ACTN1 actinin alpha 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ACTN1provided by HGNC
Official Full Name: actinin alpha 1provided by HGNC
Primary source: HGNC:HGNC:163
See related: Ensembl:ENSG00000072110 MIM:102575; AllianceGenome:HGNC:163
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: BDPLT15
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 nonmuscle, cytoskeletal, alpha actinin isoform and maps to the same site as the structurally similar erythroid beta spectrin gene. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in endometrium (RPKM 77.5), urinary bladder (RPKM 66.3) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 14q24.1; 14q22-q24

Exon count:: 27

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (68874128..68979302, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (63083135..63188360, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (69340845..69446019, complement)

Chromosome 14 - NC_000014.9 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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

ACTN1-related thrombocytopenia: Homozygosity for an ACTN1 variant results in a more severe phenotype.
Title: ACTN1-related thrombocytopenia: Homozygosity for an ACTN1 variant results in a more severe phenotype.
Actinin BioID reveals sarcomere crosstalk with oxidative metabolism through interactions with IGF2BP2.
Title: Actinin BioID reveals sarcomere crosstalk with oxidative metabolism through interactions with IGF2BP2.
alpha-Actinin1 promotes tumorigenesis and epithelial-mesenchymal transition of gastric cancer via the AKT/GSK3beta/beta-Catenin pathway.
Title: α-Actinin1 promotes tumorigenesis and epithelial-mesenchymal transition of gastric cancer via the AKT/GSK3β/β-Catenin pathway.
Distinct forms of the actin cross-linking protein alpha-actinin support macropinosome internalization and trafficking.
Title: Distinct forms of the actin cross-linking protein α-actinin support macropinosome internalization and trafficking.
Enhancement of cardiac contractility using gold-coated SU-8 cantilevers and their application to drug-induced cardiac toxicity tests.
Title: Enhancement of cardiac contractility using gold-coated SU-8 cantilevers and their application to drug-induced cardiac toxicity tests.
ACTN1 supports tumor growth by inhibiting Hippo signaling in hepatocellular carcinoma.
Title: ACTN1 supports tumor growth by inhibiting Hippo signaling in hepatocellular carcinoma.
High ACTN1 Is Associated with Poor Prognosis, and ACTN1 Silencing Suppresses Cell Proliferation and Metastasis in Oral Squamous Cell Carcinoma.
Title: High ACTN1 Is Associated with Poor Prognosis, and ACTN1 Silencing Suppresses Cell Proliferation and Metastasis in Oral Squamous Cell Carcinoma.
The G764S and E769K mutations increase cytoskeletal association of actinin in cells, and all mutant proteins colocalize with F-actin in cultured HeLa cells.
Title: Investigation of calmodulin-like and rod domain mutations suggests common molecular mechanism for α-actinin-1-linked congenital macrothrombocytopenia.
Report identifies 11 new variants in ACTN1 gene providing significant insight into the mechanisms of ACTN1-related thrombocytopenia (ACTN1-RT) and highlights the high frequency of congenital ACTN1 variants as a cause of inherited thrombocytopenia. The rod domain in ACTN1 may harbor variants resulting in actin disorganization in vitro and thrombocytopenia with normal platelet size in most cases.
Title: Novel ACTN1 variants in cases of thrombocytopenia.
Hematopoietic cell-specific Lyn substrate, HCLS1, is a versatile actin-binding protein in leukocytes. (Review)
Title: Hematopoietic cell-specific lyn substrate (HCLS1 or HS1): A versatile actin-binding protein in leukocytes.

Submit: New GeneRIF Correction See all GeneRIFs (71)

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
Platelet-type bleeding disorder 15 MedGen: C3554663 OMIM: 615193 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide and candidate gene association study of cigarette smoking behaviors. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of chronic periodontitis in a general German population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. EBI GWAS Catalog EBI GWAS CatalogPubMed
Multiethnic meta-analysis of genome-wide association studies in &gt;100 000 subjects identifies 23 fibrinogen-associated Loci but no strong evidence of a causal association between circulating fibrinogen and cardiovascular disease. 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)

Protein	Gene	Interaction	Pubs
Vpr	vpr	HIV-1 Vpr upregulates ACTN1 in HeLa cells within 12 hours of exposure	PubMed
retropepsin	gag-pol	Alpha-actinin is cleaved in vitro by HIV-1 protease at amino acid residues 166-167 and 471-472	PubMed

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D10S275 (e-PCR)
- UniSTS:147992

D14S1222 (e-PCR)
- UniSTS:70425

D14S1312 (e-PCR)
- UniSTS:34350

L18426 (e-PCR)
- UniSTS:34648

RH48588 (e-PCR)
- UniSTS:50527

SHGC-58252 (e-PCR)
- UniSTS:54125

Actn1 (e-PCR), detects polymorphism
- UniSTS:228474

RH93083 (e-PCR)
- UniSTS:89223

MARC_17931-17932:1024341335:5 (e-PCR)
- UniSTS:268442

D14S939 (e-PCR)
- UniSTS:53667

ECD17402 (e-PCR)
- UniSTS:298415

D14S931 (e-PCR)
- UniSTS:77003

RH67009 (e-PCR)
- UniSTS:84442

STS-D29544 (e-PCR)
- UniSTS:35580

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables actin binding	IEA Inferred from Electronic Annotation more info
enables actin filament binding	IBA Inferred from Biological aspect of Ancestor more info
enables actin filament binding	IDA Inferred from Direct Assay more info	PubMed
enables actin filament binding	IEA Inferred from Electronic Annotation more info
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables double-stranded RNA binding	IDA Inferred from Direct Assay more info	PubMed
enables integrin binding	IDA Inferred from Direct Assay more info	PubMed
enables integrin binding	IEA Inferred from Electronic Annotation more info
enables integrin binding	IPI Inferred from Physical Interaction more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
enables protein homodimerization activity	IEA Inferred from Electronic Annotation more info
enables structural constituent of postsynapse	IDA Inferred from Direct Assay more info	PubMed
enables structural constituent of postsynapse	IMP Inferred from Mutant Phenotype more info	PubMed
enables transcription coactivator activity	IDA Inferred from Direct Assay more info	PubMed
enables transmembrane transporter binding	IPI Inferred from Physical Interaction more info	PubMed
enables vinculin binding	IDA Inferred from Direct Assay more info	PubMed
enables vinculin binding	IEA Inferred from Electronic Annotation more info
enables vinculin 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 bundle assembly	IEA Inferred from Electronic Annotation more info
involved_in actin filament network formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in actin filament organization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in focal adhesion assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in muscle cell development	IBA Inferred from Biological aspect of Ancestor more info
NOT involved_in platelet activation	IMP Inferred from Mutant Phenotype more info	PubMed
NOT involved_in platelet aggregation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in platelet formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in platelet morphogenesis	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 postsynapse organization	IEA Inferred from Electronic Annotation more info
involved_in regulation of apoptotic process	NAS Non-traceable Author Statement 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 Z disc	IEA Inferred from Electronic Annotation more info
located_in actin cytoskeleton	IEA Inferred from Electronic Annotation more info
colocalizes_with actin filament	IDA Inferred from Direct Assay more info	PubMed
located_in anchoring junction	IEA Inferred from Electronic Annotation more info
located_in brush border	IEA Inferred from Electronic Annotation more info
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
located_in cell projection	IDA Inferred from Direct Assay more info	PubMed
located_in cell projection	IEA Inferred from Electronic Annotation more info
located_in cell-cell junction	IDA Inferred from Direct Assay more info	PubMed
is_active_in cortical actin cytoskeleton	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IEA Inferred from Electronic Annotation more info
located_in cytoskeleton	IEA Inferred from Electronic Annotation more info
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	HDA more info	PubMed
located_in fascia adherens	IEA Inferred from Electronic Annotation more info
located_in focal adhesion	HDA more info	PubMed
located_in focal adhesion	IDA Inferred from Direct Assay more info	PubMed
located_in focal adhesion	IMP Inferred from Mutant Phenotype more info	PubMed
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
is_active_in glutamatergic synapse	IMP Inferred from Mutant Phenotype more info	PubMed
located_in membrane	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
located_in platelet alpha granule lumen	TAS Traceable Author Statement more info
located_in pseudopodium	TAS Traceable Author Statement more info	PubMed
located_in ruffle	IDA Inferred from Direct Assay more info	PubMed
located_in ruffle	IEA Inferred from Electronic Annotation more info
located_in sarcomere	IEA Inferred from Electronic Annotation more info
is_active_in stress fiber	IBA Inferred from Biological aspect of Ancestor more info
located_in stress fiber	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with stress fiber	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: alpha-actinin-1

Names: F-actin cross-linking protein; actinin 1 smooth muscle; epididymis secretory sperm binding protein; non-muscle alpha-actinin-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_029480.1 RefSeqGene

Range

5001..110244

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_886

mRNA and Protein(s)

NM_001102.4 → NP_001093.1 alpha-actinin-1 isoform b

See identical proteins and their annotated locations for NP_001093.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (b) has the same N- and C-termini but is shorter compared to isoform a.

Source sequence(s)

BC003576, BC004984, BI494856, DC321454

Consensus CDS

CCDS9792.1

UniProtKB/Swiss-Prot

B3V8S3, B4DHH3, B7TY16, P12814, Q1HE25, Q9BTN1

UniProtKB/TrEMBL

A0A024R694, A0A804HK61

Related

ENSP00000193403.6, ENST00000193403.11

Conserved Domains (6) summary

cd00051
Location:750 → 817

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:395 → 622

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:634 → 733

Spectrin; Spectrin repeat

pfam08726
Location:822 → 888

EFhand_Ca_insen; Ca2+ insensitive EF hand

cd21214
Location:28 → 132

CH_ACTN_rpt1; first calponin homology (CH) domain found in the alpha-actinin family

cd21216
Location:136 → 250

CH_ACTN_rpt2; second calponin homology (CH) domain found in the alpha-actinin family
NM_001130004.2 → NP_001123476.1 alpha-actinin-1 isoform a

See identical proteins and their annotated locations for NP_001123476.1

Status: REVIEWED

Description

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

Source sequence(s)

BC004984, BI494856, DC372566, DQ496098

Consensus CDS

CCDS45130.1

UniProtKB/TrEMBL

A0A804HII9

Related

ENSP00000377941.4, ENST00000394419.9

Conserved Domains (6) summary

cd00051
Location:750 → 839

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:395 → 622

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:634 → 733

Spectrin; Spectrin repeat

pfam08726
Location:844 → 910

EFhand_Ca_insen; Ca2+ insensitive EF hand

cd21214
Location:28 → 132

CH_ACTN_rpt1; first calponin homology (CH) domain found in the alpha-actinin family

cd21216
Location:136 → 250

CH_ACTN_rpt2; second calponin homology (CH) domain found in the alpha-actinin family
NM_001130005.2 → NP_001123477.1 alpha-actinin-1 isoform c

See identical proteins and their annotated locations for NP_001123477.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (c) has the same N- and C-termini but is shorter compared to isoform a.

Source sequence(s)

BC003576, BC004984, BI494856, DC321454, EU716325

Consensus CDS

CCDS45129.1

UniProtKB/TrEMBL

A0A804HK61

Related

ENSP00000414272.2, ENST00000438964.6

Conserved Domains (6) summary

COG5126
Location:743 → 847

FRQ1; Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms]

cd00176
Location:395 → 622

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:634 → 733

Spectrin; Spectrin repeat

pfam08726
Location:817 → 883

EFhand_Ca_insen; Ca2+ insensitive EF hand

cd21214
Location:28 → 132

CH_ACTN_rpt1; first calponin homology (CH) domain found in the alpha-actinin family

cd21216
Location:136 → 250

CH_ACTN_rpt2; second calponin homology (CH) domain found in the alpha-actinin family
NM_001411035.1 → NP_001397964.1 alpha-actinin-1 isoform d

Status: REVIEWED

Source sequence(s)

AL117694

Consensus CDS

CCDS91891.1

UniProtKB/TrEMBL

A0A7I2V4Y4, A0A804HK61

Related

ENSP00000504355.1, ENST00000679147.1
NM_001411036.1 → NP_001397965.1 alpha-actinin-1 isoform e

Status: REVIEWED

Source sequence(s)

AL117694

Consensus CDS

CCDS91890.1

UniProtKB/TrEMBL

A0A804HL31, B7Z565

Related

ENSP00000508177.1, ENST00000684182.1
NM_001424012.1 → NP_001410941.1 alpha-actinin-1 isoform f

Status: REVIEWED

Source sequence(s)

AL117694

UniProtKB/TrEMBL

A0A804HK61

Related

ENSP00000508301.1, ENST00000683342.1
NM_001424013.1 → NP_001410942.1 alpha-actinin-1 isoform g

Status: REVIEWED

Source sequence(s)

AL117694

UniProtKB/TrEMBL

A0A804HK61
NM_001424014.1 → NP_001410943.1 alpha-actinin-1 isoform h

Status: REVIEWED

Source sequence(s)

AL117694

UniProtKB/TrEMBL

A0A804HK61

Related

ENSP00000439828.2, ENST00000538545.6
NM_001424015.1 → NP_001410944.1 alpha-actinin-1 isoform i

Status: REVIEWED

Source sequence(s)

AL117694

UniProtKB/TrEMBL

A0A804HK61
NM_001424016.1 → NP_001410945.1 alpha-actinin-1 isoform j

Status: REVIEWED

Source sequence(s)

AL117694

UniProtKB/TrEMBL

A0A804HKE2
NM_001424017.1 → NP_001410946.1 alpha-actinin-1 isoform k

Status: REVIEWED

Source sequence(s)

AL117694

UniProtKB/TrEMBL

B7Z565
NM_001424018.1 → NP_001410947.1 alpha-actinin-1 isoform l

Status: REVIEWED

Source sequence(s)

AL117694

UniProtKB/TrEMBL

A0A804HKE2
NM_001424019.1 → NP_001410948.1 alpha-actinin-1 isoform m

Status: REVIEWED

Source sequence(s)

AL117694

UniProtKB/TrEMBL

A0A804HK61
NM_001424020.1 → NP_001410949.1 alpha-actinin-1 isoform n

Status: REVIEWED

Source sequence(s)

AL117694

UniProtKB/TrEMBL

A0A804HK61

Related

ENST00000682522.1
NM_001424021.1 → NP_001410950.1 alpha-actinin-1 isoform o

Status: REVIEWED

Source sequence(s)

AL117694

UniProtKB/TrEMBL

A0A804HK61
NM_001424022.1 → NP_001410951.1 alpha-actinin-1 isoform p

Status: REVIEWED

Source sequence(s)

AL117694

UniProtKB/TrEMBL

B7Z565
NM_001424023.1 → NP_001410952.1 alpha-actinin-1 isoform q

Status: REVIEWED

Source sequence(s)

AL117694

UniProtKB/TrEMBL

A0A804HK61
NM_001424024.1 → NP_001410953.1 alpha-actinin-1 isoform r

Status: REVIEWED

Source sequence(s)

AL117694

UniProtKB/TrEMBL

A0A804HII9
NM_001424025.1 → NP_001410954.1 alpha-actinin-1 isoform s

Status: REVIEWED

Source sequence(s)

AL117694

UniProtKB/TrEMBL

A0A804HK61
NM_001424026.1 → NP_001410955.1 alpha-actinin-1 isoform e

Status: REVIEWED

Source sequence(s)

AL117694

UniProtKB/TrEMBL

A0A804HL31, B7Z565
NM_001424027.1 → NP_001410956.1 alpha-actinin-1 isoform t

Status: REVIEWED

Source sequence(s)

AL117694

UniProtKB/TrEMBL

A0A804HK61, A0A804HLF4

Related

ENSP00000508329.1, ENST00000682331.1
NM_001424028.1 → NP_001410957.1 alpha-actinin-1 isoform u

Status: REVIEWED

Source sequence(s)

AL117694

UniProtKB/TrEMBL

B7Z565, H9KV75

Related

ENSP00000366035.3, ENST00000376839.7
NM_001424029.1 → NP_001410958.1 alpha-actinin-1 isoform v

Status: REVIEWED

Source sequence(s)

AL117694

UniProtKB/TrEMBL

A0A804HK61
NM_001424030.1 → NP_001410959.1 alpha-actinin-1 isoform w

Status: REVIEWED

Source sequence(s)

AL117694

UniProtKB/TrEMBL

B4DFY0