NADA_APLCA
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 03-AUG-2022, entry version 120.
DE RecName: Full=ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase;
DE EC=3.2.2.6;
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;
DE AltName: Full=2'-phospho-cyclic-ADP-ribose transferase;
DE AltName: Full=ADP-ribosyl cyclase;
DE Short=ADPRC;
DE Short=ADRC;
DE AltName: Full=NAD glycohydrolase;
DE AltName: Full=NAD(+) nucleosidase;
DE Short=NADase;
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], AND PROTEIN SEQUENCE OF 25-72; 84-95; 98-114;
RP 190-209 AND 216-225.
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, AND CATALYTIC ACTIVITY.
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 CHARACTERIZATION.
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 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 the second messengers cyclic ADP-ribose and
CC nicotinate-adenine dinucleotide phosphate, the former a second
CC messenger for calcium mobilization from endoplasmic reticulum. Also has
CC cADPr hydrolase activity. {ECO:0000269|PubMed:11829748}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + NAD(+) = ADP-D-ribose + H(+) + nicotinamide;
CC Xref=Rhea:RHEA:16301, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17154, ChEBI:CHEBI:57540, ChEBI:CHEBI:57967; EC=3.2.2.6;
CC Evidence={ECO:0000269|PubMed:10861229};
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:10861229};
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.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle. Note=Localized to vesicles
CC or granules within ova of all stages.
CC -!- TISSUE SPECIFICITY: Oocytes.
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.
CC -!- SIMILARITY: Belongs to the ADP-ribosyl cyclase family. {ECO:0000305}.
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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 GeneID; 100533234; -.
DR CTD; 100533234; -.
DR OrthoDB; 1460460at2759; -.
DR BRENDA; 2.4.99.20; 390.
DR EvolutionaryTrace; P29241; -.
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 InterPro; IPR003193; ADP-ribosyl_cyclase.
DR PANTHER; PTHR10912; PTHR10912; 1.
DR Pfam; PF02267; Rib_hydrolayse; 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
