protein
Gamma-adducin
Gene
ADD3
Organism
Homo sapiens(9606)
Length
706 aa
Mass
79,155 Da
Gamma-adducin (ADD3) is a membrane-cytoskeleton-associated protein that promotes assembly of the spectrin-actin network and plays roles in actin filament capping and regulation of the actin cytoskeleton (UniProt: Q9UEY8). It binds calmodulin and is involved in myogenic reactivity of vascular and renal tissues, regulating potassium channels and controlling expression of cytoskeletal and adhesion proteins such as synaptopodin, integrins, and nephrin. The protein also promotes neurite growth.
ADD3 has been associated with cerebral palsy, spastic quadriplegic 3 (CPSQ3; MIM 617008), an autosomal recessive neurodevelopmental disorder characterized by spasticity and cognitive impairment (UniProt: Q9UEY8). Beyond this genetic link, the protein's roles in actin dynamics and cell adhesion are relevant to neuronal function more broadly.
In Alzheimer's disease, ADD3 is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of 0.53 across one fraction in a TMT-labeled proteomics study of four subcellular compartments (Chaparral AD proteomics). This upregulation may reflect altered cytoskeletal dynamics or compensatory responses in the degenerating AD brain.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↑ Up in ADP3
not detected
P2
not detected
S2
not detected
S3
+0.529
Mean log₂FC across detected fractions: +0.5291 (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-associated protein that promotes the assembly of the spectrin-actin network. Plays a role in actin filament capping (PubMed:23836506). Binds to calmodulin (Probable). Involved in myogenic reactivity of the renal afferent arteriole (Af-art), renal interlobular arteries and middle cerebral artery (MCA) to increased perfusion pressure. Involved in regulation of potassium channels in the vascular smooth muscle cells (VSMCs) of the Af-art and MCA ex vivo. Involved in regulation of glomerular capillary pressure, glomerular filtration rate (GFR) and glomerular nephrin expression in response to hypertension. Involved in renal blood flow (RBF) autoregulation. Plays a role in podocyte structure and function. Regulates globular monomer actin (G-actin) and filamentous polymer actin (F-actin) ratios in the primary podocytes affecting actin cytoskeleton organization. Regulates expression of synaptopodin, RhoA, Rac1 and CDC42 in the renal cortex and the primary podocytes. Regulates expression of nephrin in the glomeruli and in the primary podocytes, expression of nephrin and podocinin in the renal cortex, and expression of focal adhesion proteins integrin alpha-3 and integrin beta-1 in the glomeruli. Involved in cell migration and cell adhesion of podocytes, and in podocyte foot process effacement. Regulates expression of profibrotics markers MMP2, MMP9, TGF beta-1, tubular tight junction protein E-cadherin, and mesenchymal markers vimentin and alpha-SMA (By similarity). Promotes the growth of neurites (By similarity)
Disease associations
Cerebral palsy, spastic quadriplegic 3CPSQ3
A form of cerebral palsy, a group of non-progressive disorders of movement and/or posture resulting from defects in the developing central nervous system. CPSQ3 is an autosomal recessive neurodevelopmental disorder characterized by variable spasticity and cognitive impairment.
Sources
Last updated 5/8/2026, 6:36:52 AM