Reviewed, UniProtKB/Swiss-Prot Q9HAN9 (NMNA1_HUMAN)

Names and origin

Protein names

Recommended name:
    Nicotinamide mononucleotide adenylyltransferase 1
      Short name=NMN adenylyltransferase 1
    EC=2.7.7.1
Alternative name(s):
    Nicotinate-nucleotide adenylyltransferase 1
      Short name=NaMN adenylyltransferase 1
    EC=2.7.7.18

Gene names

Name:	NMNAT1
Synonyms:	NMNAT

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	279 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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 with the same efficiency. Can use triazofurin monophosphate (TrMP) as substrate. Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD+. For the pyrophosphorolytic activity, prefers NAD+ and NAAD as substrates and degrades NADH, nicotinic acid adenine dinucleotide phosphate (NHD) and nicotinamide guanine dinucleotide (NGD) less effectively. Fails to cleave phosphorylated dinucleotides NADP+, NADPH and NAADP+. Protects against axonal degeneration following mechanical or toxic insults. Ref.9
Catalytic activity	ATP + nicotinamide ribonucleotide = diphosphate + NAD+. Ref.2 ATP + nicotinate ribonucleotide = diphosphate + deamido-NAD+.
Cofactor	Divalent metal cations. Zinc confers higher activity as compared to magnesium. Ref.9 Ref.2
Enzyme regulation	Activity is strongly inhibited by galotannin. Inhibited by P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-tetraphosphate (Nap4AD). Ref.9
Pathway	Cofactor biosynthesis; NAD(+) biosynthesis; NAD(+) from nicotinamide D-ribonucleotide: step 1/1.
Subunit structure	Homohexamer. Interacts with ADPRT/PARP1. Ref.1 Ref.11
Subcellular location	Nucleus. Ref.1 Ref.6 Ref.7
Tissue specificity	Widely expressed with highest levels in skeletal muscle, heart and kidney. Also expressed in the liver pancreas and placenta. Widely expressed throughout the brain. Ref.2 Ref.3
Post-translational modification	Phosphorylated. Ref.1 Ref.8
Sequence similarities	Belongs to the eukaryotic NMN adenylyltransferase family.
Biophysicochemical properties	Kinetic parameters: KM=34 µM for NMN KM=40 µM for ATP KM=937 µM for PPi KM=59 µM for NAD+ Vmax=25 µmol/min/mg enzyme for NAD synthesis Vmax=60.5 µmol/min/µg enzyme for NAD+ cleavage Vmax=8.5 µmol/min/µg enzyme for NADH cleavage

Ontologies

Keywords
Biological process	Pyridine nucleotide biosynthesis
Cellular component	Nucleus
Ligand	ATP-binding Magnesium NAD Nucleotide-binding Zinc
Molecular function	Nucleotidyltransferase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	NAD biosynthetic process Ref.7 Inferred by curator. Source: UniProtKB
Cellular component	nucleus Ref.1 Ref.7 Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW magnesium ion binding Inferred from electronic annotation. Source: UniProtKB-KW nicotinamide-nucleotide adenylyltransferase activity Ref.2 Inferred from direct assay. Source: UniProtKB nicotinate-nucleotide adenylyltransferase activity Ref.7 Inferred from direct assay. Source: UniProtKB protein binding Ref.1 Inferred from physical interaction. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 279

279

Nicotinamide mononucleotide adenylyltransferase 1

PRO_0000135012

Regions

Nucleotide binding

15 – 24

10

ATP Potential

Nucleotide binding

222 – 227

6

ATP Potential

Motif

123 – 129

7

Nuclear localization signal Potential

Sites

Binding site

16

1

Substrate By similarity

Binding site

55

1

Substrate By similarity

Binding site

158

1

Substrate By similarity

Amino acid modifications

Modified residue

119

1

Phosphothreonine Ref.8

Experimental info

Sequence conflict

20

1

I → F in AAL76934. Ref.2

Sequence conflict

20

1

I → F in AAL76935. Ref.2

Sequence conflict

217

1

I → F in AAG33629. Ref.3

Secondary structure

1

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279

Helix Strand Turn

Details...

Beta strand

7 – 15

9

Helix

22 – 37

16

Beta strand

39 – 50

12

Helix

53 – 55

3

Helix

63 – 73

11

Turn

74 – 76

3

Beta strand

78 – 82

5

Helix

86 – 88

3

Helix

95 – 106

12

Beta strand

150 – 156

7

Helix

157 – 162

6

Turn

166 – 168

3

Helix

171 – 180

10

Beta strand

183 – 188

6

Helix

190 – 198

9

Helix

201 – 205

5

Helix

206 – 209

4

Beta strand

210 – 214

5

Helix

223 – 231

9

Helix

242 – 251

10

Helix

256 – 259

4

Turn

260 – 264

5

Helix

268 – 274

7

Sequences

	Sequence		Length	Mass (Da)
	Q9HAN9-1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 740DE872CD9C22E7	FASTA	279	31,932
	10 20 30 40 50 60 MENSEKTEVV LLACGSFNPI TNMHLRLFEL AKDYMNGTGR YTVVKGIISP VGDAYKKKGL 70 80 90 100 110 120 IPAYHRVIMA ELATKNSKWV EVDTWESLQK EWKETLKVLR HHQEKLEASD CDHQQNSPTL 130 140 150 160 170 180 ERPGRKRKWT ETQDSSQKKS LEPKTKAVPK VKLLCGADLL ESFAVPNLWK SEDITQIVAN 190 200 210 220 230 240 YGLICVTRAG NDAQKFIYES DVLWKHRSNI HVVNEWIAND ISSTKIRRAL RRGQSIRYLV 250 260 270 PDLVQEYIEK HNLYSSESED RNAGVILAPL QRNTAEAKT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of recombinant human nicotinamide mononucleotide adenylyl transferase (NMNAT), a nuclear enzyme essential for NAD synthesis." Schweiger M., Hennig K., Lerner F., Niere M., Hirsch-Kauffmann M., Specht T., Weise C., Oei S.L., Ziegler M. FEBS Lett. 492:95-100(2001) [PubMed: 11248244] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 208-225 AND 262-272, SUBCELLULAR LOCATION, PHOSPHORYLATION, INTERACTION WITH ADPRT.
[2]	"Molecular cloning, chromosomal localization, tissue mRNA levels, bacterial expression, and enzymatic properties of human NMN adenylyltransferase." Emanuelli M., Carnevali F., Saccucci F., Pierella F., Amici A., Raffaelli N., Magni G. J. Biol. Chem. 276:406-412(2001) [PubMed: 11027696] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 238-250 AND 262-272, COFACTOR, TISSUE SPECIFICITY. Tissue: Placenta.
[3]	"Human homologue of a gene mutated in the slow Wallerian degeneration (C57BL/Wld(s)) mouse." Fernando F.S., Conforti L., Tosi S., Smith A.D., Coleman M.P. Gene 284:23-29(2002) [PubMed: 11891043] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], TISSUE SPECIFICITY.
[4]	"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. , 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Eye.
[6]	"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: 12574164] [Abstract] Cited for: SUBCELLULAR LOCATION.
[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: 16118205] [Abstract] Cited for: BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION.
[8]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-119, MASS SPECTROMETRY. Tissue: Epithelium.
[9]	"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: 17402747] [Abstract] Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, ENZYME REGULATION, COFACTOR.
[10]	"Crystal structure of human nicotinamide mononucleotide adenylyltransferase in complex with NMN." Werner E., Ziegler M., Lerner F., Schweiger M., Heinemann U. FEBS Lett. 516:239-244(2002) [PubMed: 11959140] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 5-278.
[11]	"Structure of human NMN adenylyltransferase. A key nuclear enzyme for NAD homeostasis." Garavaglia S., D'Angelo I., Emanuelli M., Carnevali F., Pierella F., Magni G., Rizzi M. J. Biol. Chem. 277:8524-8530(2002) [PubMed: 11751893] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
[12]	"Structure of human nicotinamide/nicotinic acid mononucleotide adenylyltransferase. Basis for the dual substrate specificity and activation of the oncolytic agent tiazofurin." Zhou T., Kurnasov O., Tomchick D.R., Binns D.D., Grishin N.V., Marquez V.E., Osterman A.L., Zhang H. J. Biol. Chem. 277:13148-13154(2002) [PubMed: 11788603] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF314163 mRNA. Translation: AAG33632.1.
AF312734 mRNA. Translation: AAG33629.1.
AF459819 mRNA. Translation: AAL76934.1.
AF459823 , AF459820, AF459821, AF459822 Genomic DNA. Translation: AAL76935.1.
AK026065 mRNA. Translation: BAB15345.1.
BC014943 mRNA. Translation: AAH14943.1.

IPI

IPI00009726.

RefSeq

NP_073624.2.

UniGene

Hs.633762

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1GZU	X-ray	2.90	A/B/C	2-279	[»]
1KKU	X-ray	2.50	A	1-279	[»]
1KQN	X-ray	2.20	A/B/C/D/E/F	1-279	[»]
1KQO	X-ray	2.50	A/B/C/D/E/F	1-279	[»]
1KR2	X-ray	2.30	A/B/C/D/E/F	1-279	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

Q9HAN9.

PTM databases

PhosphoSite

Q9HAN9.

Proteomic databases

PeptideAtlas

Q9HAN9.

PRIDE

Q9HAN9.

Genome annotation databases

Ensembl

ENST00000377204; ENSP00000366409; ENSG00000173614; Homo sapiens. [Genome view]
ENST00000377205; ENSP00000366410; ENSG00000173614; Homo sapiens. [Genome view]
ENST00000403197; ENSP00000385131; ENSG00000173614; Homo sapiens. [Genome view]

GeneID

64802.

KEGG

hsa:64802.

NMPDR

fig|9606.3.peg.238.

UCSC

uc001aqp.1. human.

Organism-specific databases

CTD

64802.

GeneCards

GC01P009938.

H-InvDB

HIX0022239.

HGNC

HGNC:17877. NMNAT1.

MIM

608700. gene.

PharmGKB

PA31660.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q9HAN9.

HOVERGEN

Q9HAN9.

OMA

LIPAHHR.

Enzyme and pathway databases

BRENDA

2.7.7.1. 247.

Reactome

REACT_11193. Metabolism of vitamins and cofactors.

Gene expression databases

ArrayExpress

Q9HAN9.

Bgee

Q9HAN9.

CleanEx

HS_NMNAT1.

Genevestigator

Q9HAN9.

GermOnline

ENSG00000173614. Homo sapiens.

Family and domain databases

InterPro

IPR004820. Cytidylyltransf.
IPR005248. NAMN_adtrnsfrase.
IPR014729. Rossmann-like_a/b/a_fold.
[Graphical view]

Gene3D

G3DSA:3.40.50.620. Rossmann-like_a/b/a_fold. 1 hit.

PANTHER

PTHR12039. NAMN_adtrnsfrase. 1 hit.

Pfam

PF01467. CTP_transf_2. 1 hit.
[Graphical view]

TIGRFAMs

TIGR00482. NAMN_adtrnsfrase. 1 hit.

ProtoNet

Search...

Other Resources

NextBio

66892.

SOURCE

Search...

Entry information

Entry name

NMNA1_HUMAN

Accession

Primary (citable) accession number: Q9HAN9
Secondary accession number(s): Q8TAE9, Q9H247, Q9H6B6

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 9, 2003
Last sequence update:	March 1, 2001
Last modified:	November 3, 2009
This is version 72 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.