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Q9BZQ4 (NMNA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | 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 2

Short name=NMN adenylyltransferase 2
EC=2.7.7.1
Alternative name(s):
Nicotinate-nucleotide adenylyltransferase 2
Short name=NaMN adenylyltransferase 2
EC=2.7.7.18
Gene names
Name:NMNAT2
Synonyms:C1orf15, KIAA0479
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length307 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 but with a lower efficiency. Cannot use triazofurin monophosphate (TrMP) as substrate. Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD+. For the pyrophosphorolytic activity prefers NAD+, NADH and NAAD as substrates and degrades nicotinic acid adenine dinucleotide phosphate (NHD) less effectively. Fails to cleave phosphorylated dinucleotides NADP+, NADPH and NAADP+. Ref.7 Ref.8

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.5 Ref.6 Ref.8

Enzyme regulation

Inhibited by P1-(adenosine-5')-P3-(nicotinamide-riboside-5')-triphosphate (Np3AD) and P1-(adenosine-5')-P4-(nicotinamide-riboside-5')-tetraphosphate (Np4AD). Ref.8

Pathway

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

Subunit structure

Monomer. Ref.5

Subcellular location

Cytoplasm. Golgi apparatus Ref.7.

Tissue specificity

Highly expressed in brain, in particular in cerebrum, cerebellum, occipital lobe, frontal lobe, temporal lobe and putamen. Also found in the heart, skeletal muscle, pancreas and islets of Langerhans. Ref.5 Ref.6 Ref.7

Sequence similarities

Belongs to the eukaryotic NMN adenylyltransferase family.

Biophysicochemical properties

Kinetic parameters:

KM is >100 µM for triazofurin monophosphate.

KM=32 µM for NMN Ref.7 Ref.8

KM=70 µM for NAD+

KM=204 µM for ATP

KM=1119 µM for PPi

KM=14.5 µM for NaMN

KM=304 µM for NMNH

Vmax=1.1 µmol/min/mg enzyme for NAD synthesis

Vmax=3 µmol/min/mg enzyme for pyrophosphorolytic NAD+ cleavage

Vmax=7 µmol/min/mg enzyme for pyrophosphorolytic NADH cleavage

pH dependence:

Optimum pH is 6.0-9.0.

Sequence caution

The sequence BAA32324.1 differs from that shown. Reason: Erroneous initiation.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9BZQ4-1)

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: Q9BZQ4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-28: MTETTKTHVILLACGSFNPITKGHIQMF → MEIQELEEIQACQGLWEVFVTLS
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 307307Nicotinamide mononucleotide adenylyltransferase 2
PRO_0000135014

Regions

Nucleotide binding15 – 2410ATP Potential
Nucleotide binding269 – 2746ATP Potential

Sites

Binding site161Substrate By similarity
Binding site551Substrate By similarity
Binding site2021Substrate By similarity

Natural variations

Alternative sequence1 – 2828MTETT…HIQMF → MEIQELEEIQACQGLWEVFV TLS in isoform 2.
VSP_015571

Experimental info

Mutagenesis241H → A: Reduces activity by 95%. Ref.6
Mutagenesis921W → G: Reduces activity by 95%. Ref.6

Sequences

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

Last modified June 1, 2001. Version 1.
Checksum: 702F1C74B38ECECB

FASTA30734,439
        10         20         30         40         50         60 
MTETTKTHVI LLACGSFNPI TKGHIQMFER ARDYLHKTGR FIVIGGIVSP VHDSYGKQGL 

        70         80         90        100        110        120 
VSSRHRLIMC QLAVQNSDWI RVDPWECYQD TWQTTCSVLE HHRDLMKRVT GCILSNVNTP 

       130        140        150        160        170        180 
SMTPVIGQPQ NETPQPIYQN SNVATKPTAA KILGKVGESL SRICCVRPPV ERFTFVDENA 

       190        200        210        220        230        240 
NLGTVMRYEE IELRILLLCG SDLLESFCIP GLWNEADMEV IVGDFGIVVV PRDAADTDRI 

       250        260        270        280        290        300 
MNHSSILRKY KNNIMVVKDD INHPMSVVSS TKSRLALQHG DGHVVDYLSQ PVIDYILKSQ 


LYINASG 

« Hide

Isoform 2 [UniParc].

Checksum: 782C9FB1D5B0E153
Show »

FASTA30234,015

References

« Hide 'large scale' references
[1]"Cloning and characterization of 13 novel transcripts and the human RGS8 gene from the 1q25 region encompassing the hereditary prostate cancer (HPC1) locus."
Sood R., Bonner T.I., Malakowska I., Stephan D.A., Robbins C.M., Connors T.D., Morgenbesser S.D., Su K., Faruque M.U., Pinkett H., Graham C., Baxevanis A.D., Klinger K.W., Landes G.M., Trent J.M., Carpten J.D.
Genomics 73:211-222(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Characterization of cDNA clones in size-fractionated cDNA libraries from human brain."
Seki N., Ohira M., Nagase T., Ishikawa K., Miyajima N., Nakajima D., Nomura N., Ohara O.
DNA Res. 4:345-349(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[3]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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: Lung carcinoma.
[5]"Identification of a novel human nicotinamide mononucleotide adenylyltransferase."
Raffaelli N., Sorci L., Amici A., Emanuelli M., Mazzola F., Magni G.
Biochem. Biophys. Res. Commun. 297:835-840(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT, COFACTOR, TISSUE SPECIFICITY, PH DEPENDENCE.
[6]"Characterization of human brain nicotinamide 5'-mononucleotide adenylyltransferase-2 and expression in human pancreas."
Yalowitz J.A., Xiao S., Biju M.P., Antony A.C., Cummings O.W., Deeg M.A., Jayaram H.N.
Biochem. J. 377:317-326(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF HIS-24 AND TRP-92, COFACTOR, TISSUE SPECIFICITY.
[7]"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.
[8]"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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF288395 mRNA. Translation: AAG60615.1.
AB007948 mRNA. Translation: BAA32324.1. Different initiation.
AL354953, AL356981 Genomic DNA. Translation: CAH70979.1.
AL354953, AL356981, AL449223 Genomic DNA. Translation: CAH70982.1.
AL356981, AL354953 Genomic DNA. Translation: CAI15467.1.
AL356981, AL354953, AL449223 Genomic DNA. Translation: CAI15468.1.
AL449223, AL354953, AL356981 Genomic DNA. Translation: CAI16624.1.
BC020998 mRNA. Translation: AAH20998.1.
CCDSCCDS1353.1. [Q9BZQ4-1]
CCDS1354.1. [Q9BZQ4-2]
RefSeqNP_055854.1. NM_015039.3. [Q9BZQ4-1]
NP_733820.1. NM_170706.3. [Q9BZQ4-2]
UniGeneHs.497123.

3D structure databases

ProteinModelPortalQ9BZQ4.
SMRQ9BZQ4. Positions 9-109, 197-302.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116693. 1 interaction.
DIPDIP-60169N.
STRING9606.ENSP00000287713.

PTM databases

PhosphoSiteQ9BZQ4.

Polymorphism databases

DMDM30580486.

Proteomic databases

PaxDbQ9BZQ4.
PRIDEQ9BZQ4.

Protocols and materials databases

DNASU23057.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000287713; ENSP00000287713; ENSG00000157064. [Q9BZQ4-1]
ENST00000294868; ENSP00000294868; ENSG00000157064. [Q9BZQ4-2]
GeneID23057.
KEGGhsa:23057.
UCSCuc001gqb.2. human. [Q9BZQ4-2]
uc001gqc.2. human. [Q9BZQ4-1]

Organism-specific databases

CTD23057.
GeneCardsGC01M183217.
HGNCHGNC:16789. NMNAT2.
HPAHPA015240.
MIM608701. gene.
neXtProtNX_Q9BZQ4.
PharmGKBPA25604.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1057.
HOGENOMHOG000216047.
HOVERGENHBG052640.
InParanoidQ9BZQ4.
KOK06210.
OMAPMERFTF.
OrthoDBEOG7PVWPQ.
PhylomeDBQ9BZQ4.
TreeFamTF315035.

Enzyme and pathway databases

BioCycMetaCyc:HS08173-MONOMER.
BRENDA2.7.7.1. 2681.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
SABIO-RKQ9BZQ4.
UniPathwayUPA00253; UER00600.

Gene expression databases

BgeeQ9BZQ4.
CleanExHS_NMNAT2.
GenevestigatorQ9BZQ4.

Family and domain databases

Gene3D3.40.50.620. 2 hits.
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]
ProtoNetSearch...

Other

ChiTaRSNMNAT2. human.
GeneWikiNMNAT2.
GenomeRNAi23057.
NextBio44115.
PROQ9BZQ4.
SOURCESearch...

Entry information

Entry nameNMNA2_HUMAN
AccessionPrimary (citable) accession number: Q9BZQ4
Secondary accession number(s): O75067 expand/collapse secondary AC list , Q5T1Q3, Q8WU99, Q96QW1
Entry history
Integrated into UniProtKB/Swiss-Prot: May 9, 2003
Last sequence update: June 1, 2001
Last modified: July 9, 2014
This is version 107 of the entry and version 1 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

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 1

Human chromosome 1: entries, gene names and cross-references to MIM