Seroatlas · Human Serome Atlas

ACTN1

Alpha-actinin-1

Also known as: ACTN1_HUMAN

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

Protein identityUniProt · HPA

UniProt accession: P12814
Gene: ACTN1
Ensembl: ENSG00000072110
Chromosome: 14
Canonical length: 892 aa
Protein class: Disease related genes, FDA approved drug targets, Human disease related genes, Plasma proteins, Predicted intracellular proteins
Subcellular location: Plasma membrane,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, cytoskeletal, alpha actinin isoform and maps to the same site as the structurally similar erythroid beta spectrin gene. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

892 residues, UniProt reviewed canonical sequence.

>P12814|ACTN1
     1  MDHYDSQQTN DYMQPEEDWD RDLLLDPAWE KQQRKTFTAW CNSHLRKAGT QIENIEEDFR
    61  DGLKLMLLLE VISGERLAKP ERGKMRVHKI SNVNKALDFI ASKGVKLVSI GAEEIVDGNV
   121  KMTLGMIWTI ILRFAIQDIS VEETSAKEGL LLWCQRKTAP YKNVNIQNFH ISWKDGLGFC
   181  ALIHRHRPEL IDYGKLRKDD PLTNLNTAFD VAEKYLDIPK MLDAEDIVGT ARPDEKAIMT
   241  YVSSFYHAFS GAQKAETAAN RICKVLAVNQ ENEQLMEDYE KLASDLLEWI RRTIPWLENR
   301  VPENTMHAMQ QKLEDFRDYR RLHKPPKVQE KCQLEINFNT LQTKLRLSNR PAFMPSEGRM
   361  VSDINNAWGC LEQVEKGYEE WLLNEIRRLE RLDHLAEKFR QKASIHEAWT DGKEAMLRQK
   421  DYETATLSEI KALLKKHEAF ESDLAAHQDR VEQIAAIAQE LNELDYYDSP SVNARCQKIC
   481  DQWDNLGALT QKRREALERT EKLLETIDQL YLEYAKRAAP FNNWMEGAME DLQDTFIVHT
   541  IEEIQGLTTA HEQFKATLPD ADKERLAILG IHNEVSKIVQ TYHVNMAGTN PYTTITPQEI
   601  NGKWDHVRQL VPRRDQALTE EHARQQHNER LRKQFGAQAN VIGPWIQTKM EEIGRISIEM
   661  HGTLEDQLSH LRQYEKSIVN YKPKIDQLEG DHQLIQEALI FDNKHTNYTM EHIRVGWEQL
   721  LTTIARTINE VENQILTRDA KGISQEQMNE FRASFNHFDR DHSGTLGPEE FKACLISLGY
   781  DIGNDPQGEA EFARIMSIVD PNRLGVVTFQ AFIDFMSRET ADTDTADQVM ASFKILAGDK
   841  NYITMDELRR ELPPDQAEYC IARMAPYTGP DSVPGALDYM SFSTALYGES DL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ACTN1 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): 0.28
Highest tissue expression: 499 nTPM

Expression across tissuesHPA

Tissue

smooth muscle: 499 nTPM
blood vessel: 302 nTPM
seminal vesicle: 273 nTPM
colon: 179 nTPM
endometrium: 176 nTPM
urinary bladder: 172 nTPM

Single-cell type

platelets: 1,148 nCPM
neutrophils: 1,048 nCPM
salivary myoepithelial cells: 965 nCPM
smooth muscle cells: 948 nCPM
extravillous trophoblasts: 605 nCPM
neutrophil progenitors: 575 nCPM

Immune cell

neutrophil: 346 nTPM
eosinophil: 126 nTPM
naive CD4 T-cell: 97 nTPM
naive CD8 T-cell: 87 nTPM
total PBMC: 81 nTPM
classical monocyte: 63 nTPM

Brain region

basal ganglia: 99 nTPM
thalamus: 90 nTPM
medulla oblongata: 72 nTPM
cerebral cortex: 68 nTPM
white matter: 61 nTPM
choroid plexus: 59 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ACTN1.

Disease | AllUniProt

Conditions ACTN1 is implicated in, by any mechanism.

Bleeding disorder, platelet-type, 15 (BDPLT15) MIM:615193

Disease | GeneticClinVar

21 pathogenic / likely-pathogenic of 612 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Platelet-type bleeding disorder 15
Macrothrombocytopenia
Thrombocytopenia
ACTN1-related disorder
Inborn genetic diseases

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): 0.21
gnomAD pLI: 1
gnomAD missense Z: 3.36
DepMap mean gene effect: -0.04
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% 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 ACTN1 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 ACTN1 as an antibody target. Whether an autoantibody or antibody against ACTN1 could matter depends on whether native ACTN1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ACTN1 is annotated at the cell surface, where native ACTN1 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 ACTN1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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