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

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

SCOOP:	Lamp
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 ].

Gene Ontology

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)

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...

There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.

Alignment types

We make a range of alignments for each Pfam-A family:

seed: the curated alignment from which the HMM for the family is built
full: the alignment generated by searching the sequence database using the HMM
RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
UniProt: alignment generated by searching the UniProtKB sequence database using the family HMM

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View options

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

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

Key: available, not generated, — not available.

Format an alignment

	Seed (26)	Full (967)	Representative proteomes				UniProt (1820)
	Seed (26)	Full (967)	RP15 (98)	RP35 (313)	RP55 (758)	RP75 (1005)	UniProt (1820)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

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)
	Seed (26)	Full (967)	RP15 (98)	RP35 (313)	RP55 (758)	RP75 (1005)	UniProt (1820)
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

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

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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Colour assignments

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.

How the sunburst is generated

The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.

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Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.

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.

So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".

Sub-species

Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.

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Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

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.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

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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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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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.

Protein	Predicted structure	External Information
A2AR67	View 3D Structure	Click here
D3Z5W0	View 3D Structure	Click here
D3ZA00	View 3D Structure	Click here
E9QCZ6	View 3D Structure	Click here
F1R9A7	View 3D Structure	Click here
O54715	View 3D Structure	Click here
P40682	View 3D Structure	Click here
Q0KHY8	View 3D Structure	Click here
Q15904	View 3D Structure	Click here
Q52LC2	View 3D Structure	Click here
Q7JR49	View 3D Structure	Click here
Q9R1Q9	View 3D Structure	Click here

Showing 12 matches

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Family: VAS1_LD (PF05827)

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