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UniProtKB/Swiss-Prot entry Q96T66

[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name NMNA3_HUMAN
Primary accession number Q96T66
Secondary accession number Q8N4G1
Integrated into Swiss-Prot on May 10, 2004
Sequence was last modified on October 17, 2006 (Sequence version 2)
Annotations were last modified on    June 16, 2009 (Entry version 57)
Name and origin of the protein
Protein name Nicotinamide mononucleotide adenylyltransferase 3
Synonyms NMN adenylyltransferase 3
Pyridine nucleotide adenylyltransferase 3
PNAT-3
EC 2.7.7.1
Nicotinate-nucleotide adenylyltransferase 3
NaMN adenylyltransferase 3
EC 2.7.7.18
Gene name
Name: NMNAT3
ORFNames: FKSG76
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
 NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Wang Y.-G., Gong L.;
"Identification of FKSG76, a novel gene encoding a NMN adenylyltransferase.";
Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases.
[2]
 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
TISSUE=Colon, and Kidney;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan]
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[3]
 FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
DOI=10.1074/jbc.M508660200; PubMed=16118205 [NCBI, ExPASy, EBI, Israel, Japan]
Berger F., Lau C., Dahlmann M., Ziegler M.;
"Subcellular compartmentation and differential catalytic properties of the three human nicotinamide mononucleotide adenylyltransferase isoforms.";
J. Biol. Chem. 280:36334-36341(2005).
[4]
 FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, AND COFACTOR.
DOI=10.1021/bi6023379; PubMed=17402747 [NCBI, ExPASy, EBI, Israel, Japan]
Sorci L., Cimadamore F., Scotti S., Petrelli R., Cappellacci L., Franchetti P., Orsomando G., Magni G.;
"Initial-rate kinetics of human NMN-adenylyltransferases: substrate and metal ion specificity, inhibition by products and multisubstrate analogues, and isozyme contributions to NAD+ biosynthesis.";
Biochemistry 46:4912-4922(2007).
[5]
 X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH NMN, NAD AND ATP ANALOG, SUBCELLULAR LOCATION, SUBUNIT, AND TISSUE SPECIFICITY.
DOI=10.1074/jbc.M300073200; PubMed=12574164 [NCBI, ExPASy, EBI, Israel, Japan]
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).
Comments
  • FUNCTION: Catalyzes the formation of NAD(+) from nicotinamide mononucleotide (NMN) and ATP. Can also use the deamidated form; nicotinic acid mononucleotide (NaMN) as substrate with the same efficiency. Can use triazofurin monophosphate (TrMP) as substrate. Can also use GTP and ITP as nucleotide donors. Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD(+). For the pyrophosphorolytic activity, can use NAD (+), NADH, NAAD, nicotinic acid adenine dinucleotide phosphate (NHD), nicotinamide guanine dinucleotide (NGD) as substrates. Fails to cleave phosphorylated dinucleotides NADP(+), NADPH and NAADP(+). Protects against axonal degeneration following injury.
  • CATALYTIC ACTIVITY: ATP + nicotinamide ribonucleotide = diphosphate + NAD+.
  • CATALYTIC ACTIVITY: ATP + nicotinate ribonucleotide = diphosphate + deamido-NAD+.
  • COFACTOR: Divalent metal cations. Magnesium confers the highest activity.
  • ENZYME REGULATION: Activity is strongly inhibited by galotannin. Inhibited by P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-tetraphosphate (Nap4AD).
  • BIOPHYSICOCHEMICAL PROPERTIES:
    Kinetic parameters:   KM=209 µM for NMN;
    KM=130 µM for NAD+;
    KM=29 µM for ATP;
    KM=390 µM for PPi;
    KM=276 µM for GTP;
    KM=350 µM for ITP;
    KM=111 µM for NaMN;
    KM=130 µM for NMNH;
    KM=2.01 µM for triazofurin monophosphate;
    Vmax=3.6 µmol/min/mg enzyme for NAD synthesis;
    Vmax=12.8 µmol/min/mg enzyme for pyrophosphorolytic NAD+ cleavage;
    Vmax=2.9 µmol/min/mg enzyme for pyrophosphorolytic NADH cleavage;
  • PATHWAY: Cofactor biosynthesis; NAD(+) biosynthesis; NAD(+) from nicotinamide ribonucleotide: step 1/1.
  • SUBUNIT: Homotetramer.
  • SUBCELLULAR LOCATION: Mitochondrion.
  • ALTERNATIVE PRODUCTS: 2 named isoforms [FASTA] produced by alternative splicing.
    Name1
    Isoform IDQ96T66-1
    This is the isoform sequence displayed in this entry.
    Name2
    Isoform IDQ96T66-2
    Note: No experimental confirmation available.
    Features which should be applied to build the isoform sequence: VSP_010267.
  • TISSUE SPECIFICITY: Expressed in lung and spleen with lower levels in placenta and kidney.
  • SIMILARITY: Belongs to the eukaryotic NMN adenylyltransferase family.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
AF345564; AAK52726.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
BC034374; AAH34374.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
IPI IPI00290687; -.
IPI00410337; -.
RefSeq NP_835471.1; -.
UniGene Hs.208673
3D structure databases
PDB
1NUP; X-ray; 1.90 A; A/B=1-252.[ExPASy / RCSB / EBI]
1NUQ; X-ray; 1.90 A; A/B=1-252.[ExPASy / RCSB / EBI]
1NUR; X-ray; 2.15 A; A/B=1-252.[ExPASy / RCSB / EBI]
1NUS; X-ray; 2.20 A; A/B=1-252.[ExPASy / RCSB / EBI]
1NUT; X-ray; 1.90 A; A/B=1-252.[ExPASy / RCSB / EBI]
1NUU; X-ray; 1.90 A; A/B=1-252.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1NUP; -.
1NUQ; -.
1NUR; -.
1NUS; -.
1NUT; -.
1NUU; -.
ModBase Q96T66.
Enzyme and pathway databases
BRENDA 2.7.7.1; 247.
Reactome REACT_11193; Metabolism of vitamins and cofactors.
Organism-specific databases
GeneCards GC03M140761; -.
H-InvDB HIX0003718; -.
HGNC HGNC:20989; NMNAT3.
GenAtlas NMNAT3.
MIM 608702; gene. [NCBI / EBI]
PharmGKB PA134952303; -.
Gene expression databases
ArrayExpress Q96T66; -.
Bgee Q96T66; -.
CleanEx HS_NMNAT3; -.
GermOnline ENSG00000163864; Homo sapiens.
Ontologies
GO
GO:0005739; Cellular component: mitochondrion (inferred from direct assay from UniProtKB).
GO:0005524; Molecular function: ATP binding (inferred from electronic annotation from UniProtKB-KW).
GO:0000287; Molecular function: magnesium ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0000309; Molecular function: nicotinamide-nucleotide adenylyltransferase activity (inferred from electronic annotation from EC).
GO:0004515; Molecular function: nicotinate-nucleotide adenylyltransferase activity (inferred from direct assay from UniProtKB).
GO:0009435; Biological process: NAD biosynthetic process (inferred by curator from UniProtKB).
QuickGo view.
Family and domain databases
InterPro IPR004820; Cytidylyltransf.
IPR005248; NAMN_adtrnsfrase.
IPR019450; NMN_adenylylTrfase_C.
IPR014729; Rossmann-like_a/b/a_fold.
Graphical view of domain structure.
Gene3D G3DSA:3.40.50.620; Rossmann-like_a/b/a_fold; 1.
PANTHER PTHR12039; NAMN_adtrnsfrase; 1.
Pfam PF01467; CTP_transf_2; 1.
PF10362; DUF2432; 1.
Pfam graphical view of domain structure.
TIGRFAMs TIGR00482; NAMN_adtrnsfrase; 1.
Proteomic databases
PRIDE Q96T66; -.
Genome annotation databases
Ensembl ENSG00000163864; Homo sapiens. [Contig view]
GeneID 349565; -.
KEGG hsa:349565; -.
Phylogenomic databases
HOGENOM Q96T66; -.
HOVERGEN Q96T66; -.
OMA Q96T66; ILKTFQT.
Other
NextBio 99518; -.
SOURCE NMNAT3; Homo sapiens.
ProtoNet Q96T66.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Alternative splicing; ATP-binding; Magnesium; Mitochondrion; NAD; Nucleotide-binding; Nucleotidyltransferase; Pyridine nucleotide biosynthesis; Transferase.
Features
SEVIEWER logo Feature table viewer
KeyFrom   To Length Description FTId
CHAIN   1   252  252     Nicotinamide mononucleotide adenylyltransferase 3. PRO_0000135016
NP_BIND   13    22  10     ATP (Potential). 
NP_BIND   201   206  6     ATP (Potential). 
BINDING   14    14        Substrate. 
BINDING   53    53        Substrate. 
BINDING   137   137        Substrate. 
VAR_SEQ   1    37        Missing (in isoform 2). VSP_010267
CONFLICT   169   169        G -> S (in Ref. 1; AAK52726). 
STRAND   5    13  9      
HELIX   20    35  16      
STRAND   37    48  12      
STRAND   54    56  3      
HELIX   61    71  11      
HELIX   72    74  3      
STRAND   76    80  5      
HELIX   83    86  4      
STRAND   87    89  3      
HELIX   93   104  12      
STRAND   129   135  7      
HELIX   136   141  6      
TURN   145   147  3      
HELIX   150   159  10      
STRAND   162   165  4      
HELIX   172   178  7      
HELIX   180   184  5      
HELIX   186   188  3      
STRAND   189   192  4      
HELIX   202   210  9      
HELIX   221   229  9      
Sequence information
Length: 252 AA [This is the length of the unprocessed precursor] Molecular weight: 28322 Da [This is the MW of the unprocessed precursor] CRC64: 6402CFB2FE789CF4 [This is a checksum on the sequence] 
        10         20         30         40         50         60 
MKSRIPVVLL ACGSFNPITN MHLRMFEVAR DHLHQTGMYQ VIQGIISPVN DTYGKKDLAA 

        70         80         90        100        110        120 
SHHRVAMARL ALQTSDWIRV DPWESEQAQW METVKVLRHH HSKLLRSPPQ MEGPDHGKAL 

       130        140        150        160        170        180 
FSTPAAVPEL KLLCGADVLK TFQTPNLWKD AHIQEIVEKF GLVCVGRVGH DPKGYIAESP 

       190        200        210        220        230        240 
ILRMHQHNIH LAKEPVQNEI SATYIRRALG QGQSVKYLIP DAVITYIKDH GLYTKGSTWK 

       250 
GKSTQSTEGK TS
Q96T66 in FASTA format

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