Full text data of NMNAT3
NMNAT3
[Confidence: low (only semi-automatic identification from reviews)]
Nicotinamide mononucleotide adenylyltransferase 3; NMN adenylyltransferase 3 (Nicotinate-nucleotide adenylyltransferase 3; NaMN adenylyltransferase 3; 2.7.7.18; Pyridine nucleotide adenylyltransferase 3; PNAT-3; 2.7.7.1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Nicotinamide mononucleotide adenylyltransferase 3; NMN adenylyltransferase 3 (Nicotinate-nucleotide adenylyltransferase 3; NaMN adenylyltransferase 3; 2.7.7.18; Pyridine nucleotide adenylyltransferase 3; PNAT-3; 2.7.7.1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q96T66
ID NMNA3_HUMAN Reviewed; 252 AA.
AC Q96T66; B3KVR6; D3DNF2; D3DNF3; Q8N4G1;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 17-OCT-2006, sequence version 2.
DT 22-JAN-2014, entry version 103.
DE RecName: Full=Nicotinamide mononucleotide adenylyltransferase 3;
DE Short=NMN adenylyltransferase 3;
DE AltName: Full=Nicotinate-nucleotide adenylyltransferase 3;
DE Short=NaMN adenylyltransferase 3;
DE EC=2.7.7.18;
DE AltName: Full=Pyridine nucleotide adenylyltransferase 3;
DE Short=PNAT-3;
DE EC=2.7.7.1;
GN Name=NMNAT3; ORFNames=FKSG76;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Wang Y.-G., Gong L.;
RT "Identification of FKSG76, a novel gene encoding a NMN
RT adenylyltransferase.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain cortex;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Colon, and 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16118205; DOI=10.1074/jbc.M508660200;
RA Berger F., Lau C., Dahlmann M., Ziegler M.;
RT "Subcellular compartmentation and differential catalytic properties of
RT the three human nicotinamide mononucleotide adenylyltransferase
RT isoforms.";
RL J. Biol. Chem. 280:36334-36341(2005).
RN [7]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, AND
RP COFACTOR.
RX PubMed=17402747; DOI=10.1021/bi6023379;
RA Sorci L., Cimadamore F., Scotti S., Petrelli R., Cappellacci L.,
RA Franchetti P., Orsomando G., Magni G.;
RT "Initial-rate kinetics of human NMN-adenylyltransferases: substrate
RT and metal ion specificity, inhibition by products and multisubstrate
RT analogues, and isozyme contributions to NAD+ biosynthesis.";
RL Biochemistry 46:4912-4922(2007).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH NMN; NAD AND ATP
RP ANALOG, SUBCELLULAR LOCATION, SUBUNIT, AND TISSUE SPECIFICITY.
RX PubMed=12574164; DOI=10.1074/jbc.M300073200;
RA Zhang X., Kurnasov O.V., Karthikeyan S., Grishin N.V., Osterman A.L.,
RA Zhang H.;
RT "Structural characterization of a human cytosolic NMN/NaMN
RT adenylyltransferase and implication in human NAD biosynthesis.";
RL J. Biol. Chem. 278:13503-13511(2003).
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.
CC Can also use GTP and ITP as nucleotide donors. Also catalyzes the
CC reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+).
CC For the pyrophosphorolytic activity, can use NAD (+), NADH, NAAD,
CC nicotinic acid adenine dinucleotide phosphate (NHD), nicotinamide
CC guanine dinucleotide (NGD) as substrates. Fails to cleave
CC phosphorylated dinucleotides NADP(+), NADPH and NAADP(+). Protects
CC against axonal degeneration following injury.
CC -!- CATALYTIC ACTIVITY: ATP + nicotinamide ribonucleotide =
CC diphosphate + NAD(+).
CC -!- CATALYTIC ACTIVITY: ATP + beta-nicotinate-D-ribonucleotide =
CC diphosphate + deamido-NAD(+).
CC -!- COFACTOR: Divalent metal cations. Magnesium confers the highest
CC activity.
CC -!- ENZYME REGULATION: Activity is strongly inhibited by galotannin.
CC Inhibited by P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-
CC tetraphosphate (Nap4AD).
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=209 uM for NMN;
CC KM=130 uM for NAD(+);
CC KM=29 uM for ATP;
CC KM=390 uM for PPi;
CC KM=276 uM for GTP;
CC KM=350 uM for ITP;
CC KM=111 uM for NaMN;
CC KM=130 uM for NMNH;
CC KM=2.01 uM for triazofurin monophosphate;
CC Vmax=3.6 umol/min/mg enzyme for NAD synthesis;
CC Vmax=12.8 umol/min/mg enzyme for pyrophosphorolytic NAD(+)
CC cleavage;
CC Vmax=2.9 umol/min/mg enzyme for pyrophosphorolytic NADH
CC cleavage;
CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; NAD(+) from
CC nicotinamide D-ribonucleotide: step 1/1.
CC -!- SUBUNIT: Homotetramer.
CC -!- SUBCELLULAR LOCATION: Mitochondrion.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q96T66-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96T66-2; Sequence=VSP_010267;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q96T66-3; Sequence=VSP_043203;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in lung and spleen with lower levels
CC in placenta and kidney.
CC -!- SIMILARITY: Belongs to the eukaryotic NMN adenylyltransferase
CC family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF345564; AAK52726.1; -; mRNA.
DR EMBL; AK123208; BAG53878.1; -; mRNA.
DR EMBL; AC046134; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC110716; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW79023.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79024.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79025.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79030.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79031.1; -; Genomic_DNA.
DR EMBL; BC034374; AAH34374.1; -; mRNA.
DR RefSeq; NP_001186976.1; NM_001200047.1.
DR RefSeq; NP_835471.1; NM_178177.3.
DR UniGene; Hs.208673; -.
DR UniGene; Hs.745268; -.
DR PDB; 1NUP; X-ray; 1.90 A; A/B=1-252.
DR PDB; 1NUQ; X-ray; 1.90 A; A/B=1-252.
DR PDB; 1NUR; X-ray; 2.15 A; A/B=1-252.
DR PDB; 1NUS; X-ray; 2.20 A; A/B=1-252.
DR PDB; 1NUT; X-ray; 1.90 A; A/B=1-252.
DR PDB; 1NUU; X-ray; 1.90 A; A/B=1-252.
DR PDBsum; 1NUP; -.
DR PDBsum; 1NUQ; -.
DR PDBsum; 1NUR; -.
DR PDBsum; 1NUS; -.
DR PDBsum; 1NUT; -.
DR PDBsum; 1NUU; -.
DR ProteinModelPortal; Q96T66; -.
DR SMR; Q96T66; 3-235.
DR STRING; 9606.ENSP00000340523; -.
DR PhosphoSite; Q96T66; -.
DR DMDM; 116242680; -.
DR PaxDb; Q96T66; -.
DR PRIDE; Q96T66; -.
DR DNASU; 349565; -.
DR Ensembl; ENST00000296202; ENSP00000296202; ENSG00000163864.
DR Ensembl; ENST00000339837; ENSP00000340523; ENSG00000163864.
DR Ensembl; ENST00000406164; ENSP00000384319; ENSG00000163864.
DR Ensembl; ENST00000413939; ENSP00000412953; ENSG00000163864.
DR GeneID; 349565; -.
DR KEGG; hsa:349565; -.
DR UCSC; uc003etj.3; human.
DR CTD; 349565; -.
DR GeneCards; GC03M139279; -.
DR HGNC; HGNC:20989; NMNAT3.
DR MIM; 608702; gene.
DR neXtProt; NX_Q96T66; -.
DR PharmGKB; PA134952303; -.
DR eggNOG; COG1057; -.
DR HOGENOM; HOG000216047; -.
DR HOVERGEN; HBG052640; -.
DR InParanoid; Q96T66; -.
DR KO; K06210; -.
DR OMA; GYIAESP; -.
DR PhylomeDB; Q96T66; -.
DR BRENDA; 2.7.7.1; 2681.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR SABIO-RK; Q96T66; -.
DR UniPathway; UPA00253; UER00600.
DR EvolutionaryTrace; Q96T66; -.
DR GenomeRNAi; 349565; -.
DR NextBio; 99518; -.
DR PRO; PR:Q96T66; -.
DR ArrayExpress; Q96T66; -.
DR Bgee; Q96T66; -.
DR CleanEx; HS_NMNAT3; -.
DR Genevestigator; Q96T66; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0000309; F:nicotinamide-nucleotide adenylyltransferase activity; TAS:Reactome.
DR GO; GO:0004515; F:nicotinate-nucleotide adenylyltransferase activity; IDA:UniProtKB.
DR GO; GO:0009435; P:NAD biosynthetic process; IC:UniProtKB.
DR GO; GO:0009611; P:response to wounding; IEA:Ensembl.
DR GO; GO:0006767; P:water-soluble vitamin metabolic process; TAS:Reactome.
DR Gene3D; 3.40.50.620; -; 1.
DR InterPro; IPR004821; Cyt_trans-like.
DR InterPro; IPR005248; NAMN_adtrnsfrase.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR PANTHER; PTHR12039; PTHR12039; 1.
DR Pfam; PF01467; CTP_transf_2; 1.
DR TIGRFAMs; TIGR00482; TIGR00482; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Complete proteome;
KW Magnesium; Mitochondrion; NAD; Nucleotide-binding;
KW Nucleotidyltransferase; Pyridine nucleotide biosynthesis;
KW Reference proteome; Transferase.
FT CHAIN 1 252 Nicotinamide mononucleotide
FT adenylyltransferase 3.
FT /FTId=PRO_0000135016.
FT NP_BIND 13 22 ATP (Potential).
FT NP_BIND 201 206 ATP (Potential).
FT BINDING 14 14 Substrate.
FT BINDING 53 53 Substrate.
FT BINDING 137 137 Substrate.
FT VAR_SEQ 1 37 Missing (in isoform 2).
FT /FTId=VSP_010267.
FT VAR_SEQ 37 125 Missing (in isoform 3).
FT /FTId=VSP_043203.
FT CONFLICT 169 169 G -> S (in Ref. 1; AAK52726).
FT STRAND 5 13
FT HELIX 20 35
FT STRAND 37 48
FT STRAND 54 56
FT HELIX 61 71
FT HELIX 72 74
FT STRAND 76 80
FT HELIX 83 86
FT STRAND 87 89
FT HELIX 93 104
FT STRAND 129 135
FT HELIX 136 141
FT TURN 145 147
FT HELIX 150 159
FT STRAND 162 165
FT HELIX 172 178
FT HELIX 180 184
FT HELIX 186 188
FT STRAND 189 192
FT HELIX 202 210
FT HELIX 221 229
FT TURN 230 233
SQ SEQUENCE 252 AA; 28322 MW; 6402CFB2FE789CF4 CRC64;
MKSRIPVVLL ACGSFNPITN MHLRMFEVAR DHLHQTGMYQ VIQGIISPVN DTYGKKDLAA
SHHRVAMARL ALQTSDWIRV DPWESEQAQW METVKVLRHH HSKLLRSPPQ MEGPDHGKAL
FSTPAAVPEL KLLCGADVLK TFQTPNLWKD AHIQEIVEKF GLVCVGRVGH DPKGYIAESP
ILRMHQHNIH LAKEPVQNEI SATYIRRALG QGQSVKYLIP DAVITYIKDH GLYTKGSTWK
GKSTQSTEGK TS
//
ID NMNA3_HUMAN Reviewed; 252 AA.
AC Q96T66; B3KVR6; D3DNF2; D3DNF3; Q8N4G1;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
read moreDT 17-OCT-2006, sequence version 2.
DT 22-JAN-2014, entry version 103.
DE RecName: Full=Nicotinamide mononucleotide adenylyltransferase 3;
DE Short=NMN adenylyltransferase 3;
DE AltName: Full=Nicotinate-nucleotide adenylyltransferase 3;
DE Short=NaMN adenylyltransferase 3;
DE EC=2.7.7.18;
DE AltName: Full=Pyridine nucleotide adenylyltransferase 3;
DE Short=PNAT-3;
DE EC=2.7.7.1;
GN Name=NMNAT3; ORFNames=FKSG76;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Wang Y.-G., Gong L.;
RT "Identification of FKSG76, a novel gene encoding a NMN
RT adenylyltransferase.";
RL Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Brain cortex;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Colon, and 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16118205; DOI=10.1074/jbc.M508660200;
RA Berger F., Lau C., Dahlmann M., Ziegler M.;
RT "Subcellular compartmentation and differential catalytic properties of
RT the three human nicotinamide mononucleotide adenylyltransferase
RT isoforms.";
RL J. Biol. Chem. 280:36334-36341(2005).
RN [7]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, AND
RP COFACTOR.
RX PubMed=17402747; DOI=10.1021/bi6023379;
RA Sorci L., Cimadamore F., Scotti S., Petrelli R., Cappellacci L.,
RA Franchetti P., Orsomando G., Magni G.;
RT "Initial-rate kinetics of human NMN-adenylyltransferases: substrate
RT and metal ion specificity, inhibition by products and multisubstrate
RT analogues, and isozyme contributions to NAD+ biosynthesis.";
RL Biochemistry 46:4912-4922(2007).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH NMN; NAD AND ATP
RP ANALOG, SUBCELLULAR LOCATION, SUBUNIT, AND TISSUE SPECIFICITY.
RX PubMed=12574164; DOI=10.1074/jbc.M300073200;
RA Zhang X., Kurnasov O.V., Karthikeyan S., Grishin N.V., Osterman A.L.,
RA Zhang H.;
RT "Structural characterization of a human cytosolic NMN/NaMN
RT adenylyltransferase and implication in human NAD biosynthesis.";
RL J. Biol. Chem. 278:13503-13511(2003).
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.
CC Can also use GTP and ITP as nucleotide donors. Also catalyzes the
CC reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+).
CC For the pyrophosphorolytic activity, can use NAD (+), NADH, NAAD,
CC nicotinic acid adenine dinucleotide phosphate (NHD), nicotinamide
CC guanine dinucleotide (NGD) as substrates. Fails to cleave
CC phosphorylated dinucleotides NADP(+), NADPH and NAADP(+). Protects
CC against axonal degeneration following injury.
CC -!- CATALYTIC ACTIVITY: ATP + nicotinamide ribonucleotide =
CC diphosphate + NAD(+).
CC -!- CATALYTIC ACTIVITY: ATP + beta-nicotinate-D-ribonucleotide =
CC diphosphate + deamido-NAD(+).
CC -!- COFACTOR: Divalent metal cations. Magnesium confers the highest
CC activity.
CC -!- ENZYME REGULATION: Activity is strongly inhibited by galotannin.
CC Inhibited by P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-
CC tetraphosphate (Nap4AD).
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=209 uM for NMN;
CC KM=130 uM for NAD(+);
CC KM=29 uM for ATP;
CC KM=390 uM for PPi;
CC KM=276 uM for GTP;
CC KM=350 uM for ITP;
CC KM=111 uM for NaMN;
CC KM=130 uM for NMNH;
CC KM=2.01 uM for triazofurin monophosphate;
CC Vmax=3.6 umol/min/mg enzyme for NAD synthesis;
CC Vmax=12.8 umol/min/mg enzyme for pyrophosphorolytic NAD(+)
CC cleavage;
CC Vmax=2.9 umol/min/mg enzyme for pyrophosphorolytic NADH
CC cleavage;
CC -!- PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; NAD(+) from
CC nicotinamide D-ribonucleotide: step 1/1.
CC -!- SUBUNIT: Homotetramer.
CC -!- SUBCELLULAR LOCATION: Mitochondrion.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q96T66-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96T66-2; Sequence=VSP_010267;
CC Note=No experimental confirmation available;
CC Name=3;
CC IsoId=Q96T66-3; Sequence=VSP_043203;
CC Note=No experimental confirmation available;
CC -!- TISSUE SPECIFICITY: Expressed in lung and spleen with lower levels
CC in placenta and kidney.
CC -!- SIMILARITY: Belongs to the eukaryotic NMN adenylyltransferase
CC family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; AF345564; AAK52726.1; -; mRNA.
DR EMBL; AK123208; BAG53878.1; -; mRNA.
DR EMBL; AC046134; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC110716; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW79023.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79024.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79025.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79030.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79031.1; -; Genomic_DNA.
DR EMBL; BC034374; AAH34374.1; -; mRNA.
DR RefSeq; NP_001186976.1; NM_001200047.1.
DR RefSeq; NP_835471.1; NM_178177.3.
DR UniGene; Hs.208673; -.
DR UniGene; Hs.745268; -.
DR PDB; 1NUP; X-ray; 1.90 A; A/B=1-252.
DR PDB; 1NUQ; X-ray; 1.90 A; A/B=1-252.
DR PDB; 1NUR; X-ray; 2.15 A; A/B=1-252.
DR PDB; 1NUS; X-ray; 2.20 A; A/B=1-252.
DR PDB; 1NUT; X-ray; 1.90 A; A/B=1-252.
DR PDB; 1NUU; X-ray; 1.90 A; A/B=1-252.
DR PDBsum; 1NUP; -.
DR PDBsum; 1NUQ; -.
DR PDBsum; 1NUR; -.
DR PDBsum; 1NUS; -.
DR PDBsum; 1NUT; -.
DR PDBsum; 1NUU; -.
DR ProteinModelPortal; Q96T66; -.
DR SMR; Q96T66; 3-235.
DR STRING; 9606.ENSP00000340523; -.
DR PhosphoSite; Q96T66; -.
DR DMDM; 116242680; -.
DR PaxDb; Q96T66; -.
DR PRIDE; Q96T66; -.
DR DNASU; 349565; -.
DR Ensembl; ENST00000296202; ENSP00000296202; ENSG00000163864.
DR Ensembl; ENST00000339837; ENSP00000340523; ENSG00000163864.
DR Ensembl; ENST00000406164; ENSP00000384319; ENSG00000163864.
DR Ensembl; ENST00000413939; ENSP00000412953; ENSG00000163864.
DR GeneID; 349565; -.
DR KEGG; hsa:349565; -.
DR UCSC; uc003etj.3; human.
DR CTD; 349565; -.
DR GeneCards; GC03M139279; -.
DR HGNC; HGNC:20989; NMNAT3.
DR MIM; 608702; gene.
DR neXtProt; NX_Q96T66; -.
DR PharmGKB; PA134952303; -.
DR eggNOG; COG1057; -.
DR HOGENOM; HOG000216047; -.
DR HOVERGEN; HBG052640; -.
DR InParanoid; Q96T66; -.
DR KO; K06210; -.
DR OMA; GYIAESP; -.
DR PhylomeDB; Q96T66; -.
DR BRENDA; 2.7.7.1; 2681.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_116125; Disease.
DR SABIO-RK; Q96T66; -.
DR UniPathway; UPA00253; UER00600.
DR EvolutionaryTrace; Q96T66; -.
DR GenomeRNAi; 349565; -.
DR NextBio; 99518; -.
DR PRO; PR:Q96T66; -.
DR ArrayExpress; Q96T66; -.
DR Bgee; Q96T66; -.
DR CleanEx; HS_NMNAT3; -.
DR Genevestigator; Q96T66; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0000309; F:nicotinamide-nucleotide adenylyltransferase activity; TAS:Reactome.
DR GO; GO:0004515; F:nicotinate-nucleotide adenylyltransferase activity; IDA:UniProtKB.
DR GO; GO:0009435; P:NAD biosynthetic process; IC:UniProtKB.
DR GO; GO:0009611; P:response to wounding; IEA:Ensembl.
DR GO; GO:0006767; P:water-soluble vitamin metabolic process; TAS:Reactome.
DR Gene3D; 3.40.50.620; -; 1.
DR InterPro; IPR004821; Cyt_trans-like.
DR InterPro; IPR005248; NAMN_adtrnsfrase.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR PANTHER; PTHR12039; PTHR12039; 1.
DR Pfam; PF01467; CTP_transf_2; 1.
DR TIGRFAMs; TIGR00482; TIGR00482; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Complete proteome;
KW Magnesium; Mitochondrion; NAD; Nucleotide-binding;
KW Nucleotidyltransferase; Pyridine nucleotide biosynthesis;
KW Reference proteome; Transferase.
FT CHAIN 1 252 Nicotinamide mononucleotide
FT adenylyltransferase 3.
FT /FTId=PRO_0000135016.
FT NP_BIND 13 22 ATP (Potential).
FT NP_BIND 201 206 ATP (Potential).
FT BINDING 14 14 Substrate.
FT BINDING 53 53 Substrate.
FT BINDING 137 137 Substrate.
FT VAR_SEQ 1 37 Missing (in isoform 2).
FT /FTId=VSP_010267.
FT VAR_SEQ 37 125 Missing (in isoform 3).
FT /FTId=VSP_043203.
FT CONFLICT 169 169 G -> S (in Ref. 1; AAK52726).
FT STRAND 5 13
FT HELIX 20 35
FT STRAND 37 48
FT STRAND 54 56
FT HELIX 61 71
FT HELIX 72 74
FT STRAND 76 80
FT HELIX 83 86
FT STRAND 87 89
FT HELIX 93 104
FT STRAND 129 135
FT HELIX 136 141
FT TURN 145 147
FT HELIX 150 159
FT STRAND 162 165
FT HELIX 172 178
FT HELIX 180 184
FT HELIX 186 188
FT STRAND 189 192
FT HELIX 202 210
FT HELIX 221 229
FT TURN 230 233
SQ SEQUENCE 252 AA; 28322 MW; 6402CFB2FE789CF4 CRC64;
MKSRIPVVLL ACGSFNPITN MHLRMFEVAR DHLHQTGMYQ VIQGIISPVN DTYGKKDLAA
SHHRVAMARL ALQTSDWIRV DPWESEQAQW METVKVLRHH HSKLLRSPPQ MEGPDHGKAL
FSTPAAVPEL KLLCGADVLK TFQTPNLWKD AHIQEIVEKF GLVCVGRVGH DPKGYIAESP
ILRMHQHNIH LAKEPVQNEI SATYIRRALG QGQSVKYLIP DAVITYIKDH GLYTKGSTWK
GKSTQSTEGK TS
//
MIM
608702
*RECORD*
*FIELD* NO
608702
*FIELD* TI
*608702 NICOTINAMIDE NUCLEOTIDE ADENYLYLTRANSFERASE 3; NMNAT3
;;PYRIDINE NUCLEOTIDE ADENYLYLTRANSFERASE 3; PNAT3
read more*FIELD* TX
DESCRIPTION
The coenzyme NAD and its derivatives are involved in hundreds of
metabolic redox reactions and are utilized in protein ADP-ribosylation,
histone deacetylation, and in some Ca(2+) signaling pathways. NMNAT (EC
2.7.7.1) is a central enzyme in NAD biosynthesis, catalyzing the
condensation of nicotinamide mononucleotide (NMN) or nicotinic acid
mononucleotide (NaMN) with the AMP moiety of ATP to form NAD or NaAD
(Zhang et al., 2003).
CLONING
By searching databases for sequences similar to NMNAT1 (608700) followed
by PCR of a brain cDNA library, Zhang et al. (2003) cloned NMNAT3, which
they called PNAT3. The deduced 252-amino acid protein contains the
signature adenylyltransferase motif. NMNAT3 shares 50% amino acid
identity with NMNAT1 and 82% identity with mouse Nmnat3. Northern blot
analysis detected a 1.1-kb transcript expressed at high levels in lung
and spleen and at lower levels in placenta and kidney. Little to no
expression was detected in any other normal tissue examined or in any
cancer cell lines examined. Fluorescence-tagged NMNAT3 was expressed in
the cytosol of transfected HEK293 and HeLa cells. NMNAT3 was also
detected within mitochondria.
GENE FUNCTION
Zhang et al. (2003) determined that recombinant NMNAT3 showed a similar
rate of adenylyltransferase activity with either NMN or NaMN. The
activity of NMNAT3 was low compared with that of NMNAT1, but about
10-fold higher than that of NMNAT2 (608701).
BIOCHEMICAL FEATURES
Zhang et al. (2003) solved the crystal structures of NMNAT3 in its apo
form and in complexes with its substrates (an ATP analog, NMN, or both
the ATP analog and NMN) and with its products (NAD or NaAD). The
structure of monomeric NMNAT3 is similar to that of monomeric NMNAT1,
with a central parallel 6-stranded beta sheet surrounded by helices. The
active site residue arrangement is also similar to that of NMNAT1. The
main difference is that NMNAT3 forms a tetramer, while NMNAT1 forms a
hexamer.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the NMNAT3
gene to chromosome 3 (TMAP RH65003).
*FIELD* RF
1. Zhang, X.; Kurnasov, O. V.; Karthikeyan, S.; Grishin, N. V.; Osterman,
A. L.; Zhang, H.: Structural characterization of a human cytosolic
NMN/NaMN adenylyltransferase and implication in human NAD biosynthesis. J.
Biol. Chem. 278: 13503-13511, 2003.
*FIELD* CD
Patricia A. Hartz: 5/28/2004
*FIELD* ED
mgross: 05/28/2004
*RECORD*
*FIELD* NO
608702
*FIELD* TI
*608702 NICOTINAMIDE NUCLEOTIDE ADENYLYLTRANSFERASE 3; NMNAT3
;;PYRIDINE NUCLEOTIDE ADENYLYLTRANSFERASE 3; PNAT3
read more*FIELD* TX
DESCRIPTION
The coenzyme NAD and its derivatives are involved in hundreds of
metabolic redox reactions and are utilized in protein ADP-ribosylation,
histone deacetylation, and in some Ca(2+) signaling pathways. NMNAT (EC
2.7.7.1) is a central enzyme in NAD biosynthesis, catalyzing the
condensation of nicotinamide mononucleotide (NMN) or nicotinic acid
mononucleotide (NaMN) with the AMP moiety of ATP to form NAD or NaAD
(Zhang et al., 2003).
CLONING
By searching databases for sequences similar to NMNAT1 (608700) followed
by PCR of a brain cDNA library, Zhang et al. (2003) cloned NMNAT3, which
they called PNAT3. The deduced 252-amino acid protein contains the
signature adenylyltransferase motif. NMNAT3 shares 50% amino acid
identity with NMNAT1 and 82% identity with mouse Nmnat3. Northern blot
analysis detected a 1.1-kb transcript expressed at high levels in lung
and spleen and at lower levels in placenta and kidney. Little to no
expression was detected in any other normal tissue examined or in any
cancer cell lines examined. Fluorescence-tagged NMNAT3 was expressed in
the cytosol of transfected HEK293 and HeLa cells. NMNAT3 was also
detected within mitochondria.
GENE FUNCTION
Zhang et al. (2003) determined that recombinant NMNAT3 showed a similar
rate of adenylyltransferase activity with either NMN or NaMN. The
activity of NMNAT3 was low compared with that of NMNAT1, but about
10-fold higher than that of NMNAT2 (608701).
BIOCHEMICAL FEATURES
Zhang et al. (2003) solved the crystal structures of NMNAT3 in its apo
form and in complexes with its substrates (an ATP analog, NMN, or both
the ATP analog and NMN) and with its products (NAD or NaAD). The
structure of monomeric NMNAT3 is similar to that of monomeric NMNAT1,
with a central parallel 6-stranded beta sheet surrounded by helices. The
active site residue arrangement is also similar to that of NMNAT1. The
main difference is that NMNAT3 forms a tetramer, while NMNAT1 forms a
hexamer.
MAPPING
The International Radiation Hybrid Mapping Consortium mapped the NMNAT3
gene to chromosome 3 (TMAP RH65003).
*FIELD* RF
1. Zhang, X.; Kurnasov, O. V.; Karthikeyan, S.; Grishin, N. V.; Osterman,
A. L.; Zhang, H.: Structural characterization of a human cytosolic
NMN/NaMN adenylyltransferase and implication in human NAD biosynthesis. J.
Biol. Chem. 278: 13503-13511, 2003.
*FIELD* CD
Patricia A. Hartz: 5/28/2004
*FIELD* ED
mgross: 05/28/2004