P32563 (VPH1_YEAST) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
V-type proton ATPase subunit a, vacuolar isoform
Short name=V-ATPase a 1 subunit

Alternative name(s):
V-ATPase 95 kDa subunit
Vacuolar pH protein 1
Vacuolar proton pump a subunit
Vacuolar proton translocating ATPase subunit a 1

Gene names

Name:	VPH1
Ordered Locus Names:	YOR270C

Organism

Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces

Protein attributes

Sequence length	840 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Subunit of the integral membrane V0 complex of vacuolar ATPase essential for assembly and catalytic activity. Is present only in vacuolar V-ATPase complexes. Enzymes containing this subunit have a 4-fold higher ratio of proton transport to ATP hydrolysis than complexes containing the Golgi/endosomal isoform and undergo reversible dissociation of V1 and V0 in response to glucose depletion. V-ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells. Ref.7 Ref.8 Ref.13
Subunit structure	V-ATPase is an heteromultimeric enzyme composed of a peripheral catalytic V1 complex (components A to H) attached to an integral membrane V0 proton pore complex (components: a, c, c', c'', d and e). Ref.7
Subcellular location	Vacuole membrane; Multi-pass membrane protein Ref.14.
Post-translational modification	Glycosylated.
Miscellaneous	Present with 55714 molecules/cell in log phase SD medium. Ref.15
Sequence similarities	Belongs to the V-ATPase 116 kDa subunit family.

Ontologies

Keywords
Biological process	Hydrogen ion transport Ion transport Transport
Cellular component	Membrane Vacuole
Domain	Coiled coil Transmembrane Transmembrane helix
PTM	Acetylation Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	ATP hydrolysis coupled proton transport Inferred from electronic annotation. Source: InterPro cell growth Inferred from genetic interaction. Source: UniProtKB polyphosphate metabolic process Inferred from mutant phenotype. Source: SGD protein complex assembly Inferred from mutant phenotype Ref.1Ref.8. Source: SGD vacuolar acidification Inferred from mutant phenotype Ref.1. Source: SGD
Cellular component	fungal-type vacuole membrane Inferred from direct assay. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW vacuolar proton-transporting V-type ATPase, V0 domain Inferred from physical interaction Ref.1. Source: SGD
Molecular function	protein binding Inferred from physical interaction. Source: IntAct proton-transporting ATPase activity, rotational mechanism Inferred from mutant phenotype. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
VMA6	P32366	4	EBI-20455,EBI-20201
VMA7	P39111	5	EBI-20455,EBI-20272

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.6

Chain

2 – 840

839

V-type proton ATPase subunit a, vacuolar isoform

PRO_0000119224

Regions

Topological domain

2 – 404

403

Cytoplasmic Potential

Transmembrane

405 – 423

19

Helical; Potential

Topological domain

424 – 425

2

Vacuolar Potential

Transmembrane

426 – 442

17

Helical; Potential

Topological domain

443 – 456

14

Cytoplasmic Potential

Transmembrane

457 – 486

30

Helical; Potential

Topological domain

487 – 534

48

Vacuolar Potential

Transmembrane

535 – 554

20

Helical; Potential

Topological domain

555 – 572

18

Cytoplasmic Potential

Transmembrane

573 – 593

21

Helical; Potential

Topological domain

594 – 636

43

Vacuolar Potential

Transmembrane

637 – 656

20

Helical; Potential

Topological domain

657 – 719

63

Cytoplasmic Potential

Transmembrane

720 – 744

25

Helical; Potential

Topological domain

745 – 765

21

Vacuolar Potential

Transmembrane

766 – 804

39

Helical; Potential

Topological domain

805 – 840

36

Cytoplasmic Potential

Coiled coil

117 – 145

29

Potential

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.6

Modified residue

671

1

Phosphothreonine Ref.17

Modified residue

676

1

Phosphoserine Ref.17

Modified residue

677

1

Phosphoserine Ref.17

Experimental info

Mutagenesis

425

1

D → N: Reduces assembly of V-ATPase complexes and reduces ATPase activity of the assembled complexes. Ref.8

Mutagenesis

538

1

K → A: Reduces assembly of V-ATPase complexes. Ref.8

Mutagenesis

593

1

K → A: Reduces ATPase activity. Ref.8

Mutagenesis

634

1

Q → L: Reduces subunit stability. Ref.8

Mutagenesis

729

1

H → R: Reduces ATPase activity. Ref.10

Mutagenesis

735

1

R → L: Reduces subunit stability. Ref.8

Mutagenesis

739

1

L → S: Reduces ATPase activity. Ref.10

Mutagenesis

743

1

H → A, E or Y: Reduces ATPase activity. Ref.8 Ref.10

Mutagenesis

746

1

L → S: Reduces ATPase activity. Ref.10

Mutagenesis

780

1

L → S: Reduces assembly of V-ATPase complexes. Ref.10

Mutagenesis

789

1

E → A, D, H or Q: Abolishes ATPase activity and proton transport, but does not affect complex assembly. Ref.8 Ref.10

Mutagenesis

800

1

L → S: Reduces assembly of V-ATPase complexes. Ref.10

Mutagenesis

802

1

W → R: Reduces assembly of V-ATPase complexes. Ref.10

Mutagenesis

803

1

V → D: Reduces ATPase activity. Ref.10

Mutagenesis

803

1

V → F: Reduces assembly of V-ATPase complexes. Ref.10

Mutagenesis

809

1

F → L: Reduces assembly of V-ATPase complexes. Ref.10

Mutagenesis

814

1

G → D: Reduces assembly of V-ATPase complexes. Ref.10

Secondary structure

1

.

.

.

840

Helix Strand Turn

Details...

Helix

729 – 747

19

Sequences

	Sequence		Length	Mass (Da)
	P32563 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 77709A914410CD4D	FASTA	840	95,529
	10 20 30 40 50 60 MAEKEEAIFR SAEMALVQFY IPQEISRDSA YTLGQLGLVQ FRDLNSKVRA FQRTFVNEIR 70 80 90 100 110 120 RLDNVERQYR YFYSLLKKHD IKLYEGDTDK YLDGSGELYV PPSGSVIDDY VRNASYLEER 130 140 150 160 170 180 LIQMEDATDQ IEVQKNDLEQ YRFILQSGDE FFLKGDNTDS TSYMDEDMID ANGENIAAAI 190 200 210 220 230 240 GASVNYVTGV IARDKVATLE QILWRVLRGN LFFKTVEIEQ PVYDVKTREY KHKNAFIVFS 250 260 270 280 290 300 HGDLIIKRIR KIAESLDANL YDVDSSNEGR SQQLAKVNKN LSDLYTVLKT TSTTLESELY 310 320 330 340 350 360 AIAKELDSWF QDVTREKAIF EILNKSNYDT NRKILIAEGW IPRDELATLQ ARLGEMIARL 370 380 390 400 410 420 GIDVPSIIQV LDTNHTPPTF HRTNKFTAGF QSICDCYGIA QYREINAGLP TIVTFPFMFA 430 440 450 460 470 480 IMFGDMGHGF LMTLAALSLV LNEKKINKMK RGEIFDMAFT GRYIILLMGV FSMYTGFLYN 490 500 510 520 530 540 DIFSKTMTIF KSGWKWPDHW KKGESITATS VGTYPIGLDW AWHGTENALL FSNSYKMKLS 550 560 570 580 590 600 ILMGFIHMTY SYFFSLANHL YFNSMIDIIG NFIPGLLFMQ GIFGYLSVCI VYKWAVDWVK 610 620 630 640 650 660 DGKPAPGLLN MLINMFLSPG TIDDELYPHQ AKVQVFLLLM ALVCIPWLLL VKPLHFKFTH 670 680 690 700 710 720 KKKSHEPLPS TEADASSEDL EAQQLISAMD ADDAEEEEVG SGSHGEDFGD IMIHQVIHTI 730 740 750 760 770 780 EFCLNCVSHT ASYLRLWALS LAHAQLSSVL WTMTIQIAFG FRGFVGVFMT VALFAMWFAL 790 800 810 820 830 840 TCAVLVLMEG TSAMLHSLRL HWVESMSKFF VGEGLPYEPF AFEYKDMEVA VASASSSASS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The VPH1 gene encodes a 95-kDa integral membrane polypeptide required for in vivo assembly and activity of the yeast vacuolar H(+)-ATPase." Manolson M.F., Proteau D., Preston R.A., Stenbit A., Roberts B.T., Hoyt M.A., Preuss D., Mulholland J., Botstein D., Jones E.W. J. Biol. Chem. 267:14294-14303(1992) [PubMed: 1385813] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"DNA sequence analysis of the VPH1-SNF2 region on chromosome XV of Saccharomyces cerevisiae." Cheret G., Bernardi A., Sor F.J. Yeast 12:1059-1064(1996) [PubMed: 8896271] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[3]	"Sequencing analysis of a 36.8 kb fragment of yeast chromosome XV reveals 26 open reading frames including SEC63, CDC31, SUG2, GCD1, RBL2, PNT1, PAC1 and VPH1." Poirey R., Jauniaux J.-C. Yeast 13:483-487(1997) [PubMed: 9153759] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 96604 / S288c / FY1679.
[4]	"The nucleotide sequence of Saccharomyces cerevisiae chromosome XV." Dujon B., Albermann K., Aldea M., Alexandraki D., Ansorge W., Arino J., Benes V., Bohn C., Bolotin-Fukuhara M., Bordonne R., Boyer J., Camasses A., Casamayor A., Casas C., Cheret G., Cziepluch C., Daignan-Fornier B., Dang V.-D. , de Haan M., Delius H., Durand P., Fairhead C., Feldmann H., Gaillon L., Galisson F., Gamo F.-J., Gancedo C., Goffeau A., Goulding S.E., Grivell L.A., Habbig B., Hand N.J., Hani J., Hattenhorst U., Hebling U., Hernando Y., Herrero E., Heumann K., Hiesel R., Hilger F., Hofmann B., Hollenberg C.P., Hughes B., Jauniaux J.-C., Kalogeropoulos A., Katsoulou C., Kordes E., Lafuente M.J., Landt O., Louis E.J., Maarse A.C., Madania A., Mannhaupt G., Marck C., Martin R.P., Mewes H.-W., Michaux G., Paces V., Parle-McDermott A.G., Pearson B.M., Perrin A., Pettersson B., Poch O., Pohl T.M., Poirey R., Portetelle D., Pujol A., Purnelle B., Ramezani Rad M., Rechmann S., Schwager C., Schweizer M., Sor F., Sterky F., Tarassov I.A., Teodoru C., Tettelin H., Thierry A., Tobiasch E., Tzermia M., Uhlen M., Unseld M., Valens M., Vandenbol M., Vetter I., Vlcek C., Voet M., Volckaert G., Voss H., Wambutt R., Wedler H., Wiemann S., Winsor B., Wolfe K.H., Zollner A., Zumstein E., Kleine K. Nature 387:98-102(1997) [PubMed: 9169874] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 96604 / S288c / FY1679.
[5]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[6]	Bienvenut W.V., Peters C. Submitted (JUN-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-10, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY.
[7]	"Evidence for a conserved 95-120 kDa subunit associated with and essential for activity of V-ATPases." Manolson M.F., Proteau D., Jones E.W. J. Exp. Biol. 172:105-112(1992) [PubMed: 1491220] [Abstract] Cited for: FUNCTION, SUBUNIT.
[8]	"Site-directed mutagenesis of the 100-kDa subunit (Vph1p) of the yeast vacuolar (H+)-ATPase." Leng X.-H., Manolson M.F., Liu Q., Forgac M. J. Biol. Chem. 271:22487-22493(1996) [PubMed: 8798414] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ASP-425; LYS-538; LYS-593; GLN-634; ARG-735; HIS-743 AND GLU-789.
[9]	Erratum Leng X.-H., Manolson M.F., Liu Q., Forgac M. J. Biol. Chem. 271:28725-28725(1996)
[10]	"Function of the COOH-terminal domain of Vph1p in activity and assembly of the yeast V-ATPase." Leng X.-H., Manolson M.F., Forgac M. J. Biol. Chem. 273:6717-6723(1998) [PubMed: 9506970] [Abstract] Cited for: MUTAGENESIS OF HIS-729; LEU-739; HIS-743; LEU-746; LEU-780; GLU-789; LEU-800; TRP-802; VAL-803; PHE-809 AND GLY-814.
[11]	"Transmembrane topography of the 100-kDa a subunit (Vph1p) of the yeast vacuolar proton-translocating ATPase." Leng X.-H., Nishi T., Forgac M. J. Biol. Chem. 274:14655-14661(1999) [PubMed: 10329659] [Abstract] Cited for: TOPOLOGY.
[12]	"Substrate- and inhibitor-induced conformational changes in the yeast V-ATPase provide evidence for communication between the catalytic and proton-translocating sectors." Landolt-Marticorena C., Kahr W.H., Zawarinski P., Correa J., Manolson M.F. J. Biol. Chem. 274:26057-26064(1999) [PubMed: 10473553] [Abstract] Cited for: TOPOLOGY.
[13]	"Yeast V-ATPase complexes containing different isoforms of the 100-kDa a-subunit differ in coupling efficiency and in vivo dissociation." Kawasaki-Nishi S., Nishi T., Forgac M. J. Biol. Chem. 276:17941-17948(2001) [PubMed: 11278748] [Abstract] Cited for: FUNCTION.
[14]	"Global analysis of protein localization in budding yeast." Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K. Nature 425:686-691(2003) [PubMed: 14562095] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[15]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed: 14562106] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
[16]	"A global topology map of the Saccharomyces cerevisiae membrane proteome." Kim H., Melen K., Oesterberg M., von Heijne G. Proc. Natl. Acad. Sci. U.S.A. 103:11142-11147(2006) [PubMed: 16847258] [Abstract] Cited for: TOPOLOGY [LARGE SCALE ANALYSIS]. Strain: ATCC 208353 / W303-1A.
[17]	"A multidimensional chromatography technology for in-depth phosphoproteome analysis." Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H. Mol. Cell. Proteomics 7:1389-1396(2008) [PubMed: 18407956] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-671; SER-676 AND SER-677, MASS SPECTROMETRY.
[18]	"Definition of membrane topology and identification of residues important for transport in subunit a of the vacuolar ATPase." Toei M., Toei S., Forgac M. J. Biol. Chem. 286:35176-35186(2011) [PubMed: 21832060] [Abstract] Cited for: TOPOLOGY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M89778 Genomic DNA. Translation: AAA35211.1.
X89633 Genomic DNA. Translation: CAA61776.1.
Z75178 Genomic DNA. Translation: CAA99494.1.
Z75179 Genomic DNA. Translation: CAA99496.1.
BK006948 Genomic DNA. Translation: DAA11036.1.

PIR

A42970.

RefSeq

NP_014913.1. NM_001183689.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JTW	NMR	-	A	728-748	[»]
2NVJ	NMR	-	A	721-744	[»]
2RPW	NMR	-	X	728-748	[»]

ProteinModelPortal

P32563.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-2960N.

IntAct

P32563. 37 interactions.

MINT

MINT-630784.

STRING

P32563.

Protein family/group databases

TCDB

3.A.2.2.3. H+- or Na+-translocating F-type, V-type and A-type ATPase (F-ATPase) superfamily.

Proteomic databases

PeptideAtlas

P32563.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblFungi

YOR270C; YOR270C; YOR270C.

GeneID

854444.

KEGG

sce:YOR270C.

NMPDR

fig|4932.3.peg.6025.

Organism-specific databases

SGD

S000005796. VPH1.

Phylogenomic databases

eggNOG

fuNOG05994.

GeneTree

EFGT00050000006837.

HOGENOM

HBG629705.

OMA

KTESEMI.

OrthoDB

EOG4936S5.

Gene expression databases

ArrayExpress

P32563.

Genevestigator

P32563.

GermOnline

YOR270C. Saccharomyces cerevisiae.

Family and domain databases

InterPro

IPR002490. ATPase_V0/A0-cplx_116kDa_su.
[Graphical view]

KO

K02154.

PANTHER

PTHR11629. ATPase_V0/A0_116. 1 hit.

Pfam

PF01496. V_ATPase_I. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

976694.

Entry information

Entry name

VPH1_YEAST

Accession

Primary (citable) accession number: P32563
Secondary accession number(s): D6W2X0

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1993
Last sequence update:	January 23, 2007
Last modified:	January 25, 2012
This is version 119 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program