ID NADA_APLCA Reviewed; 282 AA. AC P29241; DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-1992, sequence version 1. DT 27-MAR-2024, entry version 124. DE RecName: Full=ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase {ECO:0000303|PubMed:10861229}; DE EC=3.2.2.- {ECO:0000269|PubMed:10861229, ECO:0000269|PubMed:1650254}; DE AltName: Full=2'-phospho-ADP-ribosyl cyclase; DE AltName: Full=2'-phospho-ADP-ribosyl cyclase/2'-phospho-cyclic-ADP-ribose transferase; DE EC=2.4.99.20 {ECO:0000269|PubMed:11829748, ECO:0000269|PubMed:16690024}; DE AltName: Full=2'-phospho-cyclic-ADP-ribose transferase; DE AltName: Full=ADP-ribosyl cyclase {ECO:0000303|PubMed:10861229}; DE Short=ADPRC; DE Short=ADRC; DE AltName: Full=NAD glycohydrolase; DE AltName: Full=NAD(+) nucleosidase; DE Short=NADase {ECO:0000303|PubMed:1650255}; DE Flags: Precursor; OS Aplysia californica (California sea hare). OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Gastropoda; OC Heterobranchia; Euthyneura; Tectipleura; Aplysiida; Aplysioidea; OC Aplysiidae; Aplysia. OX NCBI_TaxID=6500; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 25-72; 84-95; 98-114; RP 190-209 AND 216-225, AND TISSUE SPECIFICITY. RC TISSUE=Ovotestis; RX PubMed=1650255; DOI=10.1091/mbc.2.3.211; RA Glick D.L., Hellmich M.R., Beushausen S., Tempst P.J., Bayley H., RA Strumwasser F.; RT "Primary structure of a molluscan egg-specific NADase, a second-messenger RT enzyme."; RL Cell Regul. 2:211-218(1991). RN [2] RP PROTEIN SEQUENCE OF 25-42, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL RP PROPERTIES, AND MASS SPECTROMETRY. RC TISSUE=Ovotestis; RX PubMed=10861229; DOI=10.1042/0264-6021:3490203; RA Cakir-Kiefer C., Muller-Steffner H., Schuber F.; RT "Unifying mechanism for Aplysia ADP-ribosyl cyclase and CD38/NAD(+) RT glycohydrolases."; RL Biochem. J. 349:203-210(2000). RN [3] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION, RP AND TISSUE SPECIFICITY. RC TISSUE=Ovotestis; RX PubMed=1650254; DOI=10.1091/mbc.2.3.193; RA Hellmich M.R., Strumwasser F.; RT "Purification and characterization of a molluscan egg-specific NADase, a RT second-messenger enzyme."; RL Cell Regul. 2:193-202(1991). RN [4] RP SIMILARITY TO CD38. RX PubMed=1471258; DOI=10.1016/0968-0004(92)90337-9; RA States D.J., Walseth T.F., Lee H.C.; RT "Similarities in amino acid sequences of Aplysia ADP-ribosyl cyclase and RT human lymphocyte antigen CD38."; RL Trends Biochem. Sci. 17:495-495(1992). RN [5] RP FUNCTION IN SYNTHESIS OF NICOTINIC ACID-ADENINE DINUCLEOTIDE PHOSPHATE. RX PubMed=11829748; DOI=10.1042/0264-6021:3620125; RA Chini E.N., Chini C.C., Kato I., Takasawa S., Okamoto H.; RT "CD38 is the major enzyme responsible for synthesis of nicotinic acid- RT adenine dinucleotide phosphate in mammalian tissues."; RL Biochem. J. 362:125-130(2002). RN [6] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=16690024; DOI=10.1016/j.bbrc.2006.04.096; RA Moreschi I., Bruzzone S., Melone L., De Flora A., Zocchi E.; RT "NAADP+ synthesis from cADPRP and nicotinic acid by ADP-ribosyl cyclases."; RL Biochem. Biophys. Res. Commun. 345:573-580(2006). RN [7] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS). RX PubMed=8901875; DOI=10.1038/nsb1196-957; RA Prasad G.S., McRee D.E., Stura E.A., Levitt D.G., Lee H.C., Stout C.D.; RT "Crystal structure of Aplysia ADP ribosyl cyclase, a homologue of the RT bifunctional ectozyme CD38."; RL Nat. Struct. Biol. 3:957-964(1996). CC -!- FUNCTION: Synthesizes cyclic ADP-ribose (cADPR), a second messenger for CC calcium mobilization from endoplasmic reticulum; ADP-ribose is a minor CC product (PubMed:1650254, PubMed:10861229). Synthesizes the Ca(2+) CC mobilizer nicotinate-adenine dinucleotide phosphate from 2'-phospho- CC cADPR and nicotinic acid as well as from NADP(+) and nicotinic acid; CC with NADP(+) as substrate preferentially catalyzes NADP(+) hydrolysis CC rather than NAADP(+) synthesis, about 70-fold better at pH 7.4 CC (PubMed:11829748, PubMed:16690024). Has cADPR hydrolase activity at CC very high enzyme concentrations, which is probably not physiological CC (PubMed:10861229). The conversion of NAD(+) into ADP-ribose is also CC only observed at high enzyme concentrations and results from the CC hydrolysis of cADP-ribose (PubMed:10861229). CC {ECO:0000269|PubMed:10861229, ECO:0000269|PubMed:11829748, CC ECO:0000269|PubMed:1650254, ECO:0000269|PubMed:16690024}. CC -!- CATALYTIC ACTIVITY: CC Reaction=NAD(+) = cyclic ADP-beta-D-ribose + H(+) + nicotinamide; CC Xref=Rhea:RHEA:38611, ChEBI:CHEBI:15378, ChEBI:CHEBI:17154, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:73672; CC Evidence={ECO:0000269|PubMed:10861229, ECO:0000269|PubMed:1650254}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38612; CC Evidence={ECO:0000269|PubMed:10861229, ECO:0000269|PubMed:1650254}; CC -!- CATALYTIC ACTIVITY: CC Reaction=NADP(+) + nicotinate = nicotinamide + nicotinate-adenine CC dinucleotide phosphate; Xref=Rhea:RHEA:38599, ChEBI:CHEBI:17154, CC ChEBI:CHEBI:32544, ChEBI:CHEBI:58349, ChEBI:CHEBI:75967; CC EC=2.4.99.20; Evidence={ECO:0000269|PubMed:16690024}; CC -!- CATALYTIC ACTIVITY: CC Reaction=2'-phospho-cyclic ADP-ribose + nicotinate = nicotinate-adenine CC dinucleotide phosphate; Xref=Rhea:RHEA:38607, ChEBI:CHEBI:32544, CC ChEBI:CHEBI:75967, ChEBI:CHEBI:75970; CC Evidence={ECO:0000269|PubMed:16690024}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38608; CC Evidence={ECO:0000269|PubMed:16690024}; CC -!- ACTIVITY REGULATION: Activity is presumably regulated by its CC sequestration in vesicles before egg fertilization. After fertilization CC and upon NADase release, it could then be regulated via its potential CC phosphorylation sites. {ECO:0000305|PubMed:1650254}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1.04 mM for cADPR (hydrolysis of cADPR) CC {ECO:0000269|PubMed:10861229}; CC KM=4.6 uM for NAD(+) (synthesis of cADPR) CC {ECO:0000269|PubMed:10861229}; CC Vmax=3.34 umol/min/mg enzyme (hydrolysis of cADPR) CC {ECO:0000269|PubMed:10861229}; CC Vmax=465 umol/min/mg enzyme (synthesis of cADPR) CC {ECO:0000269|PubMed:10861229}; CC pH dependence: CC Optimum pH for NAADP(+) production is 5.0 from either CC 2'-phospho-cyclic ADP-ribose or NADP(+), activity is much higher at CC pH 5.0 than 7.4. {ECO:0000269|PubMed:16690024}; CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle {ECO:0000269|PubMed:1650254}. CC Note=Localized to vesicles or granules within ova of all stages. CC -!- TISSUE SPECIFICITY: Immature occoyctes (PubMed:1650255). Oocytes. CC {ECO:0000269|PubMed:1650255}. CC -!- DEVELOPMENTAL STAGE: Immature eggs have higher levels of NADase CC transcripts than the mature ones. CC -!- PTM: Has different isoforms which may be the result of different CC amounts of phosphorylation. {ECO:0000305|PubMed:1650254, CC ECO:0000305|PubMed:1650255}. CC -!- MASS SPECTROMETRY: Mass=28694.9; Mass_error=1.3; Method=Electrospray; CC Note=For mature protein, the difference from the calculated weight CC (29539.8 Da)may be due to isoforms.; CC Evidence={ECO:0000269|PubMed:10861229}; CC -!- SIMILARITY: Belongs to the ADP-ribosyl cyclase family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M85206; AAA65698.1; -; mRNA. DR PIR; S27769; S27769. DR RefSeq; NP_001191476.1; NM_001204547.1. DR PDB; 1LBE; X-ray; 2.40 A; A/B=25-282. DR PDB; 1R0S; X-ray; 2.00 A; A/B=25-282. DR PDB; 1R12; X-ray; 1.70 A; A/B=25-282. DR PDB; 1R15; X-ray; 2.40 A; A/B/C/D/E/F/G/H=25-282. DR PDB; 1R16; X-ray; 2.00 A; A/B=25-282. DR PDB; 3I9J; X-ray; 2.18 A; A/B=25-282. DR PDB; 3I9K; X-ray; 1.83 A; A/B=25-282. DR PDB; 3I9L; X-ray; 1.75 A; A/B=25-282. DR PDB; 3I9O; X-ray; 3.00 A; A/B=25-282. DR PDB; 3ZWM; X-ray; 2.50 A; A/B/C/D/E/F/G/H=25-282. DR PDB; 3ZWN; X-ray; 1.80 A; A/B=25-282. DR PDB; 3ZWO; X-ray; 2.00 A; A/B/C/D/E/F/G/H=24-282. DR PDB; 3ZWP; X-ray; 2.11 A; A/B/C/D/E/F/G/H=25-282. DR PDB; 3ZWV; X-ray; 2.30 A; A/B/C/D/E/F/G/H=25-282. DR PDB; 3ZWW; X-ray; 2.30 A; A/B/C/D/E/F/G/H=25-282. DR PDB; 3ZWX; X-ray; 2.60 A; A/B/C/D/E/F/G/H=25-282. DR PDB; 3ZWY; X-ray; 2.40 A; A/B/C/D/E/F/G/H=25-282. DR PDBsum; 1LBE; -. DR PDBsum; 1R0S; -. DR PDBsum; 1R12; -. DR PDBsum; 1R15; -. DR PDBsum; 1R16; -. DR PDBsum; 3I9J; -. DR PDBsum; 3I9K; -. DR PDBsum; 3I9L; -. DR PDBsum; 3I9O; -. DR PDBsum; 3ZWM; -. DR PDBsum; 3ZWN; -. DR PDBsum; 3ZWO; -. DR PDBsum; 3ZWP; -. DR PDBsum; 3ZWV; -. DR PDBsum; 3ZWW; -. DR PDBsum; 3ZWX; -. DR PDBsum; 3ZWY; -. DR AlphaFoldDB; P29241; -. DR SMR; P29241; -. DR EnsemblMetazoa; NM_001204547.1; NP_001191476.1; GeneID_100533234. DR GeneID; 100533234; -. DR CTD; 100533234; -. DR OrthoDB; 4265952at2759; -. DR BRENDA; 2.4.99.20; 390. DR EvolutionaryTrace; P29241; -. DR Proteomes; UP000694888; Unplaced. DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW. DR GO; GO:0016020; C:membrane; IEA:UniProt. DR GO; GO:0050135; F:NAD(P)+ nucleosidase activity; IEA:UniProtKB-EC. DR GO; GO:0061809; F:NAD+ nucleotidase, cyclic ADP-ribose generating; IEA:UniProtKB-EC. DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW. DR GO; GO:0007338; P:single fertilization; IEA:UniProtKB-KW. DR CDD; cd04759; Rib_hydrolase; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR InterPro; IPR003193; ADP-ribosyl_cyclase. DR PANTHER; PTHR10912; ADP-RIBOSYL CYCLASE; 1. DR PANTHER; PTHR10912:SF7; ADP-RIBOSYL CYCLASE_CYCLIC ADP-RIBOSE HYDROLASE; 1. DR Pfam; PF02267; Rib_hydrolayse; 1. DR SUPFAM; SSF52309; N-(deoxy)ribosyltransferase-like; 1. PE 1: Evidence at protein level; KW 3D-structure; Calcium; Cytoplasmic vesicle; Direct protein sequencing; KW Disulfide bond; Fertilization; Hydrolase; NAD; NADP; Phosphoprotein; KW Signal; Transferase. FT SIGNAL 1..24 FT /evidence="ECO:0000269|PubMed:10861229, FT ECO:0000269|PubMed:1650255" FT CHAIN 25..282 FT /note="ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase" FT /id="PRO_0000004030" FT DISULFID 39..58 FT DISULFID 75..155 FT DISULFID 136..149 FT DISULFID 230..251 FT DISULFID 263..272 FT HELIX 31..45 FT /evidence="ECO:0007829|PDB:1R12" FT TURN 48..50 FT /evidence="ECO:0007829|PDB:1R12" FT HELIX 58..69 FT /evidence="ECO:0007829|PDB:1R12" FT HELIX 74..76 FT /evidence="ECO:0007829|PDB:1R12" FT TURN 79..82 FT /evidence="ECO:0007829|PDB:1R12" FT HELIX 83..89 FT /evidence="ECO:0007829|PDB:1R12" FT TURN 95..97 FT /evidence="ECO:0007829|PDB:1LBE" FT STRAND 98..103 FT /evidence="ECO:0007829|PDB:1R12" FT HELIX 105..112 FT /evidence="ECO:0007829|PDB:1R12" FT TURN 113..116 FT /evidence="ECO:0007829|PDB:1R12" FT HELIX 121..123 FT /evidence="ECO:0007829|PDB:1R12" FT HELIX 125..130 FT /evidence="ECO:0007829|PDB:1R12" FT HELIX 152..154 FT /evidence="ECO:0007829|PDB:1R12" FT HELIX 157..160 FT /evidence="ECO:0007829|PDB:1R12" FT HELIX 162..174 FT /evidence="ECO:0007829|PDB:1R12" FT STRAND 177..186 FT /evidence="ECO:0007829|PDB:1R12" FT STRAND 188..190 FT /evidence="ECO:0007829|PDB:1R12" FT STRAND 195..197 FT /evidence="ECO:0007829|PDB:1LBE" FT HELIX 198..201 FT /evidence="ECO:0007829|PDB:1R12" FT HELIX 204..206 FT /evidence="ECO:0007829|PDB:1R12" FT STRAND 211..219 FT /evidence="ECO:0007829|PDB:1R12" FT STRAND 222..224 FT /evidence="ECO:0007829|PDB:1LBE" FT STRAND 230..232 FT /evidence="ECO:0007829|PDB:3I9J" FT HELIX 233..244 FT /evidence="ECO:0007829|PDB:1R12" FT STRAND 248..254 FT /evidence="ECO:0007829|PDB:1R12" FT HELIX 256..264 FT /evidence="ECO:0007829|PDB:1R12" FT HELIX 270..272 FT /evidence="ECO:0007829|PDB:1R12" SQ SEQUENCE 282 AA; 31899 MW; 4CF809DF4E30A824 CRC64; MSPVAIIACV CLAVTLTSIS PSEAIVPTRE LENVFLGRCK DYEITRYLDI LPRVRSDCSA LWKDFFKAFS FKNPCDLDLG SYKDFFTSAQ QQLPKNKVMF WSGVYDEAHD YANTGRKYIT LEDTLPGYML NSLVWCGQRA NPGFNEKVCP DFKTCPVQAR ESFWGMASSS YAHSAEGEVT YMVDGSNPKV PAYRPDSFFG KYELPNLTNK VTRVKVIVLH RLGEKIIEKC GAGSLLDLEK LVKAKHFAFD CVENPRAVLF LLCSDNPNAR ECRLAKRFYR IA //