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14  structures 407  species 3  interactions 1883  sequences 136  architectures

Family: VPS9 (PF02204)

Summary: Vacuolar sorting protein 9 (VPS9) domain

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Vacuolar sorting protein 9 (VPS9) domain Provide feedback

This domain acts as a GDP-GTP exchange factor (GEF). It activates Rab GTPases by stimulating the release of GDP and allowing GTP to bind [1].

Literature references

  1. Carney DS, Davies BA, Horazdovsky BF;, Trends Cell Biol. 2006;16:27-35.: Vps9 domain-containing proteins: activators of Rab5 GTPases from yeast to neurons. PUBMED:16330212 EPMC:16330212


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR003123

Rab proteins form a family of signal-transducing GTPases that cycle between active GTP-bound and inactive GDP-bound forms. The Rab5 GTPase is an essential regulator of endocytosis and endosome biogenesis. Rab5 is activated by GDP-GTP exchange factors (GEFs) that contain a VPS9 domain and generate the Rab5-GTP complex [PUBMED:16330212]. The VPS9 domain catalyzes nucleotide exchange on Rab5 or the yeast homologue VPS21. The domain has a length of ~140 residues and forms the central part of the yeast VPS9 (vacuolar protein sorting-associated) protein, which acts as a GEF for VPS21. Some domains which can occur in combination with the VPS9 domain are CUE, A20-type zinc finger, Ras-associating (RA), SH2, RCC1, DH, PH, rasGAP, MORN and ankyrin repeat.

Structurally, the VPS9 domain adopts a layered fold of six alpha helices. Conserved residues from the fourth and sixth helices and the loops N-terminal to these helices form the surface that interacts with Rab5 and Rab21 [PUBMED:15339665].

Some proteins known to contain a VPS9 domain:

  • Fungal Vacuolar Protein Sorting-associated protein VPS9, a guanine nucleotide exchange factor for the Rab-like GTPase VPS21. VPS9 is needed for the transport of proteins from biosynthetic and endocytic pathways into the vacuole.
  • Mammalian Rab5 GDP/GTP exchange factor or Rabex-5 (Rababtin-5 associated exchange factor for Rab5), catalyzes nucleotide exchange on RAB5A. Rabex-5 promotes endocytic membrane fusion and is involved in membrane trafficking of recycling endosomes.
  • Mammalian Ras and Rab interactor 1 (RIN1), 2 (RIN2) and 3 (RIN3).
  • Mammalian alsin or Amyotrophic Lateral Sclerosis protein 2 (ALS2). Different juvenile-onset forms of neurodegenerative diseases (ALS2, JPLS, IAHSP) are caused by mutations in the ALS2 gene, which result in truncated alsin lacking the C-terminal part of the VPS9 domain.
  • Fruit fly protein sprint, which is a RIN homologue.
  • Caenorhabditis elegans RME-6 protein, which is conserved among metazoans.

Domain organisation

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

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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, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics 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
(45)
Full
(1883)
Representative proteomes UniProt
(3974)
NCBI
(5955)
Meta
(9)
RP15
(574)
RP35
(938)
RP55
(1383)
RP75
(1734)
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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
(45)
Full
(1883)
Representative proteomes UniProt
(3974)
NCBI
(5955)
Meta
(9)
RP15
(574)
RP35
(938)
RP55
(1383)
RP75
(1734)
Alignment:
Format:
Order:
Sequence:
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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
(45)
Full
(1883)
Representative proteomes UniProt
(3974)
NCBI
(5955)
Meta
(9)
RP15
(574)
RP35
(938)
RP55
(1383)
RP75
(1734)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   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: Alignment kindly provided by SMART
Previous IDs: none
Type: Family
Author: SMART, Eberhardt R
Number in seed: 45
Number in full: 1883
Average length of the domain: 105.40 aa
Average identity of full alignment: 25 %
Average coverage of the sequence by the domain: 12.39 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 11927849 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.6 20.6
Trusted cut-off 20.6 20.7
Noise cut-off 20.5 20.3
Model length: 104
Family (HMM) version: 15
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
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Viroids Viroids Unclassified sequence Unclassified sequence

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Interactions

There are 3 interactions for this family. More...

Ras VPS9 Ras

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 VPS9 domain has been found. There are 14 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 seqence.

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