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1461  structures 97  species 5  interactions 403  sequences 64  architectures

Family: RVP (PF00077)

Summary: Retroviral aspartyl protease

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This is the Wikipedia entry entitled "Retroviral aspartyl protease". More...

Retroviral aspartyl protease Edit Wikipedia article

Retroviral aspartyl protease
Symbol RVP
Pfam PF00077
InterPro IPR001995
SCOP 1ida
OPM superfamily 108
OPM protein 2b7z

Retroviral aspartyl proteases are single domain aspartyl proteases from retroviruses, retrotransposons, and badnaviruses (plant dsDNA viruses). These proteases are generally part of a larger pol or gag polyprotein. Retroviral proteases are homologous to a single domain of the two-domain eukaryotic aspartyl proteases such as pepsins, cathepsins, and renins (Pfam PF00026).

Aspartic endopeptidases EC 3.4.23. of vertebrate, fungal and retroviral origin have been characterised.[1] More recently, aspartic endopeptidases associated with the processing of bacterial type 4 prepilin[2] and archaean preflagellin have been described.[3][4]

Structurally, aspartic endopeptidases are bilobal enzymes, each lobe contributing a catalytic Asp residue, with an extended active site cleft localized between the two lobes of the molecule. One lobe has probably evolved from the other through a gene duplication event in the distant past. In modern-day enzymes, although the three-dimensional structures are very similar, the amino acid sequences are more divergent, except for the catalytic site motif, which is very conserved. The presence and position of disulphide bridges are other conserved features of aspartic peptidases. All or most aspartate peptidases are endopeptidases. These enzymes have been assigned into clans (proteins which are evolutionary related), and further sub-divided into families, largely on the basis of their tertiary structure.

Retroviral aspartyl protease is synthesised as part of the POL polyprotein that contains; an aspartyl protease, a reverse transcriptase, RNase H and integrase. POL polyprotein undergoes specific enzymatic cleavage to yield the mature proteins.

Human proteins containing this domain



  1. ^ Szecsi PB (1992). "The aspartic proteases". Scand. J. Clin. Lab. Invest. Suppl. 210: 5–22. doi:10.3109/00365519209104650. PMID 1455179. 
  2. ^ Taylor RK, LaPointe CF (2000). "The type 4 prepilin peptidases comprise a novel family of aspartic acid proteases". J. Biol. Chem. 275 (2): 1502–10. doi:10.1074/jbc.275.2.1502. PMID 10625704. 
  3. ^ Jarrell KF, Ng SY, Chaban B (2006). "Archaeal flagella, bacterial flagella and type IV pili: a comparison of genes and posttranslational modifications". J. Mol. Microbiol. Biotechnol. 11 (3): –. doi:10.1159/000094053. PMID 16983194. 
  4. ^ Jarrell KF, Bardy SL (2003). "Cleavage of preflagellins by an aspartic acid signal peptidase is essential for flagellation in the archaeon Methanococcus voltae". Mol. Microbiol. 50 (4): 1339–1347. doi:10.1046/j.1365-2958.2003.03758.x. PMID 14622420. 

This article incorporates text from the public domain Pfam and InterPro IPR001995

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Retroviral aspartyl protease Provide feedback

Single domain aspartyl proteases from retroviruses, retrotransposons, and badnaviruses (plant dsDNA viruses). These proteases are generally part of a larger polyprotein; usually pol, more rarely gag. Retroviral proteases appear to be homologous to a single domain of the two-domain eukaryotic aspartyl proteases such as pepsins, cathepsins, and renins (PF00026).

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR018061

Aspartic peptidases, also known as aspartyl proteases (EC), are widely distributed proteolytic enzymes [PUBMED:6795036, PUBMED:2194475, PUBMED:1851433] known to exist in vertebrates, fungi, plants, protozoa, bacteria, archaea, retroviruses and some plant viruses. All known aspartic peptidases are endopeptidases. A water molecule, activated by two aspartic acid residues, acts as the nucleophile in catalysis. Aspartic peptidases can be grouped into five clans, each of which shows a unique structural fold [PUBMED:8439290].

  • Peptidases in clan AA are either bilobed (family A1 or the pepsin family) or are a homodimer (all other families in the clan, including retropepsin from HIV-1/AIDS) [PUBMED:2682266]. Each lobe consists of a single domain with a closed beta-barrel and each lobe contributes one Asp to form the active site. Most peptidases in the clan are inhibited by the naturally occurring small-molecule inhibitor pepstatin [PUBMED:4912600].
  • Clan AC contains the single family A8: the signal peptidase 2 family. Members of the family are found in all bacteria. Signal peptidase 2 processes the premurein precursor, removing the signal peptide. The peptidase has four transmembrane domains and the active site is on the periplasmic side of the cell membrane. Cleavage occurs on the amino side of a cysteine where the thiol group has been substituted by a diacylglyceryl group. Site-directed mutagenesis has identified two essential aspartic acid residues which occur in the motifs GNXXDRX and FNXAD (where X is a hydrophobic residue) [PUBMED:10497172]. No tertiary structures have been solved for any member of the family, but because of the intramembrane location, the structure is assumed not to be pepsin-like.
  • Clan AD contains two families of transmembrane endopeptidases: A22 and A24. These are also known as "GXGD peptidases" because of a common GXGD motif which includes one of the pair of catalytic aspartic acid residues. Structures are known for members of both families and show a unique, common fold with up to nine transmembrane regions [PUBMED:21765428]. The active site aspartic acids are located within a large cavity in the membrane amnd into which water can gain access [PUBMED:23254940].
  • Clan AE contains two families, A25 and A31. Tertiary structures have been solved for members of both families and show a common fold consisting of an alpha-beta-alpha sandwich, in which the beta sheet is five stranded [PUBMED:10331925, PUBMED:10864493].
  • Clan AF contains the single family A26. Members of the clan are membrane-proteins with a unique fold. Homologues are known only from bacteria. The structure of omptin (also known as OmpT) shows a cylindrical barrel containing ten beta strands inserted in the membrane with the active site residues on the outer surface [PUBMED:11566868].
  • There are two families of aspartic peptidases for which neither structure nor active site residues are known and these are not assigned to clans. Family A5 includes thermopsin, an endopeptidase found only in thermophilic archaea. Family A36 contains sporulation factor SpoIIGA, which is known to process and activate sigma factor E, one of the transcription factors that controls sporulation in bacteria [PUBMED:21751400].

This group of aspartic peptidases belong to the peptidase clan AA. The clan includes the single domain aspartic proteases from retroviruses, retrotransposons, and badnaviruses (plant dsDNA viruses) which are active as homodimers.

Family A2 includes the peptidase (retropepsin, EC from the human immunodeficiency virus and other retroviruses. In most retroviruses, the peptidase is encoded as a segment of a polyprotein (usually the pol polyprotein, which includes the peptidase, a reverse transcriptase, RNase H and an integrase, but occassionally the gag polyprotein) which it cleaves during viral maturation to release individual proteins. Some retrotransposon polyproteins also contain a homologous, retropepsin-like peptidase which is also a member of family A2.

Family A3 includes peptidases from the double-stranded DNA plant viruses known as badnaviruses or pararetroviruses. The viral genome includes genes (ORFs IV and V) that encodes polyproteins. The ORF V polyprotein contains the peptidase and a reverse transcriptase. The peptidase processes the ORF IV polyprotein, which includes the viral coat protein [PUBMED:15831103].

Family A9 includes peptidases from spumaretroviruses, and the peptidase is a component of either the gag and pol polyprotein, which is processes [PUBMED:9311808]. The structure has been solved for the peptidase from simian foamy virus and shows a retropepsin-like fold [PUBMED:18597783].

Family A11 includes polyprotein-processing peptidases from retrotransposons such as the copia transposon from Drosophila melanogaster. No tertiary structure has been solved for any member of the family, and family A11 is included in clan AA on the basis of the similar motif around the active site Asp.

Family A28 includes the yeast DNA-damage inducible protein 1 which is a component of the DNA repair pathway. The tertiary structure shows a retropepsin-like fold [PUBMED:17010377].

Family A32 includes the bacterial PerP peptidase which converts the transmembrane factor PodJ from a form that recruits proteins for pilus formation, to a truncated form that recruits proteins for stalk formation. This converts the bacterium from a motile form to the sessile form found in biofilms [PUBMED:16395329].

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 Peptidase_AA (CL0129), which has the following description:

This clan contains aspartic peptidases, including the pepsins and retropepsins. These enzymes contains a catalytic dyad composed of two aspartates. In the retropepsins one is provided by each copy of a homodimeric protein, whereas in the pepsin-like peptidases these aspartates come from a single protein composed of two duplicated domains.

The clan contains the following 14 members:

Asp Asp_protease Asp_protease_2 DUF1758 gag-asp_proteas Peptidase_A2B Peptidase_A2E Peptidase_A3 RVP RVP_2 Spuma_A9PTase TAXi_C TAXi_N Zn_protease


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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.

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Curation and family details

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Curation View help on the curation process

Seed source: Eddy SR
Previous IDs: rvp;
Type: Domain
Author: Eddy SR
Number in seed: 9
Number in full: 403
Average length of the domain: 92.50 aa
Average identity of full alignment: 21 %
Average coverage of the sequence by the domain: 15.13 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 17690987 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 20.7 20.7
Trusted cut-off 20.7 20.7
Noise cut-off 20.6 20.6
Model length: 101
Family (HMM) version: 18
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Species distribution

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Colour assignments

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


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There are 5 interactions for this family. More...

Gag_p17 Gag_p24 Gag_p6 RVP RNase_H


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 RVP domain has been found. There are 1461 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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