ADD3
Domain
Comprised of three regions: a N-terminal protease-resistant globular head region, a short connecting subdomain, and a protease-sensitive tail region.
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).
Involvement in disease
Cerebral palsy, spastic quadriplegic 3
CPSQ3
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Sumoylated.
Proteolytically cleaved by asparagine endopeptidase (AEP) into 2 fragments. Overexpression of the 1-357 fragment induces neuronal apoptosis, and overexpression of either 1-357 or 358-706 fragment increases the degeneration of dendritic spines. Overexpression of the 1-357 fragment impairs neurite outgrowth by downregulating the expression of Rac2, and induces synaptic dysfunction and cognitive impairments in tau P301S transgenic mice, a mouse model for Alzheimer disease (AD).
Sequence Similarities
Belongs to the aldolase class II family. Adducin subfamily.
Tissue Specificity
Isoform 1
ubiquitously expressed.
Cleavage fragment 1-357 is abundantly expressed in the brain of patients with Alzheimer disease (AD), but hardly detectable in age-matched control individuals (at protein level).
Cellular localization
- Cytoplasm
- Cytoskeleton
- Cell membrane
- Peripheral membrane protein
- Cytoplasmic side
- Cytoplasm
- Full-length protein and the cleavage fragment 358-706 localize mainly to the cytoplasm, while cleavage fragment 1-357 translocates from the cytoplasm to the nucleus.
Alternative names
ADDL, ADD3, Gamma-adducin, Adducin-like protein 70