Inverted formin-2 (INF2)
The protein contains 1249 amino acids for an estimated molecular weight of 135624 Da.
Severs actin filaments and accelerates their polymerization and depolymerization. (updated: March 4, 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
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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No binding partner found
The reference OMIM entry for this protein is 610982
Inverted formin 2; inf2
Formin, inverted, 2
Chromosome 14 open reading frame 173; c14orf173
DESCRIPTION
Actin filaments grow only when actin monomers have access to the fast-growing barbed end of the filament. The geometry of the filament network depends on the actions of the ARP2/3 complex (604221) and members of the formin family, such as INF2. The ARP2/3 complex binds to the sides of preexisting filaments and nucleates filaments whose barbed ends are quickly blocked by capping proteins, producing brush-like structures, such as those found at the leading edges of crawling cells. In contrast, formins bind to the barbed ends of growing filaments and protect them from capping, creating long filaments that can be cross-linked into bundles, such as those found in actin cables of yeast. Interaction of formins with actin barbed ends occurs through the formin homology-2 (FH2) domain. FH2 domains accelerate filament nucleation, move with the barbed end as the filament grows, and block capping of the barbed end by proteins such as gelsolin (GSN; 137350). The FH1 domain of formins binds to profilin (see 176610) and accelerates elongation from the FH2-bound barbed ends (Bindschadler and McGrath, 2004; Chhabra and Higgs, 2006).CLONING
By searching databases for FH2 domain sequences, Higgs and Peterson (2005) identified mouse and human INF2, a member of the inverted formin group. Inverted formins have an N-terminal FH2 domain rather than the C-terminal FH2 domain found in all other formins. By database analysis and RT-PCR, Chhabra and Higgs (2006) cloned full-length mouse Inf2. The deduced 1,274-amino acid protein has an N-terminal diaphanous inhibitory domain (DID), followed by an FH1 domain, an FH2 domain, and a C-terminal diaphanous autoregulatory domain (DAD)/ WASP (300392) homology-2 (WH2) domain. Thus, Inf2 is not an inverted formin, but is most similar to diaphanous formins (e.g., DIAPH1; 602121), which are regulated by autoinhibition via DID-DAD interaction. By immunohistochemical staining, Boyer et al. (2011) demonstrated robust IFN2 expression in peripheral nerve Schwann cells and light staining in some axons. INF2 was also expressed predominantly in podocytes in the kidney, as well as in some tubules, but not in vessels. INF2 colocalized with the myelin and lymphocyte protein (MAL; 188860) in human peripheral nerve and mouse Schwann cells, and with MAL2 (609684) in human podocytes. MAL was not present in glomeruli. In HeLa cells, INF2 showed perinuclear localization.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the C14ORF173 gene to chromosome 14 (TMAP RH102965).GENE FUNCTION
Using fluorescence microscopy to study the effects of various constructs containing domains of mouse Inf2 on actin elongation and nucleation, Chhabra and Higgs (2006) showed that Inf2 interacted with actin through a region C-terminal to the FH2 domain. This region, in combination with the FH2 domain, accelerated both polymerization and depolymerization of actin filaments. Depolymerization resulted from actin monomer-binding ability of the WH2 domain and a severing activity that depended on attachment of the FH2 domain to the C terminus. Phosphate inhibited both depolymerization and severing, suggesting that phosphate release from actin subunits in the filament triggers depolymerization. Mutation of the WH2 domain abrogated depolymerization. Korobova et al. (2013) found that actin polymerization through endoplasmic reticulum (ER)-localized INF2 was required for efficient mitochondrial fis ... 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 610982 was added.