Alpha-actinin-4 (ACTN4)
The protein contains 911 amino acids for an estimated molecular weight of 104854 Da.
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 (PubMed:15772161). 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 (PubMed:22351778). (updated: April 1, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Actin filament bundle assembly
Bicellular tight junction assembly
Blood coagulation
Negative regulation of cellular component movement
Negative regulation of substrate adhesion-dependent cell spreading
Peroxisome proliferator activated receptor signaling pathway
Platelet activation
Platelet degranulation
Positive regulation of cell migration
Positive regulation of cellular component movement
Positive regulation of NIK/NF-kappaB signaling
Positive regulation of pinocytosis
Positive regulation of sodium:proton antiporter activity
Protein localization to bicellular tight junction
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 Component
Brush border
Cell-cell junction
Cortical cytoskeleton
Cytoplasm
Cytosol
Extracellular exosome
Extracellular region
Extracellular space
Focal adhesion
Intracellular anatomical structure
Intracellular ribonucleoprotein complex
Neuron projection
Nuclear body
Nucleus
Obsolete cell
Perinuclear region of cytoplasm
Platelet alpha granule lumen
Protein complex
Protein-containing complex
Pseudopodium
Ribonucleoprotein complex
Stress fiber
Z disc
Molecular Function
Actin binding
Actin filament binding
Calcium ion binding
Chromatin DNA binding
Integrin binding
Ion channel binding
Nuclear hormone receptor binding
Nuclear receptor coactivator activity
Nucleoside binding
Poly(A) RNA binding
Protein homodimerization activity
Protein N-terminus binding
Retinoic acid receptor binding
RNA binding
RNA polymerase II transcription regulatory region sequence-specific DNA binding
Transcription coactivator activity
The reference OMIM entry for this protein is 603278
Focal segmental glomerulosclerosis 1; fsgs1
Glomerulosclerosis, focal segmental, 1
A number sign (#) is used with this entry because this form of progressive renal disease, referred to here as focal segmental glomerulosclerosis-1 (FSGS1), is caused by heterozygous mutation in the gene encoding alpha-actinin-4 (ACTN4; 604638) on chromosome 19q13.
DESCRIPTION
Focal segmental glomerulosclerosis (FSGS) is a pathologic finding in several renal disorders that manifest clinically as proteinuria and progressive decline in renal function. Some patients with FSGS develop the clinical entity called 'nephrotic syndrome' (see NPHS1; 256300), which includes massive proteinuria, hypoalbuminemia, hyperlipidemia, and edema. However, patients with FSGS may have proteinuria in the nephrotic range without other features of the nephrotic syndrome (summary by D'Agati et al., 2004; Mathis et al., 1998). D'Agati et al. (2011) provided a detailed review of FSGS, emphasizing that the disorder results from defects of the podocyte. Because of confusion in the literature regarding use of the terms 'nephrotic syndrome' and 'focal segmental glomerulosclerosis' (seeNOMENCLATURE
section), these disorders in OMIM are classified as NPHS or FSGS according to how they were first designated in the literature. - Genetic Heterogeneity of Focal Segmental Glomerulosclerosis and Nephrotic Syndrome Focal segmental glomerulosclerosis and nephrotic syndrome are genetically heterogeneous disorders representing a spectrum of hereditary renal diseases. See also FSGS2 (603965), caused by mutation in the TRPC6 gene (603652); FSGS3 (607832), associated with variation in the CD2AP gene (604241); FSGS4 (612551), mapped to chromosome 22q12; FSGS5 (613237), caused by mutation in the INF2 gene (610982); FSGS6 (614131), caused by mutation in the MYO1E gene (601479); FSGS7 (616002), caused by mutation in the PAX2 gene (167409); FSGS8 (616032), caused by mutation in the ANLN gene (616027); and FSGS9 (616220), caused by mutation in the CRB2 gene (609720). See also NPHS1 (256300), caused by mutation in the NPHS1 gene (602716); NPHS2 (600995), caused by mutation in the podocin gene (604766); NPHS3 (610725), caused by mutation in the PLCE1 gene (608414); and NPHS4 (256370), caused by mutation in the WT1 gene (607102).CLINICAL FEATURES
Mathis et al. (1992) reported a large family with variable expression of a glomerular disease associated with asymptomatic proteinuria and normal renal function (7 patients) or significant proteinuria leading to progressive renal failure (11 patients). Histopathologic changes were variable, but included focal segmental glomerulosclerosis and diffuse glomerulosclerosis. Renal failure usually occurred in the fifth decade of life. The most consistent clinical finding was proteinuria without microscopic hematuria or other significant urinary sediment elements. This disease differed from Alport syndrome (301050) and congenital nephrotic syndrome (256300) in age of onset, urinary findings, and lack of associated conditions, such as deafness. Mathis et al. (1998) provided follow-up of the family reported by Mathis et al. (1992). An individual was considered affected if he/she had (1) renal biopsy evidence of FSGS; (2) end-stage renal disease without another cause; or (3) elevated urine microalbumin excretion without another cause. The authors noted that emphasized the great variability in the phenotypic expression of the disease gene. They further stated that 'although we have termed the pathologic condition in this family ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603278 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed