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Protein

V-type proton ATPase 116 kDa subunit a isoform 2

Gene

ATP6V0A2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

GO - Molecular functioni

  1. ATPase binding Source: GO_Central
  2. proton-transporting ATPase activity, rotational mechanism Source: GO_Central

GO - Biological processi

  1. ATP hydrolysis coupled proton transport Source: InterPro
  2. ATP synthesis coupled proton transport Source: GO_Central
  3. cellular iron ion homeostasis Source: Reactome
  4. immune response Source: ProtInc
  5. insulin receptor signaling pathway Source: Reactome
  6. interaction with host Source: Reactome
  7. phagosome maturation Source: Reactome
  8. transferrin transport Source: Reactome
  9. transmembrane transport Source: Reactome
  10. vacuolar acidification Source: GO_Central
  11. vacuolar proton-transporting V-type ATPase complex assembly Source: GO_Central
Complete GO annotation...

Keywords - Biological processi

Hydrogen ion transport, Ion transport, Transport

Enzyme and pathway databases

BioCyciMetaCyc:G66-33375-MONOMER.
ReactomeiREACT_1109. Insulin receptor recycling.
REACT_121256. Phagosomal maturation (early endosomal stage).
REACT_25283. Transferrin endocytosis and recycling.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 12

Organism-specific databases

HGNCiHGNC:18481. ATP6V0A2.

Subcellular locationi

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 393393CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei394 – 41219HelicalSequence AnalysisAdd
BLAST
Topological domaini413 – 4142VacuolarSequence Analysis
Transmembranei415 – 43117HelicalSequence AnalysisAdd
BLAST
Topological domaini432 – 44514CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei446 – 47530HelicalSequence AnalysisAdd
BLAST
Topological domaini476 – 54974VacuolarSequence AnalysisAdd
BLAST
Transmembranei550 – 56920HelicalSequence AnalysisAdd
BLAST
Topological domaini570 – 58718CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei588 – 60821HelicalSequence AnalysisAdd
BLAST
Topological domaini609 – 65143VacuolarSequence AnalysisAdd
BLAST
Transmembranei652 – 67120HelicalSequence AnalysisAdd
BLAST
Topological domaini672 – 73968CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei740 – 76425HelicalSequence AnalysisAdd
BLAST
Topological domaini765 – 78521VacuolarSequence AnalysisAdd
BLAST
Transmembranei786 – 82439HelicalSequence AnalysisAdd
BLAST
Topological domaini825 – 85632CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. acrosomal vesicle Source: Ensembl
  2. cytoplasm Source: HPA
  3. endosome membrane Source: Reactome
  4. focal adhesion Source: HPA
  5. integral component of membrane Source: UniProtKB-KW
  6. lysosomal membrane Source: UniProtKB
  7. phagocytic vesicle membrane Source: Reactome
  8. plasma membrane Source: HPA
  9. vacuolar proton-transporting V-type ATPase, V0 domain Source: InterPro
  10. vacuolar proton-transporting V-type ATPase complex Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Cutis laxa, autosomal recessive, 2A1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:219200
Wrinkly skin syndrome1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA 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.

See also OMIM:278250

Organism-specific databases

MIMi219200. phenotype.
278250. phenotype.
Orphaneti357074. Autosomal recessive cutis laxa type 2, classic type.
2834. Wrinkly skin syndrome.
PharmGKBiPA38549.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 856856V-type proton ATPase 116 kDa subunit a isoform 2PRO_0000119216Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi484 – 4841N-linked (GlcNAc...)Sequence Analysis
Glycosylationi505 – 5051N-linked (GlcNAc...)Sequence Analysis
Modified residuei695 – 6951Phosphoserine1 Publication
Modified residuei700 – 7001PhosphoserineBy similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ9Y487.
PaxDbiQ9Y487.
PRIDEiQ9Y487.

PTM databases

PhosphoSiteiQ9Y487.

Expressioni

Gene expression databases

BgeeiQ9Y487.
CleanExiHS_ATP6V0A2.
ExpressionAtlasiQ9Y487. baseline and differential.
GenevestigatoriQ9Y487.

Organism-specific databases

HPAiHPA044279.

Interactioni

Subunit structurei

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.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
CYTH2Q994182EBI-988630,EBI-448974

Protein-protein interaction databases

BioGridi117089. 19 interactions.
IntActiQ9Y487. 2 interactions.
STRINGi9606.ENSP00000332247.

Structurei

3D structure databases

ProteinModelPortaliQ9Y487.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the V-ATPase 116 kDa subunit family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1269.
GeneTreeiENSGT00390000004941.
HOGENOMiHOG000037059.
HOVERGENiHBG014606.
InParanoidiQ9Y487.
KOiK02154.
OMAiEIMRMFF.
OrthoDBiEOG74FF04.
PhylomeDBiQ9Y487.
TreeFamiTF300346.

Family and domain databases

InterProiIPR002490. V-ATPase_116kDa_su.
IPR026028. V-type_ATPase_116kDa_su_euka.
[Graphical view]
PANTHERiPTHR11629. PTHR11629. 1 hit.
PfamiPF01496. V_ATPase_I. 1 hit.
[Graphical view]
PIRSFiPIRSF001293. ATP6V0A1. 1 hit.

Sequencei

Sequence statusi: Complete.

Q9Y487-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGSLFRSETM CLAQLFLQSG TAYECLSALG EKGLVQFRDL NQNVSSFQRK
60 70 80 90 100
FVGEVKRCEE LERILVYLVQ EINRADIPLP EGEASPPAPP LKQVLEMQEQ
110 120 130 140 150
LQKLEVELRE VTKNKEKLRK NLLELIEYTH MLRVTKTFVK RNVEFEPTYE
160 170 180 190 200
EFPSLESDSL LDYSCMQRLG AKLGFVSGLI NQGKVEAFEK MLWRVCKGYT
210 220 230 240 250
IVSYAELDES LEDPETGEVI KWYVFLISFW GEQIGHKVKK ICDCYHCHVY
260 270 280 290 300
PYPNTAEERR EIQEGLNTRI QDLYTVLHKT EDYLRQVLCK AAESVYSRVI
310 320 330 340 350
QVKKMKAIYH MLNMCSFDVT NKCLIAEVWC PEADLQDLRR ALEEGSRESG
360 370 380 390 400
ATIPSFMNII PTKETPPTRI RTNKFTEGFQ NIVDAYGVGS YREVNPALFT
410 420 430 440 450
IITFPFLFAV MFGDFGHGFV MFLFALLLVL NENHPRLNQS QEIMRMFFNG
460 470 480 490 500
RYILLLMGLF SVYTGLIYND CFSKSVNLFG SGWNVSAMYS SSHPPAEHKK
510 520 530 540 550
MVLWNDSVVR HNSILQLDPS IPGVFRGPYP LGIDPIWNLA TNRLTFLNSF
560 570 580 590 600
KMKMSVILGI IHMTFGVILG IFNHLHFRKK FNIYLVSIPE LLFMLCIFGY
610 620 630 640 650
LIFMIFYKWL VFSAETSRVA PSILIEFINM FLFPASKTSG LYTGQEYVQR
660 670 680 690 700
VLLVVTALSV PVLFLGKPLF LLWLHNGRSC FGVNRSGYTL IRKDSEEEVS
710 720 730 740 750
LLGSQDIEEG NHQVEDGCRE MACEEFNFGE ILMTQVIHSI EYCLGCISNT
760 770 780 790 800
ASYLRLWALS LAHAQLSDVL WAMLMRVGLR VDTTYGVLLL LPVIALFAVL
810 820 830 840 850
TIFILLIMEG LSAFLHAIRL HWVEFQNKFY VGAGTKFVPF SFSLLSSKFN

NDDSVA
Length:856
Mass (Da):98,082
Last modified:March 18, 2008 - v2
Checksum:i6C38B36FA33A92BA
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti428 – 4281L → W in AAD04632 (Ref. 1) Curated
Sequence conflicti669 – 6691L → P in BAF82080 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti685 – 6851R → Q.
Corresponds to variant rs7969410 [ dbSNP | Ensembl ].
VAR_042730
Natural varianti813 – 8131A → V.
Corresponds to variant rs17883456 [ dbSNP | Ensembl ].
VAR_042731

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF112972 mRNA. Translation: AAD04632.1.
AK289391 mRNA. Translation: BAF82080.1.
CH471054 Genomic DNA. Translation: EAW98434.1.
BC068531 mRNA. Translation: AAH68531.1.
CCDSiCCDS9254.1.
RefSeqiNP_036595.2. NM_012463.3.
UniGeneiHs.25786.

Genome annotation databases

EnsembliENST00000330342; ENSP00000332247; ENSG00000185344.
GeneIDi23545.
KEGGihsa:23545.
UCSCiuc001ufr.3. human.

Polymorphism databases

DMDMi172046607.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF112972 mRNA. Translation: AAD04632.1.
AK289391 mRNA. Translation: BAF82080.1.
CH471054 Genomic DNA. Translation: EAW98434.1.
BC068531 mRNA. Translation: AAH68531.1.
CCDSiCCDS9254.1.
RefSeqiNP_036595.2. NM_012463.3.
UniGeneiHs.25786.

3D structure databases

ProteinModelPortaliQ9Y487.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117089. 19 interactions.
IntActiQ9Y487. 2 interactions.
STRINGi9606.ENSP00000332247.

PTM databases

PhosphoSiteiQ9Y487.

Polymorphism databases

DMDMi172046607.

Proteomic databases

MaxQBiQ9Y487.
PaxDbiQ9Y487.
PRIDEiQ9Y487.

Protocols and materials databases

DNASUi23545.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000330342; ENSP00000332247; ENSG00000185344.
GeneIDi23545.
KEGGihsa:23545.
UCSCiuc001ufr.3. human.

Organism-specific databases

CTDi23545.
GeneCardsiGC12P124196.
GeneReviewsiATP6V0A2.
H-InvDBHIX0011113.
HGNCiHGNC:18481. ATP6V0A2.
HPAiHPA044279.
MIMi219200. phenotype.
278250. phenotype.
611716. gene.
neXtProtiNX_Q9Y487.
Orphaneti357074. Autosomal recessive cutis laxa type 2, classic type.
2834. Wrinkly skin syndrome.
PharmGKBiPA38549.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG1269.
GeneTreeiENSGT00390000004941.
HOGENOMiHOG000037059.
HOVERGENiHBG014606.
InParanoidiQ9Y487.
KOiK02154.
OMAiEIMRMFF.
OrthoDBiEOG74FF04.
PhylomeDBiQ9Y487.
TreeFamiTF300346.

Enzyme and pathway databases

BioCyciMetaCyc:G66-33375-MONOMER.
ReactomeiREACT_1109. Insulin receptor recycling.
REACT_121256. Phagosomal maturation (early endosomal stage).
REACT_25283. Transferrin endocytosis and recycling.

Miscellaneous databases

ChiTaRSiATP6V0A2. human.
GeneWikiiATP6V0A2.
GenomeRNAii23545.
NextBioi46076.
PROiQ9Y487.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Y487.
CleanExiHS_ATP6V0A2.
ExpressionAtlasiQ9Y487. baseline and differential.
GenevestigatoriQ9Y487.

Family and domain databases

InterProiIPR002490. V-ATPase_116kDa_su.
IPR026028. V-type_ATPase_116kDa_su_euka.
[Graphical view]
PANTHERiPTHR11629. PTHR11629. 1 hit.
PfamiPF01496. V_ATPase_I. 1 hit.
[Graphical view]
PIRSFiPIRSF001293. ATP6V0A1. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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-terminal 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. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-695, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic kidney.
  8. Cited for: INVOLVEMENT IN ARCL2A, INVOLVEMENT IN WSS, FUNCTION, SUBCELLULAR LOCATION.
  9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  10. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiVPP2_HUMAN
AccessioniPrimary (citable) accession number: Q9Y487
Secondary accession number(s): A8K026, Q6NUM0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: March 18, 2008
Last modified: March 4, 2015
This is version 130 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Caution

The N-terminal 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.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.