NMNA3_MOUSE
ID NMNA3_MOUSE Reviewed; 245 AA.
AC Q99JR6; Q58E37;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 3 {ECO:0000305};
DE Short=NMN/NaMN adenylyltransferase 3;
DE EC=2.7.7.1 {ECO:0000250|UniProtKB:Q96T66};
DE EC=2.7.7.18 {ECO:0000250|UniProtKB:Q96T66};
DE AltName: Full=Nicotinamide-nucleotide adenylyltransferase 3;
DE Short=NMN adenylyltransferase 3;
DE AltName: Full=Nicotinate-nucleotide adenylyltransferase 3;
DE Short=NaMN adenylyltransferase 3;
GN Name=Nmnat3 {ECO:0000312|MGI:MGI:1921330};
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Catalyzes the formation of NAD(+) from nicotinamide
CC mononucleotide (NMN) and ATP. Can also use the deamidated form;
CC nicotinic acid mononucleotide (NaMN) as substrate with the same
CC efficiency. Can use triazofurin monophosphate (TrMP) as substrate. Can
CC also use GTP and ITP as nucleotide donors. Also catalyzes the reverse
CC reaction, i.e. the pyrophosphorolytic cleavage of NAD(+). For the
CC pyrophosphorolytic activity, can use NAD(+), NADH, NaAD, nicotinic acid
CC adenine dinucleotide phosphate (NHD), nicotinamide guanine dinucleotide
CC (NGD) as substrates. Fails to cleave phosphorylated dinucleotides
CC NADP(+), NADPH and NaADP(+) (By similarity). Protects against axonal
CC degeneration following injury. {ECO:0000250|UniProtKB:Q96T66,
CC ECO:0000269|PubMed:16914673}.
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:0000250|UniProtKB:Q96T66};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21361;
CC Evidence={ECO:0000250|UniProtKB:Q96T66};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21362;
CC Evidence={ECO:0000250|UniProtKB:Q96T66};
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:Q96T66};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22861;
CC Evidence={ECO:0000250|UniProtKB:Q96T66};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:22862;
CC Evidence={ECO:0000250|UniProtKB:Q96T66};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC Note=Divalent metal cations. Mg(2+) confers the highest activity.
CC {ECO:0000250};
CC -!- ACTIVITY REGULATION: Activity is strongly inhibited by galotannin.
CC Inhibited by P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-
CC tetraphosphate (Nap4AD) (By similarity). {ECO:0000250}.
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: Homotetramer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:16914673}.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout development and in adulthood.
CC {ECO:0000269|PubMed:16914673}.
CC -!- SIMILARITY: Belongs to the eukaryotic NMN adenylyltransferase family.
CC {ECO:0000305}.
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DR EMBL; BC005737; AAH05737.1; -; mRNA.
DR EMBL; BC092086; AAH92086.1; -; mRNA.
DR CCDS; CCDS23423.1; -.
DR RefSeq; NP_653116.1; NM_144533.2.
DR RefSeq; XP_006511565.1; XM_006511502.3.
DR RefSeq; XP_006511566.1; XM_006511503.3.
DR RefSeq; XP_006511567.1; XM_006511504.3.
DR RefSeq; XP_011241128.1; XM_011242826.1.
DR RefSeq; XP_011241129.1; XM_011242827.1.
DR PDB; 5Z9R; X-ray; 2.00 A; A/B=1-245.
DR PDBsum; 5Z9R; -.
DR AlphaFoldDB; Q99JR6; -.
DR SMR; Q99JR6; -.
DR BioGRID; 216475; 3.
DR STRING; 10090.ENSMUSP00000108557; -.
DR iPTMnet; Q99JR6; -.
DR PhosphoSitePlus; Q99JR6; -.
DR MaxQB; Q99JR6; -.
DR PaxDb; Q99JR6; -.
DR PeptideAtlas; Q99JR6; -.
DR PRIDE; Q99JR6; -.
DR ProteomicsDB; 293866; -.
DR Antibodypedia; 33465; 191 antibodies from 28 providers.
DR DNASU; 74080; -.
DR Ensembl; ENSMUST00000112935; ENSMUSP00000108557; ENSMUSG00000032456.
DR GeneID; 74080; -.
DR KEGG; mmu:74080; -.
DR UCSC; uc009rdh.1; mouse.
DR CTD; 349565; -.
DR MGI; MGI:1921330; Nmnat3.
DR VEuPathDB; HostDB:ENSMUSG00000032456; -.
DR eggNOG; KOG3199; Eukaryota.
DR GeneTree; ENSGT00950000183179; -.
DR HOGENOM; CLU_033366_3_1_1; -.
DR InParanoid; Q99JR6; -.
DR OMA; PGLWARE; -.
DR OrthoDB; 1308027at2759; -.
DR PhylomeDB; Q99JR6; -.
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 UniPathway; UPA00253; UER00332.
DR UniPathway; UPA00253; UER00600.
DR BioGRID-ORCS; 74080; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Nmnat3; mouse.
DR PRO; PR:Q99JR6; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q99JR6; protein.
DR Bgee; ENSMUSG00000032456; Expressed in spermatocyte and 173 other tissues.
DR ExpressionAtlas; Q99JR6; baseline and differential.
DR Genevisible; Q99JR6; MM.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0000309; F:nicotinamide-nucleotide adenylyltransferase activity; IDA:MGI.
DR GO; GO:0004515; F:nicotinate-nucleotide adenylyltransferase activity; ISO:MGI.
DR GO; GO:0009435; P:NAD biosynthetic process; IDA:MGI.
DR GO; GO:0034612; P:response to tumor necrosis factor; IEA:Ensembl.
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 3D-structure; ATP-binding; Mitochondrion; NAD; Nucleotide-binding;
KW Nucleotidyltransferase; Pyridine nucleotide biosynthesis;
KW Reference proteome; Transferase.
FT CHAIN 1..245
FT /note="Nicotinamide/nicotinic acid mononucleotide
FT adenylyltransferase 3"
FT /id="PRO_0000135017"
FT BINDING 13..15
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT BINDING 22
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT BINDING 53..55
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT BINDING 56
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT BINDING 90..93
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT BINDING 134..136
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT BINDING 139
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between dimeric partners"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT BINDING 146..147
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT BINDING 202..205
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /ligand_note="ligand shared between dimeric partners"
FT /note="in other chain"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT STRAND 5..13
FT /evidence="ECO:0007829|PDB:5Z9R"
FT HELIX 20..36
FT /evidence="ECO:0007829|PDB:5Z9R"
FT STRAND 37..48
FT /evidence="ECO:0007829|PDB:5Z9R"
FT TURN 51..53
FT /evidence="ECO:0007829|PDB:5Z9R"
FT HELIX 61..71
FT /evidence="ECO:0007829|PDB:5Z9R"
FT HELIX 72..74
FT /evidence="ECO:0007829|PDB:5Z9R"
FT STRAND 76..80
FT /evidence="ECO:0007829|PDB:5Z9R"
FT HELIX 83..86
FT /evidence="ECO:0007829|PDB:5Z9R"
FT STRAND 87..89
FT /evidence="ECO:0007829|PDB:5Z9R"
FT HELIX 93..106
FT /evidence="ECO:0007829|PDB:5Z9R"
FT STRAND 128..134
FT /evidence="ECO:0007829|PDB:5Z9R"
FT HELIX 135..140
FT /evidence="ECO:0007829|PDB:5Z9R"
FT HELIX 144..146
FT /evidence="ECO:0007829|PDB:5Z9R"
FT HELIX 150..158
FT /evidence="ECO:0007829|PDB:5Z9R"
FT STRAND 161..164
FT /evidence="ECO:0007829|PDB:5Z9R"
FT HELIX 171..177
FT /evidence="ECO:0007829|PDB:5Z9R"
FT HELIX 179..183
FT /evidence="ECO:0007829|PDB:5Z9R"
FT HELIX 185..187
FT /evidence="ECO:0007829|PDB:5Z9R"
FT STRAND 188..191
FT /evidence="ECO:0007829|PDB:5Z9R"
FT HELIX 201..209
FT /evidence="ECO:0007829|PDB:5Z9R"
FT HELIX 220..229
FT /evidence="ECO:0007829|PDB:5Z9R"
FT TURN 230..232
FT /evidence="ECO:0007829|PDB:5Z9R"
SQ SEQUENCE 245 AA; 27703 MW; E46D50D81CD150BB CRC64;
MKNRIPVVLL ACGSFNPITN MHLRLFEVAR DHLHQTGRYQ VIEGIISPVN DSYGKKDLVA
SHHRVAMARL ALQTSDWIRV DPWESEQAQW METVKVLRHH HRELLRSSAQ MDGPDPSKTP
SASAALPELK LLCGADVLKT FQTPNLWKDT HIQEIVEKFG LVCVSRSGHD PERYISDSPI
LQQFQHNIHL AREPVLNEIS ATYVRKALGQ GQSVKYLLPE AVITYIRDQG LYINDGSWKG
KGKTG
