ACTN2 actinin alpha 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ACTN2provided by HGNC
Official Full Name: actinin alpha 2provided by HGNC
Primary source: HGNC:HGNC:164
See related: Ensembl:ENSG00000077522 MIM:102573; AllianceGenome:HGNC:164
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: MPD6; CMH23; CMYP8; CMD1AA; MYOCOZ
Summary: Alpha actinins belong to the spectrin gene superfamily which represents a diverse group of cytoskeletal proteins, including the alpha and beta spectrins and dystrophins. Alpha actinin is an actin-binding protein with multiple roles in different cell types. In nonmuscle cells, the cytoskeletal isoform is found along microfilament bundles and adherens-type junctions, where it is involved in binding actin to the membrane. In contrast, skeletal, cardiac, and smooth muscle isoforms are localized to the Z-disc and analogous dense bodies, where they help anchor the myofibrillar actin filaments. This gene encodes a muscle-specific, alpha actinin isoform that is expressed in both skeletal and cardiac muscles. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2013]
Expression: Restricted expression toward heart (RPKM 342.0) See more
Orthologs: mouse all
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Genomic context

Location:: 1q43

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (236686499..236764631)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (236087386..236175684)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (236849799..236927931)

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?

Recurring homozygous ACTN2 variant (p.Arg506Gly) causes a recessive myopathy.
Title: Recurring homozygous ACTN2 variant (p.Arg506Gly) causes a recessive myopathy.
Disruption of Z-Disc Function Promotes Mechanical Dysfunction in Human Myocardium: Evidence for a Dual Myofilament Modulatory Role by Alpha-Actinin 2.
Title: Disruption of Z-Disc Function Promotes Mechanical Dysfunction in Human Myocardium: Evidence for a Dual Myofilament Modulatory Role by Alpha-Actinin 2.
Cardiomyopathy-associated variants alter the structure and function of the alpha-actinin-2 actin-binding domain.
Title: Cardiomyopathy-associated variants alter the structure and function of the α-actinin-2 actin-binding domain.
Mutation update for the ACTN2 gene.
Title: Mutation update for the ACTN2 gene.
ACTN2 Mutant Causes Proteopathy in Human iPSC-Derived Cardiomyocytes.
Title: ACTN2 Mutant Causes Proteopathy in Human iPSC-Derived Cardiomyocytes.
Mono- and Biallelic Protein-Truncating Variants in Alpha-Actinin 2 Cause Cardiomyopathy Through Distinct Mechanisms.
Title: Mono- and Biallelic Protein-Truncating Variants in Alpha-Actinin 2 Cause Cardiomyopathy Through Distinct Mechanisms.
Sleeping Beauty insertional mutagenesis screen identifies the pro-metastatic roles of CNPY2 and ACTN2 in hepatocellular carcinoma tumor progression.
Title: Sleeping Beauty insertional mutagenesis screen identifies the pro-metastatic roles of CNPY2 and ACTN2 in hepatocellular carcinoma tumor progression.
Differential regulation of Actn2 and Actn3 expression during unfolded protein response in C2C12 myotubes.
Title: Differential regulation of Actn2 and Actn3 expression during unfolded protein response in C2C12 myotubes.
Cardiac MLC2 kinase is localized to the Z-disc and interacts with alpha-actinin2.
Title: Cardiac MLC2 kinase is localized to the Z-disc and interacts with α-actinin2.
CTN2 (rs6655267) and MPPED2 (rs536007) are not associated with primary dentition caries. MPPED2 (rs11031093, G Allele) is marginally associated.
Title: ACTN2 (rs6656267) and MPPED2 (rs11031093 and rs536007) polymorphisms in primary dentition caries: A case-control study.

Submit: New GeneRIF Correction See all GeneRIFs (36)

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
Dilated cardiomyopathy 1AA MedGen: C2677338 OMIM: 612158 GeneReviews: Dilated Cardiomyopathy Overview	Compare labs
Myopathy, congenital, with structured cores and z-line abnormalities MedGen: C5231445 OMIM: 618654 GeneReviews: Not available	Compare labs
Myopathy, distal, 6, adult-onset, autosomal dominant MedGen: C5203349 OMIM: 618655 GeneReviews: Not available	Compare labs
Primary dilated cardiomyopathy MedGen: C0007193 GeneReviews: Dilated Cardiomyopathy Overview	Compare labs
Primary familial hypertrophic cardiomyopathy MedGen: C0949658 GeneReviews: Hypertrophic Cardiomyopathy Overview	Compare labs

EBI GWAS Catalog

Description
Genome-wide association study of chronic periodontitis in a general German population. EBI GWAS Catalog EBI GWAS CatalogPubMed

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

ACTN2 (e-PCR)
- UniSTS:503045

D1S2059E (e-PCR)
- UniSTS:151592

ACTN2_4196 (e-PCR)
- UniSTS:471337

D1S2925 (e-PCR)
- UniSTS:52535

SHGC-12727 (e-PCR)
- UniSTS:13886

GDB:192954 (e-PCR)
- UniSTS:155733

Actn2 (e-PCR), detects polymorphism
- UniSTS:228475

AL009965 (e-PCR)
- UniSTS:17544

GDB:451691 (e-PCR)
- UniSTS:157347

D1S1759E (e-PCR)
- UniSTS:150446

G31538 (e-PCR)
- UniSTS:31701

SHGC-76572 (e-PCR)
- UniSTS:55267

ACTN2 (e-PCR)
- UniSTS:479728

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables FATZ binding	IDA Inferred from Direct Assay more info	PubMed
enables LIM domain binding	IEA Inferred from Electronic Annotation more info
enables actin filament binding	IBA Inferred from Biological aspect of Ancestor more info
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables cytoskeletal protein binding	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables integrin binding	TAS Traceable Author Statement more info	PubMed
enables nuclear receptor coactivator activity	IEA Inferred from Electronic Annotation more info
enables phosphatidylinositol-4,5-bisphosphate binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	IPI Inferred from Physical Interaction more info	PubMed
enables structural constituent of muscle	TAS Traceable Author Statement more info	PubMed
enables titin Z domain binding	IMP Inferred from Mutant Phenotype more info	PubMed
enables titin Z domain binding	IPI Inferred from Physical Interaction more info	PubMed
enables titin binding	IPI Inferred from Physical Interaction more info	PubMed
enables transmembrane transporter binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in actin cytoskeleton organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in actin filament uncapping	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cardiac muscle cell development	IEA Inferred from Electronic Annotation more info
involved_in cell adhesion	TAS Traceable Author Statement more info	PubMed
involved_in focal adhesion assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in microspike assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in muscle cell development	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of potassium ion transmembrane transporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of potassium ion transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of protein localization to cell surface	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in phospholipase C-activating angiotensin-activated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cation channel activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of endocytic recycling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of potassium ion transmembrane transporter activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of potassium ion transport	IDA Inferred from Direct Assay more info	PubMed
involved_in protein localization to plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of apoptotic process	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of membrane potential	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in sarcomere organization	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
is_active_in Z disc	IBA Inferred from Biological aspect of Ancestor more info
located_in Z disc	IDA Inferred from Direct Assay more info	PubMed
located_in actin filament	TAS Traceable Author Statement more info	PubMed
is_active_in cell junction	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cell projection	IBA Inferred from Biological aspect of Ancestor more info
is_active_in cortical actin cytoskeleton	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoskeleton	NAS Non-traceable Author Statement more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in dendritic spine	TAS Traceable Author Statement more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in filopodium	IDA Inferred from Direct Assay more info	PubMed
located_in focal adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
colocalizes_with plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in platelet alpha granule lumen	TAS Traceable Author Statement more info
located_in postsynaptic actin cytoskeleton	IEA Inferred from Electronic Annotation more info
located_in postsynaptic density membrane	IEA Inferred from Electronic Annotation more info
located_in postsynaptic density, intracellular component	IEA Inferred from Electronic Annotation more info
located_in pseudopodium	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: alpha-actinin-2

Names: F-actin cross-linking protein; alpha-actinin skeletal muscle

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_009081.2 RefSeqGene

Range

27359..105491

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_436

mRNA and Protein(s)

NM_001103.4 → NP_001094.1 alpha-actinin-2 isoform 1

See identical proteins and their annotated locations for NP_001094.1

Status: REVIEWED

Source sequence(s)

AL359185, AL359921

Consensus CDS

CCDS1613.1

UniProtKB/Swiss-Prot

B1ANE4, B2RCS5, P35609, Q86TF4, Q86TI8

UniProtKB/TrEMBL

A0A804HI95

Related

ENSP00000355537.4, ENST00000366578.6

Conserved Domains (5) summary

COG5069
Location:36 → 299

SAC6; Ca2+-binding actin-bundling protein fimbrin/plastin (EF-Hand superfamily) [Cytoskeleton]

cd00176
Location:402 → 629

SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

pfam00435
Location:281 → 391

Spectrin; Spectrin repeat

pfam08726
Location:824 → 890

EFhand_Ca_insen; Ca2+ insensitive EF hand

cl25352
Location:747 → 851

EFh_PEF; The penta-EF hand (PEF) family
NM_001278343.2 → NP_001265272.1 alpha-actinin-2 isoform 2

See identical proteins and their annotated locations for NP_001265272.1

Status: REVIEWED

Source sequence(s)

AL359185, AL359921

Consensus CDS

CCDS60455.1

UniProtKB/TrEMBL

A0A494C1A0

Related

ENSP00000443495.1, ENST00000542672.7

Conserved Domains (7) summary

cd00014
Location:152 → 257

CH; Calponin homology domain; actin-binding domain which may be present as a single copy or in tandem repeats (which increases binding affinity). The CH domain is found in cytoskeletal and signal transduction proteins, including actin-binding proteins like ...

cd00051
Location:757 → 819

EFh; EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to ...

cd00176
Location:402 → 629

SPEC; Spectrin repeats, found in several proteins involved in cytoskeletal structure; family members include spectrin, alpha-actinin and dystrophin; the spectrin repeat forms a three helix bundle with the second helix interrupted by proline in some sequences; ...

pfam00307
Location:39 → 137

CH; Calponin homology (CH) domain

pfam00435
Location:281 → 391

Spectrin; Spectrin repeat

pfam08726
Location:824 → 890

EFhand_Ca_insen; Ca2+ insensitive EF hand

pfam13499
Location:759 → 818

EF-hand_7; EF-hand domain pair