NMNA1_MOUSE
ID NMNA1_MOUSE Reviewed; 285 AA.
AC Q9EPA7; Q6B504;
DT 09-MAY-2003, integrated into UniProtKB/Swiss-Prot.
DT 09-MAY-2003, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1 {ECO:0000305};
DE Short=NMN/NaMN adenylyltransferase 1;
DE EC=2.7.7.1 {ECO:0000269|PubMed:15381699};
DE EC=2.7.7.18 {ECO:0000250|UniProtKB:Q9HAN9};
DE AltName: Full=Nicotinamide mononucleotide adenylyltransferase 1;
DE Short=NMN adenylyltransferase 1;
DE AltName: Full=Nicotinate-nucleotide adenylyltransferase 1;
DE Short=NaMN adenylyltransferase 1;
GN Name=Nmnat1; Synonyms=D4Cole1e, Nmnat;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090 {ECO:0000312|EMBL:AAG38490.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC STRAIN=129, C57BL/6J, and C57BL/Ola;
RX PubMed=11027338; DOI=10.1073/pnas.97.21.11377;
RA Conforti L., Tarlton A., Mack T.G.A., Mi W., Buckmaster E.A., Wagner D.,
RA Perry V.H., Coleman M.P.;
RT "A Ufd2/D4Cole1e chimeric protein and overexpression of Rbp7 in the slow
RT Wallerian degeneration (WldS) mouse.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:11377-11382(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND FUNCTION.
RC STRAIN=BALB/cJ; TISSUE=Liver;
RX PubMed=15381699; DOI=10.1074/jbc.m408388200;
RA Revollo J.R., Grimm A.A., Imai S.;
RT "The NAD biosynthesis pathway mediated by nicotinamide
RT phosphoribosyltransferase regulates Sir2 activity in mammalian cells.";
RL J. Biol. Chem. 279:50754-50763(2004).
RN [3]
RP FUNCTION, AND MUTAGENESIS OF TRP-170.
RX PubMed=15310905; DOI=10.1126/science.1098014;
RA Araki T., Sasaki Y., Milbrandt J.;
RT "Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal
RT degeneration.";
RL Science 305:1010-1013(2004).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF
RP 125-ARG--LYS-128.
RX PubMed=16914673; DOI=10.1523/jneurosci.2320-06.2006;
RA Sasaki Y., Araki T., Milbrandt J.;
RT "Stimulation of nicotinamide adenine dinucleotide biosynthetic pathways
RT delays axonal degeneration after axotomy.";
RL J. Neurosci. 26:8484-8491(2006).
RN [5]
RP FUNCTION.
RX PubMed=27735788; DOI=10.7554/elife.19749;
RA Sasaki Y., Nakagawa T., Mao X., DiAntonio A., Milbrandt J.;
RT "NMNAT1 inhibits axon degeneration via blockade of SARM1-mediated NAD+
RT depletion.";
RL Elife 5:0-0(2016).
CC -!- FUNCTION: Catalyzes the formation of NAD(+) from nicotinamide
CC mononucleotide (NMN) and ATP (PubMed:15381699, PubMed:27735788). Can
CC also use the deamidated form; nicotinic acid mononucleotide (NaMN) as
CC substrate with the same efficiency (By similarity). Can use triazofurin
CC monophosphate (TrMP) as substrate (By similarity). Also catalyzes the
CC reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+) (By
CC similarity). For the pyrophosphorolytic activity, prefers NAD(+) and
CC NaAD as substrates and degrades NADH, nicotinic acid adenine
CC dinucleotide phosphate (NHD) and nicotinamide guanine dinucleotide
CC (NGD) less effectively (By similarity). Involved in the synthesis of
CC ATP in the nucleus, together with PARP1, PARG and NUDT5 (By
CC similarity). Nuclear ATP generation is required for extensive chromatin
CC remodeling events that are energy-consuming (By similarity). Fails to
CC cleave phosphorylated dinucleotides NADP(+), NADPH and NaADP(+) (By
CC similarity). Protects against axonal degeneration following mechanical
CC or toxic insults (PubMed:15310905, PubMed:16914673). Delays axonal
CC degeneration after axotomy. Results in a >10-fold increase in intact
CC neurites 72 hours after injury (PubMed:16914673, PubMed:27735788).
CC {ECO:0000250|UniProtKB:Q9HAN9, ECO:0000269|PubMed:15310905,
CC ECO:0000269|PubMed:15381699, ECO:0000269|PubMed:16914673,
CC ECO:0000269|PubMed:27735788}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + beta-nicotinamide D-ribonucleotide + H(+) = diphosphate
CC + NAD(+); Xref=Rhea:RHEA:21360, ChEBI:CHEBI:14649, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57540; EC=2.7.7.1;
CC Evidence={ECO:0000269|PubMed:15381699};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21361;
CC Evidence={ECO:0000250|UniProtKB:Q9HAN9};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21362;
CC Evidence={ECO:0000250|UniProtKB:Q9HAN9};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H(+) + nicotinate beta-D-ribonucleotide = deamido-NAD(+)
CC + diphosphate; Xref=Rhea:RHEA:22860, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:57502,
CC ChEBI:CHEBI:58437; EC=2.7.7.18;
CC Evidence={ECO:0000250|UniProtKB:Q9HAN9};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22861;
CC Evidence={ECO:0000250|UniProtKB:Q9HAN9};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:22862;
CC Evidence={ECO:0000250|UniProtKB:Q9HAN9};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q9HAN9};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9HAN9};
CC Note=Divalent metal cations. Zn(2+) confers higher activity as compared
CC to Mg(2+). {ECO:0000250|UniProtKB:Q9HAN9};
CC -!- ACTIVITY REGULATION: Activity is strongly inhibited by galotannin.
CC Inhibited by P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-
CC tetraphosphate (Nap4AD). {ECO:0000250|UniProtKB:Q9HAN9}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=20.1 uM for nicotinamide mononucleotide (NMN)
CC {ECO:0000269|PubMed:15381699};
CC Vmax=34.1 umol/min/mg enzyme {ECO:0000269|PubMed:15381699};
CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; NAD(+) from
CC nicotinamide D-ribonucleotide: step 1/1.
CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; deamido-NAD(+)
CC from nicotinate D-ribonucleotide: step 1/1.
CC -!- SUBUNIT: Homohexamer. Interacts with ADPRT/PARP1.
CC {ECO:0000250|UniProtKB:Q9HAN9}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16914673}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout development and in adulthood.
CC {ECO:0000269|PubMed:16914673}.
CC -!- INDUCTION: By neuronal injury.
CC -!- MISCELLANEOUS: In strain C57BL/Ola, an 85 kb region on chromosome 4
CC containing Nmnat1 and Ube4b is triplicated. The N-terminal 70 residues
CC of Ube4b becomes linked to the complete Nmnat1 protein and encodes a
CC fusion protein located in the nucleus which is responsible for the
CC Wallerian degeneration slow (Wlds) phenotype characterized by delayed
CC Wallerian degeneration of injured axons.
CC -!- SIMILARITY: Belongs to the eukaryotic NMN adenylyltransferase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAG17285.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAG17286.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=AAG38490.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF260924; AAG17285.1; ALT_INIT; mRNA.
DR EMBL; AF260925; AAG17286.1; ALT_INIT; mRNA.
DR EMBL; AF260927; AAG38490.1; ALT_INIT; Genomic_DNA.
DR EMBL; AY679721; AAT76443.1; -; mRNA.
DR CCDS; CCDS18960.1; -.
DR RefSeq; NP_597679.1; NM_133435.1.
DR RefSeq; XP_006539168.1; XM_006539105.3.
DR AlphaFoldDB; Q9EPA7; -.
DR SMR; Q9EPA7; -.
DR BioGRID; 211485; 1.
DR IntAct; Q9EPA7; 1.
DR STRING; 10090.ENSMUSP00000030845; -.
DR iPTMnet; Q9EPA7; -.
DR PhosphoSitePlus; Q9EPA7; -.
DR EPD; Q9EPA7; -.
DR MaxQB; Q9EPA7; -.
DR PaxDb; Q9EPA7; -.
DR PRIDE; Q9EPA7; -.
DR ProteomicsDB; 293693; -.
DR Antibodypedia; 27787; 265 antibodies from 31 providers.
DR DNASU; 66454; -.
DR Ensembl; ENSMUST00000030845; ENSMUSP00000030845; ENSMUSG00000028992.
DR Ensembl; ENSMUST00000105693; ENSMUSP00000101318; ENSMUSG00000028992.
DR GeneID; 66454; -.
DR KEGG; mmu:66454; -.
DR UCSC; uc008vwj.1; mouse.
DR CTD; 64802; -.
DR MGI; MGI:1913704; Nmnat1.
DR VEuPathDB; HostDB:ENSMUSG00000028992; -.
DR eggNOG; KOG3199; Eukaryota.
DR GeneTree; ENSGT00950000183179; -.
DR HOGENOM; CLU_033366_3_0_1; -.
DR InParanoid; Q9EPA7; -.
DR OMA; QPWKENI; -.
DR OrthoDB; 1308027at2759; -.
DR PhylomeDB; Q9EPA7; -.
DR TreeFam; TF315035; -.
DR BRENDA; 2.7.7.1; 3474.
DR BRENDA; 2.7.7.18; 3474.
DR Reactome; R-MMU-196807; Nicotinate metabolism.
DR SABIO-RK; Q9EPA7; -.
DR UniPathway; UPA00253; UER00332.
DR UniPathway; UPA00253; UER00600.
DR BioGRID-ORCS; 66454; 10 hits in 72 CRISPR screens.
DR ChiTaRS; Nmnat1; mouse.
DR PRO; PR:Q9EPA7; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q9EPA7; protein.
DR Bgee; ENSMUSG00000028992; Expressed in otic placode and 199 other tissues.
DR ExpressionAtlas; Q9EPA7; baseline and differential.
DR Genevisible; Q9EPA7; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0000309; F:nicotinamide-nucleotide adenylyltransferase activity; IDA:MGI.
DR GO; GO:0004515; F:nicotinate-nucleotide adenylyltransferase activity; IDA:MGI.
DR GO; GO:1990966; P:ATP generation from poly-ADP-D-ribose; ISS:UniProtKB.
DR GO; GO:0009435; P:NAD biosynthetic process; IDA:MGI.
DR GO; GO:1902511; P:negative regulation of apoptotic DNA fragmentation; ISO:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; ISO:MGI.
DR GO; GO:1901215; P:negative regulation of neuron death; IMP:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:MGI.
DR GO; GO:0009611; P:response to wounding; IDA:MGI.
DR CDD; cd09286; NMNAT_Eukarya; 1.
DR Gene3D; 3.40.50.620; -; 1.
DR InterPro; IPR004821; Cyt_trans-like.
DR InterPro; IPR005248; NadD/NMNAT.
DR InterPro; IPR045094; NMNAT_euk.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR Pfam; PF01467; CTP_transf_like; 1.
DR TIGRFAMs; TIGR00482; TIGR00482; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Magnesium; NAD; Nucleotide-binding; Nucleotidyltransferase;
KW Nucleus; Phosphoprotein; Pyridine nucleotide biosynthesis;
KW Reference proteome; Transferase; Zinc.
FT CHAIN 1..285
FT /note="Nicotinamide/nicotinic acid mononucleotide
FT adenylyltransferase 1"
FT /id="PRO_0000135013"
FT REGION 109..149
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 123..129
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT BINDING 15..17
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q96T66,
FT ECO:0000250|UniProtKB:Q9HAN9"
FT BINDING 24
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT BINDING 55..57
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9HAN9"
FT BINDING 58
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT BINDING 92..95
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9HAN9"
FT BINDING 157..159
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT BINDING 169..170
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9HAN9"
FT BINDING 225..228
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT MOD_RES 117
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9HAN9"
FT MUTAGEN 125..128
FT /note="RKRK->AAAA: Locates to the cytoplasm. Has no effect
FT on enzyme activity or axonal protection."
FT /evidence="ECO:0000269|PubMed:16914673"
FT MUTAGEN 170
FT /note="W->A: Decrease in enzyme activity. Has no axonal
FT protective effect."
FT /evidence="ECO:0000269|PubMed:15310905"
SQ SEQUENCE 285 AA; 32355 MW; 2769D42E894EB84F CRC64;
MDSSKKTEVV LLACGSFNPI TNMHLRLFEL AKDYMHATGK YSVIKGIISP VGDAYKKKGL
IPAHHRIIMA ELATKNSHWV EVDTWESLQK EWVETVKVLR YHQEKLATGS CSYPQSSPAL
EKPGRKRKWA DQKQDSSPQK PQEPKPTGVP KVKLLCGADL LESFSVPNLW KMEDITQIVA
NFGLICITRA GSDAQKFIYE SDVLWRHQSN IHLVNEWITN DISSTKIRRA LRRGQSIRYL
VPDLVQEYIE KHELYNTESE GRNAGVTLAP LQRNAAEAKH NHSTL
