VMA1/YDL185W Summary Help

Standard Name VMA1 1
Systematic Name YDL185W
Alias CLS8 , TFP1 2
Feature Type ORF, Verified
Description Subunit A of the eight-subunit V1 peripheral membrane domain of the vacuolar H+-ATPase; protein precursor undergoes self-catalyzed splicing to yield the extein Tfp1p and the intein Vde (PI-SceI), which is a site-specific endonuclease (1, 3, 4 and see Summary Paragraph)
Name Description Vacuolar Membrane Atpase 1
Chromosomal Location
ChrIV:126787 to 130002 | ORF Map | GBrowse
Gbrowse
Genetic position: -101.43 cM
Gene Ontology Annotations All VMA1 GO evidence and references
  View Computational GO annotations for VMA1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Mutant phenotypes All VMA1 Phenotype evidence and references
Classical genetics
null
overexpression
Large-scale survey
null
overexpression
Resources
interactions All VMA1 Interaction evidence and references
462 total interaction(s) for 370 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 87
  • Affinity Capture-RNA: 3
  • Affinity Capture-Western: 23
  • Co-crystal Structure: 1
  • Co-fractionation: 8
  • Protein-peptide: 2
  • Reconstituted Complex: 2
  • Two-hybrid: 4
Genetic Interactions
  • Dosage Lethality: 2
  • Negative Genetic: 237
  • Phenotypic Suppression: 1
  • Positive Genetic: 27
  • Synthetic Growth Defect: 43
  • Synthetic Lethality: 19
  • Synthetic Rescue: 3
Resources
Expression Summary
histogram
Resources
Protein Information All VMA1 Protein evidence and references
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrIV:126787 to 130002 | ORF Map | GBrowse
This feature contains embedded feature(s): VDE
SGD ORF map
Genetic position: -101.43 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates		 Chromosomal
Coordinates		 Most Recent Updates
Coordinates Sequence
CDS 1..3216 126787..130002 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 SGDIDS000002344
SUMMARY PARAGRAPH for VMA1

VMA1 encodes the A subunit of the yeast V-ATPase V1 domain (1, 5). 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 6, 7, 8 and 9.

The A subunit (Vma1p) of the V-ATPase contains the catalytic nucleotide binding sites (6). The vma1 null mutant is viable but is calcium-sensitive, lacks vacuolar (H )-ATPase activity, and is defective in vacuolar acidification and assembly of the remaining V1 subunits (4, 1, 10, 11). Extensive mutational analysis of Vma1p has identified amino acid residues important for ATP binding and hydrolysis (12, 13). Vma1p homologs have been identified in many organisms including S. pombe (14, 9, 6); cDNAs encoding A subunit homologs have been identified in cotton and can complement the vma11 null mutant (15).

VMA1 also encodes the site-specific endonuclease PI-SceI (also called VDE), which cleaves VMA1 sequences that lack the endonuclease-coding portion to initiate homing, which introduces the endonuclease-coding sequence into the DNA (16). The V-ATPase A subunit and PI-SceI are produced as a single primary translation product that undergoes a self-catalyzed "protein splicing" reaction to release the endonuclease (5, 16, 17, 3, 18, 19). The protein splicing activity resides in the endonuclease segment, and has been well characterized (for example, see 20, 21, and 22). The substrate specificity and molecular mechanism of PI-SceI DNA cleavage have also been examined in detail; recent studies include 23, 24, 25, and 26.

Last updated: 2000-05-11

References cited on this page View Complete Literature Guide for VMA1
1) Hirata R, et al.  (1990) Molecular structure of a gene, VMA1, encoding the catalytic subunit of H(+)-translocating adenosine triphosphatase from vacuolar membranes of Saccharomyces cerevisiae. J Biol Chem 265(12):6726-33
2) Ronne, H.  (1993) Personal Communication, Mortimer Map Edition 12
3) Cooper AA, et al.  (1993) Protein splicing of the yeast TFP1 intervening protein sequence: a model for self-excision. EMBO J 12(6):2575-83
4) Shih CK, et al.  (1988) A dominant trifluoperazine resistance gene from Saccharomyces cerevisiae has homology with F0F1 ATP synthase and confers calcium-sensitive growth. Mol Cell Biol 8(8):3094-103
5) Kane PM, et al.  (1990) Protein splicing converts the yeast TFP1 gene product to the 69-kD subunit of the vacuolar H(+)-adenosine triphosphatase. Science 250(4981):651-7
6) Forgac M  (1999) Structure and properties of the vacuolar (H+)-ATPases. J Biol Chem 274(19):12951-4
7) Graham LA and Stevens TH  (1999) Assembly of the yeast vacuolar proton-translocating ATPase. J Bioenerg Biomembr 31(1):39-47
8) Kane PM  (1999) Biosynthesis and regulation of the yeast vacuolar H+-ATPase. J Bioenerg Biomembr 31(1):49-56
9) Stevens TH and Forgac M  (1997) Structure, function and regulation of the vacuolar (H+)-ATPase. Annu Rev Cell Dev Biol 13:779-808
10) Ohya Y, et al.  (1991) Calcium-sensitive cls mutants of Saccharomyces cerevisiae showing a Pet- phenotype are ascribable to defects of vacuolar membrane H(+)-ATPase activity. J Biol Chem 266(21):13971-7
11) Kane PM, et al.  (1992) Assembly and targeting of peripheral and integral membrane subunits of the yeast vacuolar H(+)-ATPase. J Biol Chem 267(1):447-54
12) Liu J and Kane PM  (1996) Mutational analysis of the catalytic subunit of the yeast vacuolar proton-translocating ATPase. Biochemistry 35(33):10938-48
13) Liu Q, et al.  (1997) Site-directed mutagenesis of the yeast V-ATPase A subunit. J Biol Chem 272(18):11750-6
14) Ghislain M and Bowman EJ  (1992) Sequence of the genes encoding subunits A and B of the vacuolar H(+)-ATPase of Schizosaccharomyces pombe. Yeast 8(9):791-9
15) Kim W, et al.  (1999) Functional complementation of yeast vma1 delta cells by a plant subunit A homolog rescues the mutant phenotype and partially restores vacuolar H(+)-ATPase activity. Plant J 17(5):501-10
16) Gimble FS and Thorner J  (1992) Homing of a DNA endonuclease gene by meiotic gene conversion in Saccharomyces cerevisiae. Nature 357(6376):301-6
17) Hirata R and Anraku Y  (1992) Mutations at the putative junction sites of the yeast VMA1 protein, the catalytic subunit of the vacuolar membrane H(+)-ATPase, inhibit its processing by protein splicing. Biochem Biophys Res Commun 188(1):40-7
18) Gimble FS and Thorner J  (1993) Purification and characterization of VDE, a site-specific endonuclease from the yeast Saccharomyces cerevisiae. J Biol Chem 268(29):21844-53
19) Chong S, et al.  (1996) Protein splicing involving the Saccharomyces cerevisiae VMA intein. The steps in the splicing pathway, side reactions leading to protein cleavage, and establishment of an in vitro splicing system. J Biol Chem 271(36):22159-68
20) Chong S, et al.  (1998) Modulation of protein splicing of the Saccharomyces cerevisiae vacuolar membrane ATPase intein. J Biol Chem 273(17):10567-77
21) Chong S and Xu MQ  (1997) Protein splicing of the Saccharomyces cerevisiae VMA intein without the endonuclease motifs. J Biol Chem 272(25):15587-90
22) Nogami S, et al.  (1997) Probing novel elements for protein splicing in the yeast Vma1 protozyme: a study of replacement mutagenesis and intragenic suppression. Genetics 147(1):73-85
23) Duan X, et al.  (1997) Crystal structure of PI-SceI, a homing endonuclease with protein splicing activity. Cell 89(4):555-64
24) Hu D, et al.  (1999) Mapping of a DNA binding region of the PI-sceI homing endonuclease by affinity cleavage and alanine-scanning mutagenesis. Biochemistry 38(39):12621-8
25) Christ F, et al.  (1999) The monomeric homing endonuclease PI-SceI has two catalytic centres for cleavage of the two strands of its DNA substrate. EMBO J 18(24):6908-16
26) Hu D, et al.  (2000) Probing the structure of the PI-SceI-DNA complex by affinity cleavage and affinity photocross-linking. J Biol Chem 275(4):2705-12