Human Gene ATP6V0A4 (ENST00000310018.7) Description and Page Index
  Description: Homo sapiens ATPase H+ transporting V0 subunit a4 (ATP6V0A4), transcript variant 2, mRNA. (from RefSeq NM_130840)
RefSeq Summary (NM_020632): 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].
Gencode Transcript: ENST00000310018.7
Gencode Gene: ENSG00000105929.16
Transcript (Including UTRs)
   Position: hg38 chr7:138,706,294-138,798,196 Size: 91,903 Total Exon Count: 22 Strand: -
Coding Region
   Position: hg38 chr7:138,706,624-138,771,247 Size: 64,624 Coding Exon Count: 20 

Page IndexSequence and LinksUniProtKB CommentsMalaCardsCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesGeneReviewsMethods
Data last updated at UCSC: 2021-01-14 15:32:12

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr7:138,706,294-138,798,196)mRNA (may differ from genome)Protein (840 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
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ReactomeUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: VPP4_HUMAN
DESCRIPTION: RecName: Full=V-type proton ATPase 116 kDa subunit a isoform 4; Short=V-ATPase 116 kDa isoform a4; AltName: Full=Vacuolar proton translocating ATPase 116 kDa subunit a isoform 4; AltName: Full=Vacuolar proton translocating ATPase 116 kDa subunit a kidney isoform;
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: 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''.
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.
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.
SIMILARITY: Belongs to the V-ATPase 116 kDa subunit family.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ATP6V0A4";

-  MalaCards Disease Associations
  MalaCards Gene Search: ATP6V0A4
Diseases sorted by gene-association score: renal tubular acidosis, distal, autosomal recessive* (1342), renal tubular acidosis (30), renal tubular acidosis, distal (24), fanconi-like syndrome (17), hyperglobulinemic purpura (11), medullary sponge kidney (9), acute thyroiditis (8), mineral metabolism disease (7), metabolic acidosis (7), familial periodic paralysis (7), xerophthalmia (6), apparent mineralocorticoid excess (6), renal tubular transport disease (5), hypokalemic periodic paralysis, type 1 (5), impaired renal function disease (5), diabetes insipidus, nephrogenic (5), bartter syndrome, type 3 (5), hypoparathyroidism-deafness-renal disease syndrome (4), primary hypomagnesemia (4), inner ear disease (4), hypophosphatemic rickets with hypercalciuria (3), autosomal recessive disease (2), urinary system disease (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 25.54 RPKM in Kidney - Cortex
Total median expression: 46.78 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -103.30283-0.365 Picture PostScript Text
3' UTR -79.80330-0.242 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR002490 - ATPase_V0/A0_a
IPR026028 - V-type_ATPase_a

Pfam Domains:
PF01496 - V-type ATPase 116kDa subunit family

ModBase Predicted Comparative 3D Structure on Q9HBG4
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGIRGD    
Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005515 protein binding
GO:0015078 hydrogen ion transmembrane transporter activity
GO:0046961 proton-transporting ATPase activity, rotational mechanism
GO:0051117 ATPase binding

Biological Process:
GO:0001503 ossification
GO:0006811 ion transport
GO:0006885 regulation of pH
GO:0007035 vacuolar acidification
GO:0007588 excretion
GO:0007605 sensory perception of sound
GO:0008286 insulin receptor signaling pathway
GO:0015986 ATP synthesis coupled proton transport
GO:0015991 ATP hydrolysis coupled proton transport
GO:0033572 transferrin transport
GO:0034220 ion transmembrane transport
GO:0070072 vacuolar proton-transporting V-type ATPase complex assembly
GO:1902600 hydrogen ion transmembrane transport

Cellular Component:
GO:0000220 vacuolar proton-transporting V-type ATPase, V0 domain
GO:0005765 lysosomal membrane
GO:0005768 endosome
GO:0005886 plasma membrane
GO:0005903 brush border
GO:0010008 endosome membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0016324 apical plasma membrane
GO:0016471 vacuolar proton-transporting V-type ATPase complex
GO:0030670 phagocytic vesicle membrane
GO:0031526 brush border membrane
GO:0033179 proton-transporting V-type ATPase, V0 domain
GO:0045177 apical part of cell
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  AF245517 - Homo sapiens vacuolar proton pump 116 kDa accessory subunit (ATP6N1B) mRNA, complete cds, alternatively spliced.
AK055789 - Homo sapiens cDNA FLJ31227 fis, clone KIDNE2004411, highly similar to Homo sapiens vacuolar proton pump 116 kDa accessory subunit (ATP6N1B) mRNA.
AK292945 - Homo sapiens cDNA FLJ78670 complete cds, highly similar to Homo sapiens ATPase, H+ transporting, lysosomal V0 subunit a isoform 4 (ATP6V0A4), transcript variant 1, mRNA.
BC109304 - Homo sapiens ATPase, H+ transporting, lysosomal V0 subunit a4, mRNA (cDNA clone MGC:130016 IMAGE:40035236), complete cds.
BC109305 - Homo sapiens ATPase, H+ transporting, lysosomal V0 subunit a4, mRNA (cDNA clone MGC:130017 IMAGE:40035237), complete cds.
JD513778 - Sequence 494802 from Patent EP1572962.
JD099510 - Sequence 80534 from Patent EP1572962.
KJ898785 - Synthetic construct Homo sapiens clone ccsbBroadEn_08179 ATP6V0A4 gene, encodes complete protein.
KJ898786 - Synthetic construct Homo sapiens clone ccsbBroadEn_08180 ATP6V0A4 gene, encodes complete protein.
KR711547 - Synthetic construct Homo sapiens clone CCSBHm_00025910 ATP6V0A4 (ATP6V0A4) mRNA, encodes complete protein.
KR711548 - Synthetic construct Homo sapiens clone CCSBHm_00025915 ATP6V0A4 (ATP6V0A4) mRNA, encodes complete protein.
KR711549 - Synthetic construct Homo sapiens clone CCSBHm_00025918 ATP6V0A4 (ATP6V0A4) mRNA, encodes complete protein.
KR711550 - Synthetic construct Homo sapiens clone CCSBHm_00025923 ATP6V0A4 (ATP6V0A4) mRNA, encodes complete protein.
JD180999 - Sequence 162023 from Patent EP1572962.
JD538105 - Sequence 519129 from Patent EP1572962.
JD538106 - Sequence 519130 from Patent EP1572962.
JD496708 - Sequence 477732 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa00190 - Oxidative phosphorylation
hsa01100 - Metabolic pathways
hsa04142 - Lysosome
hsa04966 - Collecting duct acid secretion
hsa05110 - Vibrio cholerae infection
hsa05120 - Epithelial cell signaling in Helicobacter pylori infection

Reactome (by CSHL, EBI, and GO)

Protein Q9HBG4 (Reactome details) participates in the following event(s):

R-HSA-5252133 ATP6AP1 binds V-ATPase
R-HSA-1222516 Intraphagosomal pH is lowered to 5 by V-ATPase
R-HSA-74723 Endosome acidification
R-HSA-917841 Acidification of Tf:TfR1 containing endosome
R-HSA-77387 Insulin receptor recycling
R-HSA-917977 Transferrin endocytosis and recycling
R-HSA-983712 Ion channel transport
R-HSA-74752 Signaling by Insulin receptor
R-HSA-917937 Iron uptake and transport
R-HSA-382551 Transport of small molecules
R-HSA-1222556 ROS, RNS production in phagocytes
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-168249 Innate Immune System
R-HSA-162582 Signal Transduction
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: A4D1R4, A8KA80, ATP6N1B, ATP6N2, ENST00000310018.1, ENST00000310018.2, ENST00000310018.3, ENST00000310018.4, ENST00000310018.5, ENST00000310018.6, NM_130840, Q32M47, Q9HBG4, uc003vug.1, uc003vug.2, uc003vug.3, uc003vug.4, uc003vug.5, VPP4_HUMAN
UCSC ID: ENST00000310018.7
RefSeq Accession: NM_020632
Protein: Q9HBG4 (aka VPP4_HUMAN)
CCDS: CCDS5849.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene ATP6V0A4:
hered-drta (Hereditary Distal Renal Tubular Acidosis)

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.