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Protein

Nicotinamide phosphoribosyltransferase

Gene

NAMPT

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

Functioni

Catalyzes the condensation of nicotinamide with 5-phosphoribosyl-1-pyrophosphate to yield nicotinamide mononucleotide, an intermediate in the biosynthesis of NAD. It is the rate limiting component in the mammalian NAD biosynthesis pathway. The secreted form behaves both as a cytokine with immunomodulating properties and an adipokine with anti-diabetic properties, it has no enzymatic activity, partly because of lack of activation by ATP, which has a low level in extracellular space and plasma. Plays a role in the modulation of circadian clock function. NAMPT-dependent oscillatory production of NAD regulates oscillation of clock target gene expression by releasing the core clock component: CLOCK-ARNTL/BMAL1 heterodimer from NAD-dependent SIRT1-mediated suppression (By similarity).By similarity1 Publication

Catalytic activityi

Nicotinamide D-ribonucleotide + diphosphate = nicotinamide + 5-phospho-alpha-D-ribose 1-diphosphate.

Activity regulationi

Inhibited by FK866. FK866 competes for the same binding site as nicotinamide, but due to its very low dissociation rate, it is essentially an irreversible inhibitor.1 Publication

Pathwayi: NAD(+) biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes nicotinamide D-ribonucleotide from 5-phospho-alpha-D-ribose 1-diphosphate and nicotinamide.
Proteins known to be involved in this subpathway in this organism are:
  1. Nicotinamide phosphoribosyltransferase (NAMPT)
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 nicotinamide D-ribonucleotide from 5-phospho-alpha-D-ribose 1-diphosphate and nicotinamide, the pathway NAD(+) biosynthesis and in Cofactor biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei196Diphosphate1
Binding sitei219Nicotinamide ribonucleotide1
Binding sitei247Diphosphate1
Binding sitei311Diphosphate1
Binding sitei384Nicotinamide ribonucleotide; via amide nitrogen1
Binding sitei392Nicotinamide ribonucleotide1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCytokine, Glycosyltransferase, Transferase
Biological processBiological rhythms, Pyridine nucleotide biosynthesis

Enzyme and pathway databases

BRENDAi2.4.2.12 2681
ReactomeiR-HSA-1368108 BMAL1:CLOCK,NPAS2 activates circadian gene expression
R-HSA-197264 Nicotinamide salvaging
SABIO-RKiP43490
SIGNORiP43490
UniPathwayi
UPA00253;UER00890

Names & Taxonomyi

Protein namesi
Recommended name:
Nicotinamide phosphoribosyltransferase (EC:2.4.2.12)
Short name:
NAmPRTase
Short name:
Nampt
Alternative name(s):
Pre-B-cell colony-enhancing factor 1
Short name:
Pre-B cell-enhancing factor
Visfatin
Gene namesi
Name:NAMPT
Synonyms:PBEF, PBEF1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000105835.11
HGNCiHGNC:30092 NAMPT
MIMi608764 gene
neXtProtiNX_P43490

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

Cytoplasm, Nucleus, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi219D → N or S: No effect on activity towards nicotinamide. Alters specificity, so that the enzyme acquires activity towards nicotinic acid. 1 Publication1
Mutagenesisi247H → A: Reduces activity towards nicotinamide. 1 Publication1
Mutagenesisi311R → D: Reduces activity towards nicotinamide. 1 Publication1

Organism-specific databases

DisGeNETi10135
OpenTargetsiENSG00000105835
PharmGKBiPA162396933

Chemistry databases

ChEMBLiCHEMBL1744525
DrugBankiDB05217 GMX1777
DB07656 N-[4-(1-BENZOYLPIPERIDIN-4-YL)BUTYL]-3-PYRIDIN-3-YLPROPANAMIDE

Polymorphism and mutation databases

BioMutaiNAMPT
DMDMi1172027

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002058631 – 491Nicotinamide phosphoribosyltransferaseAdd BLAST491

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei188PhosphotyrosineCombined sources1
Modified residuei472PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP43490
MaxQBiP43490
PaxDbiP43490
PeptideAtlasiP43490
PRIDEiP43490
ProteomicsDBi55638

PTM databases

iPTMnetiP43490
PhosphoSitePlusiP43490
SwissPalmiP43490

Expressioni

Tissue specificityi

Expressed in large amounts in bone marrow, liver tissue, and muscle. Also present in heart, placenta, lung, and kidney tissues.

Gene expression databases

BgeeiENSG00000105835 Expressed in 227 organ(s), highest expression level in blood
CleanExiHS_NAMPT
ExpressionAtlasiP43490 baseline and differential
GenevisibleiP43490 HS

Organism-specific databases

HPAiCAB034349
HPA047776
HPA057722

Interactioni

Subunit structurei

Homodimer.1 Publication

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi115438, 42 interactors
DIPiDIP-29218N
IntActiP43490, 15 interactors
MINTiP43490
STRINGi9606.ENSP00000222553

Chemistry databases

BindingDBiP43490

Structurei

Secondary structure

1491
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP43490
SMRiP43490
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP43490

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni311 – 313Nicotinamide ribonucleotide binding3
Regioni353 – 354Nicotinamide ribonucleotide binding2

Sequence similaritiesi

Belongs to the NAPRTase family.Curated

Phylogenomic databases

eggNOGiENOG410IEB2 Eukaryota
COG1488 LUCA
GeneTreeiENSGT00390000006647
HOGENOMiHOG000216546
HOVERGENiHBG000336
InParanoidiP43490
KOiK03462
OMAiVWYPITV
OrthoDBiEOG091G04ZB
PhylomeDBiP43490
TreeFamiTF333530

Family and domain databases

CDDicd01569 PBEF_like, 1 hit
Gene3Di3.20.20.70, 2 hits
InterProiView protein in InterPro
IPR013785 Aldolase_TIM
IPR007229 Nic_PRibTrfase-Fam
IPR016471 Nicotinamide_PRibTrfase
IPR036068 Nicotinate_pribotase_like_C
PANTHERiPTHR43816 PTHR43816, 1 hit
PfamiView protein in Pfam
PF04095 NAPRTase, 1 hit
PIRSFiPIRSF005943 NMPRT, 1 hit
SUPFAMiSSF51690 SSF51690, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

P43490-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MNPAAEAEFN ILLATDSYKV THYKQYPPNT SKVYSYFECR EKKTENSKLR
60 70 80 90 100
KVKYEETVFY GLQYILNKYL KGKVVTKEKI QEAKDVYKEH FQDDVFNEKG
110 120 130 140 150
WNYILEKYDG HLPIEIKAVP EGFVIPRGNV LFTVENTDPE CYWLTNWIET
160 170 180 190 200
ILVQSWYPIT VATNSREQKK ILAKYLLETS GNLDGLEYKL HDFGYRGVSS
210 220 230 240 250
QETAGIGASA HLVNFKGTDT VAGLALIKKY YGTKDPVPGY SVPAAEHSTI
260 270 280 290 300
TAWGKDHEKD AFEHIVTQFS SVPVSVVSDS YDIYNACEKI WGEDLRHLIV
310 320 330 340 350
SRSTQAPLII RPDSGNPLDT VLKVLEILGK KFPVTENSKG YKLLPPYLRV
360 370 380 390 400
IQGDGVDINT LQEIVEGMKQ KMWSIENIAF GSGGGLLQKL TRDLLNCSFK
410 420 430 440 450
CSYVVTNGLG INVFKDPVAD PNKRSKKGRL SLHRTPAGNF VTLEEGKGDL
460 470 480 490
EEYGQDLLHT VFKNGKVTKS YSFDEIRKNA QLNIELEAAH H
Length:491
Mass (Da):55,521
Last modified:November 1, 1995 - v1
Checksum:i6BF07B631B589AC0
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A0C4DFS8A0A0C4DFS8_HUMAN
Nicotinamide phosphoribosyltransfer...
NAMPT
368Annotation score:
C9JG65C9JG65_HUMAN
Nicotinamide phosphoribosyltransfer...
NAMPT
88Annotation score:
C9JF35C9JF35_HUMAN
Nicotinamide phosphoribosyltransfer...
NAMPT
60Annotation score:

Sequence cautioni

The sequence AAQ96862 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence EAL24400 differs from that shown. Reason: Erroneous gene model prediction.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036614176L → S in a colorectal cancer sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U02020 mRNA Translation: AAA17884.1
AK292851 mRNA Translation: BAF85540.1
AC007032 Genomic DNA Translation: AAF19249.1
AC007032 Genomic DNA Translation: AAQ96862.1 Sequence problems.
CH236947 Genomic DNA Translation: EAL24399.1
CH236947 Genomic DNA Translation: EAL24400.1 Sequence problems.
CH471070 Genomic DNA Translation: EAW83382.1
BC072439 mRNA Translation: AAH72439.1
BC106046 mRNA Translation: AAI06047.1
CCDSiCCDS5737.1
PIRiA55927
RefSeqiNP_005737.1, NM_005746.2
XP_005250157.1, XM_005250100.2
UniGeneiHs.489615

Genome annotation databases

EnsembliENST00000222553; ENSP00000222553; ENSG00000105835
GeneIDi10135
KEGGihsa:10135
UCSCiuc003vdq.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U02020 mRNA Translation: AAA17884.1
AK292851 mRNA Translation: BAF85540.1
AC007032 Genomic DNA Translation: AAF19249.1
AC007032 Genomic DNA Translation: AAQ96862.1 Sequence problems.
CH236947 Genomic DNA Translation: EAL24399.1
CH236947 Genomic DNA Translation: EAL24400.1 Sequence problems.
CH471070 Genomic DNA Translation: EAW83382.1
BC072439 mRNA Translation: AAH72439.1
BC106046 mRNA Translation: AAI06047.1
CCDSiCCDS5737.1
PIRiA55927
RefSeqiNP_005737.1, NM_005746.2
XP_005250157.1, XM_005250100.2
UniGeneiHs.489615

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2E5BX-ray2.00A/B1-491[»]
2E5CX-ray2.20A/B1-491[»]
2E5DX-ray2.00A/B1-491[»]
2GVGX-ray2.20A/B/C/D/E/F1-491[»]
2GVJX-ray2.10A/B1-491[»]
3DGRX-ray2.10A/B1-484[»]
3DHDX-ray2.00A/B1-484[»]
3DHFX-ray1.80A/B1-484[»]
3DKJX-ray2.00A/B1-484[»]
3DKLX-ray1.89A/B1-484[»]
4JNMX-ray2.20A/B1-491[»]
4JR5X-ray1.91A/B1-491[»]
4KFNX-ray1.60A/B1-491[»]
4KFOX-ray1.60A/B1-491[»]
4KFPX-ray1.84A/B1-491[»]
4L4LX-ray2.12A/B1-491[»]
4L4MX-ray2.44A/B1-491[»]
4LTSX-ray1.69A/B1-491[»]
4LV9X-ray1.81A/B1-491[»]
4LVAX-ray1.55A/B1-491[»]
4LVBX-ray1.84A/B1-491[»]
4LVDX-ray1.75A/B1-491[»]
4LVFX-ray1.50A/B1-491[»]
4LVGX-ray1.70A/B1-491[»]
4LWWX-ray1.64A/B1-491[»]
4M6PX-ray1.75A/B1-491[»]
4M6QX-ray2.41A/B1-491[»]
4N9BX-ray2.86A/B1-491[»]
4N9CX-ray1.75A/B1-491[»]
4N9DX-ray1.70A/B1-491[»]
4N9EX-ray1.72A/B1-491[»]
4O0ZX-ray2.05A/B1-491[»]
4O10X-ray1.55A/B1-491[»]
4O12X-ray2.50A/B1-491[»]
4O13X-ray1.75A/B1-491[»]
4O14X-ray1.87A/B1-491[»]
4O15X-ray1.80A/B1-491[»]
4O16X-ray1.78A1-491[»]
4O17X-ray1.82A/B1-491[»]
4O18X-ray1.92A/B1-491[»]
4O19X-ray1.75A/B1-491[»]
4O1AX-ray1.87A/B1-491[»]
4O1BX-ray1.65A/B1-491[»]
4O1CX-ray2.09A/B1-491[»]
4O1DX-ray1.70A/B1-491[»]
4O28X-ray2.00A/B1-491[»]
4WQ6X-ray1.72A/B1-491[»]
5KITX-ray1.60A/B1-491[»]
5LX3X-ray2.10A/B1-491[»]
5LX5X-ray1.88A/B1-491[»]
5NSDX-ray2.05A/B1-491[»]
5U2MX-ray1.89A/B9-485[»]
5U2NX-ray1.73A/B9-485[»]
5UPEX-ray1.93A/B1-491[»]
5UPFX-ray1.69A/B1-491[»]
5WI0X-ray2.05A/B1-491[»]
5WI1X-ray1.99A/B1-491[»]
6ATBX-ray2.53A/B/C/D1-491[»]
6AZJX-ray2.53A/B8-485[»]
6E68X-ray1.50A/B8-487[»]
ProteinModelPortaliP43490
SMRiP43490
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115438, 42 interactors
DIPiDIP-29218N
IntActiP43490, 15 interactors
MINTiP43490
STRINGi9606.ENSP00000222553

Chemistry databases

BindingDBiP43490
ChEMBLiCHEMBL1744525
DrugBankiDB05217 GMX1777
DB07656 N-[4-(1-BENZOYLPIPERIDIN-4-YL)BUTYL]-3-PYRIDIN-3-YLPROPANAMIDE

PTM databases

iPTMnetiP43490
PhosphoSitePlusiP43490
SwissPalmiP43490

Polymorphism and mutation databases

BioMutaiNAMPT
DMDMi1172027

Proteomic databases

EPDiP43490
MaxQBiP43490
PaxDbiP43490
PeptideAtlasiP43490
PRIDEiP43490
ProteomicsDBi55638

Protocols and materials databases

DNASUi10135
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000222553; ENSP00000222553; ENSG00000105835
GeneIDi10135
KEGGihsa:10135
UCSCiuc003vdq.4 human

Organism-specific databases

CTDi10135
DisGeNETi10135
EuPathDBiHostDB:ENSG00000105835.11
GeneCardsiNAMPT
HGNCiHGNC:30092 NAMPT
HPAiCAB034349
HPA047776
HPA057722
MIMi608764 gene
neXtProtiNX_P43490
OpenTargetsiENSG00000105835
PharmGKBiPA162396933
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IEB2 Eukaryota
COG1488 LUCA
GeneTreeiENSGT00390000006647
HOGENOMiHOG000216546
HOVERGENiHBG000336
InParanoidiP43490
KOiK03462
OMAiVWYPITV
OrthoDBiEOG091G04ZB
PhylomeDBiP43490
TreeFamiTF333530

Enzyme and pathway databases

UniPathwayi
UPA00253;UER00890

BRENDAi2.4.2.12 2681
ReactomeiR-HSA-1368108 BMAL1:CLOCK,NPAS2 activates circadian gene expression
R-HSA-197264 Nicotinamide salvaging
SABIO-RKiP43490
SIGNORiP43490

Miscellaneous databases

ChiTaRSiNAMPT human
EvolutionaryTraceiP43490
GeneWikiiNicotinamide_phosphoribosyltransferase
GenomeRNAii10135
PROiPR:P43490
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000105835 Expressed in 227 organ(s), highest expression level in blood
CleanExiHS_NAMPT
ExpressionAtlasiP43490 baseline and differential
GenevisibleiP43490 HS

Family and domain databases

CDDicd01569 PBEF_like, 1 hit
Gene3Di3.20.20.70, 2 hits
InterProiView protein in InterPro
IPR013785 Aldolase_TIM
IPR007229 Nic_PRibTrfase-Fam
IPR016471 Nicotinamide_PRibTrfase
IPR036068 Nicotinate_pribotase_like_C
PANTHERiPTHR43816 PTHR43816, 1 hit
PfamiView protein in Pfam
PF04095 NAPRTase, 1 hit
PIRSFiPIRSF005943 NMPRT, 1 hit
SUPFAMiSSF51690 SSF51690, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNAMPT_HUMAN
AccessioniPrimary (citable) accession number: P43490
Secondary accession number(s): A4D0Q9
, A4D0R0, Q3KQV0, Q8WW95
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: November 7, 2018
This is version 176 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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