MSS4/YDR208W Summary Help

Standard Name MSS4 1
Systematic Name YDR208W
Feature Type ORF, Verified
Description Phosphatidylinositol-4-phosphate 5-kinase; involved in actin cytoskeleton organization and cell morphogenesis; multicopy suppressor of stt4 mutation (1, 2, 3 and see Summary Paragraph)
Name Description Multicopy Suppressor of Stt4 mutation 1
Chromosomal Location
ChrIV:868224 to 870563 | ORF Map | GBrowse
Gene Ontology Annotations All MSS4 GO evidence and references
  View Computational GO annotations for MSS4
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 3 genes
Classical genetics
Large-scale survey
reduction of function
100 total interaction(s) for 83 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 10
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 2
  • Biochemical Activity: 5
  • PCA: 2
  • Two-hybrid: 1

Genetic Interactions
  • Dosage Growth Defect: 1
  • Dosage Rescue: 27
  • Negative Genetic: 7
  • Phenotypic Enhancement: 1
  • Phenotypic Suppression: 1
  • Positive Genetic: 5
  • Synthetic Growth Defect: 1
  • Synthetic Haploinsufficiency: 1
  • Synthetic Lethality: 32
  • Synthetic Rescue: 3

Expression Summary
Length (a.a.) 779
Molecular Weight (Da) 89,320
Isoelectric Point (pI) 10.13
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrIV:868224 to 870563 | ORF Map | GBrowse
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..2340 868224..870563 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 SGDIDS000002616

MSS4 encodes a phosphatidylinositol (PtdIns) 4-phosphate 5-kinase that catalyzes the phosphorylation of PtdIns 4-phosphate, the final step in the synthesis of phosphatidylinositol 4,5-bisphosphate (PtdIns[4,5]P2) (4, 2). Mss4p acts with the PtdIns 4-kinase Stt4p at the plasma membrane to generate PtdIns[4,5]P2, which is required for activation of the Rho1/Pkc1-mediated MAP kinase cascade important for normal organization of the actin cytoskeleton (5, 6). Mss4p activity and synthesis of PtdIns[4,5]P2 is also essential for sporulation, endocytosis, and membrane trafficking (7, 8). Mss4p contains a functional nuclear localization signal (NLS), and undergoes nucleocytoplasmic shuttling, thereby regulating PtdIns[4,5]P2 synthesis at the plasma membrane (6). Nucleocytoplasmic shuttling of Mss4p depends on Kap123p and Bcp1p, whereas its recruitment to the plasma membrane involves phosphorylation by the casein kinase I isoforms Yck1p and Yck2p (9). An essential role for Mss4p in the nucleus has not been demonstrated (6). Treatment of cells with ISP-1/myriocin causes defects in both the activity and subcellular localization of Mss4p (10). Mss4p is also mislocalized in cells lacking functional Csg2p, an ER-membrane protein required for mannosylation of inositolphosphorylceramide (10).

MSS4 was originally identified as a multicopy suppressor of a temperature-sensitive mutation in the STT4 PtdIns 4-kinase (1). Inactivation of either Stt4p or Mss4p results in mislocalization of the Rho-GTPase guanine nucleotide exchange factor Rom2p (5), and a shift from polarized to isotropic cell growth, such that cells severely increase in size and adopt a round shape (2). Mutations in either STT4 or MSS4 display synthetic defects with a number of mutations in genes encoding known components of the PKC1 pathway (5). mss4 null mutants are inviable, exhibiting aberrant filamentous actin localization and subsequent cell death (1, 3).

Temperature-sensitive mss4 mutant cells have only a fraction of the normal amount of PtdIns[4,5]P2, are unable to form actin cables or properly localize their actin cytoskeleton during polarized cell growth, and exhibit defective spore formation (3, 2, 7). Cells lacking functional Mss4p also partially mislocalize the PtdIns[4,5]P2-binding protein Slm1p to the cytoplasm (11, 12). Overexpression of MSS4 confers resistance to wortmannin, suppresses growth and actin defects associated with mutations in TOR2 and CMD1, and generates elevated levels of PtdIns[4,5]P2 (13, 14, 3, 15). MSS4 overexpression also alleviates the growth and secretory defects of a number of temperature-sensitive late secretion mutants, including various components of the exocyst, such as SEC8, SEC10, and SEC15 (16).

Phosphatidylinositol 4-phosphate 5-kinase activity is conserved from yeast to human (2). Homologs of Mss4p have been identified in other yeasts, including Schizosaccharomyces pombe (17) and Candida albicans (18).

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 19). PtdInsPs are also precursors of the water-soluble inositol phosphates (IPs), an important class of intracellular signaling molecules (reviewed in 20, 21 and 22).

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 (19, 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 MSS4
1) Yoshida S, et al.  (1994) Genetic interactions among genes involved in the STT4-PKC1 pathway of Saccharomyces cerevisiae. Mol Gen Genet 242(6):631-40
2) Homma K, et al.  (1998) Phosphatidylinositol-4-phosphate 5-kinase localized on the plasma membrane is essential for yeast cell morphogenesis. J Biol Chem 273(25):15779-86
3) Desrivieres S, et al.  (1998) MSS4, a phosphatidylinositol-4-phosphate 5-kinase required for organization of the actin cytoskeleton in Saccharomyces cerevisiae. J Biol Chem 273(25):15787-93
4) Boronenkov IV and Anderson RA  (1995) The sequence of phosphatidylinositol-4-phosphate 5-kinase defines a novel family of lipid kinases. J Biol Chem 270(7):2881-4
5) 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
6) Audhya A and Emr SD  (2003) Regulation of PI4,5P2 synthesis by nuclear-cytoplasmic shuttling of the Mss4 lipid kinase. EMBO J 22(16):4223-36
7) 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
8) Sun Y, et al.  (2007) PtdIns(4,5)P2 turnover is required for multiple stages during clathrin- and actin-dependent endocytic internalization. J Cell Biol 177(2):355-67
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) Kobayashi T, et al.  (2005) Disturbance of sphingolipid biosynthesis abrogates the signaling of Mss4, phosphatidylinositol-4-phosphate 5-kinase, in yeast. J Biol Chem 280(18):18087-94
11) Audhya A, et al.  (2004) Genome-wide lethality screen identifies new PI4,5P2 effectors that regulate the actin cytoskeleton. EMBO J 23(19):3747-57
12) Fadri M, et al.  (2005) The pleckstrin homology domain proteins Slm1 and Slm2 are required for actin cytoskeleton organization in yeast and bind phosphatidylinositol-4,5-bisphosphate and TORC2. Mol Biol Cell 16(4):1883-900
13) Cutler NS, et al.  (1997) STT4 is an essential phosphatidylinositol 4-kinase that is a target of wortmannin in Saccharomyces cerevisiae. J Biol Chem 272(44):27671-7
14) Helliwell SB, et al.  (1998) TOR2 is part of two related signaling pathways coordinating cell growth in Saccharomyces cerevisiae. Genetics 148(1):99-112
15) Desrivieres S, et al.  (2002) Calmodulin controls organization of the actin cytoskeleton via regulation of phosphatidylinositol (4,5)-bisphosphate synthesis in Saccharomyces cerevisiae. Biochem J 366(Pt 3):945-51
16) Routt SM, et al.  (2005) Nonclassical PITPs activate PLD via the Stt4p PtdIns-4-kinase and modulate function of late stages of exocytosis in vegetative yeast. Traffic 6(12):1157-72
17) Zhang Y, et al.  (2000) Phosphatidylinositol 4-phosphate 5-kinase Its3 and calcineurin Ppb1 coordinately regulate cytokinesis in fission yeast. J Biol Chem 275(45):35600-6
18) Hairfield ML, et al.  (2002) Phosphatidylinositol-4-phosphate 5-kinase activity is stimulated during temperature-induced morphogenesis in Candida albicans. Microbiology 148(Pt 6):1737-46
19) De Camilli P, et al.  (1996) Phosphoinositides as regulators in membrane traffic. Science 271(5255):1533-9
20) York JD  (2006) Regulation of nuclear processes by inositol polyphosphates. Biochim Biophys Acta 1761(5-6):552-9
21) Bennett M, et al.  (2006) Inositol pyrophosphates: metabolism and signaling. Cell Mol Life Sci 63(5):552-64
22) Bhandari R, et al.  (2007) Inositol pyrophosphate pyrotechnics. Cell Metab 5(5):321-3