1HRN,1SMR,2G24


Conserved Protein Domain Family
renin_like

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cd05487: renin_like 
Click on image for an interactive view with Cn3D
Renin stimulates production of angiotensin and thus affects blood pressure.
Renin, also known as angiotensinogenase, is a circulating enzyme that participates in the renin-angiotensin system that mediates extracellular volume, arterial vasoconstriction, and consequently mean arterial blood pressure. The enzyme is secreted by the kidneys from specialized juxtaglomerular cells in response to decreases in glomerular filtration rate (a consequence of low blood volume), diminished filtered sodium chloride and sympathetic nervous system innervation. The enzyme circulates in the blood stream and hydrolyzes angiotensinogen secreted from the liver into the peptide angiotensin I. Angiotensin I is further cleaved in the lungs by endothelial bound angiotensin converting enzyme (ACE) into angiotensin II, the final active peptide. Renin is a member of the aspartic protease family. Structurally, aspartic proteases are bilobal enzymes, each lobe contributing a catalytic Aspartate residue, with an extended active site cleft localized between the two lobes of the molecule. The N- and C-terminal domains, although structurally related by a 2-fold axis, have only limited sequence homology except the vicinity of the active site. This suggests that the enzymes evolved by an ancient duplication event. The active site is located at the groove formed by the two lobes, with an extended loop projecting over the cleft to form an 11-residue flap, which encloses substrates and inhibitors in the active site. Specificity is determined by nearest-neighbor hydrophobic residues surrounding the catalytic aspartates, and by three residues in the flap. The enzymes are mostly secreted from cells as inactive proenzymes that activate autocatalytically at acidic pH. This family of aspartate proteases is classified by MEROPS as the peptidase family A1 (pepsin A, clan AA).
Statistics
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PSSM-Id: 133154
View PSSM: cd05487
Aligned: 7 rows
Threshold Bit Score: 613.323
Threshold Setting Gi: 37787745
Created: 9-Jan-2008
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 2 residues -Click on image for an interactive view with Cn3D
Feature 1:catalytic residue [active site]
Evidence:
  • Citation:PMID 7608971
  • Comment:The two ASPs at the active site plays key catalytic roles in the pepsin family and conserved for all family members.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                  #                                                     
1HRN_A         9 LTNYMDTQYYGEIGIGTPpQTFKVVFDTGSSNVWVPSSKCSRLYTACVYHKLFDASdSSSYKHNGTELTLRYSTGTVSGF 88  human
AAO41706      68 LINYLDTQYFGEISIGSPaQMFNVVFDTGSANLWVPSHSCSPLYTACFTHNRYDASkSLTHIFNGTGFSIQYASGNVRGF 147 zebrafish
CAJ55261      71 LTNFRDTQYYGEISIGTPaQIFKVVFDTGSSNLWVPSHQCSPLYSACVSHNRYDSSeSSTYKPKGTKITLTYGQGYIEGF 150 Echis ocellatus
1SMR_A         9 LTNYLNSQYYGEIGIGTPpQTFKVIFDTGSANLWVPSTKCSRLYLACGIHSLYESSdSSSYMENGDDFTIHYGSGRVKGF 88  house mouse
XP_001370729  64 LTNYEDTQYYGEINIGSPpQTFKVVFDTGSSDFWVPSSQCDPLYTACEFHNRYDASkSSTYKMNGSNFIIHYASGRVKGF 143 gray short-tail...
XP_001520972  47 LTNYLDAQYFGEIGIGSPaQTFKVIFDTGSANLWVPSINCKPIHSACETHNLYDASqSQTYMENGTQIAISYVSGTVKGF 126 platypus
2G24_A         5 LTNYMDTQYYGEIGIGTPpQTFKVVFDTGSSNVWVPSSKCSRLYTACVYHKLFDASdSSSYKHNGTELTLRYSTGTVSGF 84  human
Feature 1                                                                                        
1HRN_A        89 LSQDIITVGGITVTQMFGEVTEMPALPFMLAeFDGVVGMGFieqAIGRVTPIFDNIISQGVLKEDVFSFYYnrdse-nsq 167 human
AAO41706     148 LSEDVVVVGGIPVVQVFAEATALPAIPFIFAkFDGVLGMGYpdvAIDGITPVFDRIMSQHVLKENVFSVYYsrdp---th 224 zebrafish
CAJ55261     151 LSQDIVRVADIPITQFFTEAIALPSIPFMYAhFDGVLGMGYpkqAIGGVIPVFDNIMSEKVLSENVFSVYYsrhs---es 227 Echis ocellatus
1SMR_A        89 LSQDSVTVGGITVTQTFGEVTQLPLIPFMLAqFDGVLGMGFpaqAVGGVTPVFDHILSQGVLKEKVFSVYYnrgp----h 164 house mouse
XP_001370729 144 LSQDILTIGEIKVTQVFGEVTALPLIPFGLAwFDGILGLGYpkrSMSGITPVFDNIMAEGVLKEDVFSIYYsrss----g 219 gray short-tail...
XP_001520972 127 LSQDLVTIGGIPVIQMFAEITTLPTSSFMYAkFDGVLGMGYpaqAIGGITPVFDHILTQHVLKEDVFSVYYsrnskndhm 206 platypus
2G24_A        85 LSQDIITVGGITVTQMFGEVTEMPALPFMLAeFDGVVGMGFieqAIGRVTPIFDNIISQGVLKEDVFSFYYnrdse-nsq 163 human
Feature 1                                                               #                        
1HRN_A       168 slGGQIVLGGSDPQHYeGNFHYINLIktgVWQIQMKGVSVgssTLLCEDGCLALVDTGASYISGSTSSIEKLMEALGAkk 247 human
AAO41706     225 ipGGELVLGGTDPNYHtGPFHYINTKeqgKWEVIMKGVSVgadILFCKDGCTAVIDTGSSYITGPASSISILMKTIGAve 304 zebrafish
CAJ55261     228 ntGGEIILGGSDPSHYtGDFHYVSTSregYWHVDLKGVSIenkIALCHDGCTATIDTGTSFISGPASSISVLMETIGAtl 307 Echis ocellatus
1SMR_A       165 llGGEVVLGGSDPQHYqGDFHYVSLSktdSWQITMKGVSVgssTLLCEEGCEVVVDTGSSFISAPTSSLKLIMQALGAke 244 house mouse
XP_001370729 220 knGGELILGGSDPNYYqGTFHYINTSrphFWQIQMQGVAVksyVLSCEDGCPAVVDTGTSFITGPTDSIRGLMTAIGAee 299 gray short-tail...
XP_001520972 207 vpGGEIILGGRDPTYYqGDFYYLDVSkkgFWQVNMKGVSVdrtLQFCQEGCAAMVDTGATLITGPVKDVKHMMDILGAqk 286 platypus
2G24_A       164 slGGQIVLGGSDPQHYeGNFHYINLIktgVWQIQMKGVSVgssTLLCEDGCLALVDTGASYISGSTSSIEKLMEALGAkk 243 human
Feature 1                                                                                        
1HRN_A       248 r-lfdYVVKCNEGPTLPDISFHLGGKEYTLTSADYVFqesysskklCTLAIHAMDIPPPTGPTWALGATFIRKFYTEFDR 326 human
AAO41706     305 laeggYTVSCNVVRLLPTVAFHLGGQEYSLTDEDYILwqsefgediCTVTFKALDVPPPTGPVWILGANFIARYYTEFDR 384 zebrafish
CAJ55261     308 s-rgdYVIDCNQINLLPDISFHLGDMTYSLSSSTYVLkysd--eteCTVAFSAIDIPPPRGPLWLLGATFIKQYYIEFDR 384 Echis ocellatus
1SMR_A       245 krlheYVVSCSQVPTLPDISFNLGGRAYTLSSTDYVLqypnrrdklCTVALHAMDIPPPTGPVWVLGATFIRKFYTEFDR 324 house mouse
XP_001370729 300 d-ggeYLVKCDLASTLPDISFNFDGKDFTLQGSDYVLedenqsdqmCLVAINGLDVSPPTGPLWVLGATFIRKFYVEFDR 378 gray short-tail...
XP_001520972 287 iggnmYAVDCKEVAQLPDISFHLGGRVFPLSSSDYVLqdsdfddvlCPLAFKGVDVHPPLGPLWVLGASFIRRYYIEFDR 366 platypus
2G24_A       244 r-lfdYVVKCNEGPTLPDISFHLGGKEYTLTSADYVFqesysskklCTLAIHAMDIPPPTGPTWALGATFIRKFYTEFDR 322 human
Feature 1                  
1HRN_A       327 rNNRIGFALA 336 human
AAO41706     385 gNNRIGFARA 394 zebrafish
CAJ55261     385 qNNRIGFATS 394 Echis ocellatus
1SMR_A       325 hNNRIGFALA 334 house mouse
XP_001370729 379 hNNRIGFALA 388 gray short-tailed opossum
XP_001520972 367 qNNRIGFAMA 376 platypus
2G24_A       323 rNNRIGFALA 332 human

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