9.B.131 The Post-GPI Attachment Protein (P-GAP2) Family
Glycosylphosphatidylinositol (GPI) is a complex glycolipid that serves as a membrane anchor for many cell-surface proteins, such as Thy-1 and CD48. GPI-anchored proteins (GPI-APs) play important roles in many biological processes, such as signal transduction and cell-cell interaction, through their association with lipid rafts. Fatty acid remodeling of GPI-APs in the Golgi apparatus is required for their efficient association with lipid rafts, i.e., the unsaturated fatty acid at the sn-2 position of the PI moiety is exchanged for the saturated fatty acid by PGAP2 and PGAP3 (Murakami et al., 2012). This family may be distantly related to two other TC families, 9.B.14 and 2.A.66 (see the TC# 9.B.131.1.8 entry).
References:
Protein CWH43 (Calcofluor white hypersensitive protein). Possibly 21 TMSs in a 7x3 arrangement.
The Post-GPI attachment protein factor 2, P-GAP2. (7 putative TMSs)
Animals
P-GAP2 of Homo sapiens
Post-PGI attachment protein, factor 2
Animals
P-GAP, factor 2 of Caenorhabditis elegans
Uncharacterized protein of 683 aas and 13 TMSs.
UP of Candidatus Heimdallarchaeota archaeon AB_125 (marine sediment metagenome)
Uncharacterized protein of 618 aas and 13 TMSs
UP of Chloroflexi bacterium
Uncharacterized protein of 621 aas and 13 TMSs.
UP of Chloroflexi bacterium
Uncharacteerized protein of 620 aas and 13 TMSs
UP of Anaerolineae bacterium SM23_ 63
Uncharacterized protein of 452 aas and 12 TMSs. This member of the TC#9.B.131 family may be distantly related to TC# 2.A.66.2.31 and TC# 9.B.14.1.11, suggested a superfamily relationship, but this possibility needs to be estabilshed.
UP of Lokiarchaeum sp. GC14_75
Cwh43 protein of 971 aas and 19 or 24 aas in a (1 + 2 + 3)3 or 4 TMS arrangement.
The last 5 peaks of hydrophobicity are small, and may or may not be TMSs. This protein plays a role in genetically controlled mechanisms of cell division and quiescence as cells respond to changes in the nutritional environment and for cell survival (Nakazawa et al. 2019). Temperature-sensitive (ts) mutants of the cwh43 gene in fission yeast abolish both cell proliferation and nitrogen starvation-induced G0 quiescence. Cwh43 encodes an evolutionarily conserve protein that localizes to the endoplasmic reticulum (ER). Defects in it fail to divide in low glucose, lose mitotic competence under nitrogen starvation, and affect lipid metabolism. Mutations of the pmr1 gene, which encodes an evolutionarily conserved Ca2+/Mn2+-transporting P-type ATPase, are potent extragenic suppressors of ts mutants of the cwh43 gene. These pmr1 mutations suppressed the ts phenotype of cwh43 mutants, among five P-type Ca2+- and/or Mn2+-ATPases reported in this organism. Cwh43 and Pmr1 co-localize to the ER. In cwh43 mutant cells, addition of excessive manganese to culture media enhances the severe defect in cell morphology and causes abnormal accumulation of a cell wall component, 1, 3-beta-glucan. In contrast, these abnormal phenotypes are abolished by deletion of the pmr1+ gene, as well as by removal of Mn2+ from the culture medium. Nutrition-related phenotypes of cwh43 mutant cells were rescued in the absence of Pmr1. These observations indicate that the cellular processes regulated by Cwh43 are appropriately balanced with Pmr1-mediated Mn2+ transport into the ER (Nakazawa et al. 2019).
Cwh43 of Schizosaccharomyces pombe (Fission yeast)