Pib2

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	Saccharomyces cerevisiae
Symbol	PIB2
Entrez	852861
HomoloGene	39059
RefSeq (mRNA)	NM_001180888.3
RefSeq (Prot)	NP_011492.3
UniProt	P53191
Other data
Chromosome	VII: 0.45 - 0.45 Mb
Search for Structures Swiss-model Domains InterPro

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]