NUD12_MACFA
ID NUD12_MACFA Reviewed; 462 AA.
AC Q4R7L8;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 73.
DE RecName: Full=NAD-capped RNA hydrolase NUDT12 {ECO:0000305};
DE Short=DeNADding enzyme NUDT12 {ECO:0000305};
DE EC=3.6.1.- {ECO:0000250|UniProtKB:Q9DCN1};
DE AltName: Full=NADH pyrophosphatase NUDT12 {ECO:0000305};
DE EC=3.6.1.22 {ECO:0000250|UniProtKB:Q9BQG2};
DE AltName: Full=Nucleoside diphosphate-linked moiety X motif 12 {ECO:0000305};
DE Short=Nudix motif 12 {ECO:0000305};
GN Name=NUDT12 {ECO:0000250|UniProtKB:Q9BQG2};
GN ORFNames=QtsA-14876 {ECO:0000303|Ref.1};
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: mRNA decapping enzyme that specifically removes the
CC nicotinamide adenine dinucleotide (NAD) cap from a subset of mRNAs by
CC hydrolyzing the diphosphate linkage to produce nicotinamide
CC mononucleotide (NMN) and 5' monophosphate mRNA. The NAD-cap is present
CC at the 5'-end of some RNAs; in contrast to the canonical N7
CC methylguanosine (m7G) cap, the NAD cap promotes mRNA decay.
CC Preferentially acts on NAD-capped transcripts in response to nutrient
CC stress (By similarity). Also acts on free nicotinamide adenine
CC dinucleotide molecules: hydrolyzes NAD(H) into NMN(H) and AMP, and
CC NADPH into NMNH and 2',5'-ADP. May act to regulate the concentration of
CC peroxisomal nicotinamide nucleotide cofactors required for oxidative
CC metabolism in this organelle (By similarity). Regulates the levels of
CC circadian clock components PER1, PER2, PER3 and CRY2 in the liver (By
CC similarity). {ECO:0000250|UniProtKB:Q9BQG2,
CC ECO:0000250|UniProtKB:Q9DCN1}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 5'-end NAD(+)-phospho-ribonucleoside in mRNA + H2O = a 5'-
CC end phospho-adenosine-phospho-ribonucleoside in mRNA + beta-
CC nicotinamide D-ribonucleotide + 2 H(+); Xref=Rhea:RHEA:60876,
CC Rhea:RHEA-COMP:15698, Rhea:RHEA-COMP:15719, ChEBI:CHEBI:14649,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:144029,
CC ChEBI:CHEBI:144051; Evidence={ECO:0000250|UniProtKB:Q9DCN1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60877;
CC Evidence={ECO:0000250|UniProtKB:Q9DCN1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + NAD(+) = AMP + beta-nicotinamide D-ribonucleotide + 2
CC H(+); Xref=Rhea:RHEA:11800, ChEBI:CHEBI:14649, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:456215;
CC EC=3.6.1.22; Evidence={ECO:0000250|UniProtKB:Q9BQG2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11801;
CC Evidence={ECO:0000250|UniProtKB:Q9BQG2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + NADH = AMP + 2 H(+) + reduced beta-nicotinamide D-
CC ribonucleotide; Xref=Rhea:RHEA:48868, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57945, ChEBI:CHEBI:90832,
CC ChEBI:CHEBI:456215; EC=3.6.1.22;
CC Evidence={ECO:0000250|UniProtKB:Q9BQG2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48869;
CC Evidence={ECO:0000250|UniProtKB:Q9BQG2};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + NADPH = adenosine 3',5'-bisphosphate + 2 H(+) + reduced
CC beta-nicotinamide D-ribonucleotide; Xref=Rhea:RHEA:60820,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58343, ChEBI:CHEBI:90832;
CC Evidence={ECO:0000250|UniProtKB:Q9BQG2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60821;
CC Evidence={ECO:0000250|UniProtKB:Q9BQG2};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9DCN1};
CC Note=Binds 3 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:Q9DCN1};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q9DCN1};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250|UniProtKB:Q9DCN1};
CC -!- SUBUNIT: Homodimer (By similarity). Homodimerization is essential for
CC its catalytic activity and protein stability (By similarity). Interacts
CC (via ANK repeats) with BLMH (By similarity).
CC {ECO:0000250|UniProtKB:Q9BQG2, ECO:0000250|UniProtKB:Q9DCN1}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9BQG2}.
CC Peroxisome {ECO:0000250|UniProtKB:Q9BQG2}. Cytoplasmic granule
CC {ECO:0000250|UniProtKB:Q9BQG2}. Note=Localizes to cytoplasmic granules
CC in the presence of BLMH. {ECO:0000250|UniProtKB:Q9BQG2}.
CC -!- SIMILARITY: Belongs to the Nudix hydrolase family. NudC subfamily.
CC {ECO:0000305}.
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DR EMBL; AB168797; BAE00904.1; -; mRNA.
DR RefSeq; NP_001272283.1; NM_001285354.1.
DR AlphaFoldDB; Q4R7L8; -.
DR SMR; Q4R7L8; -.
DR STRING; 9541.XP_005557531.1; -.
DR GeneID; 101867001; -.
DR CTD; 83594; -.
DR eggNOG; KOG0504; Eukaryota.
DR eggNOG; KOG3084; Eukaryota.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0005777; C:peroxisome; IEA:UniProtKB-SubCell.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0000210; F:NAD+ diphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0110153; F:RNA NAD-cap (NMN-forming) hydrolase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0032922; P:circadian regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0006402; P:mRNA catabolic process; ISS:UniProtKB.
DR GO; GO:0110155; P:NAD-cap decapping; ISS:UniProtKB.
DR Gene3D; 1.25.40.20; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR015375; NADH_PPase-like_N.
DR InterPro; IPR015797; NUDIX_hydrolase-like_dom_sf.
DR InterPro; IPR020084; NUDIX_hydrolase_CS.
DR InterPro; IPR000086; NUDIX_hydrolase_dom.
DR InterPro; IPR015376; Znr_NADH_PPase.
DR Pfam; PF12796; Ank_2; 1.
DR Pfam; PF00293; NUDIX; 1.
DR Pfam; PF09296; NUDIX-like; 1.
DR Pfam; PF09297; zf-NADH-PPase; 1.
DR SMART; SM00248; ANK; 3.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF55811; SSF55811; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 1.
DR PROSITE; PS51462; NUDIX; 1.
DR PROSITE; PS00893; NUDIX_BOX; 1.
PE 2: Evidence at transcript level;
KW ANK repeat; Cytoplasm; Hydrolase; Magnesium; Metal-binding; NAD; NADP;
KW Peroxisome; Reference proteome; Repeat; Zinc.
FT CHAIN 1..462
FT /note="NAD-capped RNA hydrolase NUDT12"
FT /id="PRO_0000260766"
FT REPEAT 11..40
FT /note="ANK 1"
FT REPEAT 45..74
FT /note="ANK 2"
FT REPEAT 78..98
FT /note="ANK 3"
FT DOMAIN 319..453
FT /note="Nudix hydrolase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00794"
FT MOTIF 355..376
FT /note="Nudix box"
FT MOTIF 460..462
FT /note="Microbody targeting signal"
FT /evidence="ECO:0000250|UniProtKB:Q9BQG2"
FT BINDING 284
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9DCN1"
FT BINDING 287
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9DCN1"
FT BINDING 302
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9DCN1"
FT BINDING 307
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q9DCN1"
FT BINDING 318
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9DCN1"
FT BINDING 354..356
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9DCN1"
FT BINDING 354
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9DCN1"
FT BINDING 370
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q9DCN1"
FT BINDING 370
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q9DCN1"
FT BINDING 370
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9DCN1"
FT BINDING 374
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9DCN1"
FT BINDING 374
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q9DCN1"
FT BINDING 374
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9DCN1"
FT BINDING 415
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q9DCN1"
FT BINDING 415
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q9DCN1"
FT BINDING 415
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9DCN1"
FT MOD_RES 185
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DCN1"
FT MOD_RES 292
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9DCN1"
SQ SEQUENCE 462 AA; 52092 MW; BD4B6171E80DCB25 CRC64;
MSSVKRSPKQ EIVTQFHCSA AEGDIAKLTG ILSHSPSLLN ETSENGWTAL MYAARNGHPE
IVQFLLEKGC DRSIVNKSRQ TALDIAVFWG YKHIANLLAT AKGGKKPWFL TNEVEECENY
FSKTLLDRKS EKRNNADWLL AKESHPATVF ILFSDLNPLV TLGGNKESFQ QPEVRLCQLN
YKDIKDYLAQ PEEITLIFLG VELEMKDKLL NYAGEVPREE EDGLVAWFAL GIDPIAAEEF
KQRHENCYFL HPPMPALLQL KEKEAGVVAQ ARSVLAWHSR YKFCPTCGNG TKIEEGGYKR
VCLKEDCPSL NGVHNTSYPR VDPVVIMQVI HPDGTRCLLG RQKRFPPGMF TCLAGFIEPG
ETIEDAVRRE VEEESGVKVG HVQYVSCQPW PMPSSLMIGC LAVAVSTEIK VDKNEIEDAR
WFTREQVLDV LTKGKQQAFF VPPSRAIAHQ LIKHWIRINP NL
