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Protein

V-type proton ATPase catalytic subunit A

Gene

ATP6V1A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Catalytic subunit of the peripheral V1 complex of vacuolar ATPase. V-ATPase vacuolar ATPase is responsible for acidifying a variety of intracellular compartments in eukaryotic cells. In aerobic conditions, involved in intracellular iron homeostasis, thus triggering the activity of Fe2+ prolyl hydroxylase (PHD) enzymes, and leading to HIF1A hydroxylation and subsequent proteasomal degradation (PubMed:28296633). May play a role in neurite development and synaptic connectivity (PubMed:29668857).2 Publications

Catalytic activityi

ATP + H2O + 4 H+(Side 1) = ADP + phosphate + 4 H+(Side 2).

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi250 – 257ATPSequence analysis8

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • proton-transporting ATPase activity, rotational mechanism Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionTranslocase
Biological processHydrogen ion transport, Ion transport, Transport
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS03781-MONOMER
ReactomeiR-HSA-1222556 ROS, RNS production in phagocytes
R-HSA-77387 Insulin receptor recycling
R-HSA-917977 Transferrin endocytosis and recycling
R-HSA-983712 Ion channel transport

Protein family/group databases

TCDBi3.A.2.2.4 the h(+)- or na(+)-translocating f-type, v-type and a-type atpase (f-atpase) superfamily

Names & Taxonomyi

Protein namesi
Recommended name:
V-type proton ATPase catalytic subunit A (EC:7.1.2.2)
Short name:
V-ATPase subunit A
Alternative name(s):
V-ATPase 69 kDa subunit
Vacuolar ATPase isoform VA68
Vacuolar proton pump subunit alpha
Gene namesi
Name:ATP6V1A
Synonyms:ATP6A1, ATP6V1A1, VPP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000114573.9
HGNCiHGNC:851 ATP6V1A
MIMi607027 gene
neXtProtiNX_P38606

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Cutis laxa, autosomal recessive, 2D (ARCL2D)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of cutis laxa, a disorder characterized by an excessive congenital skin wrinkling, a large fontanelle with delayed closure, a typical facial appearance with downslanting palpebral fissures, and a general connective tissue weakness. Most ARCL2D patients exhibit severe hypotonia as well as cardiovascular and neurologic involvement.
See also OMIM:617403
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07860672G → D in ARCL2D. 1 PublicationCorresponds to variant dbSNP:rs1060505037Ensembl.1
Natural variantiVAR_078607338R → C in ARCL2D. 1 PublicationCorresponds to variant dbSNP:rs1060505036Ensembl.1
Epileptic encephalopathy, infantile or early childhood, 3 (IECEE3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. IECEE3 is an autosomal dominant form characterized by onset of seizures in the first years of life.The severity of the phenotype is highly variable: some patients may be non-verbal and non-ambulatory with spastic quadriparesis and poor eye contact, whereas others have moderate intellectual disability.
See also OMIM:618012
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_08099527P → R in IECEE3; unknown pathological significance. 1 Publication1
Natural variantiVAR_080996100D → Y in IECEE3; loss-of-function variant leading to increased pH in intracellular organelles; affects neurite arborization and impairs the formation and maintenance of excitatory synapses, when tested in a heterologous system; not effect on subcellular location. 1 Publication1
Natural variantiVAR_080998349D → N in IECEE3; gain-of-function variant leading to decreased pH in intracellular organelles; affects neurite arborization and impairs the formation and maintenance of excitatory synapses, when tested in a heterologous system; not effect on subcellular location. 1 Publication1
Natural variantiVAR_080999371D → G in IECEE3; unknown pathological significance. 1 Publication1

Keywords - Diseasei

Disease mutation, Epilepsy

Organism-specific databases

DisGeNETi523
MalaCardsiATP6V1A
MIMi617403 phenotype
618012 phenotype
OpenTargetsiENSG00000114573
PharmGKBiPA25152

Chemistry databases

DrugBankiDB00630 Alendronic acid
DB06733 Bafilomycin A1
DB06734 Bafilomycin B1
DB01077 Etidronic acid
DB01133 Tiludronic acid

Polymorphism and mutation databases

BioMutaiATP6V1A
DMDMi22096378

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001445601 – 617V-type proton ATPase catalytic subunit AAdd BLAST617
Isoform 2 (identifier: P38606-2)
Initiator methionineiRemovedCombined sources

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei136PhosphothreonineCombined sources1
Modified residuei384PhosphoserineCombined sources1
Isoform 2 (identifier: P38606-2)
Modified residuei2N-acetylalanineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP38606
MaxQBiP38606
PaxDbiP38606
PeptideAtlasiP38606
PRIDEiP38606
ProteomicsDBi55303

PTM databases

iPTMnetiP38606
PhosphoSitePlusiP38606
SwissPalmiP38606

Expressioni

Tissue specificityi

Gene expression databases

BgeeiENSG00000114573 Expressed in 238 organ(s), highest expression level in Brodmann (1909) area 23
CleanExiHS_ATP6V1A
ExpressionAtlasiP38606 baseline and differential
GenevisibleiP38606 HS

Organism-specific databases

HPAiCAB006910
HPA035083
HPA035084

Interactioni

Subunit structurei

V-ATPase is a heteromultimeric enzyme composed of a peripheral catalytic V1 complex (main components: subunits A, B, C, D, E, and F) attached to an integral membrane V0 proton pore complex (main component: the proteolipid protein).

Protein-protein interaction databases

BioGridi107007, 103 interactors
IntActiP38606, 94 interactors
MINTiP38606
STRINGi9606.ENSP00000273398

Structurei

3D structure databases

ProteinModelPortaliP38606
SMRiP38606
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the ATPase alpha/beta chains family.Curated

Phylogenomic databases

eggNOGiKOG1352 Eukaryota
COG1155 LUCA
GeneTreeiENSGT00550000074787
HOGENOMiHOG000161057
HOVERGENiHBG053351
InParanoidiP38606
KOiK02145
OMAiQQLAKWS
OrthoDBiEOG091G03SR
PhylomeDBiP38606
TreeFamiTF300811

Family and domain databases

Gene3Di1.10.1140.10, 1 hit
2.40.30.20, 1 hit
HAMAPiMF_00309 ATP_synth_A_arch, 1 hit
InterProiView protein in InterPro
IPR031686 ATP-synth_a_Xtn
IPR023366 ATP_synth_asu-like_sf
IPR020003 ATPase_a/bsu_AS
IPR004100 ATPase_F1/V1/A1_a/bsu_N
IPR036121 ATPase_F1/V1/A1_a/bsu_N_sf
IPR000194 ATPase_F1/V1/A1_a/bsu_nucl-bd
IPR024034 ATPase_F1/V1_b/a_C
IPR005725 ATPase_V1-cplx_asu
IPR027417 P-loop_NTPase
IPR022878 V-ATPase_asu
PANTHERiPTHR43607 PTHR43607, 1 hit
PfamiView protein in Pfam
PF00006 ATP-synt_ab, 1 hit
PF02874 ATP-synt_ab_N, 1 hit
PF16886 ATP-synt_ab_Xtn, 1 hit
SUPFAMiSSF50615 SSF50615, 1 hit
SSF52540 SSF52540, 1 hit
TIGRFAMsiTIGR01042 V-ATPase_V1_A, 1 hit
PROSITEiView protein in PROSITE
PS00152 ATPASE_ALPHA_BETA, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P38606-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MDFSKLPKIL DEDKESTFGY VHGVSGPVVT ACDMAGAAMY ELVRVGHSEL
60 70 80 90 100
VGEIIRLEGD MATIQVYEET SGVSVGDPVL RTGKPLSVEL GPGIMGAIFD
110 120 130 140 150
GIQRPLSDIS SQTQSIYIPR GVNVSALSRD IKWDFTPCKN LRVGSHITGG
160 170 180 190 200
DIYGIVSENS LIKHKIMLPP RNRGTVTYIA PPGNYDTSDV VLELEFEGVK
210 220 230 240 250
EKFTMVQVWP VRQVRPVTEK LPANHPLLTG QRVLDALFPC VQGGTTAIPG
260 270 280 290 300
AFGCGKTVIS QSLSKYSNSD VIIYVGCGER GNEMSEVLRD FPELTMEVDG
310 320 330 340 350
KVESIMKRTA LVANTSNMPV AAREASIYTG ITLSEYFRDM GYHVSMMADS
360 370 380 390 400
TSRWAEALRE ISGRLAEMPA DSGYPAYLGA RLASFYERAG RVKCLGNPER
410 420 430 440 450
EGSVSIVGAV SPPGGDFSDP VTSATLGIVQ VFWGLDKKLA QRKHFPSVNW
460 470 480 490 500
LISYSKYMRA LDEYYDKHFT EFVPLRTKAK EILQEEEDLA EIVQLVGKAS
510 520 530 540 550
LAETDKITLE VAKLIKDDFL QQNGYTPYDR FCPFYKTVGM LSNMIAFYDM
560 570 580 590 600
ARRAVETTAQ SDNKITWSII REHMGDILYK LSSMKFKDPL KDGEAKIKSD
610
YAQLLEDMQN AFRSLED
Length:617
Mass (Da):68,304
Last modified:August 2, 2002 - v2
Checksum:iDB409A8731D772CB
GO
Isoform 2 (identifier: P38606-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-33: Missing.

Note: No experimental confirmation available.Combined sources
Show »
Length:584
Mass (Da):64,736
Checksum:i6F677073A4B4A48B
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JVW8C9JVW8_HUMAN
V-type proton ATPase catalytic subu...
ATP6V1A
221Annotation score:
C9JA17C9JA17_HUMAN
V-type proton ATPase catalytic subu...
ATP6V1A
184Annotation score:
F8WDJ3F8WDJ3_HUMAN
V-type proton ATPase catalytic subu...
ATP6V1A
49Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti71S → C in AAA83249 (PubMed:8463241).Curated1
Sequence conflicti89 – 90EL → DV in AAA83249 (PubMed:8463241).Curated2
Sequence conflicti211V → A in AAA83249 (PubMed:8463241).Curated1
Sequence conflicti211V → A in AAF14870 (PubMed:10931946).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_08099411D → N Found in a patient with autism spectrum disorder; unknown pathological significance. 1 Publication1
Natural variantiVAR_08099527P → R in IECEE3; unknown pathological significance. 1 Publication1
Natural variantiVAR_07860672G → D in ARCL2D. 1 PublicationCorresponds to variant dbSNP:rs1060505037Ensembl.1
Natural variantiVAR_080996100D → Y in IECEE3; loss-of-function variant leading to increased pH in intracellular organelles; affects neurite arborization and impairs the formation and maintenance of excitatory synapses, when tested in a heterologous system; not effect on subcellular location. 1 Publication1
Natural variantiVAR_080997249P → R Found in a patient with severe developmental disorder; unknown pathological significance. 1 Publication1
Natural variantiVAR_078607338R → C in ARCL2D. 1 PublicationCorresponds to variant dbSNP:rs1060505036Ensembl.1
Natural variantiVAR_080998349D → N in IECEE3; gain-of-function variant leading to decreased pH in intracellular organelles; affects neurite arborization and impairs the formation and maintenance of excitatory synapses, when tested in a heterologous system; not effect on subcellular location. 1 Publication1
Natural variantiVAR_080999371D → G in IECEE3; unknown pathological significance. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0564081 – 33Missing in isoform 2. 1 PublicationAdd BLAST33

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L09235 mRNA Translation: AAA83249.1
AF113129 mRNA Translation: AAF14870.1
BT006672 mRNA Translation: AAP35318.1
AK293804 mRNA Translation: BAH11601.1
AK314779 mRNA Translation: BAG37315.1
AC079944 Genomic DNA No translation available.
AC108693 Genomic DNA No translation available.
CH471052 Genomic DNA Translation: EAW79625.1
CH471052 Genomic DNA Translation: EAW79626.1
BC013138 mRNA Translation: AAH13138.1
CCDSiCCDS2976.1 [P38606-1]
PIRiB46091
RefSeqiNP_001681.2, NM_001690.3 [P38606-1]
UniGeneiHs.477155

Genome annotation databases

EnsembliENST00000273398; ENSP00000273398; ENSG00000114573 [P38606-1]
GeneIDi523
KEGGihsa:523
UCSCiuc003eao.4 human [P38606-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L09235 mRNA Translation: AAA83249.1
AF113129 mRNA Translation: AAF14870.1
BT006672 mRNA Translation: AAP35318.1
AK293804 mRNA Translation: BAH11601.1
AK314779 mRNA Translation: BAG37315.1
AC079944 Genomic DNA No translation available.
AC108693 Genomic DNA No translation available.
CH471052 Genomic DNA Translation: EAW79625.1
CH471052 Genomic DNA Translation: EAW79626.1
BC013138 mRNA Translation: AAH13138.1
CCDSiCCDS2976.1 [P38606-1]
PIRiB46091
RefSeqiNP_001681.2, NM_001690.3 [P38606-1]
UniGeneiHs.477155

3D structure databases

ProteinModelPortaliP38606
SMRiP38606
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107007, 103 interactors
IntActiP38606, 94 interactors
MINTiP38606
STRINGi9606.ENSP00000273398

Chemistry databases

DrugBankiDB00630 Alendronic acid
DB06733 Bafilomycin A1
DB06734 Bafilomycin B1
DB01077 Etidronic acid
DB01133 Tiludronic acid

Protein family/group databases

TCDBi3.A.2.2.4 the h(+)- or na(+)-translocating f-type, v-type and a-type atpase (f-atpase) superfamily

PTM databases

iPTMnetiP38606
PhosphoSitePlusiP38606
SwissPalmiP38606

Polymorphism and mutation databases

BioMutaiATP6V1A
DMDMi22096378

Proteomic databases

EPDiP38606
MaxQBiP38606
PaxDbiP38606
PeptideAtlasiP38606
PRIDEiP38606
ProteomicsDBi55303

Protocols and materials databases

DNASUi523
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000273398; ENSP00000273398; ENSG00000114573 [P38606-1]
GeneIDi523
KEGGihsa:523
UCSCiuc003eao.4 human [P38606-1]

Organism-specific databases

CTDi523
DisGeNETi523
EuPathDBiHostDB:ENSG00000114573.9
GeneCardsiATP6V1A
HGNCiHGNC:851 ATP6V1A
HPAiCAB006910
HPA035083
HPA035084
MalaCardsiATP6V1A
MIMi607027 gene
617403 phenotype
618012 phenotype
neXtProtiNX_P38606
OpenTargetsiENSG00000114573
PharmGKBiPA25152
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1352 Eukaryota
COG1155 LUCA
GeneTreeiENSGT00550000074787
HOGENOMiHOG000161057
HOVERGENiHBG053351
InParanoidiP38606
KOiK02145
OMAiQQLAKWS
OrthoDBiEOG091G03SR
PhylomeDBiP38606
TreeFamiTF300811

Enzyme and pathway databases

BioCyciMetaCyc:HS03781-MONOMER
ReactomeiR-HSA-1222556 ROS, RNS production in phagocytes
R-HSA-77387 Insulin receptor recycling
R-HSA-917977 Transferrin endocytosis and recycling
R-HSA-983712 Ion channel transport

Miscellaneous databases

ChiTaRSiATP6V1A human
GeneWikiiATP6V1A
GenomeRNAii523
PROiPR:P38606
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000114573 Expressed in 238 organ(s), highest expression level in Brodmann (1909) area 23
CleanExiHS_ATP6V1A
ExpressionAtlasiP38606 baseline and differential
GenevisibleiP38606 HS

Family and domain databases

Gene3Di1.10.1140.10, 1 hit
2.40.30.20, 1 hit
HAMAPiMF_00309 ATP_synth_A_arch, 1 hit
InterProiView protein in InterPro
IPR031686 ATP-synth_a_Xtn
IPR023366 ATP_synth_asu-like_sf
IPR020003 ATPase_a/bsu_AS
IPR004100 ATPase_F1/V1/A1_a/bsu_N
IPR036121 ATPase_F1/V1/A1_a/bsu_N_sf
IPR000194 ATPase_F1/V1/A1_a/bsu_nucl-bd
IPR024034 ATPase_F1/V1_b/a_C
IPR005725 ATPase_V1-cplx_asu
IPR027417 P-loop_NTPase
IPR022878 V-ATPase_asu
PANTHERiPTHR43607 PTHR43607, 1 hit
PfamiView protein in Pfam
PF00006 ATP-synt_ab, 1 hit
PF02874 ATP-synt_ab_N, 1 hit
PF16886 ATP-synt_ab_Xtn, 1 hit
SUPFAMiSSF50615 SSF50615, 1 hit
SSF52540 SSF52540, 1 hit
TIGRFAMsiTIGR01042 V-ATPase_V1_A, 1 hit
PROSITEiView protein in PROSITE
PS00152 ATPASE_ALPHA_BETA, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiVATA_HUMAN
AccessioniPrimary (citable) accession number: P38606
Secondary accession number(s): B2RBR8
, B7Z1R5, D3DN75, Q53YD9, Q96DY6, Q9UHY3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: August 2, 2002
Last modified: November 7, 2018
This is version 187 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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