PIK1/YNL267W Summary Help

Standard Name PIK1 1
Systematic Name YNL267W
Alias PIK41 2 , PIK120 2
Feature Type ORF, Verified
Description Phosphatidylinositol 4-kinase; catalyzes first step in the biosynthesis of phosphatidylinositol-4,5-biphosphate; may control cytokinesis through the actin cytoskeleton; may control nonselective autophagy and mitophagy through trafficking of Atg9p (1, 3, 4 and see Summary Paragraph)
Name Description Phosphatidyl Inositol Kinase 1
Chromosomal Location
ChrXIV:140878 to 144078 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All PIK1 GO evidence and references
  View Computational GO annotations for PIK1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 4 genes
Resources
Pathways
Classical genetics
conditional
null
overexpression
reduction of function
repressible
unspecified
Large-scale survey
conditional
null
reduction of function
repressible
Resources
197 total interaction(s) for 149 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 11
  • Affinity Capture-RNA: 2
  • Affinity Capture-Western: 8
  • Biochemical Activity: 3
  • Co-fractionation: 3
  • Reconstituted Complex: 6
  • Two-hybrid: 8

Genetic Interactions
  • Dosage Growth Defect: 2
  • Dosage Rescue: 8
  • Negative Genetic: 2
  • Phenotypic Enhancement: 4
  • Phenotypic Suppression: 3
  • Positive Genetic: 4
  • Synthetic Growth Defect: 79
  • Synthetic Lethality: 52
  • Synthetic Rescue: 2

Resources
Expression Summary
histogram
Resources
Length (a.a.) 1,066
Molecular Weight (Da) 119,922
Isoelectric Point (pI) 6.46
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXIV:140878 to 144078 | ORF Map | GBrowse
SGD ORF map
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..3201 140878..144078 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000005211
SUMMARY PARAGRAPH for PIK1

Phosphatidylinositol 4-kinases (ATP:phosphatidylinositol-4-phosphotransferase, EC 2.7.1.67) are evolutionarily conserved enzymes that catalyze the formation of phosphatidylinositol 4-phosphate and ADP from phosphatidylinositol (PtdIns or PI) and ATP, the first step in the synthesis of phosphatidylinositol phosphates (5, 6). Two types of PtdIns 4-kinases (types II and III) have been identified based on their biochemical properties (5). Type III PtdIns 4-kinases all contain a common catalytic kinase domain, which is also found in type I PtdIns 3-kinases (7, 8). There are two type III PtdIns 4-kinases in S. cerevisiae, encoded by PIK1 and STT4 (1, 9). LSB6 encodes the single type II PtdIns 4-kinase in yeast (5, 6).

Pik1p is a soluble 125-kDa enzyme (10), and Stt4p is a plasma membrane-associated 215-kDa enzyme (9, 11). Together, Pik1p and Stt4p account for the vast majority of PtdIns 4-kinase activity in wild-type yeast cells (12). The two different type III PtdIns 4-kinases synthesize discrete pools of PtdIns 4-phosphate with essential roles in cell physiology (12). Overproduction of one of these type III PtdIns 4-kinases cannot compensate for a gene disruption in the other (12). Stt4p is homologous to mammalian PtdIns 4-kinase alpha, and Pik1p to mammalian PtdIns 4-kinase beta (7).

Pik1p localizes to the nucleus and to the Golgi, where it regulates secretion (3, 12, 13, 14, 15, 16). Pik1p is also required for proper Golgi and vacuole membrane dynamics, and endocytosis (13, 12, 6). Pik1p is activated by frequenin (Frq1p), which binds Pik1p at its amino terminus, and aids in targeting Pik1p to the Golgi (17, 18, 15, 19). Pik1p also binds the 14-3-3 phosphorylation-dependent protein chaperones Bmh1p and Bmh2p (20). This interaction occurs primarily in the cytoplasm, and controls the nucleocytoplasmic shuttling and availability of Pik1p for Golgi recruitment (20). Nutrient deprivation results in a relocation of Pik1p from the Golgi to the nucleus, which is rapidly reversed upon restoration of nutrient supply (20).

pik1 null mutants are inviable, and conditional pik1 mutants exhibit defects in cytokinesis, endocytosis, protein secretion, and vacuolar dynamics (3, 1, 12, 6). Temperature-sensitive pik1 mutants also display aberrant Golgi morphology (12), and can fail to undergo meiosis and spore formation (21). Inactivation of Pik1p results in severe translation initiation defects and a marked increased in the phosphorylation of translation initiation factor eIF2alpha (22). Overexpression of PIK1 produces defects in membrane trafficking (23).

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 24 and 25). PtdInsPs are also precursors of the water-soluble inositol phosphates (IPs), an important class of intracellular signaling molecules (reviewed in 26, 27 and 28).

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 24). These stereoisomers have been shown to be restricted to certain membranes (reviewed in 24). 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 24). 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 24). 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 24).

Phosphorylation and dephosphorylation of the inositol headgroups of PtdInsPs at specific membrane locations signals the recruitment of certain proteins essential for vesicular transport (25, and reviewed in 24). 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 24).

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 24). 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 PIK1
1) Flanagan CA, et al.  (1993) Phosphatidylinositol 4-kinase: gene structure and requirement for yeast cell viability. Science 262(5138):1444-8
2) Hunter T and Plowman GD  (1997) The protein kinases of budding yeast: six score and more. Trends Biochem Sci 22(1):18-22
3) Garcia-Bustos JF, et al.  (1994) PIK1, an essential phosphatidylinositol 4-kinase associated with the yeast nucleus. EMBO J 13(10):2352-61
4) Wang K, et al.  (2012) Phosphatidylinositol 4-kinases are required for autophagic membrane trafficking. J Biol Chem 287(45):37964-72
5) Han GS, et al.  (2002) The Saccharomyces cerevisiae LSB6 gene encodes phosphatidylinositol 4-kinase activity. J Biol Chem 277(49):47709-18
6) Shelton SN, et al.  (2003) Saccharomyces cerevisiae contains a Type II phosphoinositide 4-kinase. Biochem J 371(Pt 2):533-40
7) Fruman DA, et al.  (1998) Phosphoinositide kinases. Annu Rev Biochem 67():481-507
8) Odorizzi G, et al.  (2000) Phosphoinositide signaling and the regulation of membrane trafficking in yeast. Trends Biochem Sci 25(5):229-35
9) Yoshida S, et al.  (1994) A novel gene, STT4, encodes a phosphatidylinositol 4-kinase in the PKC1 protein kinase pathway of Saccharomyces cerevisiae. J Biol Chem 269(2):1166-72
10) Flanagan CA and Thorner J  (1992) Purification and characterization of a soluble phosphatidylinositol 4-kinase from the yeast Saccharomyces cerevisiae. J Biol Chem 267(33):24117-25
11) Audhya A and Emr SD  (2002) Stt4 PI 4-kinase localizes to the plasma membrane and functions in the Pkc1-mediated MAP kinase cascade. Dev Cell 2(5):593-605
12) Audhya A, et al.  (2000) Distinct roles for the yeast phosphatidylinositol 4-kinases, Stt4p and Pik1p, in secretion, cell growth, and organelle membrane dynamics. Mol Biol Cell 11(8):2673-89
13) Hama H, et al.  (1999) Direct involvement of phosphatidylinositol 4-phosphate in secretion in the yeast Saccharomyces cerevisiae. J Biol Chem 274(48):34294-300
14) Walch-Solimena C and Novick P  (1999) The yeast phosphatidylinositol-4-OH kinase pik1 regulates secretion at the Golgi. Nat Cell Biol 1(8):523-5
15) Strahl T, et al.  (2005) Yeast phosphatidylinositol 4-kinase, Pik1, has essential roles at the Golgi and in the nucleus. J Cell Biol 171(6):967-79
16) Sciorra VA, et al.  (2005) Synthetic genetic array analysis of the PtdIns 4-kinase Pik1p identifies components in a Golgi-specific Ypt31/rab-GTPase signaling pathway. Mol Biol Cell 16(2):776-93
17) Hendricks KB, et al.  (1999) Yeast homologue of neuronal frequenin is a regulator of phosphatidylinositol-4-OH kinase. Nat Cell Biol 1(4):234-41
18) Huttner IG, et al.  (2003) Molecular interactions of yeast frequenin (Frq1) with the phosphatidylinositol 4-kinase isoform, Pik1. J Biol Chem 278(7):4862-74
19) Strahl T, et al.  (2007) Structural insights into activation of phosphatidylinositol 4-kinase (pik1) by yeast frequenin (Frq1). J Biol Chem 282(42):30949-59
20) Demmel L, et al.  (2008) Nucleocytoplasmic shuttling of the Golgi phosphatidylinositol 4-kinase pik1 is regulated by 14-3-3 proteins and coordinates Golgi function with cell growth. Mol Biol Cell 19(3):1046-61
21) Rudge SA, et al.  (2004) Roles of phosphoinositides and of Spo14p (phospholipase D)-generated phosphatidic acid during yeast sporulation. Mol Biol Cell 15(1):207-18
22) Cameroni E, et al.  (2006) Phosphatidylinositol 4-Phosphate Is Required for Translation Initiation in Saccharomyces cerevisiae. J Biol Chem 281(50):38139-49
23) Schorr M, et al.  (2001) The phosphoinositide phosphatase Sac1p controls trafficking of the yeast Chs3p chitin synthase. Curr Biol 11(18):1421-6
24) Strahl T and Thorner J  (2007) Synthesis and function of membrane phosphoinositides in budding yeast, Saccharomyces cerevisiae. Biochim Biophys Acta 1771(3):353-404
25) De Camilli P, et al.  (1996) Phosphoinositides as regulators in membrane traffic. Science 271(5255):1533-9
26) York JD  (2006) Regulation of nuclear processes by inositol polyphosphates. Biochim Biophys Acta 1761(5-6):552-9
27) Bennett M, et al.  (2006) Inositol pyrophosphates: metabolism and signaling. Cell Mol Life Sci 63(5):552-64
28) Bhandari R, et al.  (2007) Inositol pyrophosphate pyrotechnics. Cell Metab 5(5):321-3