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Aliases for ACTN4 Gene

Aliases for ACTN4 Gene

  • Actinin, Alpha 4 2 3
  • Focal Segmental Glomerulosclerosis 1 2 3
  • Non-Muscle Alpha-Actinin 4 3 4
  • FSGS1 3 6
  • FSGS 3 6
  • F-Actin Cross-Linking Protein 3
  • Actinin Alpha4 Isoform 3
  • Alpha-Actinin-4 3
  • ACTININ-4 3

External Ids for ACTN4 Gene

Previous Symbols for ACTN4 Gene

  • FSGS1

Summaries for ACTN4 Gene

Entrez Gene Summary for ACTN4 Gene

  • 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]

GeneCards Summary for ACTN4 Gene

ACTN4 (Actinin, Alpha 4) is a Protein Coding gene. Diseases associated with ACTN4 include glomerulosclerosis and glomerulosclerosis, focal segmental, 1. Among its related pathways are Regulation of actin cytoskeleton and ERK Signaling. GO annotations related to this gene include calcium ion binding and actin binding. An important paralog of this gene is ACTN2.

UniProtKB/Swiss-Prot for ACTN4 Gene

  • F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (Probable). Probably involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation (PubMed:15772161). Involved in tight junction assembly in epithelial cells probably through interaction with MICALL2. Links MICALL2 to the actin cytoskeleton and recruits it to the tight junctions (By similarity). May also function as a transcriptional coactivator, stimulating transcription mediated by the nuclear hormone receptors PPARG and RARA (PubMed:22351778).

Gene Wiki entry for ACTN4 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for ACTN4 Gene

Genomics for ACTN4 Gene

Genomic Location for ACTN4 Gene

Start:
38,647,616 bp from pter
End:
38,731,583 bp from pter
Size:
83,968 bases
Orientation:
Plus strand

Genomic View for ACTN4 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for ACTN4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ACTN4 Gene

Regulatory Elements for ACTN4 Gene

Proteins for ACTN4 Gene

  • Protein details for ACTN4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O43707-ACTN4_HUMAN
    Recommended name:
    Alpha-actinin-4
    Protein Accession:
    O43707
    Secondary Accessions:
    • A4K467
    • D6PXK4
    • O76048

    Protein attributes for ACTN4 Gene

    Size:
    911 amino acids
    Molecular mass:
    104854 Da
    Quaternary structure:
    • Homodimer; antiparallel (By similarity). Binds TRIM3 at the N-terminus (By similarity). Interacts with MICALL2 (preferentially in opened conformation); stimulated by RAB13 activation (By similarity). Identified in a complex with CASK, IQGAP1, MAGI2, NPHS1, SPTAN1 and SPTBN1 (By similarity). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs. Component of the CART complex, at least composed of ACTN4, HGS/HRS, MYO5B and TRIM3. Interacts with BAIAP1 and PDLIM2. Interacts with PPARG and RARA.
    SequenceCaution:
    • Sequence=AAC17470.1; Type=Frameshift; Positions=19, 26, 124, 130, 589, 594, 787, 806; Evidence={ECO:0000305}; Sequence=BAA24447.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for ACTN4 Gene

    Alternative splice isoforms for ACTN4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ACTN4 Gene

Proteomics data for ACTN4 Gene at MOPED

Post-translational modifications for ACTN4 Gene

  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys54, Lys181, Lys233, Lys350, Lys378, Lys417, Lys625, Lys632, and Lys859

Other Protein References for ACTN4 Gene

No data available for DME Specific Peptides for ACTN4 Gene

Domains for ACTN4 Gene

Gene Families for ACTN4 Gene

HGNC:
  • EFHAND :EF-hand domain containing

UniProtKB/Swiss-Prot:

ACTN4_HUMAN
Domain:
  • Contains one Leu-Xaa-Xaa-Leu-Leu (LXXLL) motif that mediates interaction with nuclear receptors.:
    • O43707
  • Contains 1 actin-binding domain.:
    • O43707
  • Contains 2 CH (calponin-homology) domains.:
    • O43707
  • Contains 2 EF-hand domains.:
    • O43707
Family:
  • Belongs to the alpha-actinin family.:
    • O43707
Similarity:
  • Contains 4 spectrin repeats.:
    • O43707
genes like me logo Genes that share domains with ACTN4: view

Function for ACTN4 Gene

Molecular function for ACTN4 Gene

UniProtKB/Swiss-Prot Function: F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (Probable). Probably involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation (PubMed:15772161). Involved in tight junction assembly in epithelial cells probably through interaction with MICALL2. Links MICALL2 to the actin cytoskeleton and recruits it to the tight junctions (By similarity). May also function as a transcriptional coactivator, stimulating transcription mediated by the nuclear hormone receptors PPARG and RARA (PubMed:22351778).

Gene Ontology (GO) - Molecular Function for ACTN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001882 nucleoside binding IDA 12411747
GO:0003779 actin binding TAS 8104223
GO:0005178 integrin binding TAS 8104223
GO:0005509 calcium ion binding IEA --
GO:0005515 protein binding IPI 15619032
genes like me logo Genes that share ontologies with ACTN4: view
genes like me logo Genes that share phenotypes with ACTN4: view

Animal Models for ACTN4 Gene

MGI Knock Outs for ACTN4:

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting and HOMER Transcription for ACTN4 Gene

Localization for ACTN4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ACTN4 Gene

Nucleus. Cytoplasm. Cell junction. Note=Localized in cytoplasmic mRNP granules containing untranslated mRNAs. Colocalizes with actin stress fibers. Nuclear translocation can be induced by the PI3 kinase inhibitor wortmannin or by cytochalasin D. Exclusively localized in the nucleus in a limited number of cell lines (breast cancer cell line MCF-7, oral floor cancer IMC-2, and bladder cancer KU-7). {ECO:0000269 PubMed:17289661, ECO:0000269 PubMed:9508771}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for ACTN4 Gene COMPARTMENTS Subcellular localization image for ACTN4 gene
Compartment Confidence
extracellular 5
nucleus 5
cytoskeleton 3
cytosol 3
endosome 1
plasma membrane 1

Gene Ontology (GO) - Cellular Components for ACTN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001725 stress fiber IEA --
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IDA 16502470
GO:0005634 nucleus IDA 22351778
GO:0005737 cytoplasm IDA 16791210
genes like me logo Genes that share ontologies with ACTN4: view

Pathways for ACTN4 Gene

genes like me logo Genes that share pathways with ACTN4: view

Gene Ontology (GO) - Biological Process for ACTN4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001666 response to hypoxia IEA --
GO:0002576 platelet degranulation TAS --
GO:0007596 blood coagulation TAS --
GO:0015031 protein transport IEA --
GO:0030168 platelet activation TAS --
genes like me logo Genes that share ontologies with ACTN4: view

Compounds for ACTN4 Gene

(4) Novoseek inferred chemical compound relationships for ACTN4 Gene

Compound -log(P) Hits PubMed IDs
tyrosine 5.23 2
calcium 0 2
threonine 0 1
serine 0 1
genes like me logo Genes that share compounds with ACTN4: view

Transcripts for ACTN4 Gene

Unigene Clusters for ACTN4 Gene

Actinin, alpha 4:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for ACTN4 Gene

ExUns: 1a · 1b ^ 2 ^ 3a · 3b ^ 4a · 4b ^ 5 ^ 6 ^ 7a · 7b ^ 8 ^ 9 ^ 10 ^ 11 ^ 12a · 12b ^ 13a · 13b ^ 14 ^ 15 ^ 16 ^ 17 ^ 18a · 18b ^ 19 ^
SP1: -
SP2: -
SP3:
SP4: - - - - - - - - - - -
SP5: -
SP6:
SP7: - - - - - - - - - - - - - - - - - - - - - - -
SP8:
SP9:

ExUns: 20a · 20b ^ 21a · 21b ^ 22a · 22b ^ 23a · 23b · 23c · 23d ^ 24
SP1: - - -
SP2:
SP3: - - -
SP4:
SP5:
SP6: - - -
SP7: - - - - - - - - - -
SP8: - -
SP9:

Relevant External Links for ACTN4 Gene

GeneLoc Exon Structure for
ACTN4
ECgene alternative splicing isoforms for
ACTN4

Expression for ACTN4 Gene

mRNA expression in normal human tissues for ACTN4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for ACTN4 Gene

This gene is overexpressed in Artery - Tibial (4.6).

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for ACTN4 Gene

SOURCE GeneReport for Unigene cluster for ACTN4 Gene Hs.270291

mRNA Expression by UniProt/SwissProt for ACTN4 Gene

O43707-ACTN4_HUMAN
Tissue specificity: Widely expressed.
genes like me logo Genes that share expressions with ACTN4: view

Orthologs for ACTN4 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for ACTN4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia ACTN4 36
  • 99.41 (n)
  • 100 (a)
ACTN4 37
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia ACTN4 36
  • 94.51 (n)
  • 99.12 (a)
ACTN4 37
  • 99 (a)
OneToOne
dog
(Canis familiaris)
Mammalia ACTN4 36
  • 93.08 (n)
  • 99.01 (a)
ACTN4 37
  • 99 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Actn4 36
  • 90.34 (n)
  • 97.8 (a)
Actn4 16
Actn4 37
  • 98 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia ACTN4 37
  • 96 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia -- 37
  • 96 (a)
OneToMany
-- 37
  • 88 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Actn4 36
  • 90.78 (n)
  • 98.46 (a)
chicken
(Gallus gallus)
Aves ACTN1 37
  • 93 (a)
OneToMany
ACTN4 36
  • 86.95 (n)
  • 92.92 (a)
ACTN4 37
  • 94 (a)
OneToMany
lizard
(Anolis carolinensis)
Reptilia ACTN4 37
  • 91 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia actn4 36
  • 78.36 (n)
  • 91.94 (a)
zebrafish
(Danio rerio)
Actinopterygii actn4 36
  • 79.32 (n)
  • 87.42 (a)
ACTN4 (1 of 3) 37
  • 84 (a)
OneToMany
ACTN4 (2 of 3) 37
  • 83 (a)
OneToMany
ACTN4 (3 of 3) 37
  • 97 (a)
OneToMany
wufb53f05 36
fruit fly
(Drosophila melanogaster)
Insecta Actn 38
  • 67 (a)
worm
(Caenorhabditis elegans)
Secernentea sma-1 37
  • 8 (a)
ManyToMany
bread mold
(Neurospora crassa)
Ascomycetes NCU06429 36
  • 50.58 (n)
  • 37.6 (a)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes ain1 36
  • 44.86 (n)
  • 36.47 (a)
Species with no ortholog for ACTN4:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for ACTN4 Gene

ENSEMBL:
Gene Tree for ACTN4 (if available)
TreeFam:
Gene Tree for ACTN4 (if available)

Paralogs for ACTN4 Gene

Pseudogenes.org Pseudogenes for ACTN4 Gene

genes like me logo Genes that share paralogs with ACTN4: view

Variants for ACTN4 Gene

Sequence variations from dbSNP and Humsavar for ACTN4 Gene

SNP ID Clin Chr 19 pos Sequence Context AA Info Type MAF
rs749701 -- 38,699,106(+) CCAGG(C/T)CCTGT intron-variant
rs749702 -- 38,699,255(+) GGCTG(C/T)GTGCC intron-variant
rs752067 -- 38,651,689(+) GTTAA(C/T)TATTT intron-variant
rs755690 -- 38,676,720(-) GAAGC(C/T)GTGGG intron-variant
rs883394 -- 38,714,973(+) CTTAA(C/T)GAGCA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for ACTN4 Gene

Variant ID Type Subtype PubMed ID
nsv833826 CNV Loss 17160897
nsv833827 CNV Gain 17160897
nsv833828 CNV Loss 17160897
nsv911667 CNV Gain 21882294
esv22820 CNV Loss 19812545
nsv817834 CNV Gain 17921354
nsv911668 CNV Loss 21882294
esv2718535 CNV Deletion 23290073
nsv911669 CNV Loss 21882294
dgv641e199 CNV Deletion 23128226

Relevant External Links for ACTN4 Gene

HapMap Linkage Disequilibrium report
ACTN4
Human Gene Mutation Database (HGMD)
ACTN4

Disorders for ACTN4 Gene

(1) OMIM Diseases for ACTN4 Gene (604638)

UniProtKB/Swiss-Prot

ACTN4_HUMAN
  • Focal segmental glomerulosclerosis 1 (FSGS1) [MIM:603278]: A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation. {ECO:0000269 PubMed:10700177, ECO:0000269 PubMed:18436095, ECO:0000269 PubMed:23890478}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(3) University of Copenhagen DISEASES for ACTN4 Gene

(14) Novoseek inferred disease relationships for ACTN4 Gene

Disease -log(P) Hits PubMed IDs
nphs1 90.9 7
glomerulosclerosis, focal segmental 90.5 21
nephrotic syndrome 78.9 10
glomerulosclerosis 73.4 4
proteinuria 71 7

Relevant External Links for ACTN4

Genetic Association Database (GAD)
ACTN4
Human Genome Epidemiology (HuGE) Navigator
ACTN4
genes like me logo Genes that share disorders with ACTN4: view

Publications for ACTN4 Gene

  1. Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis. (PMID: 10700177) Kaplan J.M. … Pollak M.R. (Nat. Genet. 2000) 2 3 4 23
  2. Association analysis of podocyte slit diaphragm genes as candidates for diabetic nephropathy. (PMID: 17968527) Ihalmo P. … Groop P.H. (Diabetologia 2008) 3 23 49
  3. The human non-muscle alpha-actinin protein encoded by the ACTN4 gene suppresses tumorigenicity of human neuroblastoma cells. (PMID: 10656685) Nikolopoulos S.N. … Ross R.A. (Oncogene 2000) 3 4 23
  4. Familial focal segmental glomerulosclerosis associated with an ACTN4 mutation and paternal germline mosaicism. (PMID: 18436095) Choi H.J. … Cheong H.I. (Am. J. Kidney Dis. 2008) 3 4 23
  5. ACTN4 gene mutations and single nucleotide polymorphisms in idiopathic focal segmental glomerulosclerosis. (PMID: 19142020) Dai S. … Chen N. (Nephron Clin Pract 2009) 3 23 49

Products for ACTN4 Gene

Sources for ACTN4 Gene

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