protein
Alpha-actinin-2
Gene
ACTN2
Organism
Homo sapiens(9606)
Length
894 aa
Mass
103,854 Da
Alpha-actinin-2 (ACTN2) is an F-actin cross-linking protein that anchors actin filaments to intracellular structures and functions as a bundling protein (UniProt: P35609). The protein is widely expressed and plays a structural role in cytoskeletal organization across multiple cell types.
UniProt documentation associates ACTN2 variants with several muscular and cardiac disorders, including familial hypertrophic cardiomyopathy (CMH23), dilated cardiomyopathy (CMD1AA), congenital myopathy 8 (CMYO8), and adult-onset distal myopathy 6 (MPD6), reflecting its critical role in sarcomeric and cytoskeletal integrity (UniProt: P35609).
Alpha-actinin-2 is down-regulated in Alzheimer's disease brain tissue. Analysis of post-mortem AD brain versus age-matched controls using TMT-labeled proteomics across subcellular fractions demonstrated reduced abundance with a mean log2 fold-change of −0.98 (Chaparral AD proteomics). The functional significance of this down-regulation in AD pathology remains to be determined.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
not detected
P2
not detected
S2
-1.234
S3
-0.730
Mean log₂FC across detected fractions: -0.9821 (2 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein
Disease associations
Cardiomyopathy, familial hypertrophic, 23, with or without left ventricular non-compactionCMH23
A hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.
Cardiomyopathy, dilated, 1AA, with or without left ventricular non-compactionCMD1AA
A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
Congenital myopathy 8CMYO8
An autosomal dominant muscular disorder characterized by progressive early-onset muscle weakness, gait difficulties, loss of ambulation, and respiratory insufficiency. Morphological and ultrastructural analyses of muscle biopsies reveal type 1 fiber predominance, multiple structured cores forming a circular arrangement beneath the sarcolemma, and jagged Z-lines.
Myopathy, distal, 6, adult onset, autosomal dominantMPD6
An autosomal dominant muscular disorder characterized by adult onset of asymmetric distal muscle weakness, primarily affecting the lower limbs and resulting in gait difficulties. Some patients develop involvement of proximal and upper limb muscles.
Sources
Last updated 5/8/2026, 6:37:20 AM