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    ACTN4 actinin alpha 4 [ Homo sapiens (human) ]

    Gene ID: 81, updated on 1-Mar-2024

    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
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See ACTN4 in Genome Data Viewer
    Location:
    19q13.2
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (38647649..38731589)
    RS_2023_10 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 H3K4me1 hESC enhancer GRCh37_chr19:39087374-39087874 Neighboring gene MAP4K1 antisense RNA 1 Neighboring gene mitogen-activated protein kinase kinase kinase kinase 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:39098110-39098610 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:39098611-39099111 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:39103339-39103839 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14579 Neighboring gene NANOG hESC enhancer GRCh37_chr19:39112860-39113720 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:39114367-39114868 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr19:39121815-39122606 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr19:39122654-39123853 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39125282-39126240 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39127485-39128424 Neighboring gene eukaryotic translation initiation factor 3 subunit K Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39130305-39131243 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10578 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10579 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:39139812-39140010 Neighboring gene Sharpr-MPRA regulatory region 11915 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14582 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39142765-39143374 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39143375-39143983 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:39144522-39145390 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr19:39145391-39146259 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10580 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:39148471-39149116 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39150898-39151588 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39155729-39156418 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39156419-39157108 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39157109-39157798 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14583 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14584 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14585 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14586 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14587 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:39168839-39169424 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39173979-39174762 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14589 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14590 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39184359-39184950 Neighboring gene uncharacterized LOC107985291 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:39193145-39193645 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39195255-39196024 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:39198444-39199230 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:39208396-39209241 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:39209276-39209996 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:39217269-39218152 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14592 Neighboring gene uncharacterized LOC124904711 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10581 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10582 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14593 Neighboring gene calpain 12 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10583 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

    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
     
    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 
    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 PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    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 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
     
    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

    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
      Consensus CDS
      CCDS92611.1
      UniProtKB/TrEMBL
      A0A8V8TL71, H7C144
      Related
      ENSP00000398393.2, ENST00000440400.3
      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_001411143.1NP_001398072.1  alpha-actinin-4 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AC008649, AC022144
      Consensus CDS
      CCDS92610.1
      UniProtKB/TrEMBL
      A0A8V8TL71, F5GXS2
      Related
      ENSP00000411187.4, ENST00000424234.7
    3. 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
      A4K467, D6PXK4, O43707, O76048
      UniProtKB/TrEMBL
      A0A0S2Z3G9, A0A8V8TL71
      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: GCF_000001405.40-RS_2023_10

    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 X2

      UniProtKB/TrEMBL
      A0A8V8TL71
      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 X1

      See identical proteins and their annotated locations for XP_005259338.1

      UniProtKB/TrEMBL
      A0A8V8TL71
      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

    Reference GRCh38.p14 PATCHES

    Genomic

    1. NW_014040929.1 Reference GRCh38.p14 PATCHES

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

    mRNA and Protein(s)

    1. XM_054331975.1XP_054187950.1  alpha-actinin-4 isoform X2

      UniProtKB/TrEMBL
      A0A8V8TL71
    2. XM_054331974.1XP_054187949.1  alpha-actinin-4 isoform X1

      UniProtKB/TrEMBL
      A0A8V8TL71

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

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

    mRNA and Protein(s)

    1. XM_054322244.1XP_054178219.1  alpha-actinin-4 isoform X2

      UniProtKB/TrEMBL
      A0A8V8TL71
    2. XM_054322243.1XP_054178218.1  alpha-actinin-4 isoform X1

      UniProtKB/TrEMBL
      A0A8V8TL71