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Q9Y487 (VPP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
V-type proton ATPase 116 kDa subunit a isoform 2

Short name=V-ATPase 116 kDa isoform a2
Alternative name(s):
Lysosomal H(+)-transporting ATPase V0 subunit a2
TJ6
Vacuolar proton translocating ATPase 116 kDa subunit a isoform 2
Gene names
Name:ATP6V0A2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length856 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Part of the proton channel of V-ATPases. Essential component of the endosomal pH-sensing machinery. May play a role in maintaining the Golgi functions, such as glycosylation maturation, by controlling the Golgi pH. Ref.5 Ref.8

Subunit structure

The V-ATPase is a heteromultimeric enzyme composed of at least thirteen different subunits. It has a membrane peripheral V1 sector for ATP hydrolysis and an integral V0 for proton translocation. The V1 sector comprises subunits A-H, whereas V0 includes subunits a, d, c, c', and c''. Directly interacts with PSCD2 through its N-terminal cytosolic tail in an intra-endosomal acidification-dependent manner. Disruption of this interaction results in the inhibition of endocytosis. Ref.5

Subcellular location

Cell membrane; Multi-pass membrane protein. Endosome membrane. Note: In kidney proximal tubules, also detected in subapical vesicles By similarity. Ref.5 Ref.6 Ref.8

Involvement in disease

Cutis laxa, autosomal recessive, 2A (ARCL2A) [MIM:219200]: A disorder characterized by an excessive congenital skin wrinkling, a large fontanelle with delayed closure, a typical facial appearance with downslanting palpebral fissures, a general connective tissue weakness, and varying degrees of growth and developmental delay and neurological abnormalities. Some affected individuals develop seizures and mental deterioration later in life, whereas the skin phenotype tends to become milder with age. At the molecular level, an abnormal glycosylation of serum proteins is observed in many cases.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

Wrinkly skin syndrome (WSS) [MIM:278250]: A rare autosomal recessive disorder characterized by wrinkling of the skin of the dorsum of the hands and feet, an increased number of palmar and plantar creases, wrinkled abdominal skin, multiple musculoskeletal abnormalities, microcephaly, growth failure and developmental delay.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8

Sequence similarities

Belongs to the V-ATPase 116 kDa subunit family.

Caution

The N-terminus peptide may increase IL1B secretion by peripheral blood monocytes; however as this region is probably in the cytosol, the in vivo relevance of this observation needs to be confirmed.

Ontologies

Keywords
   Biological processHydrogen ion transport
Ion transport
Transport
   Cellular componentCell membrane
Endosome
Membrane
   Coding sequence diversityPolymorphism
   DomainTransmembrane
Transmembrane helix
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processATP hydrolysis coupled proton transport

Inferred from electronic annotation. Source: InterPro

cellular iron ion homeostasis

Traceable author statement. Source: Reactome

immune response

Traceable author statement PubMed 2247090. Source: ProtInc

insulin receptor signaling pathway

Traceable author statement. Source: Reactome

interaction with host

Traceable author statement. Source: Reactome

phagosome maturation

Traceable author statement. Source: Reactome

transferrin transport

Traceable author statement. Source: Reactome

transmembrane transport

Traceable author statement. Source: Reactome

   Cellular_componentacrosomal vesicle

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from direct assay. Source: HPA

endosome membrane

Traceable author statement. Source: Reactome

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

lysosomal membrane

Inferred from direct assay PubMed 17897319. Source: UniProtKB

phagocytic vesicle membrane

Traceable author statement. Source: Reactome

plasma membrane

Inferred from direct assay. Source: HPA

vacuolar proton-transporting V-type ATPase, V0 domain

Inferred from electronic annotation. Source: InterPro

   Molecular_functionhydrogen ion transmembrane transporter activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CYTH2Q994182EBI-988630,EBI-448974

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 856856V-type proton ATPase 116 kDa subunit a isoform 2
PRO_0000119216

Regions

Topological domain1 – 393393Cytoplasmic Potential
Transmembrane394 – 41219Helical; Potential
Topological domain413 – 4142Vacuolar Potential
Transmembrane415 – 43117Helical; Potential
Topological domain432 – 44514Cytoplasmic Potential
Transmembrane446 – 47530Helical; Potential
Topological domain476 – 54974Vacuolar Potential
Transmembrane550 – 56920Helical; Potential
Topological domain570 – 58718Cytoplasmic Potential
Transmembrane588 – 60821Helical; Potential
Topological domain609 – 65143Vacuolar Potential
Transmembrane652 – 67120Helical; Potential
Topological domain672 – 73968Cytoplasmic Potential
Transmembrane740 – 76425Helical; Potential
Topological domain765 – 78521Vacuolar Potential
Transmembrane786 – 82439Helical; Potential
Topological domain825 – 85632Cytoplasmic Potential

Amino acid modifications

Modified residue6951Phosphoserine Ref.7
Modified residue7001Phosphoserine By similarity

Natural variations

Natural variant6851R → Q.
Corresponds to variant rs7969410 [ dbSNP | Ensembl ].
VAR_042730
Natural variant8131A → V.
Corresponds to variant rs17883456 [ dbSNP | Ensembl ].
VAR_042731

Experimental info

Sequence conflict4281L → W in AAD04632. Ref.1
Sequence conflict6691L → P in BAF82080. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q9Y487 [UniParc].

Last modified March 18, 2008. Version 2.
Checksum: 6C38B36FA33A92BA

FASTA85698,082
        10         20         30         40         50         60 
MGSLFRSETM CLAQLFLQSG TAYECLSALG EKGLVQFRDL NQNVSSFQRK FVGEVKRCEE 

        70         80         90        100        110        120 
LERILVYLVQ EINRADIPLP EGEASPPAPP LKQVLEMQEQ LQKLEVELRE VTKNKEKLRK 

       130        140        150        160        170        180 
NLLELIEYTH MLRVTKTFVK RNVEFEPTYE EFPSLESDSL LDYSCMQRLG AKLGFVSGLI 

       190        200        210        220        230        240 
NQGKVEAFEK MLWRVCKGYT IVSYAELDES LEDPETGEVI KWYVFLISFW GEQIGHKVKK 

       250        260        270        280        290        300 
ICDCYHCHVY PYPNTAEERR EIQEGLNTRI QDLYTVLHKT EDYLRQVLCK AAESVYSRVI 

       310        320        330        340        350        360 
QVKKMKAIYH MLNMCSFDVT NKCLIAEVWC PEADLQDLRR ALEEGSRESG ATIPSFMNII 

       370        380        390        400        410        420 
PTKETPPTRI RTNKFTEGFQ NIVDAYGVGS YREVNPALFT IITFPFLFAV MFGDFGHGFV 

       430        440        450        460        470        480 
MFLFALLLVL NENHPRLNQS QEIMRMFFNG RYILLLMGLF SVYTGLIYND CFSKSVNLFG 

       490        500        510        520        530        540 
SGWNVSAMYS SSHPPAEHKK MVLWNDSVVR HNSILQLDPS IPGVFRGPYP LGIDPIWNLA 

       550        560        570        580        590        600 
TNRLTFLNSF KMKMSVILGI IHMTFGVILG IFNHLHFRKK FNIYLVSIPE LLFMLCIFGY 

       610        620        630        640        650        660 
LIFMIFYKWL VFSAETSRVA PSILIEFINM FLFPASKTSG LYTGQEYVQR VLLVVTALSV 

       670        680        690        700        710        720 
PVLFLGKPLF LLWLHNGRSC FGVNRSGYTL IRKDSEEEVS LLGSQDIEEG NHQVEDGCRE 

       730        740        750        760        770        780 
MACEEFNFGE ILMTQVIHSI EYCLGCISNT ASYLRLWALS LAHAQLSDVL WAMLMRVGLR 

       790        800        810        820        830        840 
VDTTYGVLLL LPVIALFAVL TIFILLIMEG LSAFLHAIRL HWVEFQNKFY VGAGTKFVPF 

       850 
SFSLLSSKFN NDDSVA 

« Hide

References

« Hide 'large scale' references
[1]"Characterization of human TJ6 homolog."
Babichev Y., Isakov N.
Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Astrocyte.
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[5]"V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway."
Hurtado-Lorenzo A., Skinner M., El Annan J., Futai M., Sun-Wada G.-H., Bourgoin S., Casanova J., Wildeman A., Bechoua S., Ausiello D.A., Brown D., Marshansky V.
Nat. Cell Biol. 8:124-136(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PSCD2.
[6]"The N-terminus domain of the a2 isoform of vacuolar ATPase can regulate interleukin-1beta production from mononuclear cells in co-culture with JEG-3 choriocarcinoma cells."
Ntrivalas E., Gilman-Sachs A., Kwak-Kim J., Beaman K.
Am. J. Reprod. Immunol. 57:201-209(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[7]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-695, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic kidney.
[8]"Impaired glycosylation and cutis laxa caused by mutations in the vesicular H+-ATPase subunit ATP6V0A2."
Kornak U., Reynders E., Dimopoulou A., van Reeuwijk J., Fischer B., Rajab A., Budde B., Nuernberg P., Foulquier F., Dobyns W.B., Quelhas D., Vilarinho L., Leao-Teles E., Greally M., Seemanova E., Simandlova M., Salih M., Nanda A. expand/collapse author list , Basel-Vanagaite L., Kayserili H., Yuksel-Apak M., Larregue M., Vigneron J., Giurgea S., Lefeber D., Urban Z., Gruenewald S., Annaert W., Brunner H.G., van Bokhoven H., Wevers R., Morava E., Matthijs G., Van Maldergem L., Mundlos S.
Nat. Genet. 40:32-34(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN ARCL2A, INVOLVEMENT IN WSS, FUNCTION, SUBCELLULAR LOCATION.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF112972 mRNA. Translation: AAD04632.1.
AK289391 mRNA. Translation: BAF82080.1.
CH471054 Genomic DNA. Translation: EAW98434.1.
BC068531 mRNA. Translation: AAH68531.1.
RefSeqNP_036595.2. NM_012463.3.
UniGeneHs.25786.

3D structure databases

ProteinModelPortalQ9Y487.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117089. 9 interactions.
IntActQ9Y487. 2 interactions.
STRING9606.ENSP00000332247.

PTM databases

PhosphoSiteQ9Y487.

Polymorphism databases

DMDM172046607.

Proteomic databases

PaxDbQ9Y487.
PRIDEQ9Y487.

Protocols and materials databases

DNASU23545.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000330342; ENSP00000332247; ENSG00000185344.
GeneID23545.
KEGGhsa:23545.
UCSCuc001ufr.3. human.

Organism-specific databases

CTD23545.
GeneCardsGC12P124196.
H-InvDBHIX0011113.
HGNCHGNC:18481. ATP6V0A2.
HPAHPA044279.
MIM219200. phenotype.
278250. phenotype.
611716. gene.
neXtProtNX_Q9Y487.
Orphanet357074. Autosomal recessive cutis laxa type 2, classic type.
2834. Wrinkly skin syndrome.
PharmGKBPA38549.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1269.
HOGENOMHOG000037059.
HOVERGENHBG014606.
InParanoidQ9Y487.
KOK02154.
OMAEIMRMFF.
OrthoDBEOG74FF04.
PhylomeDBQ9Y487.
TreeFamTF300346.

Enzyme and pathway databases

BioCycMetaCyc:G66-33375-MONOMER.
ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpressQ9Y487.
BgeeQ9Y487.
CleanExHS_ATP6V0A2.
GenevestigatorQ9Y487.

Family and domain databases

InterProIPR002490. V-ATPase_116kDa_su.
IPR026028. V-type_ATPase_116kDa_su_euka.
[Graphical view]
PANTHERPTHR11629. PTHR11629. 1 hit.
PfamPF01496. V_ATPase_I. 1 hit.
[Graphical view]
PIRSFPIRSF001293. ATP6V0A1. 1 hit.
ProtoNetSearch...

Other

ChiTaRSATP6V0A2. human.
GeneWikiATP6V0A2.
GenomeRNAi23545.
NextBio46076.
PROQ9Y487.
SOURCESearch...

Entry information

Entry nameVPP2_HUMAN
AccessionPrimary (citable) accession number: Q9Y487
Secondary accession number(s): A8K026, Q6NUM0
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: March 18, 2008
Last modified: April 16, 2014
This is version 121 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM