Q9BZQ4 (NMNA2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	307 AA.
Sequence status	Complete.
Protein existence	Evidence 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.

Ontologies

Keywords
Biological process	Pyridine nucleotide biosynthesis
Cellular component	Cytoplasm Golgi apparatus
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Magnesium NAD Nucleotide-binding
Molecular function	Nucleotidyltransferase Transferase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	NAD biosynthetic process Inferred by curator Ref.7. Source: UniProtKB water-soluble vitamin metabolic process Traceable author statement. Source: Reactome
Cellular_component	Golgi membrane Traceable author statement. Source: Reactome late endosome Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay. Source: HPA synapse Inferred from electronic annotation. Source: Compara trans-Golgi network Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW nicotinamide-nucleotide adenylyltransferase activity Traceable author statement. Source: Reactome nicotinate-nucleotide adenylyltransferase activity Inferred from direct assay Ref.7. Source: UniProtKB
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 307	307	Nicotinamide mononucleotide adenylyltransferase 2		PRO_0000135014
Regions
	Nucleotide binding	15 – 24	10	ATP Potential
	Nucleotide binding	269 – 274	6	ATP Potential
Sites
	Binding site	16	1	Substrate By similarity
	Binding site	55	1	Substrate By similarity
	Binding site	202	1	Substrate By similarity
Natural variations
	Alternative sequence	1 – 28	28	MTETT…HIQMF → MEIQELEEIQACQGLWEVFV TLS in isoform 2.		VSP_015571
Experimental info
	Mutagenesis	24	1	H → A: Reduces activity by 95%. Ref.6
	Mutagenesis	92	1	W → G: Reduces activity by 95%. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2001. Version 1. Checksum: 702F1C74B38ECECB	FASTA	307	34,439
	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
	Isoform 2 [UniParc]. Checksum: 782C9FB1D5B0E153	FASTA	302	34,015
	10 20 30 40 50 60 MEIQELEEIQ ACQGLWEVFV TLSERARDYL HKTGRFIVIG GIVSPVHDSY GKQGLVSSRH 70 80 90 100 110 120 RLIMCQLAVQ NSDWIRVDPW ECYQDTWQTT CSVLEHHRDL MKRVTGCILS NVNTPSMTPV 130 140 150 160 170 180 IGQPQNETPQ PIYQNSNVAT KPTAAKILGK VGESLSRICC VRPPVERFTF VDENANLGTV 190 200 210 220 230 240 MRYEEIELRI LLLCGSDLLE SFCIPGLWNE ADMEVIVGDF GIVVVPRDAA DTDRIMNHSS 250 260 270 280 290 300 ILRKYKNNIM VVKDDINHPM SVVSSTKSRL ALQHGDGHVV DYLSQPVIDY ILKSQLYINA SG

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI00102878. IPI00289183.
RefSeq	NP_055854.1. NM_015039.3. NP_733820.1. NM_170706.3.
UniGene	Hs.497123.
3D structure databases
ProteinModelPortal	Q9BZQ4.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000287713.
PTM databases
PhosphoSite	Q9BZQ4.
Polymorphism databases
DMDM	30580486.
Proteomic databases
PaxDb	Q9BZQ4.
PRIDE	Q9BZQ4.
Protocols and materials databases
DNASU	23057.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000287713; ENSP00000287713; ENSG00000157064. ENST00000294868; ENSP00000294868; ENSG00000157064.
GeneID	23057.
KEGG	hsa:23057.
UCSC	uc001gqb.2. human. uc001gqc.2. human.
Organism-specific databases
CTD	23057.
GeneCards	GC01M183217.
HGNC	HGNC:16789. NMNAT2.
HPA	HPA015240.
MIM	608701. gene.
neXtProt	NX_Q9BZQ4.
PharmGKB	PA25604.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1057.
HOGENOM	HOG000216047.
HOVERGEN	HBG052640.
InParanoid	Q9BZQ4.
KO	K06210.
OMA	PMERFTF.
OrthoDB	EOG4N30PB.
PhylomeDB	Q9BZQ4.
Enzyme and pathway databases
BRENDA	2.7.7.1. 2681.
Reactome	REACT_111217. Metabolism.
SABIO-RK	Q9BZQ4.
UniPathway	UPA00253; UER00600.
Gene expression databases
Bgee	Q9BZQ4.
CleanEx	HS_NMNAT2.
Genevestigator	Q9BZQ4.
GermOnline	ENSG00000157064. Homo sapiens.
Family and domain databases
Gene3D	3.40.50.620. 2 hits.
InterPro	IPR004821. Cyt_trans-like. IPR005248. NAMN_adtrnsfrase. IPR014729. Rossmann-like_a/b/a_fold. [Graphical view]
PANTHER	PTHR12039. PTHR12039. 1 hit.
Pfam	PF01467. CTP_transf_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	NMNAT2. human.
GenomeRNAi	23057.
NextBio	44115.
SOURCE	Search...

Entry information

Entry name

NMNA2_HUMAN

Accession

Primary (citable) accession number: Q9BZQ4
Secondary accession number(s): O75067 , Q5T1Q3, Q8WU99, Q96QW1

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 9, 2003
Last sequence update:	June 1, 2001
Last modified:	May 1, 2013
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.