Conserved Protein Domain Family

cd05470: pepsin_retropepsin_like 
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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).
PSSM-Id: 133137
View PSSM: cd05470
Aligned: 17 rows
Threshold Bit Score: 58.9307
Threshold Setting Gi: 6729982
Created: 7-Sep-2007
Updated: 2-Oct-2020
Aligned Rows:
Conserved site includes 7 residues -Click on image for an interactive view with Cn3D
Feature 1:inhibitor binding site
  • Structure:1b11_a,Feline Immunodeficiency Virus Protease complexed with inhibitor Tl-3-093.
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Sequence Alignment
Format: Row Display: Color Bits: Type Selection:
Feature 1                        # # #                                                     ###   
1YM4_A        32 VEMTVgsppqtLNILVDTGSSNFAVGaaphpflhryyqr----------------------qlsstyrdlrkgvYVPYtq 89  human
1B11_A        13 ILIFVng--ypIKFLLDTGADITILNrrdfqvkn---------------------------------siengrqNMIGvg 57  Feline immunode...
1PPL_E        19 TPVTIgg--ttLNLNFDTGSADLWVFstelpasqqsghsvy-------------------npsatgkelsgytwSISYgd 77  Penicillium jan...
1G0V_A        17 TDITLgtppqnFKVILDTGSSNLWVPsnecgslacflhsky------------------dheasssykangtefAIQYgt 78  baker's yeast
1HRN_A        19 GEIGIgtppqtFKVVFDTGSSNVWVPsskcsrlytacvyhkl----------------fdasdsssykhngtelTLRYst 82  human
AAX74242     127 VNGRVng--arVHFLVDTGASSVVLSqedaeragid-----------------------------taslnysvpIMTAng 175 Brucella abortu...
NP_001008172  72 GVISIgtppqsFRVVFDTGSSNLWVPskkckwtdiacwlhrk----------------ydskksstykangtefAIHYgt 135 western clawed ...
1T6G_B        18 IPFHDg-----ASLVLDVAGPLVWSTcdggqppaeipcssptcllana----ypapgcpapscgsdkhdkpctaYPYNpv 88  bread wheat
1ZAP_A        16 ADITVgsnnqkLNVIVDTGSSDLWVPdvnidcqvtysdqtadfckq---------kgtydpsgssasqdlntpfSIGYgd 86  Candida albicans
XP_955372     84 IYMGIgnpkvkQMLIIDTGSQQINVAcgnspscgkhsldnynyqnsvtykpidcesdsckiieggcdlerscifSETYse 163 Theileria annul...
Feature 1                                                             #   
1YM4_A        90 --gKWEGElg-tDLVSIphgpn------vtvrANIAAitesdkffingsnweGILGL 137 human
1B11_A        58 --gGKRGTnyinVHLEIrdenyk----tqcifGNVCVledn-------sliqPLLGR 101 Feline immunodeficiency virus
1PPL_E        78 -gsSASGNvf-tDSVTVggvt--------ahgQAVQAaqqisaqfqqdtnndGLLGL 124 Penicillium janthinellum
1G0V_A        79 --gSLEGYis-qDTLSIgdlt--------ipkQDFAEatsepgltfafgkfdGILGL 124 baker's yeast
1HRN_A        83 --gTVSGFls-qDIITVggi---------tvtQMFGEvtempalpfmlaefdGVVGM 127 human
AAX74242     176 --qARAASit-iATLQIgdie--------rhnVRAMVtkeg-------lltgSLLGM 214 Brucella abortus biovar 1 str. 9-941
NP_001008172 136 --gSLTGFls-tDTVSVgsls--------vksQTFAEaitqpgitfvaakfdGILGM 181 western clawed frog
1T6G_B        89 sgaCAAGSls-hTRFVAnttdgskpvskvnvgVLAACapsklla-slprgstGVAGL 143 bread wheat
1ZAP_A        87 -gsSSQGTly-kDTVGFggvs--------iknQVLADvdst-------sidqGILGV 126 Candida albicans
XP_955372    164 --gSNVKGmyigDLVSFdtdedss--dlssffDYIGCvthesam-irsqitnGILGL 215 Theileria annulata strain Ankara

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