Phosphatase and actin regulator 4 (PHACTR4)
The protein contains 702 amino acids for an estimated molecular weight of 78211 Da.
Regulator of protein phosphatase 1 (PP1) required for neural tube and optic fissure closure, and enteric neural crest cell (ENCCs) migration during development. Acts as an activator of PP1 by interacting with PPP1CA and preventing phosphorylation of PPP1CA at 'Thr-320'. During neural tube closure, localizes to the ventral neural tube and activates PP1, leading to down-regulate cell proliferation within cranial neural tissue and the neural retina. Also acts as a regulator of migration of enteric neural crest cells (ENCCs) by activating PP1, leading to dephosphorylation and subsequent activation of cofilin (COF1 or COF2) and repression of the integrin signaling through the RHO/ROCK pathway (By similarity). (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.
- 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.
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 cytoskeleton organization
Closure of optic fissure
Enteric nervous system development
Negative regulation of integrin-mediated signaling pathway
Neural crest cell migration
Neural tube closure
Positive regulation of catalytic activity
Regulation of cell cycle
Rho protein signal transduction
The reference OMIM entry for this protein is 608726
Phosphatase and actin regulator 4; phactr4
CLONING
By searching databases for sequences similar to rat Phactr1 (608723), Allen et al. (2004) identified a family of 4 PHACTR genes in mouse and human, including PHACTR4. The PHACTR proteins share highest similarity in sequences surrounding the N- and C-terminal RPEL repeats and in the C-terminal actin- and protein phosphatase-1 (PP1; see 176875)-binding domains. In situ hybridization of rat brain showed Phactr4 highly expressed in periventricular regions, cerebellum, and hippocampus.GENE FUNCTION
Allen et al. (2004) determined that mouse Phactr4 coprecipitated with both PP1 and actin following expression in human embryonic kidney cells.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the PHACTR4 gene to chromosome 1 (TMAP SHGC-74491).ANIMAL MODEL
Using N-ethyl-N-nitrosourea mutagenesis screens, Kim et al. (2007) isolated the 'humpty dumpty' (humdy) mutant mouse line, which showed failure to close the neural tube and optic fissure, causing exencephaly and retinal coloboma. Homozygous humdy embryos exhibited complete exencephaly, and most died by embryonic day 14.5, although a few survived to birth and died shortly thereafter. About 8% of heterozygous embryos displayed a midbrain-specific exencephaly, indicating an incompletely penetrant dominant effect. Humdy was due to a missense mutation in the Pp1-binding domain of Phactr4 that specifically disrupted binding of Pp1 to Phactr4, leading to increased inhibitory phosphorylation of thr320 on Pp1 in the ventral neural tube and eye and disruption of Pp1 activity toward its target, Rb (RB1; 614041). Consequently, Rb became hyperphosphorylated and inactivated, leading to derepression of E2f (see E2F1; 189971) target genes. Loss of Phactr4 function resulted in shortening of the cell cycle, an increase in proliferating neural progenitors, and ectopic cell division and/or cell cycle exit defects in differentiating cells of the humdy neural tube and retina. Loss of a single E2f1 allele rescued the exencephaly, coloboma, and proliferation/differentiation defects of humdy mice, indicating that the critical target of Phactr4 is the cell cycle regulator E2f1. ... 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 608726 was added.