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FLASH GENE
Symbol ACTN4 contributors: mct - updated : 03-02-2015
HGNC name actinin, alpha 4
HGNC id 166
Corresponding disease
FSGS1 focal segmental glomerulosclerosis 1
Location 19q13.2      Physical location : 39.138.326 - 39.221.170
Synonym name
  • actinin alpha4 isoform
  • non muscle cell actin-binding protein
  • F-actin cross-linking protein
  • Synonym symbol(s) FSGS, DKFZp686K23158, FSGS1
    DNA
    TYPE functioning gene
    STRUCTURE 82.84 kb     21 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - D19S222 - D19S213 - D19S416 - D19S208 - D19S191 - D19S609 - D19S610 - D19S224 - D19S220 - D19S228 - D19S422 - ACTN4 - D19S190 - D19S200 - D19S223 - D19S420 - qter
    Authors Kaplan (00)
    Physical map
    PPP1R14A 19q13.13-q13.2 protein phosphatase 1, regulatory (inhibitor) subunit 14A SPINT2 19q13.1 serine protease inhibitor, Kunitz type, 2 IMUP 19q13.13 serine protease inhibitor, Kunitz type, 2 LOC90522 19q13.13 similar to putative transmembrane protein; homolog of yeast Golgi membrane protein Yif1p (Yip1p-interacting factor) KCNK6 19q13.1 potassium channel, subfamily K, member 6 DKFZP434A1022 PSMD8 19q13.13 proteasome (prosome, macropain) 26S subunit, non-ATPase, 8 GGN 19q13.13 gametogenetin LOC388538 19 similar to SPRED-3 LOC147965 19q13.2 hypothetical protein LOC147965 RASGRP4 19q13.1 RAS guanyl releasing protein 4 RYR1 19q13.1 ryanodine receptor 1 (skeletal) MAP4K1 19q13.2 mitogen-activated protein kinase kinase kinase kinase 1 eIF3k 19q13.2 mitogen-activated protein kinase kinase kinase kinase 1 ACTN4 19q13 actinin, alpha 4 CAPN12 19q13.2 calpain 12 LGALS7 19q13.2 lectin, galactoside-binding, soluble, 7 (galectin 7) LGALS4 19q13.2 lectin, galactoside-binding, soluble, 4 (galectin 4) ECH1 19q13.1 enoyl Coenzyme A hydratase 1, peroxisomal HNRPL 19q13.2 heterogeneous nuclear ribonucleoprotein L FLJ45909 19q13.2 FLJ45909 protein SIRT2 19q13 sirtuin (silent mating type information regulation 2 homolog) 2 (S. cerevisiae) NFKBIB 19q13.1 nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, beta LOC388539 19 LOC388539 SARS2 19q13.2 seryl-tRNA synthetase 2 MRPS12 19q13.11 mitochondrial ribosomal protein S12 FBXO26 19q13.2 F-box only protein 26
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 - 3893 - 911 - 2012 22908231
  • possess an unusual LXXLL nuclear receptor interacting motif
  • interact with ESR1, although ACTN4 (Iso) binds ESR1 more strongly
  • - splicing - - - - 2012 22908231
  • possess an unusual LXXLL nuclear receptor interacting motif
  • interact with ESR1, more strongly as full length
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon highly
     mouthtongue  highly
    Reproductivefemale systembreastmammary gland highly
    Urinarykidneynephron  highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Muscularsmooth   
    Muscularstriatumcardiac  
    Muscularstriatumskeletal  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Urinarypodocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period fetal
    Text restricted domain of developing CNS
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two calponin homology domain in the N terminal region
  • tyrosine residue at position 49 of homeodomain
  • helix turn helix protein (homeobox)
  • extended LXXLL motif that is critical for interactions with both receptors and co-activators
  • three actin-binding sites (ABSs), designated ABS1, ABS2, and ABS3
  • five spectrin repeats and two EF-hands in the C terminal region, and C-terminal tail is essential for maintaining its normal actin binding activity and localization within cytoplasm and also its colocalization with actin in the lamellipodia of locomoting fibroblasts
  • HOMOLOGY
    interspecies ortholog to murine Actn4
    Homologene
    FAMILY
  • actin family
  • CATEGORY motor/contractile , structural protein
    SUBCELLULAR LOCALIZATION extracellular
        plasma membrane,junction,adherens
        intracellular
    intracellular,cytoplasm,cytoskeleton,microfilament
    intracellular,nucleus
    text
  • microfilament bundles and adherens-type junctions in non muscle cells
  • abundant in the actin cytoskeleton
  • also nuclear localization
  • localized predominantly in the cytoskeleton, ACTN4 is also found in the nucleus of certain cell types , is also able to translocate from the cytosol into the nucleus in response to extracellular stimuli
  • resides both in the cytoplasm and nucleus and physically associates with various transcription factors
  • basic FUNCTION
  • regulating in the cytoplasm the actin cytoskeleton and increasing cellular motility
  • playing a role in the metastatic potential of cancers
  • with ACTN1 are differentially regulated during the development and progression of astrocytomas because each of these isoforms uniquely contributes to distinct malignant properties of astrocytoma cells
  • with ACTN1 make critical and distinct contributions to cytoskeletal organization, rigidity-sensing, and motility of glioma cells
  • in the cytoplasm, participates in structural organisation of the cytoskeleton via cross-linking of actin filaments
  • likely, nuclear ACTN4 plays role in pre-mRNA packaging, maturation and trafficking
  • plays an important role in coupling actin nucleation to assembly at cadherin-based cell-cell adhesive contacts
  • function of ACTN4 in nuclear receptor-mediated transcriptional activation in kidney podocytes
  • may have a general role in regulating nuclear hormone receptor responses
  • role for actinin-4 in regulating the steering mechanism of keratinocytes via profound effects on their matrix adhesion sites
  • actin-binding protein that participates in cytoskeleton organisation
  • is essential for normal glomerular function in the kidney
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • component of the slit membrane of the glomerular podocytes
  • FHL1 exists as part of a complex that binds with PDLIM1, GSN and ACTN1
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • contributes to SLC2A4 traffic, likely by tethering SLCV2A4 vesicles to the cortical actin cytoskeleton
  • association of ACTN4 with different ribonucleoproteins suggests that a major function of nuclear ACTN4 may be regulation of mRNA metabolism and signaling
  • correlation between the levels of ACTN4 and PDLIM1, which form a complex in normal podocytes, in human glomerular diseases
  • ACTN4 interacts with and enhances transcriptional activation by RARA
  • suppresses cell migration, at least partially, by inhibiting ACTN4 function
  • KNG1, through its domain 5 inhibits collagen-mediated cancer cell adhesion and invasion in association with ACTN4
  • associates with various transcription factors
  • in the nucleus, ACTN4 functions as a selective transcriptional co-activator of RELA
  • SLK interacts with TPR and ACTN4 in cells, and these protein-protein interactions may control the subcellular localization and the biological activity of SLK
  • PDLIM1 negatively regulates NFKB1-mediated signaling in the cytoplasm (PDLIM1 sequestered p65 subunit of NFKB1 in the cytoplasm and suppressed its nuclear translocation in an NFKBIA-independent, but ACTN4-dependent manner
  • cell & other
    REGULATION
    Other anchored to particular cell domains through interaction of RNF22 to alpha-actinin 4 (ACTN4)
    phosphorylated on tyrosine residues after stimulation with EGF, although ACTN4 was phosphorylated to the greater extent as ACTN1 (EGF regulates the actin binding activity of ACTN4 by inducing tyrosyl-directed phosphorylation)
    ASSOCIATED DISORDERS
    corresponding disease(s) FSGS1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   LOH    
    in neuroblastoma cells
    tumoral     --over  
    in high-grade astrocytomas compared to normal brains and low grade astrocytomas
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS