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ACTN4 actinin alpha 4 [ Homo sapiens (human) ]

Gene ID: 81, updated on 12-Aug-2022

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
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Genomic context

See ACTN4 in Genome Data Viewer
Location:
19q13.2
Exon count:
23
Annotation release Status Assembly Chr Location
110 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (38647649..38731589)
110 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (41451629..41535643)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (39138289..39222229)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene MAP4K1 antisense RNA 1 Neighboring gene mitogen-activated protein kinase kinase kinase kinase 1 Neighboring gene eukaryotic translation initiation factor 3 subunit K Neighboring gene Sharpr-MPRA regulatory region 11915 Neighboring gene Sharpr-MPRA regulatory region 8317 Neighboring gene uncharacterized LOC107985291 Neighboring gene uncharacterized LOC124904711 Neighboring gene calpain 12 Neighboring gene galectin 7

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

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
Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.
EBI GWAS Catalog

HIV-1 interactions

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

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • DKFZp686K23158

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables RNA binding HDA 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
PubMed 
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 N-terminus binding IEA
Inferred from Electronic Annotation
more info
 
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
PubMed 
involved_in muscle cell development IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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 DNA-templated transcription IEA
Inferred from Electronic Annotation
more info
 
involved_in positive regulation of NIK/NF-kappaB signaling IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in positive regulation of cell migration 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 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 regulation of nucleic acid-templated transcription IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in response to hypoxia IEA
Inferred from Electronic Annotation
more info
 
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
PubMed 
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
PubMed 
is_active_in cell projection IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
is_active_in cortical actin cytoskeleton IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
located_in cytoplasm HDA PubMed 
located_in cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
located_in cytosol IDA
Inferred from Direct Assay
more info
 
located_in extracellular exosome HDA PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
 
located_in extracellular space HDA PubMed 
located_in focal adhesion HDA PubMed 
located_in neuron projection IEA
Inferred from Electronic Annotation
more info
 
located_in nuclear body IDA
Inferred from Direct Assay
more info
 
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
PubMed 
located_in platelet alpha granule lumen TAS
Traceable Author Statement
more info
 
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 
is_active_in stress fiber IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 

General protein information

Preferred Names
alpha-actinin-4
Names
focal segmental glomerulosclerosis 1
non-muscle alpha-actinin 4

NCBI Reference Sequences (RefSeq)

NEW Try the new Transcript table

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

  1. NG_007082.2 RefSeqGene

    Range
    4963..88903
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

    Status: REVIEWED

    Source sequence(s)
    AC008649, AC022144, BM841805, HY048627, R66605
    UniProtKB/TrEMBL
    H7C144
    Related
    ENSP00000398393.2, ENST00000440400.2
    Conserved Domains (5) summary
    COG5126
    Location:762866
    FRQ1; Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms]
    cd00176
    Location:414640
    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:836902
    EFhand_Ca_insen; Ca2+ insensitive EF hand
    cd21214
    Location:47151
    CH_ACTN_rpt1; first calponin homology (CH) domain found in the alpha-actinin family
    cd21216
    Location:155269
    CH_ACTN_rpt2; second calponin homology (CH) domain found in the alpha-actinin family
  2. NM_004924.6NP_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
    O43707, O76048
    UniProtKB/TrEMBL
    A0A0S2Z3G9
    Related
    ENSP00000252699.2, ENST00000252699.7
    Conserved Domains (5) summary
    PTZ00184
    Location:759868
    PTZ00184; calmodulin; Provisional
    cd00176
    Location:414640
    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:841907
    EFhand_Ca_insen; Ca2+ insensitive EF hand
    cd21214
    Location:47151
    CH_ACTN_rpt1; first calponin homology (CH) domain found in the alpha-actinin family
    cd21216
    Location:155269
    CH_ACTN_rpt2; second calponin homology (CH) domain found in the alpha-actinin family

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 110 details...Open this link in a new tab

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

    Range
    38647649..38731589
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017027331.3XP_016882820.1  alpha-actinin-4 isoform X3

    Conserved Domains (5) summary
    PTZ00184
    Location:759890
    PTZ00184; calmodulin; Provisional
    cd00176
    Location:414640
    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:863929
    EFhand_Ca_insen; Ca2+ insensitive EF hand
    cd21214
    Location:47151
    CH_ACTN_rpt1; first calponin homology (CH) domain found in the alpha-actinin family
    cd21216
    Location:155269
    CH_ACTN_rpt2; second calponin homology (CH) domain found in the alpha-actinin family
  2. XM_005259281.6XP_005259338.1  alpha-actinin-4 isoform X2

    See identical proteins and their annotated locations for XP_005259338.1

    Conserved Domains (5) summary
    COG5126
    Location:762866
    FRQ1; Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms]
    cd00176
    Location:414640
    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:836902
    EFhand_Ca_insen; Ca2+ insensitive EF hand
    cd21214
    Location:47151
    CH_ACTN_rpt1; first calponin homology (CH) domain found in the alpha-actinin family
    cd21216
    Location:155269
    CH_ACTN_rpt2; second calponin homology (CH) domain found in the alpha-actinin family
  3. XM_006723406.4XP_006723469.1  alpha-actinin-4 isoform X1

    See identical proteins and their annotated locations for XP_006723469.1

    UniProtKB/TrEMBL
    F5GXS2
    Related
    ENSP00000411187.4, ENST00000424234.7
    Conserved Domains (5) summary
    PTZ00184
    Location:759868
    PTZ00184; calmodulin; Provisional
    cd00176
    Location:414640
    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:841907
    EFhand_Ca_insen; Ca2+ insensitive EF hand
    cd21214
    Location:47151
    CH_ACTN_rpt1; first calponin homology (CH) domain found in the alpha-actinin family
    cd21216
    Location:155269
    CH_ACTN_rpt2; second calponin homology (CH) domain found in the alpha-actinin family

Reference GRCh38.p14 PATCHES

Genomic

  1. NW_014040929.1 Reference GRCh38.p14 PATCHES

    Range
    57285..141225
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060943.1 Alternate T2T-CHM13v2.0

    Range
    41451629..41535643
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)