Q96T66 (NMNA3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	252 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. 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

Ontologies

Keywords
Biological process	Pyridine nucleotide biosynthesis
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Magnesium NAD Nucleotide-binding
Molecular function	Nucleotidyltransferase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	NAD biosynthetic process Inferred by curator Ref.6. Source: UniProtKB response to wounding Inferred from electronic annotation. Source: Compara water-soluble vitamin metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome mitochondrion Inferred from direct assay Ref.6. Source: UniProtKB
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.6. Source: UniProtKB
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 252

252

Nicotinamide mononucleotide adenylyltransferase 3

PRO_0000135016

Regions

Nucleotide binding

13 – 22

10

ATP Potential

Nucleotide binding

201 – 206

6

ATP Potential

Sites

Binding site

14

1

Substrate

Binding site

53

1

Substrate

Binding site

137

1

Substrate

Natural variations

Alternative sequence

1 – 37

37

Missing in isoform 2.

VSP_010267

Alternative sequence

37 – 125

89

Missing in isoform 3.

VSP_043203

Experimental info

Sequence conflict

169

1

G → S in AAK52726. Ref.1

Secondary structure

1

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252

Helix Strand Turn

Details...

Beta strand

5 – 13

9

Helix

20 – 35

16

Beta strand

37 – 48

12

Beta strand

54 – 56

3

Helix

61 – 71

11

Helix

72 – 74

3

Beta strand

76 – 80

5

Helix

83 – 86

4

Beta strand

87 – 89

3

Helix

93 – 104

12

Beta strand

129 – 135

7

Helix

136 – 141

6

Turn

145 – 147

3

Helix

150 – 159

10

Beta strand

162 – 165

4

Helix

172 – 178

7

Helix

180 – 184

5

Helix

186 – 188

3

Beta strand

189 – 192

4

Helix

202 – 210

9

Helix

221 – 229

9

Turn

230 – 233

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 17, 2006. Version 2. Checksum: 6402CFB2FE789CF4	FASTA	252	28,322
	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
	Isoform 2 [UniParc]. Checksum: 0E445A25C77E1800	FASTA	215	24,119
	10 20 30 40 50 60 MYQVIQGIIS PVNDTYGKKD LAASHHRVAM ARLALQTSDW IRVDPWESEQ AQWMETVKVL 70 80 90 100 110 120 RHHHSKLLRS PPQMEGPDHG KALFSTPAAV PELKLLCGAD VLKTFQTPNL WKDAHIQEIV 130 140 150 160 170 180 EKFGLVCVGR VGHDPKGYIA ESPILRMHQH NIHLAKEPVQ NEISATYIRR ALGQGQSVKY 190 200 210 LIPDAVITYI KDHGLYTKGS TWKGKSTQST EGKTS
	Isoform 3 [UniParc]. Checksum: 0E9550BF1ADADFF2	FASTA	163	18,255
	10 20 30 40 50 60 MKSRIPVVLL ACGSFNPITN MHLRMFEVAR DHLHQTAVPE LKLLCGADVL KTFQTPNLWK 70 80 90 100 110 120 DAHIQEIVEK FGLVCVGRVG HDPKGYIAES PILRMHQHNI HLAKEPVQNE ISATYIRRAL 130 140 150 160 GQGQSVKYLI PDAVITYIKD HGLYTKGSTW KGKSTQSTEG KTS

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.

IPI

IPI00290687.
IPI00410337.
IPI00797651.

RefSeq

NP_001186976.1. NM_001200047.1.
NP_835471.1. NM_178177.3.

UniGene

Hs.208673.
Hs.733090.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NUP	X-ray	1.90	A/B	1-252	[»]
1NUQ	X-ray	1.90	A/B	1-252	[»]
1NUR	X-ray	2.15	A/B	1-252	[»]
1NUS	X-ray	2.20	A/B	1-252	[»]
1NUT	X-ray	1.90	A/B	1-252	[»]
1NUU	X-ray	1.90	A/B	1-252	[»]

ProteinModelPortal

Q96T66.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000340523.

PTM databases

PhosphoSite

Q96T66.

Polymorphism databases

DMDM

116242680.

Proteomic databases

PaxDb

Q96T66.

PRIDE

Q96T66.

Protocols and materials databases

DNASU

349565.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000296202; ENSP00000296202; ENSG00000163864.
ENST00000339837; ENSP00000340523; ENSG00000163864.
ENST00000406164; ENSP00000384319; ENSG00000163864.
ENST00000413939; ENSP00000412953; ENSG00000163864.

GeneID

349565.

KEGG

hsa:349565.

UCSC

uc003etj.3. human.

Organism-specific databases

CTD

349565.

GeneCards

GC03M139279.

HGNC

HGNC:20989. NMNAT3.

MIM

608702. gene.

neXtProt

NX_Q96T66.

PharmGKB

PA134952303.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1057.

HOGENOM

HOG000216047.

HOVERGEN

HBG052640.

InParanoid

Q96T66.

KO

K06210.

OMA

QTGMYQV.

PhylomeDB

Q96T66.

Enzyme and pathway databases

BRENDA

2.7.7.1. 2681.

Reactome

REACT_111217. Metabolism.

SABIO-RK

Q96T66.

UniPathway

UPA00253; UER00600.

Gene expression databases

ArrayExpress

Q96T66.

Bgee

Q96T66.

CleanEx

HS_NMNAT3.

Genevestigator

Q96T66.

GermOnline

ENSG00000163864. Homo sapiens.

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

EvolutionaryTrace

Q96T66.

GenomeRNAi

349565.

NextBio

99518.

SOURCE

Search...

Entry information

Entry name

NMNA3_HUMAN

Accession

Primary (citable) accession number: Q96T66
Secondary accession number(s): B3KVR6 , D3DNF2, D3DNF3, Q8N4G1

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2004
Last sequence update:	October 17, 2006
Last modified:	May 1, 2013
This is version 97 of the entry and version 2 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.