NMNA2_DANRE
ID NMNA2_DANRE Reviewed; 304 AA.
AC Q6PC93; Q1LVF2;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 2 {ECO:0000305};
DE Short=NMN/NaMN adenylyltransferase 2;
DE EC=2.7.7.1 {ECO:0000250|UniProtKB:Q9BZQ4};
DE EC=2.7.7.18 {ECO:0000250|UniProtKB:Q9BZQ4};
DE AltName: Full=Nicotinamide mononucleotide adenylyltransferase 2;
DE Short=NMN adenylyltransferase 2;
DE AltName: Full=Nicotinate-nucleotide adenylyltransferase 2;
DE Short=NaMN adenylyltransferase 2;
GN Name=nmnat2; ORFNames=si:dkey-161l11.3;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Retina;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Nicotinamide/nicotinate-nucleotide adenylyltransferase that
CC acts as an axon maintenance factor (By similarity). Catalyzes the
CC formation of NAD(+) from nicotinamide mononucleotide (NMN) and ATP. Can
CC also use the deamidated form; nicotinic acid mononucleotide (NaMN) as
CC substrate but with a lower efficiency. Also catalyzes the reverse
CC reaction, i.e. the pyrophosphorolytic cleavage of NAD(+). For the
CC pyrophosphorolytic activity prefers NAD(+), NADH and NaAD as substrates
CC and degrades nicotinic acid adenine dinucleotide phosphate (NHD) less
CC effectively. Axon survival factor required for the maintenance of
CC healthy axons: acts by delaying Wallerian axon degeneration, an
CC evolutionarily conserved process that drives the loss of damaged axons
CC (By similarity). {ECO:0000250|UniProtKB:Q8BNJ3,
CC ECO:0000250|UniProtKB:Q9BZQ4}.
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:Q9BZQ4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21361;
CC Evidence={ECO:0000250|UniProtKB:Q9BZQ4};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21362;
CC Evidence={ECO:0000250|UniProtKB:Q9BZQ4};
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:Q9BZQ4};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22861;
CC Evidence={ECO:0000250|UniProtKB:Q9BZQ4};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:22862;
CC Evidence={ECO:0000250|UniProtKB:Q9BZQ4};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q9BZQ4};
CC Note=Divalent metal cations. Mg(2+) confers the highest activity.
CC {ECO:0000250|UniProtKB:Q9BZQ4};
CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; NAD(+) from
CC nicotinamide D-ribonucleotide: step 1/1.
CC {ECO:0000250|UniProtKB:Q9BZQ4}.
CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; deamido-NAD(+)
CC from nicotinate D-ribonucleotide: step 1/1.
CC {ECO:0000250|UniProtKB:Q9BZQ4}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q9BZQ4}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q8BNJ3}; Lipid-anchor
CC {ECO:0000250|UniProtKB:Q8BNJ3}. Cytoplasmic vesicle membrane
CC {ECO:0000250|UniProtKB:Q8BNJ3}; Lipid-anchor
CC {ECO:0000250|UniProtKB:Q8BNJ3}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q9BZQ4}. Cell projection, axon
CC {ECO:0000250|UniProtKB:Q8BNJ3}. Note=Delivered to axons with Golgi-
CC derived cytoplasmic vesicles. {ECO:0000250|UniProtKB:Q8BNJ3}.
CC -!- SIMILARITY: Belongs to the eukaryotic NMN adenylyltransferase family.
CC {ECO:0000305}.
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DR EMBL; BX681417; CAK05286.1; -; Genomic_DNA.
DR EMBL; BC059430; AAH59430.1; -; mRNA.
DR RefSeq; NP_956298.1; NM_200004.1.
DR AlphaFoldDB; Q6PC93; -.
DR SMR; Q6PC93; -.
DR STRING; 7955.ENSDARP00000004144; -.
DR PaxDb; Q6PC93; -.
DR GeneID; 336257; -.
DR KEGG; dre:336257; -.
DR CTD; 23057; -.
DR ZFIN; ZDB-GENE-030131-8201; nmnat2.
DR eggNOG; KOG3199; Eukaryota.
DR InParanoid; Q6PC93; -.
DR OrthoDB; 1308027at2759; -.
DR PhylomeDB; Q6PC93; -.
DR TreeFam; TF315035; -.
DR Reactome; R-DRE-196807; Nicotinate metabolism.
DR UniPathway; UPA00253; UER00332.
DR UniPathway; UPA00253; UER00600.
DR PRO; PR:Q6PC93; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IBA:GO_Central.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0000309; F:nicotinamide-nucleotide adenylyltransferase activity; IBA:GO_Central.
DR GO; GO:0004515; F:nicotinate-nucleotide adenylyltransferase activity; IBA:GO_Central.
DR GO; GO:0009435; P:NAD biosynthetic process; IBA:GO_Central.
DR CDD; cd09286; NMNAT_Eukarya; 1.
DR Gene3D; 3.40.50.620; -; 1.
DR InterPro; IPR004821; Cyt_trans-like.
DR InterPro; IPR045094; NMNAT_euk.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR Pfam; PF01467; CTP_transf_like; 1.
PE 2: Evidence at transcript level;
KW ATP-binding; Cell projection; Cytoplasm; Cytoplasmic vesicle;
KW Golgi apparatus; Lipoprotein; Membrane; NAD; Nucleotide-binding;
KW Nucleotidyltransferase; Palmitate; Pyridine nucleotide biosynthesis;
KW Reference proteome; Transferase.
FT CHAIN 1..304
FT /note="Nicotinamide/nicotinic acid mononucleotide
FT adenylyltransferase 2"
FT /id="PRO_0000328663"
FT BINDING 15..17
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
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:Q96T66"
FT BINDING 92..95
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT BINDING 197..199
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT BINDING 209..210
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT BINDING 268..271
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT LIPID 161
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q8BNJ3"
FT LIPID 162
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q8BNJ3"
FT CONFLICT 261
FT /note="P -> T (in Ref. 1; CAK05286)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 304 AA; 34209 MW; 60217B2E4A1D9D0F CRC64;
MTENTKTHVI LLSCGSFNPI TKGHIHMFEK AREYLHKTGR FIVIGGIVSP VHDSYGKPGL
VPSRHRLTMC QLAVQSSDWI RVDPWECYQD TWQTTCSVLE HHRDLMKRVT GCILSNVNTP
STTPVIGQPQ NETSAIYQNT VNKSVAIKFW GKMSESLGKI CCVRPHMDRF TFVDENANLG
TAMRYEEIEL RILLLCGSDL LESFCIPGLW NESDMEVIVG DFGIVVVPRD GADTERIMNH
SSVLRKHKDN IIVVKDEIDH PMSIVSSTKS RLALQHGDGH VVDYLSQPVI DYILQSQLYI
NASG
