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Protein

V-type proton ATPase subunit S1

Gene

ATP6AP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Accessory subunit of the proton-transporting vacuolar (V)-ATPase protein pump, which is required for luminal acidification of secretory vesicles. Guides the V-type ATPase into specialized subcellular compartments, such as neuroendocrine regulated secretory vesicles or the ruffled border of the osteoclast, thereby regulating its activity. Involved in membrane trafficking and Ca2+-dependent membrane fusion. May play a role in the assembly of the V-type ATPase complex. 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).1 Publication1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

BioCyciMetaCyc:HS01034-MONOMER.
ReactomeiR-HSA-77387. Insulin receptor recycling.
R-HSA-917977. Transferrin endocytosis and recycling.
R-HSA-983712. Ion channel transport.

Names & Taxonomyi

Protein namesi
Recommended name:
V-type proton ATPase subunit S1
Short name:
V-ATPase subunit S1
Alternative name(s):
Protein XAP-3
V-ATPase Ac45 subunit
V-ATPase S1 accessory protein
Vacuolar proton pump subunit S1
Gene namesi
Name:ATP6AP1
Synonyms:ATP6IP1, ATP6S1, VATPS1, XAP3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

EuPathDBiHostDB:ENSG00000071553.16.
HGNCiHGNC:868. ATP6AP1.

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini42 – 419VacuolarSequence analysisAdd BLAST378
Transmembranei420 – 440HelicalSequence analysisAdd BLAST21
Topological domaini441 – 470CytoplasmicSequence analysisAdd BLAST30

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency 47 (IMD47)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA complex immunodeficiency syndrome characterized by hypogammaglobulinemia, recurrent bacterial infections, defective glycosylation of serum proteins, and liver disease with neonatal jaundice and hepatosplenomegaly. Some patients may also have neurologic features, including seizures, mild intellectual disability, and behavioral abnormalities. Inheritance is X-linked recessive.
See also OMIM:300972
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_077021144L → P in IMD47. 1 PublicationCorresponds to variant dbSNP:rs878853276Ensembl.1
Natural variantiVAR_077022313Y → C in IMD47; probable loss of proton-transporting V-type ATPase complex assembly in yeast; unable to restore V-ATPase-dependent growth in Voa1 mutant yeast. 1 PublicationCorresponds to variant dbSNP:rs878853278Ensembl.1
Natural variantiVAR_077023346E → K in IMD47; probable loss of proton-transporting V-type ATPase complex assembly in yeast; unable to restore V-ATPase-dependent growth in Voa1 mutant yeast. 1 PublicationCorresponds to variant dbSNP:rs878853277Ensembl.1
Natural variantiVAR_077024428M → I in IMD47; restores V-ATPase-dependent growth in Voa1 mutant yeast. 1 PublicationCorresponds to variant dbSNP:rs878853275Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi470V → VKKNN: Retained in the endoplasmic reticulum when transfected into yeast cells. Restores V-ATPase-dependent growth in Voa1 mutant yeast. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi537.
MalaCardsiATP6AP1.
MIMi300972. phenotype.
OpenTargetsiENSG00000071553.
PharmGKBiPA25145.

Chemistry databases

ChEMBLiCHEMBL4790.

Polymorphism and mutation databases

BioMutaiATP6AP1.
DMDMi12230759.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 41Sequence analysisAdd BLAST41
ChainiPRO_000000254342 – 470V-type proton ATPase subunit S1Add BLAST429

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi170N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi261N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi273N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi296N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi303N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi350N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi357N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei465PhosphoserineCombined sources1

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ15904.
MaxQBiQ15904.
PaxDbiQ15904.
PeptideAtlasiQ15904.
PRIDEiQ15904.

PTM databases

iPTMnetiQ15904.
PhosphoSitePlusiQ15904.

Expressioni

Tissue specificityi

widely expressed, with highest levels in brain and lowest in liver and duodenum.1 Publication

Gene expression databases

BgeeiENSG00000071553.
CleanExiHS_ATP6AP1.
ExpressionAtlasiQ15904. baseline and differential.
GenevisibleiQ15904. HS.

Organism-specific databases

HPAiCAB015218.

Interactioni

Subunit structurei

Accessory component of the multisubunit proton-transporting vacuolar (V)-ATPase protein pump.1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi107019. 39 interactors.
IntActiQ15904. 24 interactors.
MINTiMINT-4722342.
STRINGi9606.ENSP00000358777.

Chemistry databases

BindingDBiQ15904.

Structurei

3D structure databases

ProteinModelPortaliQ15904.
SMRiQ15904.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the vacuolar ATPase subunit S1 family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3868. Eukaryota.
ENOG410XTHY. LUCA.
GeneTreeiENSGT00530000063584.
HOGENOMiHOG000000706.
HOVERGENiHBG001090.
InParanoidiQ15904.
KOiK03662.
OMAiHITSDMQ.
OrthoDBiEOG091G0772.
PhylomeDBiQ15904.
TreeFamiTF325819.

Family and domain databases

InterProiView protein in InterPro
IPR008388. ATPase_V1-cplx_s1su.
PANTHERiPTHR12471. PTHR12471. 1 hit.
PfamiView protein in Pfam
PF05827. ATP-synt_S1. 1 hit.

Sequencei

Sequence statusi: Complete.

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

Q15904-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMAAMATARV RMGPRCAQAL WRMPWLPVFL SLAAAAAAAA AEQQVPLVLW
60 70 80 90 100
SSDRDLWAPA ADTHEGHITS DLQLSTYLDP ALELGPRNVL LFLQDKLSIE
110 120 130 140 150
DFTAYGGVFG NKQDSAFSNL ENALDLAPSS LVLPAVDWYA VSTLTTYLQE
160 170 180 190 200
KLGASPLHVD LATLRELKLN ASLPALLLIR LPYTASSGLM APREVLTGND
210 220 230 240 250
EVIGQVLSTL KSEDVPYTAA LTAVRPSRVA RDVAVVAGGL GRQLLQKQPV
260 270 280 290 300
SPVIHPPVSY NDTAPRILFW AQNFSVAYKD QWEDLTPLTF GVQELNLTGS
310 320 330 340 350
FWNDSFARLS LTYERLFGTT VTFKFILANR LYPVSARHWF TMERLEVHSN
360 370 380 390 400
GSVAYFNASQ VTGPSIYSFH CEYVSSLSKK GSLLVARTQP SPWQMMLQDF
410 420 430 440 450
QIQAFNVMGE QFSYASDCAS FFSPGIWMGL LTSLFMLFIF TYGLHMILSL
460 470
KTMDRFDDHK GPTISLTQIV
Length:470
Mass (Da):52,026
Last modified:January 11, 2001 - v2
Checksum:iA71C7EF0E90D0652
GO

Sequence cautioni

The sequence BAA03938 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAB66785 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti68I → V in BAC11520 (PubMed:16303743).Curated1
Sequence conflicti74L → P in BAC11520 (PubMed:16303743).Curated1
Sequence conflicti229V → A in AK026519 (PubMed:14702039).Curated1
Sequence conflicti307A → T in AK026519 (PubMed:14702039).Curated1
Sequence conflicti335S → F in AK026519 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_077021144L → P in IMD47. 1 PublicationCorresponds to variant dbSNP:rs878853276Ensembl.1
Natural variantiVAR_077022313Y → C in IMD47; probable loss of proton-transporting V-type ATPase complex assembly in yeast; unable to restore V-ATPase-dependent growth in Voa1 mutant yeast. 1 PublicationCorresponds to variant dbSNP:rs878853278Ensembl.1
Natural variantiVAR_077023346E → K in IMD47; probable loss of proton-transporting V-type ATPase complex assembly in yeast; unable to restore V-ATPase-dependent growth in Voa1 mutant yeast. 1 PublicationCorresponds to variant dbSNP:rs878853277Ensembl.1
Natural variantiVAR_077024428M → I in IMD47; restores V-ATPase-dependent growth in Voa1 mutant yeast. 1 PublicationCorresponds to variant dbSNP:rs878853275Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L44140 Genomic DNA. No translation available.
AL136851 mRNA. Translation: CAB66785.1. Different initiation.
AK026519 mRNA. No translation available.
AK289452 mRNA. Translation: BAF82141.1.
AK075284 mRNA. Translation: BAC11520.1.
BX936347 Genomic DNA. No translation available.
BX936385 Genomic DNA. No translation available.
CH471172 Genomic DNA. Translation: EAW72715.1.
BC000724 mRNA. Translation: AAH00724.1.
D16469 mRNA. Translation: BAA03938.1. Different initiation.
CCDSiCCDS35451.1.
RefSeqiNP_001174.2. NM_001183.5.
XP_011529481.1. XM_011531179.1.
UniGeneiHs.633817.
Hs.6551.

Genome annotation databases

EnsembliENST00000369762; ENSP00000358777; ENSG00000071553.
GeneIDi537.
KEGGihsa:537.
UCSCiuc004flf.3. human.

Similar proteinsi

Entry informationi

Entry nameiVAS1_HUMAN
AccessioniPrimary (citable) accession number: Q15904
Secondary accession number(s): A6ZKI4, Q8NBT4, Q9H0C7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: January 11, 2001
Last modified: November 22, 2017
This is version 174 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. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families