NMNA2_RAT
ID NMNA2_RAT Reviewed; 307 AA.
AC Q0HA29;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 104.
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;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Xing J., Cao G., Zhang L., Chen J.;
RT "Nicotinamide nucleotide adenylyltransferase is neuroprotective against
RT ischemic injury.";
RL Submitted (APR-2005) 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. Cannot use triazofurin
CC monophosphate (TrMP) as substrate. Also catalyzes the reverse reaction,
CC 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. Fails to cleave phosphorylated dinucleotides NADP(+),
CC NADPH and NaADP(+) (By similarity). Axon survival factor required for
CC the maintenance of healthy axons: acts by delaying Wallerian axon
CC degeneration, an evolutionarily conserved process that drives the loss
CC of damaged axons (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 -!- ACTIVITY REGULATION: Inhibited by P1-(adenosine-5')-P3-(nicotinamide-
CC riboside-5')-triphosphate (Np3AD) and P1-(adenosine-5')-P4-
CC (nicotinamide-riboside-5')-tetraphosphate (Np4AD).
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 -!- PTM: Degraded in response to injured neurite. Degradation is probably
CC caused by ubiquitination by MYCBP2 (By similarity). Ubiquitinated on
CC threonine and/or serine residues by MYCBP2; consequences of threonine
CC and/or serine ubiquitination are however unclear (By similarity).
CC {ECO:0000250|UniProtKB:Q8BNJ3, ECO:0000250|UniProtKB:Q9BZQ4}.
CC -!- PTM: Palmitoylated; palmitoylation is required for membrane
CC association. {ECO:0000250|UniProtKB:Q8BNJ3}.
CC -!- SIMILARITY: Belongs to the eukaryotic NMN adenylyltransferase family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; DQ022370; AAY87457.1; -; mRNA.
DR RefSeq; NP_001041507.1; NM_001048042.1.
DR AlphaFoldDB; Q0HA29; -.
DR SMR; Q0HA29; -.
DR STRING; 10116.ENSRNOP00000029020; -.
DR SwissPalm; Q0HA29; -.
DR PaxDb; Q0HA29; -.
DR PRIDE; Q0HA29; -.
DR GeneID; 289095; -.
DR KEGG; rno:289095; -.
DR UCSC; RGD:1307331; rat.
DR CTD; 23057; -.
DR RGD; 1307331; Nmnat2.
DR eggNOG; KOG3199; Eukaryota.
DR InParanoid; Q0HA29; -.
DR OrthoDB; 1308027at2759; -.
DR PhylomeDB; Q0HA29; -.
DR Reactome; R-RNO-196807; Nicotinate metabolism.
DR UniPathway; UPA00253; UER00332.
DR UniPathway; UPA00253; UER00600.
DR PRO; PR:Q0HA29; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005770; C:late endosome; ISO:RGD.
DR GO; GO:0045202; C:synapse; ISO:RGD.
DR GO; GO:0005802; C:trans-Golgi network; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:1904385; P:cellular response to angiotensin; IEP:RGD.
DR GO; GO:0009435; P:NAD biosynthetic process; IMP:RGD.
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; Ubl conjugation.
FT CHAIN 1..307
FT /note="Nicotinamide/nicotinic acid mononucleotide
FT adenylyltransferase 2"
FT /id="PRO_0000328662"
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 200..202
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT BINDING 212..213
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT BINDING 271..274
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q96T66"
FT LIPID 164
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q8BNJ3"
FT LIPID 165
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q8BNJ3"
SQ SEQUENCE 307 AA; 34445 MW; EDE5DAB7B03AE1AA CRC64;
MTETTKTHVI LLACGSFNPI TKGHIQMFER ARDYLHKTGR FIVIGGIVSP VHDSYGKQGL
VSSRHRLIMC QLAVQNSDWI RVDPWECYQD TWQTTCSVLE HHRDLMKRVT GCILSNVNTP
SMTPVIGQPQ HENTQPIYQN SNVPTKPTAA KILGKVGESL GRICCVRPPV ERFTFVDENA
NLGTVMRYEE IELRILLLCG SDLLESFCIP GLWNEADMEV IVGDFGIVVV PRDAADADRI
MNHSSILRKY KNNIMVVKDD INHPMSVVSS TKSRLALQHG DGHVVDYLSQ PVIDYILKSQ
LYINASG
