2AFM,2AFU,2AFX,3PB4,4FAI,4MHN


Conserved Protein Domain Family
M28_QC_like

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cd03880: M28_QC_like 
Click on image for an interactive view with Cn3D
M28 Zn-peptidase glutaminyl cyclase
Peptidase M28 family, glutaminyl cyclase (QC; EC 2.3.2.5) subfamily. QC is involved in N-terminal glutamine cyclization of many endocrine peptides and is typically abundant in brain tissue. N-terminal glutamine residue cyclization is an important post-translational event in the processing of numerous bioactive proteins, including neuropeptides, hormones, and cytokines during their maturation in the secretory pathway. The N-terminal pGlu protects them from exopeptidase degradation and/or enables them to have proper conformation for binding to their receptors. QCs are highly conserved from yeast to human. In humans, several genetic diseases, such as osteoporosis, appear to result from mutations of the QC gene. N-terminal glutamate cyclization into pyroglutamate (pGlu) is a reaction that may be related to the formation of several plaque-forming peptides, such as amyloid-(A) peptides and collagen-like Alzheimer amyloid plaque component, which play a pivotal role in Alzheimer's disease.
Statistics
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PSSM-Id: 349876
Aligned: 36 rows
Threshold Bit Score: 341.911
Created: 3-Jun-2005
Updated: 25-Oct-2021
Structure
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Program:
Drawing:
Aligned Rows:
 
metal bindingactive site
Conserved site includes 3 residues -Click on image for an interactive view with Cn3D
Feature 1: metal binding site [ion binding site], 3 residue positions
Conserved feature residue pattern:D [NE] HClick to see conserved feature residue pattern help
Evidence:
  • Comment:Human glutaminyl cyclase (QC) contains a single zinc ion, structurally equivalent to the first and higher-affinity zinc (Zn1) found in the two-zinc or binuclear proteases in this superfamily.
  • Structure:2AFU: Human glutaminyl cyclase binds Zn; contacts at 4.0A

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                                        
2AFM_A        19 SALRQIAEgt------siSEMWQNDLQPLLIERYPGSPGSYAARQHIMQRIQRLqa------dWVLEIDTFLSQTpyg-- 84  human
2AFU_A        19 SALRQIAEgt------siSEMWQNDLQPLLIERYPGSPGSYAARQHIMQRIQRLqa------dWVLEIDTFLSQTpyg-- 84  human
CAG80144      31 EGLQYLHKnfpte-kylaIDDPNGLLQPILIPRVPDTDGIREVQKFITDFVSTQtysegevpgWDVQLDVFQEDTpik-- 107 Yarrowia lipoly...
EAL17781      30 SQLKRLIQldp----pqfSSVTDGHLGKLLIPRPSGSENNTLVQNYISSVFSKLg--------WHEEKTPFTSATpig-- 95  Cryptococcus ne...
AAW26344      35 LTLDHMLEkfqn---rstRTSLERIFNNINIVRDVGSPGHLKVRKFIMEYLEKRg--------WTTELDTFTENTvig-- 101 Schistosoma jap...
EAL89960      35 ETLKSLPRpkn-----dfDIHNGALLAPILRPRVPGTLGSTAVLNHFADFFRTSlp------nWKIEFQNSTSKTpfshg 103 Aspergillus fum...
BAE56694      34 KTLTHLPRpnt-----dfNIHNGTLLSPNLQTRVPGSPGSEATRSHFTNFFAKTlp------hWKIEFQNSTAKSdtn-- 100 Aspergillus oryzae
BAE62510      26 ADLEALLHpd-------gDTNIQTILAPLLRPRVPGTPGSELVRNYIIQFFNSAlp------lWTTELQVSSSKTpvsgs 92  Aspergillus oryzae
XP_001214146  24 ETLLRLPRpgp-----dfNIHDGRILAPILRTRVPDTPGSTAVRNHFIDFFHSSlp------eWTIEPHSFTAITpvsgg 92  Aspergillus ter...
EDO65282      51 CTLQHLTFgpssdfdihnGFGSSSLLAPILIPRVPGTEGSRLVQQHFVDFFSSQlp------dWTLEWQNSTSTTpatgs 124 Neurospora cras...
Feature 1                                                        #                               
2AFM_A        85 -yrSFSNIISTLNPt-----AKRHLVLACHYDSKYFSHwnnrvFVGATDSAVPCAMMLELARALDKkllslk-------- 150 human
2AFU_A        85 -yrSFSNIISTLNPt-----AKRHLVLACHYDSKYFSHwnnrvFVGATDSAVPCAMMLELARALDKkllslk-------- 150 human
CAG80144     108 envTFTNILVKRDPpnakkgHTGYITIAAHYDTLIKPEg----FVGAIDSAVPCALMLYTIKAIDEaitrkwkemk---- 179 Yarrowia lipoly...
EAL17781      96 -diDFTNLVYTFDPd-----APRKLVLAAHFDSKWYPDypanqFIGATDSAAPCAILLSIAEFLTPflnsrqsrissgq- 168 Cryptococcus ne...
AAW26344     102 -ikTFHNIIACKENp----eYKKYLILACHYDSKLIPN-----FVGSTDSAMPCSIILKIVDILNHgiea---------- 161 Schistosoma jap...
EAL89960     104 kevPFVNFIASRDPpwaavgDVGRLTLVAHYDSKYKPEg----FIGATDSAAPCAIIMHTMRSIDAalskkweamq---- 175 Aspergillus fum...
BAE56694     101 -eiPIINIIATRDPpgipagNISRLTLVAHYDSMNSPEg----FIGAIDSAAPCAIIMHAVRSIDAalsrkwg------- 168 Aspergillus oryzae
BAE62510      93 qriPFVNIIAYRSPpglnetDVGWLTLVAHYDSLKDPEg----FIGAIDSAAPCSIIMSAVRSIDAaltrkwdnm----- 163 Aspergillus oryzae
XP_001214146  93 rnvRFTNFIAFRDHpgaeegNTTRLTMVAHADSKLRPTg----FIGAIDSAAPCAMIMHAARSIDKaltrkws------- 161 Aspergillus ter...
EDO65282     125 qliPFANLILRRDPpwakagNVKRLTLAAHYDSLFRPEg----FIGAVDSAAPCAILMAVARAVDGalgrrwegvmaake 200 Neurospora cras...
Feature 1                                            #                                           
2AFM_A       151 -----------------tvsdskPDLSLQLIFFDGEEAFl-HWSp--qDSLYGSRHLAAKMastphpp--------garg 202 human
2AFU_A       151 -----------------tvsdskPDLSLQLIFFDGQEAFl-HWSp--qDSLYGSRHLAAKMastphpp--------garg 202 human
CAG80144     180 -------------aepdrfseheKTTGIQFLFFDGEEAFh-SWSd--tDSTYGSRHLAQLMdqtynev--------nsar 235 Yarrowia lipoly...
EAL17781     169 -----------pflrdgfdeeeeAETTIQIIFFDGEEAFh-DWTd--mDSIYGARYLAEEWsetylppahpltrrrmhph 234 Cryptococcus ne...
AAW26344     162 --------------------ikkSDIGLKVMFFDGEEAFv-KWTa--nDSLYGSRHLAAKWstpses-----------sn 207 Schistosoma jap...
EAL89960     176 -------------aqgrtdasleDQKGIQVLFLDGEEAFd-LWTd--tDSLYGARALAEHWdsqvhpa--------msvy 231 Aspergillus fum...
BAE56694     169 -----------------tlptvqKAEGIQVIFTDGEEAIypDWM----EILFGARSLAAEWentrypp--------asry 219 Aspergillus oryzae
BAE62510     164 ---------------ssipggthEQYGIQVIFTDGEESF--GNTltanDGLYGSRSLAAHWavdkyps--------taky 218 Aspergillus oryzae
XP_001214146 162 ----------------cgdnspaAAQGVQIIFTDGEERFs-DPPvdimDQLYGSRALATDWgmqkyps--------tary 216 Aspergillus ter...
EDO65282     201 kregggerdagdgledeeggeeeEEKGVQIVLFDGEEAWe-RWTn--tDSTYGSRALAEAWqsspyea--------ssth 269 Neurospora cras...
Feature 1                                                                                        
2AFM_A       203 tsqLHGMDLLVLLDLIGAPNPTFPNFFpnSARWFERLQAIEHELHelgllkd------hslegrYFQNYSYGGv------ 270 human
2AFU_A       203 tsqLHGMDLLVLLDLIGAPNPTFPNFFpnSARWFERLQAIEHELHelgllkd------hslegrYFQNYSYGGv------ 270 human
CAG80144     236 qtwLAEMEYLVLLDLIGHKDTYIPSFFrnTHWQYEVFASLEQRIRdiglsar------mdeketIFTEGKPAFfrg---a 306 Yarrowia lipoly...
EAL17781     235 ptmLDTIDHLVLFDLLGNKHSSIRSFFreTDWLFDRMANGDERLReeglvev------ekgedgWFRTERGRKg------ 302 Cryptococcus ne...
AAW26344     208 qteLSKINLLVLLDLLGSKHPHIPKYHyeDRGSYSLLSELEKKMRfsnllka-----sgennkpYFGDHSPYR------- 275 Schistosoma jap...
EAL89960     232 ktpLSSISLFVLLDLLGSKSPYIQSYFatTHWAYQKLAALEKRLRdlklfkss---sgdaserpWFADGAKNEhqlttag 308 Aspergillus fum...
BAE56694     220 ssrLKAISLFVLLDLLGSREPKIASYFntTHHVYKRAAVLEKRLRglnqfk-------stgtrpWFVDVDRDTigan-rf 291 Aspergillus oryzae
BAE62510     219 etrLSSISLLVLLDLLGAKNPQIASYYpvTHFDYQRLAALESRLRelgqlks-----sgihgksWFVDRTTDVrslk-rq 292 Aspergillus oryzae
XP_001214146 217 anrLASISLFVLLDLLGASNPAISSRSnvTNWAYKNLVRLEGRFRdlggfqstqnktdisasrsWFIDTGKGAdele-pd 295 Aspergillus ter...
EDO65282     270 snrLESISLLVLLDLLGAGNPRIPSYFwdTHGAYKDLAKIETRLRklgvleta---paspflpdSEKPYNRFTrg----- 341 Neurospora cras...
Feature 1                                         #                            
2AFM_A       271 -IQDDHIPFLRrGVPVLHLIPs-----PFPEVWHTMDDNEENLDESTIDNLNKILQVFVLEY 326 human
2AFU_A       271 -IQDDHIPFLRrGVPVLHLIPs-----PFPEVWHTMDDNEENLDESTIDNLNKILQVFVLEY 326 human
CAG80144     307 vIGDDHLPFLHrGVPVLHLIPs-----HFPPVWHKIDDNAKNLHFPDISEWGLLTSSFVANQ 363 Yarrowia lipolytica CLIB99
EAL17781     303 mVGDDHVPFLNrGVSVLHVISv-----PFPSVWHTIADDTAALSLPAIRRWNRILRVFVCEY 359 Cryptococcus neoformans var. neof...
AAW26344     276 -IDDDHLPFVEkGVPVLHLIPm-----PFPSVWHTTNDNATNIDWDTSVDLLLLIELFVRTY 331 Schistosoma japonicum
EAL89960     309 sIQDDHIPFLArGVEILHVIDasp-mtGFPSVWHSMDDDGEHLDLDTVEDWSLLFTAFAAEW 369 Aspergillus fumigatus Af293
BAE56694     292 pIYDDQVPFEErGVDVLHLIDanpdtgRFPNVWHTLEDTGENLDLDVLGDWSVLLIAFMVEW 353 Aspergillus oryzae
BAE62510     293 pVEDDQVPFSGlGVKVLHVIDadpttgEFPSVWHTPDDDENHLDFDTIRDWSLLITAFAAEW 354 Aspergillus oryzae
XP_001214146 296 hILDDHVPFADrGVDVLPIIDhhp-vrGFPRVWHTLDDDGEHLDMAVVGDWSLLVSAFMAEW 356 Aspergillus terreus NIH2624
EDO65282     342 yIQDDHVPFMErGVKVLHIIPt-----PFPPVWHTMDDDGEHLDLPTVRDWAKIMTVFVAEW 398 Neurospora crassa OR74A

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