Cellular and retroviral pepsin-like aspartate proteases; This family includes both cellular and retroviral pepsin-like aspartate proteases. The cellular pepsin and pepsin-like enzymes are twice as long as their retroviral counterparts. The cellular pepsin-like aspartic proteases are found in mammals, plants, fungi and bacteria. These well known and extensively characterized enzymes include pepsins, chymosin, rennin, cathepsins, and fungal aspartic proteases. Several have long been known to be medically (rennin, cathepsin D and E, pepsin) or commercially (chymosin) important. The eukaryotic pepsin-like proteases contain two domains possessing similar topological features. The N- and C-terminal domains, although structurally related by a 2-fold axis, have only limited sequence homology except in the vicinity of the active site. This suggests that the enzymes evolved by an ancient duplication event. The eukaryotic pepsin-like proteases have two active site ASP residues with each N- and C-terminal lobe contributing one residue. While the fungal and mammalian pepsins are bilobal proteins, retropepsins function as dimers and the monomer resembles structure of the N- or C-terminal domains of eukaryotic enzyme. The active site motif (Asp-Thr/Ser-Gly-Ser) is conserved between the retroviral and eukaryotic proteases and between the N-and C-terminal of eukaryotic pepsin-like proteases. The retropepsin-like family includes pepsin-like aspartate proteases from retroviruses, retrotransposons and retroelements; as well as eukaryotic DNA-damage-inducible proteins (DDIs), and bacterial aspartate peptidases. Retropepsin is synthesized as part of the POL polyprotein that contains an aspartyl-protease, a reverse transcriptase, RNase H, and an integrase. The POL polyprotein undergoes specific enzymatic cleavage to yield the mature proteins. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A) and A2 (retropepsin family).

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2775959027   2 LRVAVDTGTQHNQISAGCLRRLGLGKRVPQAPGGDLAP------ESTSQVEQVELELGQETVACSAQVVDVDSPEFCLGL 75
Cdd:cd05480    10 LRALVDTGCQYNLISAACLDRLGLKERVLKAKAEEEAPslptsvKVIGQIERLVLQLGQLTVECSAQVVDDNEKNFSLGL 89

                          90
                  ....*....|....
gi 2775959027  76 QTLLSLKCCIDLDR 89
Cdd:cd05480    90 QTLKSLKCVINLEK 103

NRIP_C; putative nuclear receptor interacting protein; Proteins in this family have been described as probable nuclear receptor interacting proteins. The C-terminal domain of this family is homologous to the retroviral aspartyl protease domain. The domain is structurally related to one lobe of the pepsin molecule. The conserved active site aspartate occurs within a motif (Asp-Thr/Ser-Gly), as it does in pepsin. Asp residues are ligands of an activated water molecule in all examples where catalytic residues have been identified. This group of aspartate peptidases is classified by MEROPS as the peptidase family A2 (retropepsin family, clan AA), subfamily A2A.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2775959027   2 LRVAVDTGTQHNQISAGCLRRLGLGKRVPQAPGGDLAP------ESTSQVEQVELELGQETVACSAQVVDVDSPEFCLGL 75
Cdd:cd05480    10 LRALVDTGCQYNLISAACLDRLGLKERVLKAKAEEEAPslptsvKVIGQIERLVLQLGQLTVECSAQVVDDNEKNFSLGL 89

                          90
                  ....*....|....
gi 2775959027  76 QTLLSLKCCIDLDR 89
Cdd:cd05480    90 QTLKSLKCVINLEK 103

NRIP_C; putative nuclear receptor interacting protein; Proteins in this family have been described as probable nuclear receptor interacting proteins. The C-terminal domain of this family is homologous to the retroviral aspartyl protease domain. The domain is structurally related to one lobe of the pepsin molecule. The conserved active site aspartate occurs within a motif (Asp-Thr/Ser-Gly), as it does in pepsin. Asp residues are ligands of an activated water molecule in all examples where catalytic residues have been identified. This group of aspartate peptidases is classified by MEROPS as the peptidase family A2 (retropepsin family, clan AA), subfamily A2A.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2775959027   2 LRVAVDTGTQHNQISAGCLRRLGLGKRVPQAPGGDLAP------ESTSQVEQVELELGQETVACSAQVVDVDSPEFCLGL 75
Cdd:cd05480    10 LRALVDTGCQYNLISAACLDRLGLKERVLKAKAEEEAPslptsvKVIGQIERLVLQLGQLTVECSAQVVDDNEKNFSLGL 89

                          90
                  ....*....|....
gi 2775959027  76 QTLLSLKCCIDLDR 89
Cdd:cd05480    90 QTLKSLKCVINLEK 103

Retropepsins; pepsin-like aspartate proteases; The family includes pepsin-like aspartate proteases from retroviruses, retrotransposons and retroelements, as well as eukaryotic dna-damage-inducible proteins (DDIs), and bacterial aspartate peptidases. While fungal and mammalian pepsins are bilobal proteins with structurally related N and C-terminals, retropepsins are half as long as their fungal and mammalian counterparts. The monomers are structurally related to one lobe of the pepsin molecule and retropepsins function as homodimers. The active site aspartate occurs within a motif (Asp-Thr/Ser-Gly), as it does in pepsin. Retroviral aspartyl protease is synthesized as part of the POL polyprotein that contains an aspartyl protease, a reverse transcriptase, RNase H, and an integrase. The POL polyprotein undergoes specific enzymatic cleavage to yield the mature proteins. In aspartate peptidases, Asp residues are ligands of an activated water molecule in all examples where catalytic residues have been identified. This group of aspartate peptidases is classified by MEROPS as the peptidase family A2 (retropepsin family, clan AA), subfamily A2A.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2775959027   2 LRVAVDTGTQHNQISAGCLRRLGLGKRVP------QAPGGDlAPESTSQVEQVELELGQETVACSAQVVDVDSPEFCLGL 75
Cdd:cd00303    10 VRALVDSGASVNFISESLAKKLGLPPRLLptplkvKGANGS-SVKTLGVILPVTIGIGGKTFTVDFYVLDLLSYDVILGR 88

                  ...
gi 2775959027  76 QTL 78
Cdd:cd00303    89 PWL 91