protein
Ankyrin-3
aka ANK-3
Gene
ANK3
Organism
Homo sapiens(9606)
Length
4377 aa
Mass
480,410 Da
Ankyrin-3 (ANK3) is a large membrane-cytoskeleton linker protein that maintains and targets ion channels and cell adhesion molecules at specialized neuronal compartments, including the nodes of Ranvier and axonal initial segments (UniProt: Q12955). It also regulates ion channel activity and promotes localization of cardiac proteins to cell-cell junctions. Beyond its structural roles, ANK3 contributes to intracellular adhesion and junctional conductance in myocytes.
ANK3 is expressed broadly across tissues and has been associated with intellectual developmental disorder, autosomal recessive 37 (MRT37), a neurodevelopmental condition characterized by global developmental delay and neurological symptoms (UniProt: Q12955). Its functions in neuronal organization and ion homeostasis implicate it in brain development and neuronal function.
In Alzheimer's Disease, ANK3 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of −0.749 across subcellular fractions. This reduction may reflect compromised neuronal cytoskeleton integrity or altered ion channel organization in AD pathology, though the functional consequences of this downregulation require further investigation.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
-0.749
P2
not detected
S2
not detected
S3
not detected
Mean log₂FC across detected fractions: -0.749 (1 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
Membrane-cytoskeleton linker. May participate in the maintenance/targeting of ion channels and cell adhesion molecules at the nodes of Ranvier and axonal initial segments (PubMed:7836469). In skeletal muscle, required for costamere localization of DMD and betaDAG1 (By similarity). Regulates KCNA1 channel activity in function of dietary Mg(2+) levels, and thereby contributes to the regulation of renal Mg(2+) reabsorption (PubMed:23903368). Required for intracellular adhesion and junctional conductance in myocytes, potentially via stabilization of GJA1/CX43 protein abundance and promotion of PKP2, GJA1/CX43, and SCN5A/Nav1.5 localization to cell-cell junctions (By similarity)
May be part of a Golgi-specific membrane cytoskeleton in association with beta-spectrin
Disease associations
Intellectual developmental disorder, autosomal recessive 37MRT37
A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRT37 patients manifest delayed global development with speech delay, hypotonia, spasticity, and a sleep disorder. Severe behavioral abnormalities include aggression, hyperactivity, and grinding of the teeth.
Sources
Last updated 5/8/2026, 6:33:42 AM