ATP6V0A4

Protein identityUniProt · HPA

UniProt accession

Q9HBG4

Gene

ATP6V0A4

Ensembl

ENSG00000105929

Chromosome

7

Canonical length

840 aa

Protein class

Disease related genes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins, Transporters

Subcellular location

Cytosol

OverviewNCBI Gene

This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of intracellular compartments of eukaryotic cells. V-ATPase dependent acidification is necessary for such intracellular processes as protein sorting, zymogen activation, receptor-mediated endocytosis, and synaptic vesicle proton gradient generation. V-ATPase is composed of a cytosolic V1 domain and a transmembrane V0 domain. The V1 domain consists of three A and three B subunits, two G subunits plus the C, D, E, F, and H subunits. The V1 domain contains the ATP catalytic site. The V0 domain consists of five different subunits: a, c, c', c'', and d. This gene is one of four genes in man and mouse that encode different isoforms of the a subunit. Alternatively spliced transcript variants encoding the same protein have been described. Mutations in this gene are associated with renal tubular acidosis associated with preserved hearing. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

840 residues, UniProt reviewed canonical sequence.

>Q9HBG4|ATP6V0A4
     1  MVSVFRSEEM CLSQLFLQVE AAYCCVAELG ELGLVQFKDL NMNVNSFQRK FVNEVRRCES
    61  LERILRFLED EMQNEIVVQL LEKSPLTPLP REMITLETVL EKLEGELQEA NQNQQALKQS
   121  FLELTELKYL LKKTQDFFET ETNLADDFFT EDTSGLLELK AVPAYMTGKL GFIAGVINRE
   181  RMASFERLLW RICRGNVYLK FSEMDAPLED PVTKEEIQKN IFIIFYQGEQ LRQKIKKICD
   241  GFRATVYPCP EPAVERREML ESVNVRLEDL ITVITQTESH RQRLLQEAAA NWHSWLIKVQ
   301  KMKAVYHILN MCNIDVTQQC VIAEIWFPVA DATRIKRALE QGMELSGSSM APIMTTVQSK
   361  TAPPTFNRTN KFTAGFQNIV DAYGVGSYRE INPAPYTIIT FPFLFAVMFG DCGHGTVMLL
   421  AALWMILNER RLLSQKTDNE IWNTFFHGRY LILLMGIFSI YTGLIYNDCF SKSLNIFGSS
   481  WSVQPMFRNG TWNTHVMEES LYLQLDPAIP GVYFGNPYPF GIDPIWNLAS NKLTFLNSYK
   541  MKMSVILGIV QMVFGVILSL FNHIYFRRTL NIILQFIPEM IFILCLFGYL VFMIIFKWCC
   601  FDVHVSQHAP SILIHFINMF LFNYSDSSNA PLYKHQQEVQ SFFVVMALIS VPWMLLIKPF
   661  ILRASHRKSQ LQASRIQEDA TENIEGDSSS PSSRSGQRTS ADTHGALDDH GEEFNFGDVF
   721  VHQAIHTIEY CLGCISNTAS YLRLWALSLA HAQLSEVLWT MVMNSGLQTR GWGGIVGVFI
   781  IFAVFAVLTV AILLIMEGLS AFLHALRLHW VEFQNKFYVG DGYKFSPFSF KHILDGTAEE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ATP6V0A4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

8

Mean surface accessibility (rSASA)

0.32

Highest tissue expression

74 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ATP6V0A4.

Disease | AllUniProt

Conditions ATP6V0A4 is implicated in, by any mechanism.

• Renal tubular acidosis, distal, 3, with or without sensorineural hearing loss (DRTA3) MIM:602722

Disease | GeneticClinVar

87 pathogenic / likely-pathogenic of 646 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Renal tubular acidosis, distal, 3, with or without sensorineural hearing loss
• Autosomal recessive distal renal tubular acidosis
• ATP6V0A4-related disorder
• Distal renal tubular acidosis
• Renal tubulopathies

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1

gnomAD pLI

0

gnomAD missense Z

0.85

DepMap mean gene effect

-0.04

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• intracellular pH reduction
• ossification
• proton transmembrane transport
• regulation of pH
• renal tubular secretion
• sensory perception of sound
• synaptic vesicle lumen acidification
• vacuolar acidification

Molecular functions

• ATPase binding
• proton-transporting ATPase activity, rotational mechanism

Cellular components

• apical part of cell
• apical plasma membrane
• basolateral plasma membrane
• brush border membrane
• endosome
• endosome membrane
• extracellular exosome
• lysosomal membrane
• phagocytic vesicle membrane
• plasma membrane
• proton-transporting V-type ATPase complex
• synaptic vesicle membrane
• vacuolar proton-transporting V-type ATPase complex
• vacuolar proton-transporting V-type ATPase, V0 domain

Protein domainsUniProt · Pfam · InterPro

• V-type ATPase, V0 complex, 116kDa subunit family
• ATPase, V0 complex, subunit 116kDa, eukaryotic
• V-type ATPase 116kDa subunit family

KeywordsUniProt

• Cell membrane
• Hydrogen ion transport
• Ion transport
• Membrane
• Transmembrane
• Transmembrane helix
• Transport

InteractionsUniProt · HPA

Protein binding partners of ATP6V0A4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ATP6AP1
• ATP6V0C
• ATP6V0D2