ATP6V1A

Protein identityUniProt · HPA

UniProt accession

P38606

Gene

ATP6V1A

Ensembl

ENSG00000114573

Chromosome

3

Canonical length

617 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins, Transporters

Subcellular location

Nucleoplasm,Vesicles,Cytosol

OverviewNCBI Gene

This gene encodes a component of vacuolar ATPase (V-ATPase), a multisubunit enzyme that mediates acidification of eukaryotic intracellular organelles. V-ATPase dependent organelle 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. Additional isoforms of many of the V1 and V0 subunit proteins are encoded by multiple genes or alternatively spliced transcript variants. This encoded protein is one of two V1 domain A subunit isoforms and is found in all tissues. Transcript variants derived from alternative polyadenylation exist. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

617 residues, UniProt reviewed canonical sequence.

>P38606|ATP6V1A
     1  MDFSKLPKIL DEDKESTFGY VHGVSGPVVT ACDMAGAAMY ELVRVGHSEL VGEIIRLEGD
    61  MATIQVYEET SGVSVGDPVL RTGKPLSVEL GPGIMGAIFD GIQRPLSDIS SQTQSIYIPR
   121  GVNVSALSRD IKWDFTPCKN LRVGSHITGG DIYGIVSENS LIKHKIMLPP RNRGTVTYIA
   181  PPGNYDTSDV VLELEFEGVK EKFTMVQVWP VRQVRPVTEK LPANHPLLTG QRVLDALFPC
   241  VQGGTTAIPG AFGCGKTVIS QSLSKYSNSD VIIYVGCGER GNEMSEVLRD FPELTMEVDG
   301  KVESIMKRTA LVANTSNMPV AAREASIYTG ITLSEYFRDM GYHVSMMADS TSRWAEALRE
   361  ISGRLAEMPA DSGYPAYLGA RLASFYERAG RVKCLGNPER EGSVSIVGAV SPPGGDFSDP
   421  VTSATLGIVQ VFWGLDKKLA QRKHFPSVNW LISYSKYMRA LDEYYDKHFT EFVPLRTKAK
   481  EILQEEEDLA EIVQLVGKAS LAETDKITLE VAKLIKDDFL QQNGYTPYDR FCPFYKTVGM
   541  LSNMIAFYDM ARRAVETTAQ SDNKITWSII REHMGDILYK LSSMKFKDPL KDGEAKIKSD
   601  YAQLLEDMQN AFRSLED

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ATP6V1A 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

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.23

Highest tissue expression

87 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ATP6V1A.

Disease | AllUniProt

Conditions ATP6V1A is implicated in, by any mechanism.

• Cutis laxa, autosomal recessive, 2D (ARCL2D) MIM:617403
• Epileptic encephalopathy, infantile or early childhood, 3 (IECEE3) MIM:618012

Disease | GeneticClinVar

26 pathogenic / likely-pathogenic of 455 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Developmental and epileptic encephalopathy 93
• Autosomal recessive cutis laxa type 2D
• Inborn genetic diseases
• Cerebral visual impairment and intellectual disability
• Encephalopathy

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)

0.36

gnomAD pLI

0.87

gnomAD missense Z

3.37

DepMap mean gene effect

-1.91

DepMap dependency class

pan

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 8% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• ATP metabolic process
• cellular response to increased oxygen levels
• endosomal lumen acidification
• Golgi lumen acidification
• intracellular iron ion homeostasis
• intracellular pH reduction
• lysosomal lumen acidification
• proton transmembrane transport
• regulation of macroautophagy
• synaptic vesicle lumen acidification
• vacuolar acidification

Molecular functions

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

Cellular components

• apical plasma membrane
• clathrin-coated vesicle membrane
• cytosol
• endosome membrane
• extracellular exosome
• extrinsic component of synaptic vesicle membrane
• Golgi membrane
• lysosomal membrane
• membrane
• microvillus
• nucleoplasm
• plasma membrane
• proton-transporting two-sector ATPase complex
• proton-transporting V-type ATPase complex
• secretory granule
• vacuolar proton-transporting V-type ATPase, V1 domain

Protein domainsUniProt · Pfam · InterPro

• ATPase, F1/V1/A1 complex, alpha/beta subunit, nucleotide-binding domain
• ATPase, F1/V1/A1 complex, alpha/beta subunit, N-terminal domain
• ATPase, alpha/beta subunit, nucleotide-binding domain, active site
• ATP synthase subunit alpha, N-terminal domain-like superfamily
• ATPase, F1/V1 complex, beta/alpha subunit, C-terminal
• P-loop containing nucleoside triphosphate hydrolase
• ATPase, F1/V1/A1 complex, alpha/beta subunit, N-terminal domain superfamily
• ATP synthase A/B type, C-terminal domain
• ATP synthase alpha/beta family, nucleotide-binding domain
• ATP synthase alpha/beta family, beta-barrel domain
• C-terminal domain of V and A type ATP synthase
• ATPase, V1 complex, subunit A
• V-type ATP synthase catalytic alpha chain
• ATPsynthase alpha/beta subunit, barrel-sandwich domain
• ATPsynthase alpha/beta subunit barrel-sandwich domain

KeywordsUniProt

• Acetylation
• ATP-binding
• Cytoplasm
• Cytoplasmic vesicle
• Epilepsy
• Hydrogen ion transport
• Ion transport
• Lysosome
• Membrane
• Nucleotide-binding
• Phosphoprotein
• Translocase
• Transport

InteractionsUniProt · HPA

Protein binding partners of ATP6V1A in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• WFS1
• CRYAB
• MTOR
• ATP6AP2
• ATP6V0A1
• ATP6V0D1
• ATP6V1B1
• ATP6V1B2
• ATP6V1C1
• ATP6V1C2
• ATP6V1D
• ATP6V1E1
• ATP6V1F
• ATP6V1G1
• ATP6V1H
• RAB7A