Q9Y487 (VPP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:

ATP6V0A2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	856 AA.
Sequence status	Complete.
Protein existence	Evidence 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]: 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 process	Hydrogen ion transport Ion transport Transport
Cellular component	Cell membrane Endosome Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ATP 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_component	acrosomal vesicle Inferred from electronic annotation. Source: Compara endosome membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW 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_function	hydrogen ion transmembrane transporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CYTH2	Q99418	2	EBI-988630,EBI-448974

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 856	856	V-type proton ATPase 116 kDa subunit a isoform 2		PRO_0000119216
Regions
	Topological domain	1 – 393	393	Cytoplasmic Potential
	Transmembrane	394 – 412	19	Helical; Potential
	Topological domain	413 – 414	2	Vacuolar Potential
	Transmembrane	415 – 431	17	Helical; Potential
	Topological domain	432 – 445	14	Cytoplasmic Potential
	Transmembrane	446 – 475	30	Helical; Potential
	Topological domain	476 – 549	74	Vacuolar Potential
	Transmembrane	550 – 569	20	Helical; Potential
	Topological domain	570 – 587	18	Cytoplasmic Potential
	Transmembrane	588 – 608	21	Helical; Potential
	Topological domain	609 – 651	43	Vacuolar Potential
	Transmembrane	652 – 671	20	Helical; Potential
	Topological domain	672 – 739	68	Cytoplasmic Potential
	Transmembrane	740 – 764	25	Helical; Potential
	Topological domain	765 – 785	21	Vacuolar Potential
	Transmembrane	786 – 824	39	Helical; Potential
	Topological domain	825 – 856	32	Cytoplasmic Potential
Amino acid modifications
	Modified residue	695	1	Phosphoserine Ref.7
	Modified residue	700	1	Phosphoserine By similarity
Natural variations
	Natural variant	685	1	R → Q. Corresponds to variant rs7969410 [ dbSNP | Ensembl ].		VAR_042730
	Natural variant	813	1	A → V. Corresponds to variant rs17883456 [ dbSNP | Ensembl ].		VAR_042731
Experimental info
	Sequence conflict	428	1	L → W in AAD04632. Ref.1
	Sequence conflict	669	1	L → P in BAF82080. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9Y487 [UniParc]. Last modified March 18, 2008. Version 2. Checksum: 6C38B36FA33A92BA	FASTA	856	98,082
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY. 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. , 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

GeneReviews

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.
IPI	IPI00000425.
RefSeq	NP_036595.2. NM_012463.3.
UniGene	Hs.25786.
3D structure databases
ProteinModelPortal	Q9Y487.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y487. 2 interactions.
STRING	9606.ENSP00000332247.
PTM databases
PhosphoSite	Q9Y487.
Polymorphism databases
DMDM	172046607.
Proteomic databases
PaxDb	Q9Y487.
PRIDE	Q9Y487.
Protocols and materials databases
DNASU	23545.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000330342; ENSP00000332247; ENSG00000185344.
GeneID	23545.
KEGG	hsa:23545.
UCSC	uc001ufr.3. human.
Organism-specific databases
CTD	23545.
GeneCards	GC12P124196.
H-InvDB	HIX0011113.
HGNC	HGNC:18481. ATP6V0A2.
HPA	HPA044279.
MIM	219200. phenotype. 278250. phenotype. 611716. gene.
neXtProt	NX_Q9Y487.
Orphanet	90350. Autosomal recessive cutis laxa type 2. 2834. Wrinkly skin syndrome.
PharmGKB	PA38549.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1269.
HOGENOM	HOG000037059.
HOVERGEN	HBG014606.
InParanoid	Q9Y487.
KO	K02154.
OMA	EILMTQV.
OrthoDB	EOG4J6RQ7.
PhylomeDB	Q9Y487.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction. REACT_116125. Disease. REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q9Y487.
Bgee	Q9Y487.
CleanEx	HS_ATP6V0A2.
Genevestigator	Q9Y487.
GermOnline	ENSG00000185344. Homo sapiens.
Family and domain databases
InterPro	IPR002490. V-ATPase_116kDa_su. IPR026028. V-type_ATPase_116kDa_su_euka. [Graphical view]
PANTHER	PTHR11629. PTHR11629. 1 hit.
Pfam	PF01496. V_ATPase_I. 1 hit. [Graphical view]
PIRSF	PIRSF001293. ATP6V0A1. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	ATP6V0A2. human.
GenomeRNAi	23545.
NextBio	46076.
SOURCE	Search...

Entry information

Entry name

VPP2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 112 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.