2I65,1ISJ,1LBE


Conserved Protein Domain Family
Rib_hydrolase
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cd04759: Rib_hydrolase 
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ADP-ribosyl cyclase, also known as cyclic ADP-ribose hydrolase or CD38
ADP-ribosyl cyclase (EC:3.2.2.5) synthesizes the second messenger cyclic-ADP ribose (cADPR), which in turn releases calcium from internal stores. Mammals possess two membrane proteins, CD38 and BST-1/CD157, which exhibit ADP-ribosyl cyclase activity, as well as intracellular soluble ADP-ribose cyclases. CD38 is involved in differentiation, adhesion, and cell proliferation, and has been implicated in diseases such as AIDS, diabetes, and B-cell chronic lymphocytic leukemia. The extramembrane domain of CD38 acts as a multifunctional enzyme, and can synthesize cADPR from NAD+, hydrolyze NAD+ and cADPR to ADPR, as well as catalyze the exchange of the nicotinamide group of NADP+ with nicotinic acid under acidic conditions, to yield NAADP+ (nicotinic acid-adenine dinucleotide phosphate), a metabolite involved in Ca2+ mobilization from acidic stores.
Links
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Statistics
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PSSM-Id: 212498
Aligned: 25 rows
Threshold Bit Score: 262.995
Created: 12-Dec-2003
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
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NAD binding
Conserved site includes 10 residues -Click on image for an interactive view with Cn3D
Feature 1:NAD binding site [chemical binding site]
Evidence:
  • Structure:1ISJ: Human BST-1/CD157 binds nicotinamide mononucleotide (NMN), contacts at 4.0A
  • Structure:2I65: Human CD38 binds NAD+, contacts at 4.0A
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Sequence Alignment
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Format: Row Display: Color Bits: Type Selection: 
Feature 1                                                                                     ###
2I65_A        16 GTTKRFPETVLARCVKYTeihp-------emrHVDCQSVWDAFKGAFIsKHPCDITEEDYQPLMKLGTQTVPcNKILLWS 88  human
1ISJ_A         6 GTSAHLRDIFLGRCAEYRalls------peqrNKDCTAIWEAFKVALD-KDPCSVLPSDYDLFITLSRHSIPrDKSLFWE 78  human
NP_001188317  55 GTTRNLREIVLGRCYSYLaegh------aelrDKDCLKIWESLKAAFVhKNPCNATTEDYRPLMELTSHPVPcNESLFWS 128 chicken
NP_001003143  61 GTTAHFYEILLGRCYTYTqvvr------peqrHTDCQKIGKAFTSAFLsKDPCGSTEQDYRPLMELTTQIVPcDKTVFWS 134 dog
CBN82129      14 GTTPNIKHIVVGRCYNYItlvn-------pslRYDCEDIWRQFEEAVArQSSCNVTVEDYRQMFYAMPQTWPcDRFLFWS 86  European seabass
AAI29623      51 GTTQNLQDIVLGRCYNYVtmnp-------gigKKNCDAIWQALTGAVYkKNPCNITQEDYKPLADLALQTIPcNKTLLWS 123 African clawed ...
NP_001186972  32 GTTPNLESITIGRCYDYIrvvn------pavgEKNCSELWEAFRNAFInKDPCNILPQHFELFFKLSLHAIPtDKSLFWE 105 chicken
XP_002108468  22 GTTHNIKEIFIGRCYGYIalqnf-----tlrpGVTCPSLWQEFSRVFVnREPCEVDPTQYSRFLIESSSPVPpNKALFWS 96  Trichoplax adha...
ABQ09455      50 GTDIDLREIFIGRCADFKagrvnptvdlnelrMKNCTHLWNLFHSTFKyREACNVTRPMYKEFVAEATITIPsNKSAFWD 129 purple urchin
XP_002108470  33 GTTPRIDQIFIGRCSDYQasht-------mehEVDCHELWMTFSSVFAnLDPCKVQTAGYDKFIEKSSVPIPqDGSVFWS 105 Trichoplax adha...

Feature 1            #               ##        #                                       #         
2I65_A        89 R--IKDLAHQFTQvqrDMFTLEDTLLGYLADDLTWCGEFd----tSKINYQSCPdwrkdCSn--nPVSVFWKTVSRRFAE 160 human
1ISJ_A        79 N--SHLLVNSFADntrRFMPLSDVLYGRVADFLSWCRQKa----dSGLDYQSCPts-edCEn--nPVDSFWKRASIQYSK 149 human
NP_001188317 129 R--TYDLVHLYSKcnhHFLTLEDTFLGYMLDGLSWCGDPs----aPGINYESCPkw-seCEr--sSGSVFWKMASKMFAE 199 chicken
NP_001003143 135 K--SSELAHDYTRvqrDMYTLEDTLLGYMADGLKWCGDTs----sSEMNYQSCPhwredCSn--nSVSVFWNTVSKRFAE 206 dog
CBN82129      87 K--TRTLMHSYAAvvrHFWTLEDTLVGYMFNDLIWCGQEe----dSGFDFSSCPew-saCRn--hPVYSLWRQASQNFAE 157 European seabass
AAI29623     124 K--TNSLVHRYTKasqDLLTLEDTFLGSMFDSLMWCGMSy----sSEMNYDSCPaw-neCDn--nAISAFWKMASATFAK 194 African clawed ...
NP_001186972 106 N--NQLLVNSFSSrarRYMALGDTLFGFFGDFLNWCGQEn----sTGLDYESCPta-aeCEn--nAVDAFWRMASMTYAQ 176 chicken
XP_002108468  97 G--VYDFVSSYVQavdDVLVISQTFTGFLLDKLTWCGRFkstpqsEGINYLYCNds-qgCSh--rNMLSFWALASREFAK 171 Trichoplax adha...
ABQ09455     130 GwtIYDTVHSYAKegrRSWSLEYTLMGYLINNLKFCGQEe----ePGLRYDSCPgp-deCGfakgCADAFWAEASINFAK 204 purple urchin
XP_002108470 106 G--TYDFTHSYVKtvgNLYTLEDVLPGYLVNSLTWCGQEk----sPGINYETCSdp-qgCNk--nNTYDFWAKMSTWFAK 176 Trichoplax adha...

Feature 1                                #    #                                                  
2I65_A       161 AACdVVHVMLDGSrs--kIFDKDSTFGSVQVHNLqpeKVQTLEAWVIHGgr--edSRDLCQDPTIKELESIISKrNIQFS 236 human
1ISJ_A       150 DSSgVIHVMLNGSep-tgAYPIKGFFADYEIPNLqkeKITRIEIWVMHEig--gpNVESCGEGSMKVLEKRLKDmGFQYS 226 human
NP_001188317 200 AACgVVHVMLNGSie-agAFRTSSVFGSVEIFNLnpdKVSEIRIWLMNDig--gpQSDSCSGYSIKKLRNILEErNFKIT 276 chicken
NP_001003143 207 DACgVVHVVLNGSis--nTFDEKSTFGRVEVFNLhpeKVHTLKAWVMHNie--svPSDSCSSSSVNNLKQILKTrNIIFI 282 dog
CBN82129     158 MACgNITVLLNGSiv--nAFSRKSMFGSVELDGLnprRVDYVNIKVVTNle--gpFIESCSEGSIVDLLQILQSrGFRWT 233 European seabass
AAI29623     195 ASCgVVNVMLNGSad-ggVARKESILRTVEVPSMnvnAVSEVRLWIIDDle--gpDKNSCDTESAVELKDYIEQhKLPFS 271 African clawed ...
NP_001186972 177 HSSgVIHVLLNGSae-ggAYPVKGFFADYEIPHLqrdKISQIDIWVVDDie--gpNIDSCGHNTVQILEDRLKTlGYSVT 253 chicken
XP_002108468 172 SASgLVRVLLTSDnk-tpAFNNQSIFGSIELPNLspqKVSKVEIMVMHGlnskpnQIDRCGIGSIKELQNILTShNFTWS 250 Trichoplax adha...
ABQ09455     205 QAKgQVRVFFDSNreggaFHNNNSYFAQYELINMdpdAVENVNIYLVTEle--tkSGDNCTSPSIQELIGILKEkNIRYT 282 purple urchin
XP_002108470 177 SASgSVQVILNAGrd--pAFASDSFFAKFELPNLphdKVNKIEIIVVHGid--gkDNPKCGSGSIKELQSLIEQyNFAWT 252 Trichoplax adha...

Feature 1                              
2I65_A       237 CKNIyRPDKFLQCVKNpeDSSC 258 human
1ISJ_A       227 CINDyRPVKLLQCVDHstHPDC 248 human
NP_001188317 277 CEDNyRPVQLLQCVHNpdHPDC 298 chicken
NP_001003143 283 CQNNyRPVRLLQCVKNpeHSSC 304 dog
CBN82129     234 CTDNdQTLMILQCIQNpkQSSC 255 European seabass
AAI29623     272 CIDNyRPVQLLQCIETpdLPAC 293 African clawed frog
NP_001186972 254 CTDNyKPVMFLLCLDNpdHSKC 275 chicken
XP_002108468 251 CQDNpKSVLHHLCTKNpnNFHC 272 Trichoplax adhaerens
ABQ09455     283 CYEQpRDVLHLLCIDGneSDEC 304 purple urchin
XP_002108470 253 CADN-PGLIIIFTFRF--NFYL 271 Trichoplax adhaerens

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