Pib2
Yeast protein
From Wikipedia, the free encyclopedia
Phosphatidylinositol 3-phosphate-binding protein 2 (Pib2) is a yeast protein involved in the regulation of TORC1 signaling[1][2][3][4][5] and lysosomal membrane permeabilization.[1] It is essential for the reactivation of TORC1 following exposure to rapamycin or nutrient starvation.[1][2][3][4]
| Phosphatidylinositol 3-phosphate-binding protein 2 | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Organism | |||||||
| Symbol | PIB2 | ||||||
| Entrez | 852861 | ||||||
| Orthologs | NCBI: entry; OMA: entry | ||||||
| RefSeq (mRNA) | NM_001180888.3 | ||||||
| RefSeq (Prot) | NP_011492.3 | ||||||
| UniProt | P53191 | ||||||
| Other data | |||||||
| Chromosome | VII: 0.45 - 0.45 Mb | ||||||
| |||||||
Discovery
Pib2 was first identified as a FYVE domain-containing protein able to bind phosphatidylinositol 3-phosphate (PI3P).[6] Pib2 was later identified in a screen for rapamycin sensitivity, along with several other TORC1 regulatory proteins (including Ego1, Gtr1, Gtr2, and other key TORC1 related proteins).[7]
Structure
Pib2 is a 70.6 kDa protein with 635 amino acids (Uniprot - P53191). Pib2 has 5 weakly conserved motifs among fungi and 2 universally conserved motifs.[1] The partially conserved motifs are found in the N-terminal region of the protein and are generally referred to as regions A-E[1][4] The universally conserved motifs include a phosphatidylinositol-3-phosphate (PI3P)-binding FYVE domain, and a short tail motif at the C-terminus.[1]
Mammalian homologs
Pib2 has 2 mammalian homologs, Phafin1 (also known as LAPF or PLEKHF1) and Phafin2 (EAPF or PLEKHF2). The phafin proteins each have a PH (pleckstrin homology) domain and FYVE domain.[1] Phafin1 also has a tail motif similar to that of Pib2.[1] These proteins have not been shown to be involved in the regulation of mammalian TORC1 signaling but have been shown to be involved in related processes.[8][9]
Function
TORC1 regulation
In Saccharomyces cerevisiae, Pib2 has been shown to be involved in regulating TORC1 signaling.[1][2][3][4][5] Pib2 is found at the yeast vacuole and endosomes.[1][10] The PI3P binding FYVE domain of Pib2 is key for this localization.[1][3] Pib2 also interacts with some TORC1 components, including Kog1 and Tor1,[1][3][4][5] and has been shown to be necessary for TORC1 reactivation following inhibition by rapamycin or nutrient starvation.[1][2][3][4] Additionally, Pib2 is essential for TORC1 reactivation by stimulation with leucine and glutamine.[2][4]
In terms of TORC1 reactivation, it has been observed that Pib2 can have both a positive and negative effect. The C-terminus of Pib2 is key for TORC1 reactivation, whereas the N-terminal region has an inhibitory effect on TORC1 reactivation.[1][3]
Lysosomal membrane permeabilization
Lysosomal membrane permeabilization (LMP) is a process which is important for inducing cell death in a range of animals and plants.[1][11][12][13][14] LMP also occurs in Saccharomyces cerevisiae during sporulation.[15] Pib2 has been implicated in the regulation of this process in stressed yeast through the promotion of TORC1 activity.[1]