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Q96T66 (NMNA3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Nicotinamide mononucleotide adenylyltransferase 3

Short name=NMN adenylyltransferase 3
Alternative name(s):
Nicotinate-nucleotide adenylyltransferase 3
Short name=NaMN adenylyltransferase 3
EC=2.7.7.18
Pyridine nucleotide adenylyltransferase 3
Short name=PNAT-3
EC=2.7.7.1
Gene names
Name:NMNAT3
ORF Names:FKSG76
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length252 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (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. Ref.6 Ref.7

Catalytic activity

ATP + nicotinamide ribonucleotide = diphosphate + NAD+.

ATP + beta-nicotinate-D-ribonucleotide = diphosphate + deamido-NAD+.

Cofactor

Divalent metal cations. Magnesium confers the highest activity. Ref.7

Enzyme regulation

Activity is strongly inhibited by galotannin. Inhibited by P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-tetraphosphate (Nap4AD). Ref.7

Pathway

Cofactor biosynthesis; NAD(+) biosynthesis; NAD(+) from nicotinamide D-ribonucleotide: step 1/1.

Subunit structure

Homotetramer. Ref.8

Subcellular location

Mitochondrion Ref.6 Ref.8.

Tissue specificity

Expressed in lung and spleen with lower levels in placenta and kidney. Ref.6 Ref.8

Sequence similarities

Belongs to the eukaryotic NMN adenylyltransferase family.

Biophysicochemical properties

Kinetic parameters:

KM=209 µM for NMN Ref.6 Ref.7

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

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q96T66-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q96T66-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-37: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q96T66-3)

The sequence of this isoform differs from the canonical sequence as follows:
     37-125: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 252252Nicotinamide mononucleotide adenylyltransferase 3
PRO_0000135016

Regions

Nucleotide binding13 – 2210ATP Potential
Nucleotide binding201 – 2066ATP Potential

Sites

Binding site141Substrate
Binding site531Substrate
Binding site1371Substrate

Natural variations

Alternative sequence1 – 3737Missing in isoform 2.
VSP_010267
Alternative sequence37 – 12589Missing in isoform 3.
VSP_043203

Experimental info

Sequence conflict1691G → S in AAK52726. Ref.1

Secondary structure

........................................ 252
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 17, 2006. Version 2.
Checksum: 6402CFB2FE789CF4

FASTA25228,322
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 0E445A25C77E1800
Show »

FASTA21524,119
Isoform 3 [UniParc].

Checksum: 0E9550BF1ADADFF2
Show »

FASTA16318,255

References

« Hide 'large scale' references
[1]"Identification of FKSG76, a novel gene encoding a NMN adenylyltransferase."
Wang Y.-G., Gong L.
Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
Tissue: Brain cortex.
[3]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Colon and Kidney.
[6]"Subcellular compartmentation and differential catalytic properties of the three human nicotinamide mononucleotide adenylyltransferase isoforms."
Berger F., Lau C., Dahlmann M., Ziegler M.
J. Biol. Chem. 280:36334-36341(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[7]"Initial-rate kinetics of human NMN-adenylyltransferases: substrate and metal ion specificity, inhibition by products and multisubstrate analogues, and isozyme contributions to NAD+ biosynthesis."
Sorci L., Cimadamore F., Scotti S., Petrelli R., Cappellacci L., Franchetti P., Orsomando G., Magni G.
Biochemistry 46:4912-4922(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, COFACTOR.
[8]"Structural characterization of a human cytosolic NMN/NaMN adenylyltransferase and implication in human NAD biosynthesis."
Zhang X., Kurnasov O.V., Karthikeyan S., Grishin N.V., Osterman A.L., Zhang H.
J. Biol. Chem. 278:13503-13511(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH NMN; NAD AND ATP ANALOG, SUBCELLULAR LOCATION, SUBUNIT, TISSUE SPECIFICITY.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF345564 mRNA. Translation: AAK52726.1.
AK123208 mRNA. Translation: BAG53878.1.
AC046134 Genomic DNA. No translation available.
AC110716 Genomic DNA. No translation available.
CH471052 Genomic DNA. Translation: EAW79023.1.
CH471052 Genomic DNA. Translation: EAW79024.1.
CH471052 Genomic DNA. Translation: EAW79025.1.
CH471052 Genomic DNA. Translation: EAW79030.1.
CH471052 Genomic DNA. Translation: EAW79031.1.
BC034374 mRNA. Translation: AAH34374.1.
RefSeqNP_001186976.1. NM_001200047.1.
NP_835471.1. NM_178177.3.
UniGeneHs.208673.
Hs.745268.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1NUPX-ray1.90A/B1-252[»]
1NUQX-ray1.90A/B1-252[»]
1NURX-ray2.15A/B1-252[»]
1NUSX-ray2.20A/B1-252[»]
1NUTX-ray1.90A/B1-252[»]
1NUUX-ray1.90A/B1-252[»]
ProteinModelPortalQ96T66.
SMRQ96T66. Positions 3-235.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000340523.

PTM databases

PhosphoSiteQ96T66.

Polymorphism databases

DMDM116242680.

Proteomic databases

PaxDbQ96T66.
PRIDEQ96T66.

Protocols and materials databases

DNASU349565.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000296202; ENSP00000296202; ENSG00000163864. [Q96T66-1]
ENST00000339837; ENSP00000340523; ENSG00000163864. [Q96T66-2]
ENST00000406164; ENSP00000384319; ENSG00000163864. [Q96T66-2]
ENST00000413939; ENSP00000412953; ENSG00000163864. [Q96T66-3]
GeneID349565.
KEGGhsa:349565.
UCSCuc003etj.3. human. [Q96T66-1]
uc010hul.3. human. [Q96T66-3]

Organism-specific databases

CTD349565.
GeneCardsGC03M139279.
HGNCHGNC:20989. NMNAT3.
HPAHPA057402.
MIM608702. gene.
neXtProtNX_Q96T66.
PharmGKBPA134952303.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1057.
HOGENOMHOG000216047.
HOVERGENHBG052640.
InParanoidQ96T66.
KOK06210.
OMAGYIAESP.
PhylomeDBQ96T66.
TreeFamTF315035.

Enzyme and pathway databases

BRENDA2.7.7.1. 2681.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
SABIO-RKQ96T66.
UniPathwayUPA00253; UER00600.

Gene expression databases

ArrayExpressQ96T66.
BgeeQ96T66.
CleanExHS_NMNAT3.
GenevestigatorQ96T66.

Family and domain databases

Gene3D3.40.50.620. 1 hit.
InterProIPR004821. Cyt_trans-like.
IPR005248. NAMN_adtrnsfrase.
IPR014729. Rossmann-like_a/b/a_fold.
[Graphical view]
PANTHERPTHR12039. PTHR12039. 1 hit.
PfamPF01467. CTP_transf_2. 1 hit.
[Graphical view]
TIGRFAMsTIGR00482. TIGR00482. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceQ96T66.
GenomeRNAi349565.
NextBio99518.
PROQ96T66.
SOURCESearch...

Entry information

Entry nameNMNA3_HUMAN
AccessionPrimary (citable) accession number: Q96T66
Secondary accession number(s): B3KVR6 expand/collapse secondary AC list , D3DNF2, D3DNF3, Q8N4G1
Entry history
Integrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: October 17, 2006
Last modified: April 16, 2014
This is version 106 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM