UniProtKB - Q96T66 (NMNA3_HUMAN)
Protein
Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 3
Gene
NMNAT3
Organism
Homo sapiens (Human)
Status
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
Cofactori
Mg2+1 PublicationNote: Divalent metal cations. Mg2+ confers the highest activity.1 Publication
Activity regulationi
Activity is strongly inhibited by galotannin. Inhibited by P1-(adenosine-5')-P4-(nicotinic-acid-riboside-5')-tetraphosphate (Nap4AD).1 Publication
Kineticsi
- KM=209 µM for NMN2 Publications
- KM=130 µM for NAD+2 Publications
- KM=29 µM for ATP2 Publications
- KM=390 µM for PPi2 Publications
- KM=276 µM for GTP2 Publications
- KM=350 µM for ITP2 Publications
- KM=111 µM for NaMN2 Publications
- KM=130 µM for NMNH2 Publications
- KM=2.01 µM for triazofurin monophosphate2 Publications
- Vmax=3.6 µmol/min/mg enzyme for NAD synthesis2 Publications
- Vmax=12.8 µmol/min/mg enzyme for pyrophosphorolytic NAD+ cleavage2 Publications
- Vmax=2.9 µmol/min/mg enzyme for pyrophosphorolytic NADH cleavage2 Publications
: NAD(+) biosynthesis Pathwayi
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:
- Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 2 (NMNAT2), Nicotinamide-nucleotide adenylyltransferase (NMNAT1), Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1 (NMNAT1), Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 3 (NMNAT3), Nicotinamide-nucleotide adenylyltransferase (NMNAT3), Nicotinamide-nucleotide adenylyltransferase
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:
- Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 2 (NMNAT2), Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1 (NMNAT1), Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 3 (NMNAT3)
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 22 | ATP1 Publication | 1 | |
Binding sitei | 56 | ATP1 Publication | 1 | |
Binding sitei | 140 | ATP; shared with dimeric partner1 Publication | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 13 – 15 | ATP1 Publication | 3 | |
Nucleotide bindingi | 135 – 137 | ATP1 Publication | 3 | |
Nucleotide bindingi | 203 – 206 | ATP1 Publication | 4 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- nicotinamide-nucleotide adenylyltransferase activity Source: GO_Central
- nicotinate-nucleotide adenylyltransferase activity Source: UniProtKB
GO - Biological processi
- NAD biosynthetic process Source: GO_Central
- NAD metabolic process Source: Reactome
- nucleotide biosynthetic process Source: UniProtKB
Keywordsi
Molecular function | Nucleotidyltransferase, Transferase |
Biological process | Pyridine nucleotide biosynthesis |
Ligand | ATP-binding, Magnesium, NAD, Nucleotide-binding |
Enzyme and pathway databases
BioCyci | MetaCyc:HS08953-MONOMER |
BRENDAi | 2.7.7.1, 2681 2.7.7.18, 2681 |
PathwayCommonsi | Q96T66 |
Reactomei | R-HSA-196807, Nicotinate metabolism |
SABIO-RKi | Q96T66 |
UniPathwayi | UPA00253;UER00332 UPA00253;UER00600 |
Names & Taxonomyi
Protein namesi | Recommended name: Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 3CuratedShort name: NMN/NaMN adenylyltransferase 3 Alternative name(s): |
Gene namesi | Name:NMNAT3 ORF Names:FKSG76 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:20989, NMNAT3 |
MIMi | 608702, gene |
neXtProti | NX_Q96T66 |
VEuPathDBi | HostDB:ENSG00000163864.14 |
Subcellular locationi
Mitochondrion
- Mitochondrion 2 Publications
Mitochondrion
- mitochondrial matrix Source: Reactome
- mitochondrion Source: UniProtKB
Nucleus
- nucleus Source: GO_Central
Keywords - Cellular componenti
MitochondrionPathology & Biotechi
Organism-specific databases
DisGeNETi | 349565 |
OpenTargetsi | ENSG00000163864 |
PharmGKBi | PA134952303 |
Miscellaneous databases
Pharosi | Q96T66, Tbio |
Chemistry databases
DrugBanki | DB02596, alpha,beta-Methyleneadenosine 5'-triphosphate DB04099, Deamido-Nad DB03227, Nicotinamide Mononucleotide |
Genetic variation databases
BioMutai | NMNAT3 |
DMDMi | 116242680 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000135016 | 1 – 252 | Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 3Add BLAST | 252 |
Proteomic databases
EPDi | Q96T66 |
jPOSTi | Q96T66 |
MassIVEi | Q96T66 |
MaxQBi | Q96T66 |
PaxDbi | Q96T66 |
PeptideAtlasi | Q96T66 |
PRIDEi | Q96T66 |
ProteomicsDBi | 78200 [Q96T66-1] 78201 [Q96T66-2] 78202 [Q96T66-3] |
PTM databases
iPTMneti | Q96T66 |
PhosphoSitePlusi | Q96T66 |
Expressioni
Tissue specificityi
Expressed in lung and spleen with lower levels in placenta and kidney.2 Publications
Gene expression databases
Bgeei | ENSG00000163864, Expressed in muscle tissue and 199 other tissues |
ExpressionAtlasi | Q96T66, baseline and differential |
Genevisiblei | Q96T66, HS |
Organism-specific databases
HPAi | ENSG00000163864, Low tissue specificity |
Interactioni
Subunit structurei
Homotetramer.
1 PublicationProtein-protein interaction databases
BioGRIDi | 131564, 6 interactors |
IntActi | Q96T66, 4 interactors |
STRINGi | 9606.ENSP00000340523 |
Miscellaneous databases
RNActi | Q96T66, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q96T66 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q96T66 |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 53 – 55 | Substrate binding1 Publication | 3 | |
Regioni | 90 – 93 | Substrate binding1 Publication | 4 | |
Regioni | 147 – 148 | Substrate binding1 Publication | 2 |
Sequence similaritiesi
Belongs to the eukaryotic NMN adenylyltransferase family.Curated
Phylogenomic databases
eggNOGi | KOG3199, Eukaryota |
GeneTreei | ENSGT00950000183179 |
HOGENOMi | CLU_033366_3_1_1 |
InParanoidi | Q96T66 |
OMAi | HNIYTEE |
PhylomeDBi | Q96T66 |
TreeFami | TF315035 |
Family and domain databases
Gene3Di | 3.40.50.620, 1 hit |
InterProi | View protein in InterPro IPR004821, Cyt_trans-like IPR005248, NadD/NMNAT IPR014729, Rossmann-like_a/b/a_fold |
Pfami | View protein in Pfam PF01467, CTP_transf_like, 1 hit |
TIGRFAMsi | TIGR00482, TIGR00482, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 10 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q96T66-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 10 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A2R8YFG2 | A0A2R8YFG2_HUMAN | Nicotinamide-nucleotide adenylyltra... | NMNAT3 | 346 | Annotation score: | ||
A0A2R8YGL3 | A0A2R8YGL3_HUMAN | tRNA-uridine aminocarboxypropyltran... | NMNAT3 | 194 | Annotation score: | ||
D6RGH7 | D6RGH7_HUMAN | Nicotinamide/nicotinic acid mononuc... | NMNAT3 | 100 | Annotation score: | ||
D6RHV4 | D6RHV4_HUMAN | Nicotinamide/nicotinic acid mononuc... | NMNAT3 | 113 | Annotation score: | ||
D6RGG8 | D6RGG8_HUMAN | Nicotinamide nucleotide adenylyltra... | NMNAT3 hCG_2022373 | 98 | Annotation score: | ||
D6REC8 | D6REC8_HUMAN | Nicotinamide nucleotide adenylyltra... | NMNAT3 hCG_2022373 | 63 | Annotation score: | ||
D6R975 | D6R975_HUMAN | Nicotinamide nucleotide adenylyltra... | NMNAT3 hCG_2022373 | 98 | Annotation score: | ||
A0A2R8Y594 | A0A2R8Y594_HUMAN | Nicotinamide nucleotide adenylyltra... | NMNAT3 hCG_2022373 | 170 | Annotation score: | ||
A0A2R8YE08 | A0A2R8YE08_HUMAN | Nicotinamide/nicotinic acid mononuc... | NMNAT3 | 157 | Annotation score: | ||
A0A2R8YEU0 | A0A2R8YEU0_HUMAN | Nicotinamide/nicotinic acid mononuc... | NMNAT3 | 194 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 169 | G → S in AAK52726 (Ref. 1) Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_010267 | 1 – 37 | Missing in isoform 2. 1 PublicationAdd BLAST | 37 | |
Alternative sequenceiVSP_043203 | 37 – 125 | Missing in isoform 3. 1 PublicationAdd BLAST | 89 |
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 |
CCDSi | CCDS3111.1 [Q96T66-2] CCDS56282.1 [Q96T66-3] CCDS82846.1 [Q96T66-1] |
RefSeqi | NP_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] |
Genome annotation databases
Ensembli | ENST00000296202; ENSP00000296202; ENSG00000163864 [Q96T66-1] ENST00000339837; ENSP00000340523; ENSG00000163864 [Q96T66-2] ENST00000413939; ENSP00000412953; ENSG00000163864 [Q96T66-3] |
GeneIDi | 349565 |
KEGGi | hsa:349565 |
UCSCi | uc003etj.4, human [Q96T66-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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 |
CCDSi | CCDS3111.1 [Q96T66-2] CCDS56282.1 [Q96T66-3] CCDS82846.1 [Q96T66-1] |
RefSeqi | NP_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] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB 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 | [»] | |
SMRi | Q96T66 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 131564, 6 interactors |
IntActi | Q96T66, 4 interactors |
STRINGi | 9606.ENSP00000340523 |
Chemistry databases
DrugBanki | DB02596, alpha,beta-Methyleneadenosine 5'-triphosphate DB04099, Deamido-Nad DB03227, Nicotinamide Mononucleotide |
PTM databases
iPTMneti | Q96T66 |
PhosphoSitePlusi | Q96T66 |
Genetic variation databases
BioMutai | NMNAT3 |
DMDMi | 116242680 |
Proteomic databases
EPDi | Q96T66 |
jPOSTi | Q96T66 |
MassIVEi | Q96T66 |
MaxQBi | Q96T66 |
PaxDbi | Q96T66 |
PeptideAtlasi | Q96T66 |
PRIDEi | Q96T66 |
ProteomicsDBi | 78200 [Q96T66-1] 78201 [Q96T66-2] 78202 [Q96T66-3] |
Protocols and materials databases
Antibodypediai | 33465, 181 antibodies |
DNASUi | 349565 |
Genome annotation databases
Ensembli | ENST00000296202; ENSP00000296202; ENSG00000163864 [Q96T66-1] ENST00000339837; ENSP00000340523; ENSG00000163864 [Q96T66-2] ENST00000413939; ENSP00000412953; ENSG00000163864 [Q96T66-3] |
GeneIDi | 349565 |
KEGGi | hsa:349565 |
UCSCi | uc003etj.4, human [Q96T66-1] |
Organism-specific databases
CTDi | 349565 |
DisGeNETi | 349565 |
GeneCardsi | NMNAT3 |
HGNCi | HGNC:20989, NMNAT3 |
HPAi | ENSG00000163864, Low tissue specificity |
MIMi | 608702, gene |
neXtProti | NX_Q96T66 |
OpenTargetsi | ENSG00000163864 |
PharmGKBi | PA134952303 |
VEuPathDBi | HostDB:ENSG00000163864.14 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3199, Eukaryota |
GeneTreei | ENSGT00950000183179 |
HOGENOMi | CLU_033366_3_1_1 |
InParanoidi | Q96T66 |
OMAi | HNIYTEE |
PhylomeDBi | Q96T66 |
TreeFami | TF315035 |
Enzyme and pathway databases
UniPathwayi | UPA00253;UER00332 UPA00253;UER00600 |
BioCyci | MetaCyc:HS08953-MONOMER |
BRENDAi | 2.7.7.1, 2681 2.7.7.18, 2681 |
PathwayCommonsi | Q96T66 |
Reactomei | R-HSA-196807, Nicotinate metabolism |
SABIO-RKi | Q96T66 |
Miscellaneous databases
BioGRID-ORCSi | 349565, 7 hits in 994 CRISPR screens |
ChiTaRSi | NMNAT3, human |
EvolutionaryTracei | Q96T66 |
GenomeRNAii | 349565 |
Pharosi | Q96T66, Tbio |
PROi | PR:Q96T66 |
RNActi | Q96T66, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000163864, Expressed in muscle tissue and 199 other tissues |
ExpressionAtlasi | Q96T66, baseline and differential |
Genevisiblei | Q96T66, HS |
Family and domain databases
Gene3Di | 3.40.50.620, 1 hit |
InterProi | View protein in InterPro IPR004821, Cyt_trans-like IPR005248, NadD/NMNAT IPR014729, Rossmann-like_a/b/a_fold |
Pfami | View protein in Pfam PF01467, CTP_transf_like, 1 hit |
TIGRFAMsi | TIGR00482, TIGR00482, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | NMNA3_HUMAN | |
Accessioni | Q96T66Primary (citable) accession number: Q96T66 Secondary accession number(s): B3KVR6 Q8N4G1 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 10, 2004 |
Last sequence update: | October 17, 2006 | |
Last modified: | April 7, 2021 | |
This is version 155 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 3
Human chromosome 3: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families