Q9HBG4 (VPP4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
V-type proton ATPase 116 kDa subunit a isoform 4
Short name=V-ATPase 116 kDa isoform a4

Alternative name(s):
Vacuolar proton translocating ATPase 116 kDa subunit a isoform 4
Vacuolar proton translocating ATPase 116 kDa subunit a kidney isoform

Gene names

Name:	ATP6V0A4
Synonyms:	ATP6N1B, ATP6N2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	840 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Part of the proton channel of the V-ATPase that is involved in normal vectorial acid transport into the urine by the kidney By similarity.
Subunit structure	The V-ATPase is an 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''.
Subcellular location	Apical cell membrane; Multi-pass membrane protein. Note: Present at high density almost exclusively on the apical surface of alpha-intercalated cells in the cortical collecting ducts of the distal nephron.
Tissue specificity	Expressed in adult and fetal kidney. Found in the inner ear. Ref.7
Involvement in disease	Defects in ATP6V0A4 are the cause of distal renal tubular acidosis with preserved hearing (RTADR) [MIM:602722]. RTADR is an autosomal recessive form of distal renal tubular acidosis (dRTA), a group of disorders characterized by functional failure of alpha-intercalated cells of the cortical collecting duct of the distal nephron, where vectorial proton transport is required for urinary acidification. Functional failure of alpha-intercalated cells results in metabolic acidosis accompanied by disturbances of potassium balance, urinary calcium solubility, bone physiology and growth. Ref.1 Ref.7
Sequence similarities	Belongs to the V-ATPase 116 kDa subunit family.

Ontologies

Keywords
Biological process	Hydrogen ion transport Ion transport Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cellular iron ion homeostasis Traceable author statement. Source: Reactome excretion Inferred from mutant phenotype Ref.7. Source: HGNC insulin receptor signaling pathway Traceable author statement. Source: Reactome ossification Inferred from mutant phenotype Ref.1. Source: HGNC regulation of pH Inferred from mutant phenotype Ref.1. Source: HGNC sensory perception of sound Inferred from mutant phenotype Ref.7. Source: HGNC transferrin transport Traceable author statement. Source: Reactome
Cellular component	apical plasma membrane Inferred from direct assay. Source: UniProtKB brush border membrane Inferred from direct assay. Source: HGNC endosome membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW proton-transporting two-sector ATPase complex, proton-transporting domain Inferred from electronic annotation. Source: InterPro
Molecular function	ATPase binding Inferred from physical interaction. Source: UniProtKB hydrogen ion transmembrane transporter activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 840	840	V-type proton ATPase 116 kDa subunit a isoform 4		PRO_0000119219
Regions
	Topological domain	1 – 390	390	Cytoplasmic Potential
	Transmembrane	391 – 409	19	Helical; Potential
	Topological domain	410 – 411	2	Vacuolar Potential
	Transmembrane	412 – 428	17	Helical; Potential
	Topological domain	429 – 443	15	Cytoplasmic Potential
	Transmembrane	444 – 473	30	Helical; Potential
	Topological domain	474 – 538	65	Vacuolar Potential
	Transmembrane	539 – 558	20	Helical; Potential
	Topological domain	559 – 576	18	Cytoplasmic Potential
	Transmembrane	577 – 597	21	Helical; Potential
	Topological domain	598 – 642	45	Vacuolar Potential
	Transmembrane	643 – 662	20	Helical; Potential
	Topological domain	663 – 727	65	Cytoplasmic Potential
	Transmembrane	728 – 752	25	Helical; Potential
	Topological domain	753 – 773	21	Vacuolar Potential
	Transmembrane	774 – 812	39	Helical; Potential
	Topological domain	813 – 840	28	Cytoplasmic Potential
Natural variations
	Natural variant	2	1	V → A. Ref.1 Ref.2 Corresponds to variant rs10258719 [ dbSNP | Ensembl ].		VAR_020992
	Natural variant	175	1	G → D in RTADR. Ref.7		VAR_020993
	Natural variant	237	1	Missing in RTADR.		VAR_020994
	Natural variant	449	1	R → H in RTADR. Ref.7		VAR_020995
	Natural variant	524	1	P → L in RTADR. Ref.1		VAR_017255
	Natural variant	554	1	F → L. Corresponds to variant rs1026435 [ dbSNP | Ensembl ].		VAR_066612
	Natural variant	580	1	M → T in RTADR. Ref.1 Corresponds to variant rs3807153 [ dbSNP | Ensembl ].		VAR_017256
	Natural variant	604	1	H → Q. Corresponds to variant rs3807154 [ dbSNP | Ensembl ].		VAR_066613
	Natural variant	807	1	R → Q in RTADR. Ref.7 Corresponds to variant rs28939081 [ dbSNP | Ensembl ].		VAR_020996
	Natural variant	820	1	G → R in RTADR. Ref.1		VAR_017257
Experimental info
	Sequence conflict	252	1	P → R in AAI09305. Ref.6
	Sequence conflict	252	1	P → R in AAI09306. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Q9HBG4 [UniParc]. Last modified October 5, 2010. Version 2. Checksum: 449964EBC01D4649	FASTA	840	96,386
	10 20 30 40 50 60 MVSVFRSEEM CLSQLFLQVE AAYCCVAELG ELGLVQFKDL NMNVNSFQRK FVNEVRRCES 70 80 90 100 110 120 LERILRFLED EMQNEIVVQL LEKSPLTPLP REMITLETVL EKLEGELQEA NQNQQALKQS 130 140 150 160 170 180 FLELTELKYL LKKTQDFFET ETNLADDFFT EDTSGLLELK AVPAYMTGKL GFIAGVINRE 190 200 210 220 230 240 RMASFERLLW RICRGNVYLK FSEMDAPLED PVTKEEIQKN IFIIFYQGEQ LRQKIKKICD 250 260 270 280 290 300 GFRATVYPCP EPAVERREML ESVNVRLEDL ITVITQTESH RQRLLQEAAA NWHSWLIKVQ 310 320 330 340 350 360 KMKAVYHILN MCNIDVTQQC VIAEIWFPVA DATRIKRALE QGMELSGSSM APIMTTVQSK 370 380 390 400 410 420 TAPPTFNRTN KFTAGFQNIV DAYGVGSYRE INPAPYTIIT FPFLFAVMFG DCGHGTVMLL 430 440 450 460 470 480 AALWMILNER RLLSQKTDNE IWNTFFHGRY LILLMGIFSI YTGLIYNDCF SKSLNIFGSS 490 500 510 520 530 540 WSVQPMFRNG TWNTHVMEES LYLQLDPAIP GVYFGNPYPF GIDPIWNLAS NKLTFLNSYK 550 560 570 580 590 600 MKMSVILGIV QMVFGVILSL FNHIYFRRTL NIILQFIPEM IFILCLFGYL VFMIIFKWCC 610 620 630 640 650 660 FDVHVSQHAP SILIHFINMF LFNYSDSSNA PLYKHQQEVQ SFFVVMALIS VPWMLLIKPF 670 680 690 700 710 720 ILRASHRKSQ LQASRIQEDA TENIEGDSSS PSSRSGQRTS ADTHGALDDH GEEFNFGDVF 730 740 750 760 770 780 VHQAIHTIEY CLGCISNTAS YLRLWALSLA HAQLSEVLWT MVMNSGLQTR GWGGIVGVFI 790 800 810 820 830 840 IFAVFAVLTV AILLIMEGLS AFLHALRLHW VEFQNKFYVG DGYKFSPFSF KHILDGTAEE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Mutations in ATP6N1B, encoding a new kidney vacuolar proton pump 116-kD subunit, cause recessive distal renal tubular acidosis with preserved hearing." Smith A.N., Skaug J., Choate K.A., Nayir A., Bakkaloglu A., Ozen S., Hulton S.A., Sanjad S.A., Al-Sabban E.A., Lifton R.P., Scherer S.W., Karet F.E. Nat. Genet. 26:71-75(2000) [PubMed: 10973252] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS RTADR LEU-524; THR-580 AND ARG-820, VARIANT ALA-2. Tissue: Kidney.
[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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT ALA-2. Tissue: Trachea.
[3]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed: 12690205] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton 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].
[6]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	"Novel ATP6V1B1 and ATP6V0A4 mutations in autosomal recessive distal renal tubular acidosis with new evidence for hearing loss." Stover E.H., Borthwick K.J., Bavalia C., Eady N., Fritz D.M., Rungroj N., Giersch A.B.S., Morton C.C., Axon P.R., Akil I., Al-Sabban E.A., Baguley D.M., Bianca S., Bakkaloglu A., Bircan Z., Chauveau D., Clermont M.-J., Guala A. , Hulton S.A., Kroes H., Li Volti G., Mir S., Mocan H., Nayir A., Ozen S., Rodriguez Soriano J., Sanjad S.A., Tasic V., Taylor C.M., Topaloglu R., Smith A.N., Karet F.E. J. Med. Genet. 39:796-803(2002) [PubMed: 12414817] [Abstract] Cited for: TISSUE SPECIFICITY, VARIANTS RTADR ASP-175; LYS-237 DEL; HIS-449 AND GLN-807.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF245517 mRNA. Translation: AAG11415.1. AK292945 mRNA. Translation: BAF85634.1. AC018663 Genomic DNA. No translation available. AC020983 Genomic DNA. No translation available. CH236950 Genomic DNA. Translation: EAL24043.1. CH471070 Genomic DNA. Translation: EAW83892.1. BC109304 mRNA. Translation: AAI09305.1. BC109305 mRNA. Translation: AAI09306.1.
IPI	IPI00009852.
RefSeq	NP_065683.2. NM_020632.2. NP_570855.2. NM_130840.2. NP_570856.2. NM_130841.2.
UniGene	Hs.98967.
3D structure databases
ProteinModelPortal	Q9HBG4.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9HBG4.
Protein family/group databases
TCDB	3.A.2.2.4. H+- or Na+-translocating F-type, V-type and A-type ATPase (F-ATPase) superfamily.
PTM databases
PhosphoSite	Q9HBG4.
Polymorphism databases
DMDM	308153516.
Proteomic databases
PRIDE	Q9HBG4.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000310018; ENSP00000308122; ENSG00000105929. ENST00000353492; ENSP00000253856; ENSG00000105929. ENST00000393054; ENSP00000376774; ENSG00000105929.
GeneID	50617.
KEGG	hsa:50617.
Organism-specific databases
CTD	50617.
GeneCards	GC07M138391.
H-InvDB	HIX0007123.
HGNC	HGNC:866. ATP6V0A4.
HPA	HPA018029.
MIM	602722. phenotype. 605239. gene.
neXtProt	NX_Q9HBG4.
Orphanet	18. Distal renal tubular acidosis.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00390000004941.
HOGENOM	HBG629705.
HOVERGEN	HBG014606.
InParanoid	Q9HBG4.
OMA	HVSQHAP.
OrthoDB	EOG4DJJVS.
PhylomeDB	Q9HBG4.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction. REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	Q9HBG4.
Bgee	Q9HBG4.
CleanEx	HS_ATP6V0A4.
Genevestigator	Q9HBG4.
GermOnline	ENSG00000105929. Homo sapiens.
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
SOURCE	Search...

Entry information

Entry name

VPP4_HUMAN

Accession

Primary (citable) accession number: Q9HBG4
Secondary accession number(s): A4D1R4, A8KA80, Q32M47

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 14, 2003
Last sequence update:	October 5, 2010
Last modified:	January 25, 2012
This is version 89 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.