Q9EPA7 (NMNA1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

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:	D4Cole1e, Nmnat

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	285 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 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+ By similarity. Protects against axonal degeneration following mechanical or toxic insults. Delays axonal degeneration after axotomy. Results in a >10-fold increase in intact neurites 72 hours after injury. Ref.3 Ref.4
Catalytic activity	ATP + nicotinamide ribonucleotide = diphosphate + NAD+. UniProtKB Q9HAN9 ATP + beta-nicotinate-D-ribonucleotide = diphosphate + deamido-NAD+.
Cofactor	Divalent metal cations. Zinc confers higher activity than magnesium By similarity.
Enzyme regulation	Activity is strongly inhibited by galotannin. Inhibited by P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-tetraphosphate (Nap4AD) By similarity.
Pathway	Cofactor biosynthesis; NAD(+) biosynthesis; NAD(+) from nicotinamide D-ribonucleotide: step 1/1.
Subunit structure	Homohexamer. Interacts with ADPRT/PARP1 By similarity. UniProtKB Q9HAN9
Subcellular location	Nucleus Ref.4.
Developmental stage	Expressed throughout development and in adulthood. Ref.4
Induction	By neuronal injury.
Post-translational modification	Phosphorylated By similarity. UniProtKB Q9HAN9
Miscellaneous	In strain C57BL/Ola, an 85 kb region on chromosome 4 containing Nmnat1 and Ube4b is triplicated. The N-terminal 70 residues of Ube4b becomes linked to the complete Nmnat1 protein and encodes a fusion protein located in the nucleus which is responsible for the Wallerian degeneration slow (Wlds) phenotype characterized by delayed Wallerian degeneration of injured axons.
Sequence similarities	Belongs to the eukaryotic NMN adenylyltransferase family.
Biophysicochemical properties	Kinetic parameters: KM=20.1 µM for nicotinamide mononucleotide (NMN) Ref.2 Vmax=34.1 µmol/min/mg enzyme
Sequence caution	The sequence AAG17285.1 differs from that shown. Reason: Erroneous initiation. The sequence AAG17286.1 differs from that shown. Reason: Erroneous initiation. The sequence AAG38490.1 differs from that shown. Reason: Erroneous initiation.

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	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	NAD biosynthetic process Inferred from electronic annotation. Source: UniProtKB-UniPathway
Cellular_component	nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW nicotinamide-nucleotide adenylyltransferase activity Inferred from sequence or structural similarity. Source: UniProtKB nicotinate-nucleotide adenylyltransferase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 285	285	Nicotinamide mononucleotide adenylyltransferase 1		PRO_0000135013
Regions
	Nucleotide binding	15 – 24	10	ATP Potential
	Nucleotide binding	223 – 228	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	159	1	Substrate By similarity
Experimental info
	Mutagenesis	125 – 128	4	RKRK → AAAA: Locates to the cytoplasm. Has no affect on enzyme activity or axonal protection. Ref.4
	Mutagenesis	170	1	W → A: Decrease in enzyme activity. Has no axonal protective effect. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q9EPA7 [UniParc]. Last modified May 9, 2003. Version 2. Checksum: 2769D42E894EB84F	FASTA	285	32,355
	10 20 30 40 50 60 MDSSKKTEVV LLACGSFNPI TNMHLRLFEL AKDYMHATGK YSVIKGIISP VGDAYKKKGL 70 80 90 100 110 120 IPAHHRIIMA ELATKNSHWV EVDTWESLQK EWVETVKVLR YHQEKLATGS CSYPQSSPAL 130 140 150 160 170 180 EKPGRKRKWA DQKQDSSPQK PQEPKPTGVP KVKLLCGADL LESFSVPNLW KMEDITQIVA 190 200 210 220 230 240 NFGLICITRA GSDAQKFIYE SDVLWRHQSN IHLVNEWITN DISSTKIRRA LRRGQSIRYL 250 260 270 280 VPDLVQEYIE KHELYNTESE GRNAGVTLAP LQRNAAEAKH NHSTL

References

[1]	"A Ufd2/D4Cole1e chimeric protein and overexpression of Rbp7 in the slow Wallerian degeneration (WldS) mouse." Conforti L., Tarlton A., Mack T.G.A., Mi W., Buckmaster E.A., Wagner D., Perry V.H., Coleman M.P. Proc. Natl. Acad. Sci. U.S.A. 97:11377-11382(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. Strain: 129, C57BL/6J and C57BL/Ola.
[2]	"The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells." Revollo J.R., Grimm A.A., Imai S. J. Biol. Chem. 279:50754-50763(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], BIOPHYSICOCHEMICAL PROPERTIES. Strain: BALB/c. Tissue: Liver.
[3]	"Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration." Araki T., Sasaki Y., Milbrandt J. Science 305:1010-1013(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF TRP-170.
[4]	"Stimulation of nicotinamide adenine dinucleotide biosynthetic pathways delays axonal degeneration after axotomy." Sasaki Y., Araki T., Milbrandt J. J. Neurosci. 26:8484-8491(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, MUTAGENESIS OF 125-ARG--LYS-128.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF260924 mRNA. Translation: AAG17285.1. Different initiation. AF260925 mRNA. Translation: AAG17286.1. Different initiation. AF260927 Genomic DNA. Translation: AAG38490.1. Different initiation. AY679721 mRNA. Translation: AAT76443.1.
IPI	IPI00109667.
RefSeq	NP_597679.1. NM_133435.1.
UniGene	Mm.76062.
3D structure databases
ProteinModelPortal	Q9EPA7.
SMR	Q9EPA7. Positions 6-276.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000030845.
PTM databases
PhosphoSite	Q9EPA7.
Proteomic databases
PaxDb	Q9EPA7.
PRIDE	Q9EPA7.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000030845; ENSMUSP00000030845; ENSMUSG00000028992. ENSMUST00000105693; ENSMUSP00000101318; ENSMUSG00000028992.
GeneID	66454.
KEGG	mmu:66454.
UCSC	uc008vwj.1. mouse.
Organism-specific databases
CTD	64802.
MGI	MGI:1913704. Nmnat1.
Phylogenomic databases
eggNOG	COG1057.
GeneTree	ENSGT00530000063189.
HOGENOM	HOG000216047.
HOVERGEN	HBG052640.
InParanoid	Q9EPA7.
KO	K06210.
OMA	LISAHHR.
OrthoDB	EOG48SGV2.
Enzyme and pathway databases
BRENDA	2.7.7.1. 3474.
SABIO-RK	Q9EPA7.
UniPathway	UPA00253; UER00600.
Gene expression databases
ArrayExpress	Q9EPA7.
Bgee	Q9EPA7.
CleanEx	MM_NMNAT1.
Genevestigator	Q9EPA7.
GermOnline	ENSMUSG00000028992. Mus musculus.
Family and domain databases
Gene3D	3.40.50.620. 1 hit.
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]
TIGRFAMs	TIGR00482. TIGR00482. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	NMNAT1. mouse.
NextBio	321736.
SOURCE	Search...

Entry information

Entry name

NMNA1_MOUSE

Accession

Primary (citable) accession number: Q9EPA7
Secondary accession number(s): Q6B504

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 9, 2003
Last sequence update:	May 9, 2003
Last modified:	May 29, 2013
This is version 94 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program