Family A2

Family

Summary Holotypes Alignment Tree Genomes Structure Literature H-seq M-seq

A2A

Summary Holotypes Alignment Tree Genomes Literature

A2B

Summary Holotypes Alignment Tree Genomes Literature

A2C

Summary Holotypes Alignment Tree Genomes Literature

A2D

Summary Holotypes Alignment Tree Genomes Literature

A2E

Summary Holotypes Alignment Genomes Literature

A2G

Summary Holotypes Alignment Tree Genomes Literature

Summary for family A2

NamePeptidase family A2 (retropepsin family)
Family type peptidaseA02.001 - HIV-1 retropepsin (human immunodeficiency virus 1), MEROPS Accession MER0001449 (peptidase unit: 504-599)
Content of familyPeptidase family A2 contains endopeptidases.
History Identifier created: Biochem.J. 290:205-218 (1993)
The retropepsins were discovered in the late 1980"s because of their essential role in the maturation of the human immunodeficiency virus (HIV) responsible for acquired immunodeficiency syndome (AIDS).
Catalytic typeAspartic
Active siteActivated water is the nucleophile in peptidases in family A2, as in all of clan AA. The water molecule is bound by two aspartic residues, one from each monomer of the homo-dimeric molecule. The retropepsin monomer also includes a structural element equivalent to the "flap" over the active site cleft in pepsin (A01.001). In pepsin, a tyrosine residue on the flap is important for substrate binding. In the retropepsin dimer, the two flaps form a beta-sheet that interacts with the substrate.
Activities and specificitiesPeptidases in family A2 are maximally active in the range pH 4-6 (Ido et al., 1991).
InhibitorsNo protein inhibitors of the retropepsins are known. Pepstatin inhibits peptidases from families A1 and A2. Potent, small-molecule inhibitors of the retropepsins have been developed for use in the management of AIDS.
Molecular structureThe tertiary structure of the Rous sarcoma virus peptidase (A02.015) was solved in 1980 (Misono et al., 1980) and that of HIV-1 retropepsin (A02.001) in 1989 (Miller et al., 1989; Navia et al., 1989). The peptidase contains only beta secondary structural elements. Retropepsins are active only as their homodimers. The monomers are structurally related to one lobe of the pepsin (A01.001) molecule, and family A2 is included in clan AA. Each active site aspartate occurs within a DTG motif, as it does in pepsin. It should be noted, however, that DTG is a commonly-occurring motif and the presence of this motif alone is not evidence that the protein is an aspartic peptidase; for example, the DTG motif also occurs in the subtilisin family (S8).
ClanAA
Basis of clan assignmentProtein fold of the peptidase unit for members of this family resembles pepsin, the type example for clan AA.
Distribution of family Bacteria details  
Archaea -  
Protozoa details  
Fungi details  
Plants details  
Animals details  
Viruses details  
Biological functionsRetropepsin is autolytically released from the gag-pol polyprotein and the peptidase has to dimerize to be active. How this process is initiated is not known, but it may follow release of retropepsin monomers from the viral polyprotein by host peptidases. Similar processes occur in other retroid viruses, including important pathogens such as human T-cell leukemia virus, equine infectious anemia virus, mouse mammary tumor virus and Rous avian sarcoma virus. Homologous proteins are encoded in mammalian genomes, including the product of the human vprt gene and the mouse intracisternal A-particle, but the functions and origins of these are unknown.
Pharmaceutical and biotech relevanceThe HIV-1 retropepsin has been studied intensively as a target for treatment of AIDS. Amongst the many effective inhibitors of the enzyme that are now marketed as drugs is ritonavir (Kempf et al., 1998).
ReviewsDunn & Rao (2004), and other chapters in the same volume.
Statistics for family A2Sequences:1396
Identifiers:51
Identifiers with PDB entries:14
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Subfamily A2A
Name Peptidase subfamily A2A
Subfamily type peptidase A02.001 - HIV-1 retropepsin (human immunodeficiency virus 1), MEROPS Accession MER0001449 (peptidase unit: 504-599)
Active site residues D525 
Statistics Sequences: 1166
Identifiers: 41
Identifiers with PDB entries: 9
Other databases CATH 2.40.70.10
HOMSTRAD rvp
HSSP 4phv
INTERPRO IPR001995
INTERPRO IPR018061
PFAM PF00077
PFAM PF12382
SCOP 50631
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
HIV-1 retropepsinA02.001Yes
HIV-2 retropepsinA02.002Yes
simian immunodeficiency virus retropepsinA02.003-
bovine immunodeficiency virus retropepsinA02.005Yes
Visna lentivirus-type retropepsinA02.006Yes
feline immunodeficiency virus retropepsinA02.007Yes
murine leukemia virus-type retropepsinA02.008Yes
Mason-Pfizer leukemia virus retropepsinA02.009Yes
mouse mammary tumor virus retropepsinA02.010-
human endogenous retrovirus K retropepsinA02.011-
bovine leukemia virus retropepsinA02.013Yes
intracisternal A-particle retropepsinA02.016-
multiple-sclerosis-associated retrovirus retropepsinA02.019-
porcine endogenous retrovirus peptidaseA02.020-
rabbit endogenous retrovirus endopeptidaseA02.024-
S71-related human endogenous retropepsinA02.053-
RTVL-H-type putative peptidaseA02.055-
human endogenous retrovirus retropepsin homologue 1A02.056-
human endogenous retrovirus retropepsin homologue 2A02.057-
type D-like endogenous retrovirus peptidase (Mus musculus)A02.060-
Ulysses retrotransposon retropepsinA02.061-
endogenous retrovirus retropepsin pseudogene 1 (Homo sapiens chromosome 14)A02.P01-
endogenous retrovirus retropepsin pseudogene 2 (Homo sapiens chromosome 8)A02.P02-
endogenous retrovirus retropepsin pseudogene 3 (Homo sapiens chromosome 17)A02.P03-
endogenous retrovirus retropepsin pseudogene 5 (Homo sapiens chromosome 12)A02.P04-
endogenous retrovirus retropepsin pseudogene 6 (Homo sapiens chromosome 7)A02.P05-
endogenous retrovirus retropepsin pseudogene 7 (Homo sapiens chromosome 6)A02.P06-
endogenous retrovirus retropepsin pseudogene 8 (Homo sapiens chromosome Y)A02.P07-
endogenous retrovirus retropepsin pseudogene 9 (Homo sapiens chromosome 19)A02.P08-
endogenous retrovirus retropepsin pseudogene 10 (Homo sapiens chromosome 12)A02.P09-
endogenous retrovirus retropepsin pseudogene 11 (Homo sapiens chromosome 17)A02.P10-
endogenous retrovirus retropepsin pseudogene 12 (Homo sapiens chromosome 11)A02.P11-
endogenous retrovirus retropepsin pseudogene 13 (Homo sapiens chromosome 2 and similar)A02.P12-
endogenous retrovirus retropepsin pseudogene 14 (Homo sapiens chromosome 2)A02.P13-
endogenous retrovirus retropepsin pseudogene 15 (Homo sapiens chromosome 4)A02.P14-
endogenous retrovirus retropepsin pseudogene 16A02.P15-
endogenous retrovirus retropepsin pseudogene 17 (Homo sapiens chromosome 8)A02.P16-
endogenous retrovirus retropepsin pseudogene 18 (Homo sapiens chromosome 4)A02.P17-
endogenous retrovirus retropepsin pseudogene 19 (Homo sapiens chromosome 16)A02.P18-
endogenous retrovirus retropepsin pseudogene 21 (Homo sapiens)A02.P19-
endogenous retrovirus retropepsin pseudogene 22 (Homo sapiens chromosome X)A02.P20-
subfamily A2A non-peptidase homologuesnon-peptidase homologue-
subfamily A2A unassigned peptidasesunassignedYes
Subfamily A2B
Name Peptidase subfamily A2B
Subfamily type peptidase A02.022 - Ty3 transposon peptidase (Saccharomyces cerevisiae), MEROPS Accession MER0001325 (peptidase unit: 310-442)
Active site residues D336 
Statistics Sequences: 24
Identifiers: 1
Identifiers with PDB entries: 1
Other databases INTERPRO IPR021109
PANTHER PTHR24559
PFAM PF12384
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
Ty3 transposon peptidaseA02.022Yes
subfamily A2B non-peptidase homologuesnon-peptidase homologue-
subfamily A2B unassigned peptidasesunassigned-
Subfamily A2C
Name Peptidase subfamily A2C
Subfamily type peptidase A02.021 - Gypsy transposon peptidase (Drosophila melanogaster), MEROPS Accession MER0011130 (peptidase unit: 10-107)
Active site residues D29 
Statistics Sequences: 31
Identifiers: 2
Identifiers with PDB entries: 0
Other databases INTERPRO IPR001995
PFAM PF00077
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
Gypsy transposon peptidaseA02.021-
retrotransposon 17.6 peptidaseA02.052-
subfamily A2D non-peptidase homologuesnon-peptidase homologue-
subfamily A2C unassigned peptidasesunassigned-
Subfamily A2D
Name Peptidase subfamily A2D
Subfamily type peptidase A02.054 - Osvaldo retrotransposon peptidase (Drosophila buzzatii), MEROPS Accession MER0001816 (peptidase unit: 154-252)
Active site residues D178 
Statistics Sequences: 125
Identifiers: 3
Identifiers with PDB entries: 1
Other databases PFAM PF00077
PFAM PF13650
PFAM PF13975
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
equine infectious anaemia virus retropepsinA02.004Yes
Osvaldo retrotransposon peptidaseA02.054-
walleye dermal sarcoma virus retropepsinA02.063-
subfamily A2D non-peptidase homologuesnon-peptidase homologue-
subfamily A2D unassigned peptidasesunassigned-
Subfamily A2E
Name Peptidase subfamily A2E