INP52/YNL106C Summary Help

Standard Name INP52 1
Systematic Name YNL106C
Alias SJL2 2
Feature Type ORF, Verified
Description Polyphosphatidylinositol phosphatase; dephosphorylates a number of phosphatidylinositol phosphates (PtdInsPs, PIPs) to PI; involved in endocytosis; hyperosmotic stress causes translocation to actin patches; synaptojanin-like protein with a Sac1 domain; INP52 has a paralog, INP53, that arose from the whole genome duplication (3, 4, 5, 6, 7 and see Summary Paragraph)
Name Description INositol polyphosphate 5-Phosphatase 8
Chromosomal Location
ChrXIV:424495 to 420944 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gene Ontology Annotations All INP52 GO evidence and references
  View Computational GO annotations for INP52
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 3 genes
Classical genetics
Large-scale survey
184 total interaction(s) for 126 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 25
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 3
  • Co-localization: 1
  • Co-purification: 1
  • PCA: 2
  • Protein-peptide: 2
  • Reconstituted Complex: 1
  • Two-hybrid: 3

Genetic Interactions
  • Dosage Rescue: 17
  • Negative Genetic: 54
  • Phenotypic Enhancement: 7
  • Phenotypic Suppression: 1
  • Positive Genetic: 17
  • Synthetic Growth Defect: 36
  • Synthetic Lethality: 11
  • Synthetic Rescue: 2

Expression Summary
Length (a.a.) 1,183
Molecular Weight (Da) 133,330
Isoelectric Point (pI) 8.97
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrXIV:424495 to 420944 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..3552 424495..420944 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000005050

INP51, INP52, INP53, and INP54 encode members of a conserved family of phosphoinositde phosphatases that contain an inositol polyphosphate 5-phosphatase domain (reviewed in 9 and 6). This domain in these enzymes specifically hydrolyzes phosphates at position 5 of inositol rings, PtdIns[4,5]P2 being the preferred substrate (3). Inp52p is partially redundant in function with both Inp51p and Inp53p, but these latter two proteins have cellular functions that are independent of each other (1). None of the genes is essential for growth, however a triple deletion of inp51 inp52 inp53 is lethal (1). The inviability of the triple-null strain can be rescued by expressing mouse Inpp5b (inositol polyphospate 5-phosphatase II, 10).

Inp51p, Inp52p, and Inp53p also possess a second catalytic domain known as the Sac1-like domain, which is highly conserved and also found in the IP phosphatases Sac1p, Fig4p, and mammalian synaptojanin-1 (SYNJ1) and synaptojanin-2 (SYNJ2) (reviewed in 9 and 6). The Sac1-like domain of Inp52p and Inp53p enables these proteins to recognize and dephosphorylate a broader range of substrates including PtdIns[3]P, PtdIns[4]P, and PtdIns[3,5]P2 (3). Although Inp51p contains a Sac1-like domain, this domain is non-functional due to mutations of key residues in the highly conserved CX5R(T/S) domain.

In addition to Inp51p and Inp53p, Inp52p function also partially overlaps with that of the phophoinositide phosphatases Sac1p and Ymr1p (reviewed in 9). Inp52p localizes to the cytoplasm, nucleus, and actin cortical patches at the plasma membrane (reviewed in 9). Inp52p actin cortical patch localization is dependent on Abp1p (11). inp52 null mutants are mildly increased in cold-tolerance and are defective in sister-chromatid pairing during meiosis (1, 12).

Due to their partial redundancy, some INP phenotypes can only be observed, or are enhanced, in certain strain backgrounds. inp51 inp52 and inp52 inp53 double null strains show defects in cell growth, endocytosis, actin cytoskeleton organization, and bud site selection. These double mutants also show a thickening of the cell wall, have fragmented vacuoles, and are osmosensitive. inp52 inp53 strains also exhibit increased cold-tolerance, and increased levels of PtdIns[4,5]P2 and PtdIns[3,5]P2 (2, 1, 4, 3, and reviewed in 9).

About Phosphatidylinositol Phosphate Biosynthesis

The phosphorylated products of phosphatidylinositol (PtdIns, PI), collectively referred to as phosphoinositides or phosphatidylinositol phosphates (PtdInsPs, PIPs), are membrane-bound lipids that function as structural components of membranes, as well as regulators of many cellular processes in eukaryotes, including vesicle-mediated membrane trafficking, cell wall integrity, and actin cytoskeleton organization (reviewed in 9 and 13). PtdInsPs are also precursors of the water-soluble inositol phosphates (IPs), an important class of intracellular signaling molecules (reviewed in 14, 15 and 16).

The inositol ring of the membrane phospholipids and the water-soluble IPs are readily phosphorylated and dephosphorylated at a number of positions making them well suited as key regulators. PtdIns can be phosphorylated at one or a combination of positions (3', 4', or 5') on the inositol headgroup, generating a set of unique stereoisomers that have specific biological functions (reviewed in 9). These stereoisomers have been shown to be restricted to certain membranes (reviewed in 9). Phosphatidylinositol 4-phosphate (PtdIns4P) is the major PtdInsP species of the Golgi apparatus, where it plays a role in the vesicular trafficking of secretory proteins from the Golgi to the plasma membrane (reviewed in 9). Phosphatidylinositol 4,5-bisphosphate (PtdIns[4,5]P2) is the major species found at the plasma membrane and is involved in the regulation of actin cytoskeleton organization, as well as cell wall integrity, and heat shock response pathways (reviewed in 9). Phosphatidylinositol 3-phosphate (PtdIns3P) is found predominantly at endosomal membranes and in multivesicular bodies (MVB), where it plays a role in endosomal and vacuolar membrane trafficking. Phosphatidylinositol 3,5-bisphosphate (PtdIns[3,5]P2) is found on vacuolar membranes where it plays an important role in the MVB sorting pathway (reviewed in 9).

Phosphorylation and dephosphorylation of the inositol headgroups of PtdInsPs at specific membrane locations signals the recruitment of certain proteins essential for vesicular transport (13, and reviewed in 9). PtdInsPs recruit proteins that contain PtdInsP-specific binding domains, such as the well-studied pleckstrin homology (PH) domain that recognizes the phosphorylation pattern of specific PtdInsP inositol headgroups (reviewed in 9).

A number of kinases and phosphatases are involved in the generation and interconversions of PtdInsPs, the majority of which have been well conserved during evolution (reviewed in 9). The PtdInsP kinases, in contrast to the lipid phosphatases, have a higher degree of specificity. While each kinase appears to phosphorylate only one substrate, many of the lipid phosphatases can dephosphorylate a number of substrates.

Last updated: 2008-05-08 Contact SGD

References cited on this page View Complete Literature Guide for INP52
1) Stolz LE, et al.  (1998) Identification and characterization of an essential family of inositol polyphosphate 5-phosphatases (INP51, INP52 and INP53 gene products) in the yeast Saccharomyces cerevisiae. Genetics 148(4):1715-29
2) Srinivasan S, et al.  (1997) Disruption of three phosphatidylinositol-polyphosphate 5-phosphatase genes from Saccharomyces cerevisiae results in pleiotropic abnormalities of vacuole morphology, cell shape, and osmohomeostasis. Eur J Cell Biol 74(4):350-60
3) Guo S, et al.  (1999) SAC1-like domains of yeast SAC1, INP52, and INP53 and of human synaptojanin encode polyphosphoinositide phosphatases. J Biol Chem 274(19):12990-5
4) Singer-Kruger B, et al.  (1998) Synaptojanin family members are implicated in endocytic membrane traffic in yeast. J Cell Sci 111 ( Pt 22):3347-56
5) Ooms LM, et al.  (2000) The yeast inositol polyphosphate 5-phosphatases inp52p and inp53p translocate to actin patches following hyperosmotic stress: mechanism for regulating phosphatidylinositol 4,5-bisphosphate at plasma membrane invaginations. Mol Cell Biol 20(24):9376-90
6) Hughes WE, et al.  (2000) Sac phosphatase domain proteins. Biochem J 350 Pt 2():337-52
7) Byrne KP and Wolfe KH  (2005) The Yeast Gene Order Browser: combining curated homology and syntenic context reveals gene fate in polyploid species. Genome Res 15(10):1456-61
8) Stolz LE, et al.  (1998) INP51, a yeast inositol polyphosphate 5-phosphatase required for phosphatidylinositol 4,5-bisphosphate homeostasis and whose absence confers a cold-resistant phenotype. J Biol Chem 273(19):11852-61
9) Strahl T and Thorner J  (2007) Synthesis and function of membrane phosphoinositides in budding yeast, Saccharomyces cerevisiae. Biochim Biophys Acta 1771(3):353-404
10) O'malley CJ, et al.  (2001) Mammalian inositol polyphosphate 5-phosphatase II can compensate for the absence of all three yeast Sac1-like-domain-containing 5-phosphatases. Biochem J 355(Pt 3):805-17
11) Stefan CJ, et al.  (2005) The phosphoinositide phosphatase Sjl2 is recruited to cortical actin patches in the control of vesicle formation and fission during endocytosis. Mol Cell Biol 25(8):2910-23
12) Thompson DA and Stahl FW  (1999) Genetic control of recombination partner preference in yeast meiosis. Isolation and characterization of mutants elevated for meiotic unequal sister-chromatid recombination. Genetics 153(2):621-41
13) De Camilli P, et al.  (1996) Phosphoinositides as regulators in membrane traffic. Science 271(5255):1533-9
14) York JD  (2006) Regulation of nuclear processes by inositol polyphosphates. Biochim Biophys Acta 1761(5-6):552-9
15) Bennett M, et al.  (2006) Inositol pyrophosphates: metabolism and signaling. Cell Mol Life Sci 63(5):552-64
16) Bhandari R, et al.  (2007) Inositol pyrophosphate pyrotechnics. Cell Metab 5(5):321-3