly expressed in several tissues and organs including brain, skin, kidney, liver, spleen, and lung.
Title: Obscurins: Goliaths and Davids take over non-muscle tissues.
the obscurin kinase domains, SK1 and SK2, are active enzymes with distinct substrate specificities.
Title: The kinase domains of obscurin interact with intercellular adhesion proteins.
Obscurin, by targeting ankB at the M band, contributes to the organization of subsarcolemma microtubules, localization of dystrophin at costameres, and maintenance of sarcolemmal integrity.
Title: Obscurin is required for ankyrinB-dependent dystrophin localization and sarcolemma integrity.
the organization of obscurin at different locations in the sarcomere changes during muscle development and that this might affect the interaction with ank1.5.
Title: Localization of ank1.5 in the sarcoplasmic reticulum precedes that of SERCA and RyR: relationship with the organization of obscurin in developing sarcomeres.
the Rho-GEF domain of obscurin interacts with RanBP9 and that both can interact with the N-terminal region of titin to influence the formation of the Z-disk and A/I junction
Title: The rho-guanine nucleotide exchange factor domain of obscurin regulates assembly of titin at the Z-disk through interactions with Ran binding protein 9.

Submit: New GeneRIF Correction See all GeneRIFs (12)

Variation

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Alleles

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

Spontaneous (1) 1 citation
Targeted (4) 1 citation
Chemically induced (ENU) (1)
Endonuclease-mediated (2)

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 ankyrin binding	ISO Inferred from Sequence Orthology more info
enables cadherin 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	IEA Inferred from Electronic Annotation more info
enables kinase activity	IEA Inferred from Electronic Annotation more info
enables lipid binding	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables phosphatidylinositol bisphosphate binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphatidylinositol-3,4,5-trisphosphate binding	ISO Inferred from Sequence Orthology more info
enables phosphatidylinositol-3,4-bisphosphate binding	ISO Inferred from Sequence Orthology more info
enables phosphatidylinositol-3-phosphate binding	ISO Inferred from Sequence Orthology more info
enables phosphatidylinositol-4,5-bisphosphate binding	ISO Inferred from Sequence Orthology more info
enables phosphatidylinositol-4-phosphate binding	ISO Inferred from Sequence Orthology more info
enables phosphatidylinositol-5-phosphate binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine kinase activity	IEA Inferred from Electronic Annotation more info
enables titin binding	ISO Inferred from Sequence Orthology more info
enables transferase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within cell differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within multicellular organism development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in M band	IDA Inferred from Direct Assay more info	PubMed
located_in M band	ISO Inferred from Sequence Orthology more info
located_in Z disc	IDA Inferred from Direct Assay more info	PubMed
located_in Z disc	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in extracellular region	IEA Inferred from Electronic Annotation more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in intercalated disc	IDA Inferred from Direct Assay more info	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in nuclear body	ISO Inferred from Sequence Orthology more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	ISO Inferred from Sequence Orthology more info
located_in sarcolemma	IDA Inferred from Direct Assay more info	PubMed
located_in sarcomere	ISO Inferred from Sequence Orthology more info
located_in striated muscle myosin thick filament	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: obscurin

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

NP_001164983.2

EC 2.7.11.1

NP_954603.3

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.

mRNA and Protein(s)

NM_001171512.3 → NP_001164983.2 obscurin isoform 1

Status: VALIDATED

Source sequence(s)

AL645854, AL662809

Consensus CDS

CCDS56775.1

UniProtKB/Swiss-Prot

A2AAJ9, A2AB85, B2FDE7, Q695L2, Q811H7

UniProtKB/TrEMBL

H7BX05

Related

ENSMUSP00000038264.8, ENSMUST00000047441.14

Conserved Domains (15) summary

cd00096
Location:5375 → 5444

Ig; Immunoglobulin domain

smart00408
Location:6350 → 6418

IGc2; Immunoglobulin C-2 Type

cd12025
Location:5831 → 5893

SH3_Obscurin_like; Src homology 3 domain of Obscurin and similar proteins

smart00060
Location:7620 → 7698

FN3; Fibronectin type 3 domain

smart00220
Location:6562 → 6815

S_TKc; Serine/Threonine protein kinases, catalytic domain

smart00409
Location:246 → 326

IG; Immunoglobulin

smart00410
Location:6349 → 6427

IG_like; Immunoglobulin like

cd00063
Location:4749 → 4834

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:9 → 98

I-set; Immunoglobulin I-set domain

cd13239
Location:6111 → 6235

PH_Obscurin; Obscurin pleckstrin homology (PH) domain

pfam00047
Location:4211 → 4279

ig; Immunoglobulin domain

pfam13895
Location:3258 → 3337

Ig_2; Immunoglobulin domain

cl02571
Location:5926 → 6102

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:8 → 90

Ig; Immunoglobulin domain

cl21453
Location:6559 → 6815

PKc_like; Protein Kinases, catalytic domain
NM_001428368.1 → NP_001415297.1 obscurin isoform 3

Status: VALIDATED

Source sequence(s)

AL645854, AL662809
NM_199152.4 → NP_954603.3 obscurin isoform 2

Status: VALIDATED

Source sequence(s)

AL645854, AL662809

Consensus CDS

CCDS56774.1

UniProtKB/TrEMBL

E9QQ96, Z4YJE4

Related

ENSMUSP00000049737.8, ENSMUST00000052872.15

Conserved Domains (14) summary

cd00096
Location:6028 → 6097

Ig; Immunoglobulin domain

smart00015
Location:5754 → 5775

IQ; Calmodulin-binding motif

smart00408
Location:7003 → 7071

IGc2; Immunoglobulin C-2 Type

cd12025
Location:6484 → 6546

SH3_Obscurin_like; Src homology 3 domain of Obscurin and similar proteins

smart00409
Location:7002 → 7080

IG; Immunoglobulin

smart00410
Location:5317 → 5398

IG_like; Immunoglobulin like

cd00063
Location:5402 → 5487

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:9 → 98

I-set; Immunoglobulin I-set domain

cd13239
Location:6764 → 6888

PH_Obscurin; Obscurin pleckstrin homology (PH) domain

pfam00047
Location:4772 → 4840

ig; Immunoglobulin domain

pfam00169
Location:6778 → 6882

PH; PH domain

pfam13895
Location:3467 → 3546

Ig_2; Immunoglobulin domain

cl02571
Location:6579 → 6755

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:8 → 90

Ig; Immunoglobulin domain