Summary: V-type proton ATPase subunit S1, luminal domain
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V-type proton ATPase subunit S1, luminal domain Provide feedback
This entry represents the luminal domain (LD) found in eukaryotic V-type proton ATPase subunit S1 involved in V-ATPase V0 assembly, including Ac45 subunit (ATP6AP1) [1,2]. This domain folds as a globular beta-prism structure which is structurally similar to LAMP1-3, thus, the LD domain of Ac45 is an evolutionarily conserved member of the LAMP family . Ac45 is an ER membrane protein that guides the V-type ATPase into specialised subcellular compartments  and is critical for Vo complex assembly as it connects to multiple Vo subunits and phospholipids in the c-ring . Missense mutations in the X-linked ATP6AP1 gene cause immunodeficiency in males that leads to recurrent bacterial infection, hepatopathy, cognitive impairment, and abnormal protein glycosylation .
Supek F, Supekova L, Mandiyan S, Pan YC, Nelson H, Nelson N; , J Biol Chem 1994;269:24102-24106.: A novel accessory subunit for vacuolar H(+)-ATPase from chromaffin granules. PUBMED:7929063 EPMC:7929063
Wang L, Wu D, Robinson CV, Wu H, Fu TM;, Mol Cell. 2020;80:501-511.: Structures of a Complete Human V-ATPase Reveal Mechanisms of Its Assembly. PUBMED:33065002 EPMC:33065002
Miles AL, Burr SP, Grice GL, Nathan JA;, Elife. 2017; [Epub ahead of print]: The vacuolar-ATPase complex and assembly factors, TMEM199 and CCDC115, control HIF1alpha prolyl hydroxylation by regulating cellular iron levels. PUBMED:28296633 EPMC:28296633
Internal database links
|Similarity to PfamA using HHSearch:||Lamp|
This tab holds annotation information from the InterPro database.
InterPro entry IPR008388
V-ATPases (also known as V1V0-ATPase or vacuolar ATPase) are found in the eukaryotic endomembrane system, and in the plasma membrane of prokaryotes and certain specialised eukaryotic cells. V-ATPases hydrolyse ATP to drive a proton pump, and are involved in a variety of vital intra- and inter-cellular processes such as receptor mediated endocytosis, protein trafficking, active transport of metabolites, homeostasis and neurotransmitter release [ PUBMED:15629643 ]. V-ATPases are composed of two linked complexes: the V1 complex (subunits A-H) contains the catalytic core that hydrolyses ATP, while the V0 complex (subunits a, c, c', c'', d) forms the membrane-spanning pore. V-ATPases may have an additional role in membrane fusion through binding to t-SNARE proteins [ PUBMED:15907459 ].
Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.
There are several different types of transmembrane ATPases, which can differ in function (ATP hydrolysis and/or synthesis), structure (e.g., F-, V- and A-ATPases, which contain rotary motors) and in the type of ions they transport [ PUBMED:15473999 , PUBMED:15078220 ]. The different types include:
- F-ATPases (ATP synthases, F1F0-ATPases), which are found in mitochondria, chloroplasts and bacterial plasma membranes where they are the prime producers of ATP, using the proton gradient generated by oxidative phosphorylation (mitochondria) or photosynthesis (chloroplasts).
- V-ATPases (V1V0-ATPases), which are primarily found in eukaryotes and they function as proton pumps that acidify intracellular compartments and, in some cases, transport protons across the plasma membrane [ PUBMED:20450191 ]. They are also found in bacteria [ PUBMED:9741106 ].
- A-ATPases (A1A0-ATPases), which are found in Archaea and function like F-ATPases, though with respect to their structure and some inhibitor responses, A-ATPases are more closely related to the V-ATPases [ PUBMED:18937357 , PUBMED:1385979 ].
- P-ATPases (E1E2-ATPases), which are found in bacteria and in eukaryotic plasma membranes and organelles, and function to transport a variety of different ions across membranes.
- E-ATPases, which are cell-surface enzymes that hydrolyse a range of NTPs, including extracellular ATP.
This entry represents the S1 subunit (or subunit AC45) found in the V1 complex of V-ATPases. This subunit is synthesized as an N-glycosylated 60kDa precursor that is intracellularly cleaved to a protein of about 45kDa. This subunit may assist the V-ATPase in the acidification of neuroendocrine granules [ PUBMED:10336633 ].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||proton-transporting V-type ATPase, V1 domain (GO:0033180)|
|Biological process||proton transmembrane transport (GO:1902600)|
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This family is a member of clan LAMP (CL0721), which has the following description:
This superfamily includes LAMP and LAMP-like members which are structurally similar. The luminal domain has a beta-prim structure composed of 10 beta-strands, in which beta-4-8 form a planar beta-sheet and beta-1-3, 9 and 10 assembly into a bent beta-sheet opposing the planar beta-sheet .
The clan contains the following 2 members:Lamp VAS1_LD
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
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|Seed source:||Pfam-B_8145 (release 8.0)|
|Number in seed:||26|
|Number in full:||967|
|Average length of the domain:||135.7 aa|
|Average identity of full alignment:||32 %|
|Average coverage of the sequence by the domain:||36.96 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||15|
|Download:||download the raw HMM for this family|
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Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
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For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
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We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the VAS1_LD domain has been found. There are 7 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
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AlphaFold Structure Predictions
The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.