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Protein

Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 3

Gene

NMNAT3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

ATP + nicotinamide ribonucleotide = diphosphate + NAD+.
ATP + beta-nicotinate-D-ribonucleotide = diphosphate + deamido-NAD+.

Cofactori

Mg2+1 PublicationNote: Divalent metal cations. Mg2+ confers the highest activity.1 Publication

Enzyme regulationi

Activity is strongly inhibited by galotannin. Inhibited by P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-tetraphosphate (Nap4AD).1 Publication

Kineticsi

  1. KM=209 µM for NMN2 Publications
  2. KM=130 µM for NAD+2 Publications
  3. KM=29 µM for ATP2 Publications
  4. KM=390 µM for PPi2 Publications
  5. KM=276 µM for GTP2 Publications
  6. KM=350 µM for ITP2 Publications
  7. KM=111 µM for NaMN2 Publications
  8. KM=130 µM for NMNH2 Publications
  9. KM=2.01 µM for triazofurin monophosphate2 Publications
  1. Vmax=3.6 µmol/min/mg enzyme for NAD synthesis2 Publications
  2. Vmax=12.8 µmol/min/mg enzyme for pyrophosphorolytic NAD+ cleavage2 Publications
  3. Vmax=2.9 µmol/min/mg enzyme for pyrophosphorolytic NADH cleavage2 Publications

Pathwayi: NAD(+) biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes NAD(+) from nicotinamide D-ribonucleotide.
Proteins known to be involved in this subpathway in this organism are:
  1. Nicotinamide-nucleotide adenylyltransferase, Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1 (NMNAT1), Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 3 (NMNAT3), Nicotinamide-nucleotide adenylyltransferase, Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 2 (NMNAT2), Nicotinamide-nucleotide adenylyltransferase (NMNAT1)
This subpathway is part of the pathway NAD(+) biosynthesis, which is itself part of Cofactor biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes NAD(+) from nicotinamide D-ribonucleotide, the pathway NAD(+) biosynthesis and in Cofactor biosynthesis.

Pathwayi: NAD(+) biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes deamido-NAD(+) from nicotinate D-ribonucleotide.
Proteins known to be involved in this subpathway in this organism are:
  1. Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1 (NMNAT1), Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 3 (NMNAT3), Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 2 (NMNAT2)
This subpathway is part of the pathway NAD(+) biosynthesis, which is itself part of Cofactor biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes deamido-NAD(+) from nicotinate D-ribonucleotide, the pathway NAD(+) biosynthesis and in Cofactor biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei22ATP1 Publication1
Binding sitei56ATP1 Publication1
Binding sitei140ATP; shared with dimeric partner1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi13 – 15ATP1 Publication3
Nucleotide bindingi135 – 137ATP1 Publication3
Nucleotide bindingi203 – 206ATP1 Publication4

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Nucleotidyltransferase, Transferase

Keywords - Biological processi

Pyridine nucleotide biosynthesis

Keywords - Ligandi

ATP-binding, Magnesium, NAD, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS08953-MONOMER.
ZFISH:HS08953-MONOMER.
BRENDAi2.7.7.1. 2681.
2.7.7.18. 2681.
ReactomeiR-HSA-196807. Nicotinate metabolism.
SABIO-RKQ96T66.
UniPathwayiUPA00253; UER00332.
UPA00253; UER00600.

Names & Taxonomyi

Protein namesi
Recommended name:
Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 3Curated
Short name:
NMN/NaMN adenylyltransferase 3
Alternative name(s):
Nicotinamide-nucleotide adenylyltransferase 3
Short name:
NMN adenylyltransferase 3
Nicotinate-nucleotide adenylyltransferase 3 (EC:2.7.7.18)
Short name:
NaMN adenylyltransferase 3
Pyridine nucleotide adenylyltransferase 3 (EC:2.7.7.1)
Short name:
PNAT-3
Gene namesi
Name:NMNAT3
ORF Names:FKSG76
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:20989. NMNAT3.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • mitochondrion Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Organism-specific databases

DisGeNETi349565.
OpenTargetsiENSG00000163864.
PharmGKBiPA134952303.

Polymorphism and mutation databases

DMDMi116242680.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001350161 – 252Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 3Add BLAST252

Proteomic databases

EPDiQ96T66.
MaxQBiQ96T66.
PaxDbiQ96T66.
PeptideAtlasiQ96T66.
PRIDEiQ96T66.

PTM databases

iPTMnetiQ96T66.
PhosphoSitePlusiQ96T66.

Expressioni

Tissue specificityi

Expressed in lung and spleen with lower levels in placenta and kidney.2 Publications

Gene expression databases

BgeeiENSG00000163864.
CleanExiHS_NMNAT3.
ExpressionAtlasiQ96T66. baseline and differential.
GenevisibleiQ96T66. HS.

Organism-specific databases

HPAiHPA057402.

Interactioni

Subunit structurei

Homotetramer.1 Publication

Protein-protein interaction databases

BioGridi131564. 4 interactors.
STRINGi9606.ENSP00000340523.

Structurei

Secondary structure

1252
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 13Combined sources9
Helixi20 – 35Combined sources16
Beta strandi37 – 48Combined sources12
Beta strandi54 – 56Combined sources3
Helixi61 – 71Combined sources11
Helixi72 – 74Combined sources3
Beta strandi76 – 80Combined sources5
Helixi83 – 86Combined sources4
Beta strandi87 – 89Combined sources3
Helixi93 – 104Combined sources12
Beta strandi129 – 135Combined sources7
Helixi136 – 141Combined sources6
Turni145 – 147Combined sources3
Helixi150 – 159Combined sources10
Beta strandi162 – 165Combined sources4
Helixi172 – 178Combined sources7
Helixi180 – 184Combined sources5
Helixi186 – 188Combined sources3
Beta strandi189 – 192Combined sources4
Helixi202 – 210Combined sources9
Helixi221 – 229Combined sources9
Turni230 – 233Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1NUPX-ray1.90A/B1-252[»]
1NUQX-ray1.90A/B1-252[»]
1NURX-ray2.15A/B1-252[»]
1NUSX-ray2.20A/B1-252[»]
1NUTX-ray1.90A/B1-252[»]
1NUUX-ray1.90A/B1-252[»]
ProteinModelPortaliQ96T66.
SMRiQ96T66.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96T66.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni53 – 55Substrate binding1 Publication3
Regioni90 – 93Substrate binding1 Publication4
Regioni147 – 148Substrate binding1 Publication2

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3199. Eukaryota.
COG1057. LUCA.
GeneTreeiENSGT00530000063189.
HOGENOMiHOG000216047.
HOVERGENiHBG052640.
InParanoidiQ96T66.
KOiK06210.
OMAiGMYQVIQ.
OrthoDBiEOG091G0JTI.
PhylomeDBiQ96T66.
TreeFamiTF315035.

Family and domain databases

Gene3Di3.40.50.620. 1 hit.
InterProiIPR004821. Cyt_trans-like.
IPR005248. NAMN_adtrnsfrase.
IPR014729. Rossmann-like_a/b/a_fold.
[Graphical view]
PANTHERiPTHR12039. PTHR12039. 1 hit.
PfamiPF01467. CTP_transf_like. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00482. TIGR00482. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96T66-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MKSRIPVVLL ACGSFNPITN MHLRMFEVAR DHLHQTGMYQ VIQGIISPVN
60 70 80 90 100
DTYGKKDLAA SHHRVAMARL ALQTSDWIRV DPWESEQAQW METVKVLRHH
110 120 130 140 150
HSKLLRSPPQ MEGPDHGKAL FSTPAAVPEL KLLCGADVLK TFQTPNLWKD
160 170 180 190 200
AHIQEIVEKF GLVCVGRVGH DPKGYIAESP ILRMHQHNIH LAKEPVQNEI
210 220 230 240 250
SATYIRRALG QGQSVKYLIP DAVITYIKDH GLYTKGSTWK GKSTQSTEGK

TS
Length:252
Mass (Da):28,322
Last modified:October 17, 2006 - v2
Checksum:i6402CFB2FE789CF4
GO
Isoform 2 (identifier: Q96T66-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-37: Missing.

Note: No experimental confirmation available.
Show »
Length:215
Mass (Da):24,119
Checksum:i0E445A25C77E1800
GO
Isoform 3 (identifier: Q96T66-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     37-125: Missing.

Note: No experimental confirmation available.
Show »
Length:163
Mass (Da):18,255
Checksum:i0E9550BF1ADADFF2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti169G → S in AAK52726 (Ref. 1) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0102671 – 37Missing in isoform 2. 1 PublicationAdd BLAST37
Alternative sequenceiVSP_04320337 – 125Missing in isoform 3. 1 PublicationAdd BLAST89

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3111.1. [Q96T66-2]
CCDS56282.1. [Q96T66-3]
CCDS82846.1. [Q96T66-1]
RefSeqiNP_001186976.1. NM_001200047.2. [Q96T66-3]
NP_001307440.1. NM_001320511.1. [Q96T66-1]
NP_001307441.1. NM_001320512.1. [Q96T66-1]
NP_835471.1. NM_178177.4. [Q96T66-2]
XP_011511092.1. XM_011512790.1. [Q96T66-2]
XP_011511093.1. XM_011512791.2. [Q96T66-2]
XP_016861824.1. XM_017006335.1. [Q96T66-1]
XP_016861825.1. XM_017006336.1. [Q96T66-1]
XP_016861826.1. XM_017006337.1. [Q96T66-1]
XP_016861827.1. XM_017006338.1. [Q96T66-2]
UniGeneiHs.208673.
Hs.745268.

Genome annotation databases

EnsembliENST00000296202; ENSP00000296202; ENSG00000163864. [Q96T66-1]
ENST00000339837; ENSP00000340523; ENSG00000163864. [Q96T66-2]
ENST00000413939; ENSP00000412953; ENSG00000163864. [Q96T66-3]
GeneIDi349565.
KEGGihsa:349565.
UCSCiuc003etj.4. human. [Q96T66-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3111.1. [Q96T66-2]
CCDS56282.1. [Q96T66-3]
CCDS82846.1. [Q96T66-1]
RefSeqiNP_001186976.1. NM_001200047.2. [Q96T66-3]
NP_001307440.1. NM_001320511.1. [Q96T66-1]
NP_001307441.1. NM_001320512.1. [Q96T66-1]
NP_835471.1. NM_178177.4. [Q96T66-2]
XP_011511092.1. XM_011512790.1. [Q96T66-2]
XP_011511093.1. XM_011512791.2. [Q96T66-2]
XP_016861824.1. XM_017006335.1. [Q96T66-1]
XP_016861825.1. XM_017006336.1. [Q96T66-1]
XP_016861826.1. XM_017006337.1. [Q96T66-1]
XP_016861827.1. XM_017006338.1. [Q96T66-2]
UniGeneiHs.208673.
Hs.745268.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1NUPX-ray1.90A/B1-252[»]
1NUQX-ray1.90A/B1-252[»]
1NURX-ray2.15A/B1-252[»]
1NUSX-ray2.20A/B1-252[»]
1NUTX-ray1.90A/B1-252[»]
1NUUX-ray1.90A/B1-252[»]
ProteinModelPortaliQ96T66.
SMRiQ96T66.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi131564. 4 interactors.
STRINGi9606.ENSP00000340523.

PTM databases

iPTMnetiQ96T66.
PhosphoSitePlusiQ96T66.

Polymorphism and mutation databases

DMDMi116242680.

Proteomic databases

EPDiQ96T66.
MaxQBiQ96T66.
PaxDbiQ96T66.
PeptideAtlasiQ96T66.
PRIDEiQ96T66.

Protocols and materials databases

DNASUi349565.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000296202; ENSP00000296202; ENSG00000163864. [Q96T66-1]
ENST00000339837; ENSP00000340523; ENSG00000163864. [Q96T66-2]
ENST00000413939; ENSP00000412953; ENSG00000163864. [Q96T66-3]
GeneIDi349565.
KEGGihsa:349565.
UCSCiuc003etj.4. human. [Q96T66-1]

Organism-specific databases

CTDi349565.
DisGeNETi349565.
GeneCardsiNMNAT3.
HGNCiHGNC:20989. NMNAT3.
HPAiHPA057402.
MIMi608702. gene.
neXtProtiNX_Q96T66.
OpenTargetsiENSG00000163864.
PharmGKBiPA134952303.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3199. Eukaryota.
COG1057. LUCA.
GeneTreeiENSGT00530000063189.
HOGENOMiHOG000216047.
HOVERGENiHBG052640.
InParanoidiQ96T66.
KOiK06210.
OMAiGMYQVIQ.
OrthoDBiEOG091G0JTI.
PhylomeDBiQ96T66.
TreeFamiTF315035.

Enzyme and pathway databases

UniPathwayiUPA00253; UER00332.
UPA00253; UER00600.
BioCyciMetaCyc:HS08953-MONOMER.
ZFISH:HS08953-MONOMER.
BRENDAi2.7.7.1. 2681.
2.7.7.18. 2681.
ReactomeiR-HSA-196807. Nicotinate metabolism.
SABIO-RKQ96T66.

Miscellaneous databases

ChiTaRSiNMNAT3. human.
EvolutionaryTraceiQ96T66.
GenomeRNAii349565.
PROiQ96T66.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163864.
CleanExiHS_NMNAT3.
ExpressionAtlasiQ96T66. baseline and differential.
GenevisibleiQ96T66. HS.

Family and domain databases

Gene3Di3.40.50.620. 1 hit.
InterProiIPR004821. Cyt_trans-like.
IPR005248. NAMN_adtrnsfrase.
IPR014729. Rossmann-like_a/b/a_fold.
[Graphical view]
PANTHERiPTHR12039. PTHR12039. 1 hit.
PfamiPF01467. CTP_transf_like. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00482. TIGR00482. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiNMNA3_HUMAN
AccessioniPrimary (citable) accession number: Q96T66
Secondary accession number(s): B3KVR6
, D3DNF2, D3DNF3, Q8N4G1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: October 17, 2006
Last modified: November 2, 2016
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.