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Protein

Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 2

Gene

NMNAT2

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

Functioni

Nicotinamide/nicotinate-nucleotide adenylyltransferase that acts as an axon maintenance factor (By similarity). Catalyzes the formation of NAD+ from nicotinamide mononucleotide (NMN) and ATP (PubMed:16118205, PubMed:17402747). Can also use the deamidated form; nicotinic acid mononucleotide (NaMN) as substrate but with a lower efficiency (PubMed:16118205, PubMed:17402747). Cannot use triazofurin monophosphate (TrMP) as substrate (PubMed:16118205, PubMed:17402747). Also catalyzes the reverse reaction, i.e. the pyrophosphorolytic cleavage of NAD+ (PubMed:16118205, PubMed:17402747). For the pyrophosphorolytic activity prefers NAD+, NADH and NaAD as substrates and degrades nicotinic acid adenine dinucleotide phosphate (NHD) less effectively (PubMed:16118205, PubMed:17402747). Fails to cleave phosphorylated dinucleotides NADP+, NADPH and NaADP+ (PubMed:16118205, PubMed:17402747). Axon survival factor required for the maintenance of healthy axons: acts by delaying Wallerian axon degeneration, an evolutionarily conserved process that drives the loss of damaged axons (By similarity).By similarity2 Publications

Catalytic activityi

ATP + nicotinamide ribonucleotide = diphosphate + NAD+.2 Publications
ATP + beta-nicotinate-D-ribonucleotide = diphosphate + deamido-NAD+.2 Publications

Cofactori

Mg2+3 PublicationsNote: Divalent metal cations. Mg2+ confers the highest activity.3 Publications

Activity regulationi

Inhibited by P1-(adenosine-5')-P3-(nicotinamide-riboside-5')-triphosphate (Np3AD) and P1-(adenosine-5')-P4-(nicotinamide-riboside-5')-tetraphosphate (Np4AD).1 Publication

Kineticsi

KM is >100 µM for triazofurin monophosphate.
  1. KM=32 µM for NMN2 Publications
  2. KM=70 µM for NAD+2 Publications
  3. KM=204 µM for ATP2 Publications
  4. KM=1119 µM for PPi2 Publications
  5. KM=14.5 µM for NaMN2 Publications
  6. KM=304 µM for NMNH2 Publications
  1. Vmax=1.1 µmol/min/mg enzyme for NAD synthesis2 Publications
  2. Vmax=3 µmol/min/mg enzyme for pyrophosphorolytic NAD+ cleavage2 Publications
  3. Vmax=7 µmol/min/mg enzyme for pyrophosphorolytic NADH cleavage2 Publications

pH dependencei

Optimum pH is 6.0-9.0.3 Publications

Pathwayi: NAD(+) biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes NAD(+) from nicotinamide D-ribonucleotide.2 Publications
Proteins known to be involved in this subpathway in this organism are:
  1. Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 2 (NMNAT2), Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1 (NMNAT1), Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 3 (NMNAT3), Nicotinamide-nucleotide adenylyltransferase, Nicotinamide-nucleotide adenylyltransferase (NMNAT1), Nicotinamide-nucleotide adenylyltransferase (nadD), Nicotinamide-nucleotide adenylyltransferase (NMNAT3)
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.2 Publications
Proteins known to be involved in this subpathway in this organism are:
  1. Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 2 (NMNAT2), Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 1 (NMNAT1), Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 3 (NMNAT3)
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 sitei24ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi15 – 17ATPBy similarity3
Nucleotide bindingi200 – 202ATPBy similarity3
Nucleotide bindingi271 – 274ATPBy similarity4

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • nicotinamide-nucleotide adenylyltransferase activity Source: GO_Central
  • nicotinate-nucleotide adenylyltransferase activity Source: UniProtKB

GO - Biological processi

  • 'de novo' NAD biosynthetic process from aspartate Source: GO_Central
  • NAD biosynthetic process Source: UniProtKB
  • NAD metabolic process Source: Reactome

Keywordsi

Molecular functionNucleotidyltransferase, Transferase
Biological processPyridine nucleotide biosynthesis
LigandATP-binding, Magnesium, NAD, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS08173-MONOMER
BRENDAi2.7.7.1 2681
2.7.7.18 2681
ReactomeiR-HSA-196807 Nicotinate metabolism
SABIO-RKiQ9BZQ4
UniPathwayi
UPA00253;UER00332

UPA00253;UER00600

Names & Taxonomyi

Protein namesi
Recommended name:
Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 2Curated (EC:2.7.7.12 Publications, EC:2.7.7.182 Publications)
Short name:
NMN/NaMN adenylyltransferase 2
Alternative name(s):
Nicotinamide mononucleotide adenylyltransferase 2
Short name:
NMN adenylyltransferase 2
Nicotinate-nucleotide adenylyltransferase 2
Short name:
NaMN adenylyltransferase 2
Gene namesi
Name:NMNAT2Imported
Synonyms:C1orf15Imported, KIAA04791 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000157064.10
HGNCiHGNC:16789 NMNAT2
MIMi608701 gene
neXtProtiNX_Q9BZQ4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell projection, Cytoplasm, Cytoplasmic vesicle, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi24H → A: Reduces activity by 95%. 1 Publication1
Mutagenesisi92W → G: Reduces activity by 95%. 1 Publication1

Organism-specific databases

DisGeNETi23057
OpenTargetsiENSG00000157064
PharmGKBiPA25604

Polymorphism and mutation databases

BioMutaiNMNAT2
DMDMi30580486

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001350141 – 307Nicotinamide/nicotinic acid mononucleotide adenylyltransferase 2Add BLAST307

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Lipidationi164S-palmitoyl cysteineBy similarity1
Lipidationi165S-palmitoyl cysteineBy similarity1

Post-translational modificationi

Degraded in response to injured neurite. Degradation is probably caused by ubiquitination by MYCBP2 (By similarity). Ubiquitinated on threonine and/or serine residues by MYCBP2; consequences of threonine and/or serine ubiquitination are however unclear (PubMed:29643511).By similarity1 Publication
Palmitoylated; palmitoylation is required for membrane association.By similarity

Keywords - PTMi

Lipoprotein, Palmitate, Ubl conjugation

Proteomic databases

PaxDbiQ9BZQ4
PeptideAtlasiQ9BZQ4
PRIDEiQ9BZQ4
ProteomicsDBi79890
79891 [Q9BZQ4-2]

PTM databases

iPTMnetiQ9BZQ4
PhosphoSitePlusiQ9BZQ4
SwissPalmiQ9BZQ4

Expressioni

Tissue specificityi

Highly expressed in brain, in particular in cerebrum, cerebellum, occipital lobe, frontal lobe, temporal lobe and putamen. Also found in the heart, skeletal muscle, pancreas and islets of Langerhans.3 Publications

Gene expression databases

BgeeiENSG00000157064 Expressed in 144 organ(s), highest expression level in middle temporal gyrus
CleanExiHS_NMNAT2
GenevisibleiQ9BZQ4 HS

Organism-specific databases

HPAiHPA061714

Interactioni

Subunit structurei

Monomer.1 Publication

Protein-protein interaction databases

BioGridi116693, 2 interactors
CORUMiQ9BZQ4
DIPiDIP-60169N
STRINGi9606.ENSP00000287713

Structurei

3D structure databases

ProteinModelPortaliQ9BZQ4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni55 – 57Substrate bindingBy similarity3
Regioni92 – 95Substrate bindingBy similarity4
Regioni212 – 213Substrate bindingBy similarity2

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG3199 Eukaryota
COG1057 LUCA
GeneTreeiENSGT00530000063189
HOGENOMiHOG000216047
HOVERGENiHBG052640
InParanoidiQ9BZQ4
KOiK06210
OMAiYILQSQL
OrthoDBiEOG091G0JTI
PhylomeDBiQ9BZQ4
TreeFamiTF315035

Family and domain databases

InterProiView protein in InterPro
IPR004821 Cyt_trans-like
PfamiView protein in Pfam
PF01467 CTP_transf_like, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q9BZQ4-1) [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
MTETTKTHVI LLACGSFNPI TKGHIQMFER ARDYLHKTGR FIVIGGIVSP
60 70 80 90 100
VHDSYGKQGL VSSRHRLIMC QLAVQNSDWI RVDPWECYQD TWQTTCSVLE
110 120 130 140 150
HHRDLMKRVT GCILSNVNTP SMTPVIGQPQ NETPQPIYQN SNVATKPTAA
160 170 180 190 200
KILGKVGESL SRICCVRPPV ERFTFVDENA NLGTVMRYEE IELRILLLCG
210 220 230 240 250
SDLLESFCIP GLWNEADMEV IVGDFGIVVV PRDAADTDRI MNHSSILRKY
260 270 280 290 300
KNNIMVVKDD INHPMSVVSS TKSRLALQHG DGHVVDYLSQ PVIDYILKSQ

LYINASG
Length:307
Mass (Da):34,439
Last modified:June 1, 2001 - v1
Checksum:i702F1C74B38ECECB
GO
Isoform 2 (identifier: Q9BZQ4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-28: MTETTKTHVILLACGSFNPITKGHIQMF → MEIQELEEIQACQGLWEVFVTLS

Note: No experimental confirmation available.
Show »
Length:302
Mass (Da):34,015
Checksum:i782C9FB1D5B0E153
GO

Sequence cautioni

The sequence BAA32324 differs from that shown. Reason: Erroneous initiation.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0155711 – 28MTETT…HIQMF → MEIQELEEIQACQGLWEVFV TLS in isoform 2. 1 PublicationAdd BLAST28

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF288395 mRNA Translation: AAG60615.1
AB007948 mRNA Translation: BAA32324.1 Different initiation.
AL354953 Genomic DNA No translation available.
AL356981 Genomic DNA No translation available.
AL449223 Genomic DNA No translation available.
BC020998 mRNA Translation: AAH20998.1
CCDSiCCDS1353.1 [Q9BZQ4-1]
CCDS1354.1 [Q9BZQ4-2]
RefSeqiNP_055854.1, NM_015039.3 [Q9BZQ4-1]
NP_733820.1, NM_170706.3 [Q9BZQ4-2]
UniGeneiHs.497123

Genome annotation databases

EnsembliENST00000287713; ENSP00000287713; ENSG00000157064 [Q9BZQ4-1]
ENST00000294868; ENSP00000294868; ENSG00000157064 [Q9BZQ4-2]
GeneIDi23057
KEGGihsa:23057
UCSCiuc001gqb.2 human [Q9BZQ4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF288395 mRNA Translation: AAG60615.1
AB007948 mRNA Translation: BAA32324.1 Different initiation.
AL354953 Genomic DNA No translation available.
AL356981 Genomic DNA No translation available.
AL449223 Genomic DNA No translation available.
BC020998 mRNA Translation: AAH20998.1
CCDSiCCDS1353.1 [Q9BZQ4-1]
CCDS1354.1 [Q9BZQ4-2]
RefSeqiNP_055854.1, NM_015039.3 [Q9BZQ4-1]
NP_733820.1, NM_170706.3 [Q9BZQ4-2]
UniGeneiHs.497123

3D structure databases

ProteinModelPortaliQ9BZQ4
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116693, 2 interactors
CORUMiQ9BZQ4
DIPiDIP-60169N
STRINGi9606.ENSP00000287713

PTM databases

iPTMnetiQ9BZQ4
PhosphoSitePlusiQ9BZQ4
SwissPalmiQ9BZQ4

Polymorphism and mutation databases

BioMutaiNMNAT2
DMDMi30580486

Proteomic databases

PaxDbiQ9BZQ4
PeptideAtlasiQ9BZQ4
PRIDEiQ9BZQ4
ProteomicsDBi79890
79891 [Q9BZQ4-2]

Protocols and materials databases

DNASUi23057
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000287713; ENSP00000287713; ENSG00000157064 [Q9BZQ4-1]
ENST00000294868; ENSP00000294868; ENSG00000157064 [Q9BZQ4-2]
GeneIDi23057
KEGGihsa:23057
UCSCiuc001gqb.2 human [Q9BZQ4-1]

Organism-specific databases

CTDi23057
DisGeNETi23057
EuPathDBiHostDB:ENSG00000157064.10
GeneCardsiNMNAT2
HGNCiHGNC:16789 NMNAT2
HPAiHPA061714
MIMi608701 gene
neXtProtiNX_Q9BZQ4
OpenTargetsiENSG00000157064
PharmGKBiPA25604
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3199 Eukaryota
COG1057 LUCA
GeneTreeiENSGT00530000063189
HOGENOMiHOG000216047
HOVERGENiHBG052640
InParanoidiQ9BZQ4
KOiK06210
OMAiYILQSQL
OrthoDBiEOG091G0JTI
PhylomeDBiQ9BZQ4
TreeFamiTF315035

Enzyme and pathway databases

UniPathwayi
UPA00253;UER00332

UPA00253;UER00600

BioCyciMetaCyc:HS08173-MONOMER
BRENDAi2.7.7.1 2681
2.7.7.18 2681
ReactomeiR-HSA-196807 Nicotinate metabolism
SABIO-RKiQ9BZQ4

Miscellaneous databases

ChiTaRSiNMNAT2 human
GeneWikiiNMNAT2
GenomeRNAii23057
PROiPR:Q9BZQ4
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000157064 Expressed in 144 organ(s), highest expression level in middle temporal gyrus
CleanExiHS_NMNAT2
GenevisibleiQ9BZQ4 HS

Family and domain databases

InterProiView protein in InterPro
IPR004821 Cyt_trans-like
PfamiView protein in Pfam
PF01467 CTP_transf_like, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNMNA2_HUMAN
AccessioniPrimary (citable) accession number: Q9BZQ4
Secondary accession number(s): O75067
, Q5T1Q3, Q8WU99, Q96QW1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 9, 2003
Last sequence update: June 1, 2001
Last modified: November 7, 2018
This is version 137 of the entry and version 1 of the sequence. See 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

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PATHWAY comments
    Index of metabolic and biosynthesis pathways
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Main funding by: National Institutes of Health

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