P15920 (VPP2_MOUSE) 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):
Immune suppressor factor J6B7
Short name=ISF
Lysosomal H(+)-transporting ATPase V0 subunit a2
ShIF
Vacuolar proton translocating ATPase 116 kDa subunit a isoform 2

Gene names

Name:	Atp6v0a2
Synonyms:	Atp6n1b, Tj6

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

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 By similarity. 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.7
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.7
Subcellular location	Cell membrane; Multi-pass membrane protein. Endosome membrane. Note: In kidney proximal tubules, detected in subapical early endosomes. Ref.7
Tissue specificity	Relatively high expression in kidney and liver. Lower levels in the spleen, testis, and skeletal muscle. Also expressed in the thymus. Ref.6
Sequence similarities	Belongs to the V-ATPase 116 kDa subunit family.
Sequence caution	The sequence AAL57303.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Hydrogen ion transport Ion transport Transport
Cellular component	Cell membrane Endosome Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	ATP hydrolysis coupled proton transport Inferred from electronic annotation. Source: InterPro
Cellular_component	acrosomal vesicle Inferred from direct assay PubMed 11872743. Source: MGI endosome membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell 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	P63034	5	EBI-988456,EBI-988425

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P15920-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P15920-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-593: Missing.

Note: No experimental confirmation available.

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_0000119217

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.8 Ref.9

Modified residue

700

1

Phosphoserine Ref.8 Ref.9

Natural variations

Alternative sequence

1 – 593

593

Missing in isoform 2.

VSP_032088

Experimental info

Sequence conflict

486

1

S → C in AAA39336. Ref.1

Sequence conflict

486

1

S → C in CAA38968. Ref.1

Sequence conflict

791

1

Missing in AAA39336. Ref.1

Sequence conflict

791

1

Missing in CAA38968. Ref.1

Secondary structure

1

.

.

.

856

Helix Strand Turn

Details...

Helix

4 – 16

13

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 11, 2001. Version 2. Checksum: 6A0D593F6F401E22	FASTA	856	98,145
	10 20 30 40 50 60 MGSLFRSESM CLAQLFLQSG TAYECLSALG EKGLVQFRDL NQNVSSFQRK FVGEVKRCEE 70 80 90 100 110 120 LERILVYLVQ EITRADIPLP EGEASPPAPP LKHVLEMQEQ LQKLEVELRE VTKNKEKLRK 130 140 150 160 170 180 NLLELVEYTH MLRVTKTFLK RNVEFEPTYE EFPALENDSL LDYSCMQRLG AKLGFVSGLI 190 200 210 220 230 240 QQGRVEAFER MLWRACKGYT IVTYAELDEC LEDPETGEVI KWYVFLISFW GEQIGHKVKK 250 260 270 280 290 300 ICDCYHCHIY PYPNTAEERR EIQEGLNTRI QDLYTVLHKT EDYLRQVLCK AAESVCSRVV 310 320 330 340 350 360 QVRKMKAIYH MLNMCSFDVT NKCLIAEVWC PEVDLPGLRR ALEEGSRESG ATIPSFMNTI 370 380 390 400 410 420 PTKETPPTLI RTNKFTEGFQ NIVDAYGVGS YREVNPALFT IITFPFLFAV MFGDFGHGFV 430 440 450 460 470 480 MFLFALLLVL NENHPRLSQS QEILRMFFDG RYILLLMGLF SVYTGLIYND CFSKSVNLFG 490 500 510 520 530 540 SGWNVSAMYS SSHSPEEQRK MVLWNDSTIR HSRTLQLDPN IPGVFRGPYP FGIDPIWNLA 550 560 570 580 590 600 TNRLTFLNSF KMKMSVILGI FHMTFGVVLG IFNHLHFRKK FNVYLVSVPE ILFMLCIFGY 610 620 630 640 650 660 LIFMIIYKWL AYSAETSREA PSILIEFINM FLFPTSKTHG LYPGQAHVQR VLVALTVLAV 670 680 690 700 710 720 PVLFLGKPLF LLWLHNGRNC FGMSRSGYTL VRKDSEEEVS LLGNQDIEEG NSRMEEGCRE 730 740 750 760 770 780 VTCEEFNFGE ILMTQAIHSI EYCLGCISNT ASYLRLWALS LAHAQLSDVL WAMLMRVGLR 790 800 810 820 830 840 VDTTYGVLLL LPVMAFFAVL TIFILLVMEG LSAFLHAIRL HWVEFQNKFY VGAGTKFVPF 850 SFSLLSSKFS NDDSIA
	Isoform 2 [UniParc]. Checksum: 0A1BDE2F82C0C02C	FASTA	263	29,740
	10 20 30 40 50 60 MLCIFGYLIF MIIYKWLAYS AETSREAPSI LIEFINMFLF PTSKTHGLYP GQAHVQRVLV 70 80 90 100 110 120 ALTVLAVPVL FLGKPLFLLW LHNGRNCFGM SRSGYTLVRK DSEEEVSLLG NQDIEEGNSR 130 140 150 160 170 180 MEEGCREVTC EEFNFGEILM TQAIHSIEYC LGCISNTASY LRLWALSLAH AQLSDVLWAM 190 200 210 220 230 240 LMRVGLRVDT TYGVLLLLPV MAFFAVLTIF ILLVMEGLSA FLHAIRLHWV EFQNKFYVGA 250 260 GTKFVPFSFS LLSSKFSNDD SIA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of a cDNA for a T cell produced molecule with a putative immune regulatory role." Lee C.-K., Ghoshal K., Beaman K.D. Mol. Immunol. 27:1137-1144(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Three subunit a isoforms of mouse vacuolar H+-ATPase. Preferential expression of the a3 isoform during osteoclast differentiation." Toyomura T., Oka T., Yamaguchi C., Wada Y., Futai M. J. Biol. Chem. 275:8760-8765(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	"Molecular cloning and expression of three isoforms of the 100-kDa a subunit of the mouse vacuolar proton-translocating ATPase." Nishi T., Forgac M. J. Biol. Chem. 275:6824-6830(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Brain and Heart.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: NOD. Tissue: Dendritic cell and Wolffian duct.
[5]	"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] (ISOFORM 1). Tissue: Mammary tumor.
[6]	"A novel secreted form of immune suppressor factor with high homology to vacuolar ATPases identified by a forward genetic approach of functional screening based on cell proliferation." Tulin E.E., Onoda N., Maeda M., Hasegawa M., Nosaka T., Nomura H., Asano S., Kitamura T. J. Biol. Chem. 276:27519-27526(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 569-856, TISSUE SPECIFICITY.
[7]	"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.
[8]	"Large-scale phosphorylation analysis of mouse liver." Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-695 AND SER-700, MASS SPECTROMETRY. Tissue: Liver.
[9]	"The phagosomal proteome in interferon-gamma-activated macrophages." Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P. Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-695 AND SER-700, MASS SPECTROMETRY. Tissue: Macrophage.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M31226 mRNA. Translation: AAA39336.1.
X55184 mRNA. Translation: CAA38968.1.
AB022323 mRNA. Translation: BAA93007.1.
AF218252 mRNA. Translation: AAF59921.1.
AK032909 mRNA. Translation: BAC28081.1.
AK155055 mRNA. Translation: BAE33017.1.
BC108991 mRNA. Translation: AAI08992.1.
BC108992 mRNA. Translation: AAI08993.1.
BC112905 mRNA. Translation: AAI12906.1.
AF388674 mRNA. Translation: AAL57303.1. Different initiation.

IPI

IPI00135975.
IPI00889297.

PIR

JH0287.

RefSeq

NP_035726.2. NM_011596.4.

UniGene

Mm.1158.
Mm.392098.
Mm.490281.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2LX4	NMR	-	A	1-17	[»]

ProteinModelPortal

P15920.

ModBase

Search...

Protein-protein interaction databases

IntAct

P15920. 1 interaction.

PTM databases

PhosphoSite

P15920.

Proteomic databases

PaxDb

P15920.

PRIDE

P15920.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000037865; ENSMUSP00000039737; ENSMUSG00000038023.

GeneID

21871.

KEGG

mmu:21871.

UCSC

uc008zqk.1. mouse.
uc008zqn.1. mouse.

Organism-specific databases

CTD

23545.

MGI

MGI:104855. Atp6v0a2.

Phylogenomic databases

eggNOG

COG1269.

GeneTree

ENSGT00390000004941.

HOGENOM

HOG000037059.

HOVERGEN

HBG014606.

InParanoid

P15920.

KO

K02154.

OMA

EILMTQV.

OrthoDB

EOG4J6RQ7.

Gene expression databases

Bgee

P15920.

CleanEx

MM_ATP6V0A2.

Genevestigator

P15920.

GermOnline

ENSMUSG00000038023. Mus musculus.

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

NextBio

301372.

SOURCE

Search...

Entry information

Entry name

VPP2_MOUSE

Accession

Primary (citable) accession number: P15920
Secondary accession number(s): A4FU82 , Q3U2X3, Q8VHU0, Q9JHJ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	January 11, 2001
Last modified:	April 3, 2013
This is version 126 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program