ACTN4 actinin alpha 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ACTN4provided by HGNC
Official Full Name: actinin alpha 4provided by HGNC
Primary source: HGNC:HGNC:166
See related: Ensembl:ENSG00000130402 MIM:604638; AllianceGenome:HGNC:166
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: FSGS; FSGS1; ACTININ-4
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, alpha actinin isoform which is concentrated in the cytoplasm, and thought to be involved in metastatic processes. Mutations in this gene have been associated with focal and segmental glomerulosclerosis. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in placenta (RPKM 105.3), kidney (RPKM 104.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 19q13.2

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (38647649..38731589)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (41451629..41535643)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (39138289..39222229)

Chromosome 19 - NC_000019.10 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 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?

Association of ACTN4 Gene Mutation with Primary Nephrotic Syndrome in Children in Guangxi Autonomous Region, China.
Title: Association of ACTN4 Gene Mutation with Primary Nephrotic Syndrome in Children in Guangxi Autonomous Region, China.
Actinin-4 controls survival signaling in B cells by limiting the lateral mobility of B-cell antigen receptors.
Title: Actinin-4 controls survival signaling in B cells by limiting the lateral mobility of B-cell antigen receptors.
Protein tyrosine phosphatase 1B is a regulator of alpha-actinin4 in the glomerular podocyte.
Title: Protein tyrosine phosphatase 1B is a regulator of alpha-actinin4 in the glomerular podocyte.
PHF23 promotes NSCLC proliferation, metastasis, and chemoresistance via stabilization of ACTN4 and activation of the ERK pathway.
Title: PHF23 promotes NSCLC proliferation, metastasis, and chemoresistance via stabilization of ACTN4 and activation of the ERK pathway.
Analysis of the association of NPHS2 and ACTN4 genes polymorphism with nephrotic syndrome in Egyptian children.
Title: Analysis of the association of NPHS2 and ACTN4 genes polymorphism with nephrotic syndrome in Egyptian children.
Single Nucleotide Polymorphism rs9277336 Controls the Nuclear Alpha Actinin 4-Human Leukocyte Antigen-DPA1 Axis and Pulmonary Endothelial Pathophenotypes in Pulmonary Arterial Hypertension.
Title: Single Nucleotide Polymorphism rs9277336 Controls the Nuclear Alpha Actinin 4-Human Leukocyte Antigen-DPA1 Axis and Pulmonary Endothelial Pathophenotypes in Pulmonary Arterial Hypertension.
Alpha-actnin-4 (ACTN4) selectively affects the DNA double-strand breaks repair in non-small lung carcinoma cells.
Title: Alpha-actnin-4 (ACTN4) selectively affects the DNA double-strand breaks repair in non-small lung carcinoma cells.
Hsa_circ_0097922 promotes tamoxifen resistance and cell malignant behaviour of breast cancer cells by regulating ACTN4 expression via miR-876-3p.
Title: Hsa_circ_0097922 promotes tamoxifen resistance and cell malignant behaviour of breast cancer cells by regulating ACTN4 expression via miR-876-3p.
C-Mannosylated tryptophan-containing WSPW peptide binds to actinin-4 and alters E-cadherin subcellular localization in lung epithelial-like A549 cells.
Title: C-Mannosylated tryptophan-containing WSPW peptide binds to actinin-4 and alters E-cadherin subcellular localization in lung epithelial-like A549 cells.
The deubiquitinase OTUD3 stabilizes ACTN4 to drive growth and metastasis of hepatocellular carcinoma.
Title: The deubiquitinase OTUD3 stabilizes ACTN4 to drive growth and metastasis of hepatocellular carcinoma.

Submit: New GeneRIF Correction See all GeneRIFs (133)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Focal segmental glomerulosclerosis 1 MedGen: C4551527 OMIM: 603278 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide meta-analysis identifies new susceptibility loci for migraine. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders. 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)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope transmembrane glycoprotein gp41	env	The interaction of the long cytoplasmic tail of HIV-1 gp41 with the carboxy-terminal regulatory domain of p115-RhoGEF inhibits p115-mediated actin stress fiber formation and activation of serum response factor (SRF)	PubMed
Vpr	vpr	HIV-1 Vpr upregulates ACTN4 in HeLa cells within 12 hours of exposure	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-145914 (e-PCR)
- UniSTS:174874

A008Q24 (e-PCR)
- UniSTS:5922

RH35900 (e-PCR)
- UniSTS:49249

SHGC-16522 (e-PCR)
- UniSTS:66920

MARC_12245-12246:1008698037:1 (e-PCR)
- UniSTS:267380

MARC_12245-12246:1043934929:1 (e-PCR)
- UniSTS:267380

D19S1071 (e-PCR)
- UniSTS:14453

Actn4 (e-PCR), detects polymorphism
- UniSTS:228477

D19S589 (e-PCR)
- UniSTS:49296

WI-17325 (e-PCR)
- UniSTS:41621

RH16012 (e-PCR)
- UniSTS:20642

D19S422 (e-PCR), detects polymorphism
- UniSTS:13754

D4S439E (e-PCR)
- UniSTS:147389

SHGC-145808 (e-PCR)
- UniSTS:174804

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables RNA binding	HDA more info	PubMed
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables actin binding	TAS Traceable Author Statement more info	PubMed
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	IMP Inferred from Mutant Phenotype more info	PubMed
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables chromatin DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables integrin binding	TAS Traceable Author Statement more info	PubMed
enables nuclear receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables nuclear receptor coactivator activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables nuclear retinoic acid receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables nucleoside binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables transcription coactivator activity	IMP Inferred from Mutant Phenotype 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 muscle cell development	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of substrate adhesion-dependent cell spreading	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in peroxisome proliferator activated receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of non-canonical NF-kappaB signal transduction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of sodium:proton antiporter activity	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein transport	IEA Inferred from Electronic Annotation more info
involved_in regulation of apoptotic process	NAS Non-traceable Author Statement more info	PubMed
involved_in retinoic acid receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in tumor necrosis factor-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in vesicle transport along actin filament	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
colocalizes_with actin cytoskeleton	IDA Inferred from Direct Assay more info	PubMed
located_in actin cytoskeleton	IDA Inferred from Direct Assay 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 cytoplasm	HDA more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
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 focal adhesion	HDA more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in perinuclear region of cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in platelet alpha granule lumen	TAS Traceable Author Statement more info
is_active_in postsynaptic actin cytoskeleton	IDA Inferred from Direct Assay more info	PubMed
is_active_in postsynaptic actin cytoskeleton	IMP Inferred from Mutant Phenotype more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
located_in pseudopodium	TAS Traceable Author Statement more info	PubMed
part_of ribonucleoprotein complex	IDA Inferred from Direct Assay more info	PubMed
located_in stress fiber	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: alpha-actinin-4

Names: focal segmental glomerulosclerosis 1; non-muscle alpha-actinin 4

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_007082.2 RefSeqGene

Range

4963..88903

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001322033.2 → NP_001308962.1 alpha-actinin-4 isoform 2

Status: REVIEWED

Source sequence(s)

AC008649, AC022144, BM841805, HY048627, R66605

Consensus CDS

CCDS92611.1

UniProtKB/TrEMBL

A0A8V8TL71, H7C144

Related

ENSP00000398393.2, ENST00000440400.3

Conserved Domains (5) summary

COG5126
Location:762 → 866

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

cd00176
Location:414 → 640

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; ...

pfam08726
Location:836 → 902

EFhand_Ca_insen; Ca2+ insensitive EF hand

cd21214
Location:47 → 151

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

cd21216
Location:155 → 269

CH_ACTN_rpt2; second calponin homology (CH) domain found in the alpha-actinin family
NM_001411143.1 → NP_001398072.1 alpha-actinin-4 isoform 3

Status: REVIEWED

Source sequence(s)

AC008649, AC022144

Consensus CDS

CCDS92610.1

UniProtKB/TrEMBL

F5GXS2

Related

ENSP00000411187.4, ENST00000424234.7
NM_004924.6 → NP_004915.2 alpha-actinin-4 isoform 1

See identical proteins and their annotated locations for NP_004915.2

Status: REVIEWED

Source sequence(s)

AC022144, BC005033, BM841805, HY048627, R66605

Consensus CDS

CCDS12518.1

UniProtKB/Swiss-Prot

A4K467, D6PXK4, O43707, O76048

UniProtKB/TrEMBL

A0A0S2Z3G9, A0A8V8TL71

Related

ENSP00000252699.2, ENST00000252699.7

Conserved Domains (5) summary

PTZ00184
Location:759 → 868

PTZ00184; calmodulin; Provisional

cd00176
Location:414 → 640

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; ...

pfam08726
Location:841 → 907

EFhand_Ca_insen; Ca2+ insensitive EF hand

cd21214
Location:47 → 151

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

cd21216
Location:155 → 269

CH_ACTN_rpt2; second calponin homology (CH) domain found in the alpha-actinin family

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

38647649..38731589

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017027331.3 → XP_016882820.1 alpha-actinin-4 isoform X2

UniProtKB/TrEMBL

A0A8V8TL71

Conserved Domains (5) summary

PTZ00184
Location:759 → 890

PTZ00184; calmodulin; Provisional

cd00176
Location:414 → 640

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; ...

pfam08726
Location:863 → 929

EFhand_Ca_insen; Ca2+ insensitive EF hand

cd21214
Location:47 → 151

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

cd21216
Location:155 → 269

CH_ACTN_rpt2; second calponin homology (CH) domain found in the alpha-actinin family
XM_005259281.6 → XP_005259338.1 alpha-actinin-4 isoform X1

See identical proteins and their annotated locations for XP_005259338.1

UniProtKB/TrEMBL

A0A8V8TL71

Conserved Domains (5) summary

COG5126
Location:762 → 866

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

cd00176
Location:414 → 640

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; ...

pfam08726
Location:836 → 902

EFhand_Ca_insen; Ca2+ insensitive EF hand

cd21214
Location:47 → 151

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

cd21216
Location:155 → 269

CH_ACTN_rpt2; second calponin homology (CH) domain found in the alpha-actinin family