ACTN4

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, alpha actinin isoform which is concentrated in the cytoplasm, and thought to be involved in metastatic processes. Mutations in this gene have been associated with focal and segmental glomerulosclerosis. [provided by RefSeq, Jul 2008]

Full Name

Actinin Alpha 4

Function

F-actin cross-linking protein which is thought to anchor actin to a variety of intracellular structures. This is a bundling protein (Probable). Probably involved in vesicular trafficking via its association with the CART complex. The CART complex is necessary for efficient transferrin receptor recycling but not for EGFR degradation. Involved in tight junction assembly in epithelial cells probably through interaction with MICALL2. Links MICALL2 to the actin cytoskeleton and recruits it to the tight junctions (By similarity). May also function as a transcriptional coactivator, stimulating transcription mediated by the nuclear hormone receptors PPARG and RARA.

Biological Process

Negative regulation of substrate adhesion-dependent cell spreading
Peroxisome proliferator activated receptor signaling pathway
Platelet degranulation
Positive regulation of cell migration
Positive regulation of cellular component movement
Positive regulation of NIK/NF-kappaB signaling
Positive regulation of sodium:proton antiporter activity
Protein transport
Regulation of apoptotic process
Regulation of nucleic acid-templated transcription
Response to hypoxia
Retinoic acid receptor signaling pathway
Tumor necrosis factor-mediated signaling pathway
Vesicle transport along actin filament

Cellular Location

Nucleus; Cytoplasm; Stress fiber; Cell junction. Localized in cytoplasmic mRNP granules containing untranslated mRNAs. Nuclear translocation can be induced by the PI3 kinase inhibitor wortmannin or by cytochalasin D. Exclusively localized in the nucleus in a limited number of cell lines (breast cancer cell line MCF-7, oral floor cancer IMC-2, and bladder cancer KU-7).

Involvement in disease

Focal segmental glomerulosclerosis 1 (FSGS1): A renal pathology defined by the presence of segmental sclerosis in glomeruli and resulting in proteinuria, reduced glomerular filtration rate and progressive decline in renal function. Renal insufficiency often progresses to end-stage renal disease, a highly morbid state requiring either dialysis therapy or kidney transplantation.