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3.A.2.2.4
The ubiquitous 14 subunit vacuolar H+-ATPase, V1/V0, has been implicated in various human diseases including osteopetrosis, renal tubule acidosis, and cancer (Hinton et al., 2009).  The transmembrane enzyme, Ribonuclease kappa, RNASEK (137 aas; 2 TMSs; UniProt acc# Q6P5S7), closely associates with the V-ATPase and is required for its function; its loss prevents the early events of endocytosis and the replication of multiple pathogenic viruses (Perreira et al. 2015).  Cryo-EM allowed the construction of an atomic model, defining the enzyme's ATP:proton ratio as 3:10 and revealing a homolog of yeast subunit f in the membrane region, which appeared to be RNAseK (Abbas et al. 2020). The c ring encloses the transmembrane anchors for cleaved ATP6AP1/Ac45 and ATP6AP2/PRR, the latter of which is the (pro)renin receptor that, in other contexts, is involved in both Wnt signaling and the renin-angiotensin system that regulates blood pressure. This structure shows how ATP6AP1/Ac45 and ATP6AP2/PRR enable assembly of the enzyme's catalytic and membrane regions (Abbas et al. 2020).

Accession Number:O75348
Protein Name:V-ATPase subunit G1
Length:118
Molecular Weight:13758.00
Species:Homo sapiens (Human) [9606]
Location1 / Topology2 / Orientation3: Endomembrane system1 / Peripheral membrane protein2
Substrate H+

Cross database links:

Genevestigator: O75348
eggNOG: prNOG21247
HEGENOM: HBG621942
RefSeq: NP_004879.1   
Entrez Gene ID: 9550   
Pfam: PF03179   
Drugbank: Drugbank Link   
OMIM: 607296  gene
KEGG: hsa:9550   

Gene Ontology

GO:0005829 C:cytosol
GO:0005886 C:plasma membrane
GO:0051117 F:ATPase binding
GO:0015992 P:proton transport

References (4)

[1] “Identification of genes expressed in human CD34(+) hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning.”  Mao M.et.al.   9653160
[2] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[3] “Molecular cloning and characterization of novel tissue-specific isoforms of the human vacuolar H(+)-ATPase C, G and d subunits, and their evaluation in autosomal recessive distal renal tubular acidosis.”  Smith A.N.et.al.   12384298
[4] “Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.”  Gauci S.et.al.   19413330

External Searches:

  • Search: DB with
  • BLAST ExPASy (Swiss Institute of Bioinformatics (SIB) BLAST)
  • CDD Search (Conserved Domain Database)
  • Search COGs (Clusters of Orthologous Groups of proteins)
  • 2° Structure (Network Protein Sequence Analysis)

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MASQSQGIQQ LLQAEKRAAE KVSEARKRKN RRLKQAKEEA QAEIEQYRLQ REKEFKAKEA 
61:	AALGSRGSCS TEVEKETQEK MTILQTYFRQ NRDEVLDNLL AFVCDIRPEI HENYRING