VPH1/YOR270C Summary Help

Standard Name VPH1 1, 2
Systematic Name YOR270C
Feature Type ORF, Verified
Description Subunit a of vacuolar-ATPase V0 domain; one of two isoforms (Vph1p and Stv1p); Vph1p is located in V-ATPase complexes of the vacuole while Stv1p is located in V-ATPase complexes of the Golgi and endosomes; relative distribution to the vacuolar membrane decreases upon DNA replication stress (1, 3, 4, 5, 6 and see Summary Paragraph)
Name Description Vacuolar pH 1, 2
Chromosomal Location
ChrXV:830574 to 828052 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Gene Ontology Annotations All VPH1 GO evidence and references
  View Computational GO annotations for VPH1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
High-throughput
Regulators 3 genes
Resources
Classical genetics
null
Large-scale survey
null
Resources
276 total interaction(s) for 158 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 30
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 39
  • Co-crystal Structure: 2
  • Co-fractionation: 10
  • Co-localization: 2
  • FRET: 2
  • PCA: 11
  • Protein-peptide: 5
  • Reconstituted Complex: 5
  • Two-hybrid: 3

Genetic Interactions
  • Dosage Growth Defect: 2
  • Dosage Lethality: 1
  • Dosage Rescue: 2
  • Negative Genetic: 113
  • Phenotypic Enhancement: 2
  • Phenotypic Suppression: 1
  • Positive Genetic: 31
  • Synthetic Growth Defect: 9
  • Synthetic Lethality: 2
  • Synthetic Rescue: 1

Resources
Expression Summary
histogram
Resources
Length (a.a.) 840
Molecular Weight (Da) 95,528
Isoelectric Point (pI) 5.24
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXV:830574 to 828052 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
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..2523 830574..828052 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 SGDIDS000005796
SUMMARY PARAGRAPH for VPH1

VPH1 is one of two yeast genes encoding isoforms of the a subunit of the yeast V-ATPase V0 domain (1, 7, 3). Vacuolar (H )-ATPases (V-ATPases) are ATP-dependent proton pumps that acidify intracellular vacuolar compartments. Vacuolar acidification is important for many cellular processes, including endocytosis, targeting of newly synthesized lysosomal enzymes, and other molecular targeting processes. The V-ATPase consists of two separable domains. The V1 domain has eight known subunits, is peripherally associated with the vacuolar membrane, and catalyzes ATP hydrolysis. The V0 domain is an integral membrane structure of five subunits, and transports protons across the membrane. The structure, function, and assembly of V-ATPases are reviewed in references 8, 4, 9 and 10.

The vph1 null mutant is viable but lacks V-ATPase activity and ATP-dependent proton pumping, and is defective in vacuolar acidification (1). The nucleotide-binding subunits of the V1 domain are present but not associated with the vacuolar membrane in vph1-1 mutant cells (1). The vph1-1 mutation also alters cellular phosphate trafficking (11). Point mutations have identified amino acid residues in Vph1p that are likely to be involved in proton transport, ATPase activity, and V-ATPase holoenzyme assembly (12, 13).

The vph1 null mutant shows a modest growth defect at neutral pH or in the presence of excess calcium; deletion of both VPH1 and STV1, which encodes the second a subunit isoform, causes a more severe growth defect, similar to the phenotypes of other V-ATPases subunit nulls (3). Overproduction of Stv1p partially restores vacuolar acidification in the vph1 null mutant (3). Vph1p and Stv1p show different localization patterns in indirect immunofluorescence assays, suggesting that they may be equivalent subunits for V-ATPases located on different organelles (3).

Vph1p interacts directly with two V-ATPase assembly factors, Vma12p and Vma22p (14). In the absence of Vma22p, Vph1p is degraded in the ER (15).

Stv1p and Vph1p are 55% identical and proteins similar to Vph1p have also been identified in rat, mouse, C. elegans and humans (7). Mutations in the isoforms of human V-ATPase most similar to Vph1p, a3 and a4, result in osteopetrosis and distal renal tubular acidosis, respectively (16, 17).

Last updated: 2000-05-17 Contact SGD

References cited on this page View Complete Literature Guide for VPH1
1) Manolson MF, et al.  (1992) The VPH1 gene encodes a 95-kDa integral membrane polypeptide required for in vivo assembly and activity of the yeast vacuolar H(+)-ATPase. J Biol Chem 267(20):14294-303
2) Preston RA, et al.  (1989) Assay of vacuolar pH in yeast and identification of acidification-defective mutants. Proc Natl Acad Sci U S A 86(18):7027-31
3) Manolson MF, et al.  (1994) STV1 gene encodes functional homologue of 95-kDa yeast vacuolar H(+)-ATPase subunit Vph1p. J Biol Chem 269(19):14064-74
4) Graham LA and Stevens TH  (1999) Assembly of the yeast vacuolar proton-translocating ATPase. J Bioenerg Biomembr 31(1):39-47
5) Kawasaki-Nishi S, et al.  (2001) Yeast V-ATPase complexes containing different isoforms of the 100-kDa a-subunit differ in coupling efficiency and in vivo dissociation. J Biol Chem 276(21):17941-8
6) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
7) Manolson MF, et al.  (1992) Evidence for a conserved 95-120 kDa subunit associated with and essential for activity of V-ATPases. J Exp Biol 172():105-12
8) Forgac M  (1999) Structure and properties of the vacuolar (H+)-ATPases. J Biol Chem 274(19):12951-4
9) Kane PM  (1999) Biosynthesis and regulation of the yeast vacuolar H+-ATPase. J Bioenerg Biomembr 31(1):49-56
10) Stevens TH and Forgac M  (1997) Structure, function and regulation of the vacuolar (H+)-ATPase. Annu Rev Cell Dev Biol 13:779-808
11) Castrol CD, et al.  (1999) NMR-Observed phosphate trafficking and polyphosphate dynamics in wild-type and vph1-1 mutant Saccharomyces cerevisae in response to stresses. Biotechnol Prog 15(1):65-73
12) Leng XH, et al.  (1996) Site-directed mutagenesis of the 100-kDa subunit (Vph1p) of the yeast vacuolar (H+)-ATPase. J Biol Chem 271(37):22487-93
13) Leng XH, et al.  (1998) Function of the COOH-terminal domain of Vph1p in activity and assembly of the yeast V-ATPase. J Biol Chem 273(12):6717-23
14) Graham LA, et al.  (1998) Assembly of the yeast vacuolar H+-ATPase occurs in the endoplasmic reticulum and requires a Vma12p/Vma22p assembly complex. J Cell Biol 142(1):39-49
15) Hill K and Cooper AA  (2000) Degradation of unassembled Vph1p reveals novel aspects of the yeast ER quality control system. EMBO J 19(4):550-61
16) Ochotny NM, et al.  (2006) Effects of Human a3 and a4 Mutations That Result in Osteopetrosis and Distal Renal Tubular Acidosis on Yeast V-ATPase Expression and Activity. J Biol Chem 281(36):26102-11
17) Kornak U, et al.  (2000) Mutations in the a3 subunit of the vacuolar H(+)-ATPase cause infantile malignant osteopetrosis. Hum Mol Genet 9(13):2059-63