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7  structures 365  species 0  interactions 967  sequences 13  architectures

Family: VAS1_LD (PF05827)

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 [2]. Ac45 is an ER membrane protein that guides the V-type ATPase into specialised subcellular compartments [3] and is critical for Vo complex assembly as it connects to multiple Vo subunits and phospholipids in the c-ring [2]. 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 [2].

Literature references

  1. 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

  2. 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

  3. 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

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 ].

Gene Ontology

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Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

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 [1].

The clan contains the following 2 members:

Lamp VAS1_LD

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets and the UniProtKB sequence database. More...

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(26)
Full
(967)
Representative proteomes UniProt
(1820)
RP15
(98)
RP35
(313)
RP55
(758)
RP75
(1005)
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PP/heatmap 1 View           

1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(26)
Full
(967)
Representative proteomes UniProt
(1820)
RP15
(98)
RP35
(313)
RP55
(758)
RP75
(1005)
Alignment:
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We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(26)
Full
(967)
Representative proteomes UniProt
(1820)
RP15
(98)
RP35
(313)
RP55
(758)
RP75
(1005)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_8145 (release 8.0)
Previous IDs: ATP-synt_S1;
Type: Domain
Sequence Ontology: SO:0000417
Author: Moxon SJ
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 information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 26.9 26.9
Trusted cut-off 26.9 26.9
Noise cut-off 26.8 26.8
Model length: 140
Family (HMM) version: 15
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

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Structures

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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