Seroatlas · Human Serome Atlas

ACTN4

Alpha-actinin-4

Also known as: ACTN4_HUMAN, FSGS1

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: O43707
Gene: ACTN4
Ensembl: ENSG00000130402
Chromosome: 19
Canonical length: 911 aa
Protein class: Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins
Subcellular location: Actin filaments,Focal adhesion sites,Primary cilium,Primary cilium transition zone,Cytosol
Quaternary structure: Homodimer

OverviewNCBI 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]

Canonical amino-acid sequenceUniProt

911 residues, UniProt reviewed canonical sequence.

>O43707|ACTN4
     1  MVDYHAANQS YQYGPSSAGN GAGGGGSMGD YMAQEDDWDR DLLLDPAWEK QQRKTFTAWC
    61  NSHLRKAGTQ IENIDEDFRD GLKLMLLLEV ISGERLPKPE RGKMRVHKIN NVNKALDFIA
   121  SKGVKLVSIG AEEIVDGNAK MTLGMIWTII LRFAIQDISV EETSAKEGLL LWCQRKTAPY
   181  KNVNVQNFHI SWKDGLAFNA LIHRHRPELI EYDKLRKDDP VTNLNNAFEV AEKYLDIPKM
   241  LDAEDIVNTA RPDEKAIMTY VSSFYHAFSG AQKAETAANR ICKVLAVNQE NEHLMEDYEK
   301  LASDLLEWIR RTIPWLEDRV PQKTIQEMQQ KLEDFRDYRR VHKPPKVQEK CQLEINFNTL
   361  QTKLRLSNRP AFMPSEGKMV SDINNGWQHL EQAEKGYEEW LLNEIRRLER LDHLAEKFRQ
   421  KASIHEAWTD GKEAMLKHRD YETATLSDIK ALIRKHEAFE SDLAAHQDRV EQIAAIAQEL
   481  NELDYYDSHN VNTRCQKICD QWDALGSLTH SRREALEKTE KQLEAIDQLH LEYAKRAAPF
   541  NNWMESAMED LQDMFIVHTI EEIEGLISAH DQFKSTLPDA DREREAILAI HKEAQRIAES
   601  NHIKLSGSNP YTTVTPQIIN SKWEKVQQLV PKRDHALLEE QSKQQSNEHL RRQFASQANV
   661  VGPWIQTKME EIGRISIEMN GTLEDQLSHL KQYERSIVDY KPNLDLLEQQ HQLIQEALIF
   721  DNKHTNYTME HIRVGWEQLL TTIARTINEV ENQILTRDAK GISQEQMQEF RASFNHFDKD
   781  HGGALGPEEF KACLISLGYD VENDRQGEAE FNRIMSLVDP NHSGLVTFQA FIDFMSRETT
   841  DTDTADQVIA SFKVLAGDKN FITAEELRRE LPPDQAEYCI ARMAPYQGPD AVPGALDYKS
   901  FSTALYGESD L

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ACTN4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Cell surface
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0.29
Highest tissue expression: 540 nTPM

Expression across tissuesHPA

Tissue

blood vessel: 540 nTPM
endometrium: 254 nTPM
esophagus: 221 nTPM
fallopian tube: 182 nTPM
skin: 174 nTPM
vagina: 171 nTPM

Single-cell type

podocytes: 1,069 nCPM
renal connecting tubule cells: 376 nCPM
papillary tip epithelial cells: 279 nCPM
proximal tubule cells: 261 nCPM
distal convoluted tubule cells: 249 nCPM
renal collecting duct intercalated cells: 238 nCPM

Immune cell

NK-cell: 27 nTPM
eosinophil: 18 nTPM
neutrophil: 17 nTPM
gdT-cell: 13 nTPM
memory CD8 T-cell: 13 nTPM
plasmacytoid DC: 12 nTPM

Brain region

choroid plexus: 183 nTPM
white matter: 180 nTPM
medulla oblongata: 149 nTPM
pons: 138 nTPM
cerebellum: 137 nTPM
midbrain: 135 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ACTN4.

Disease | AllUniProt

Conditions ACTN4 is implicated in, by any mechanism.

Focal segmental glomerulosclerosis 1 (FSGS1) MIM:603278

Disease | GeneticClinVar

17 pathogenic / likely-pathogenic of 564 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Focal segmental glomerulosclerosis 1
ACTN4-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.1
gnomAD pLI: 1
gnomAD missense Z: 4.16
DepMap mean gene effect: 0.02
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 8% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of ACTN4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads ACTN4 as an antibody target. Whether an autoantibody or antibody against ACTN4 could matter depends on whether native ACTN4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ACTN4 is annotated at the cell surface, where native ACTN4 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.

Annotation status

The present source text does not explicitly label ACTN4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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