Cofilin-1 (CFL1)
The protein contains 166 amino acids for an estimated molecular weight of 18502 Da.
Binds to F-actin and exhibits pH-sensitive F-actin depolymerizing activity (PubMed:11812157). In conjunction with the subcortical maternal complex (SCMC), plays an essential role for zygotes to progress beyond the first embryonic cell divisions via regulation of actin dynamics (PubMed:15580268). Required for the centralization of the mitotic spindle and symmetric division of zygotes (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization in epithelial cells (PubMed:21834987). Required for the up-regulation of atypical chemokine receptor ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation (PubMed:23633677). Required for neural tube morphogenesis and neural crest cell migration (By similarity). (updated: Feb. 10, 2021)
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.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- 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.
This protein is annotated as membranous in UniProt.
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Biological Process
Actin cytoskeleton organization
Actin filament depolymerization
Actin filament fragmentation
Actin filament severing
Axon guidance
Blood coagulation
Cell motility
Cytoskeleton organization
Ephrin receptor signaling pathway
Establishment of cell polarity
Establishment of spindle localization
Fc-gamma receptor signaling pathway involved in phagocytosis
Innate immune response
Interleukin-12-mediated signaling pathway
Mitotic cytokinesis
Negative regulation of apoptotic process
Negative regulation of cell size
Neural crest cell migration
Neural fold formation
Platelet activation
Platelet degranulation
Positive regulation by host of viral process
Positive regulation of actin filament depolymerization
Positive regulation of embryonic development
Protein import into nucleus
Protein phosphorylation
Regulation of cell morphogenesis
Regulation of dendritic spine morphogenesis
Response to amino acid
Response to virus
Rho protein signal transduction
Viral process
The reference OMIM entry for this protein is 601442
Cofilin 1; cfl1
Cofilin, nonmuscle
DESCRIPTION
Cofilin is a widely distributed intracellular actin-modulating protein that binds and depolymerizes filamentous F-actin and inhibits the polymerization of monomeric G-actin in a pH-dependent manner. It is involved in the translocation of actin-cofilin complex from cytoplasm to nucleus (summary by Gillett et al., 1996).CLONING
Two cofilin isoforms have been identified in mouse: muscle, or M-type (601443) and nonmuscle, or NM-type (Ono et al., 1994). The mouse M-type cofilin is expressed in heart, skeletal muscle, and testis, whereas the NM-type is found in a wide variety of tissues, including heart and testis. NM-type cofilin expression is minimal in mature mammalian skeletal muscle. Ogawa et al. (1990) isolated a cDNA encoding a placentally expressed cofilin. Gillett et al. (1996) cloned CFL1, a nonmuscle-type cofilin, from a human promyelocytic cDNA library. The cDNA encodes a 166-amino acid polypeptide with a molecular mass of approximately 18.5 kD.GENE FUNCTION
Cofilin exhibits actin-depolymerizing activity that is inhibited as a result of its phosphorylation by LIM kinase (see 601329). Maekawa et al. (1999) demonstrated that cofilin was phosphorylated during lysophosphatidic acid-induced, Rho-mediated neurite retraction. This phosphorylation was sensitive to Y-27632, a specific inhibitor of the Rho-associated kinase ROCK (601702). ROCK, which is a downstream effector of Rho, did not phosphorylate cofilin directly but phosphorylated LIM kinase, which in turn was activated to phosphorylate cofilin. Maekawa et al. (1999) concluded that phosphorylation of LIM kinase by ROCK and, consequently, increased phosphorylation of cofilin by LIM kinase, contribute to Rho-induced reorganization of the actin cytoskeleton. Kuhn et al. (2000) reviewed evidence from studies of several avian and mammalian primary neural cultures and neuronal cell lines that showed a role for ADF and cofilin in neurite outgrowth. To study the in vivo biochemical action of cofilin and the subsequent cellular response, Ghosh et al. (2004) used a general caging method for proteins that are regulated by phosphorylation. By acute and local activation of a chemically engineered, light-sensitive phosphocofilin mimic, they demonstrated that cofilin polymerizes actin, generates protrusions, and determines the direction of cell migration. Ghosh et al. (2004) proposed a role for cofilin that is distinct from its role as an actin-depolymerizing factor. Yang et al. (2014) had previously found that mouse seipin (BSCL2; 606158) promotes adipogenesis to accommodate storage of excess nutrients in the form of lipids, whereas it inhibits lipid droplet production and accumulation in preadipocytes and other nonadipocyte lineages. Using mass spectrometry to identify proteins that interacted with seipin in adipose tissue lysates, Yang et al. (2014) identified the scaffold protein 14-3-3-beta (YWHAB; 601289). Interaction of seipin with 14-3-3-beta did not depend on insulin stimulation. In insulin (INS; 176730)-stimulated 3T3-L1 mouse adipocytes, 14-3-3-beta interacted with the actin-severing protein cofilin-1, and this interaction required serine phosphorylation of cofilin-1. Adipogenesis in 3T3-L1 cells was accompanied by remodeling of the actin cytoskeleton from central stress fibers to the cell cortex, concomitant with lipid droplet accumulation. Knockdown of seipin, 14-3-3-beta, or cofilin-1 in 3T3-L1 cells impaired adipocyte development and i ... More on the omim web site
Feb. 16, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601442 was added.
Jan. 27, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed