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Record Information
Version3.6
Creation Date2005-11-16 15:48:42 UTC
Update Date2014-09-22 19:38:34 UTC
HMDB IDHMDB01406
Secondary Accession NumbersNone
Metabolite Identification
Common NameNiacinamide
DescriptionNiacinamide or vitamin B3 is an important compound functioning as a component of the coenzyme NAD. Its primary significance is in the prevention and/or cure of blacktongue and pellagra. Most animals cannot manufacture this compound in amounts sufficient to prevent nutritional deficiency and it therefore must be supplemented through dietary intake. Niacinamide is used to increase the effect of radiation therapy on tumor cells. Niacin (nicotinic acid) and niacinamide, while both labeled as vitamin B3 also have different applications. Niacinamide is useful in arthritis and early-onset type I diabetes while niacin is an effective reducer of high cholesterol levels.
Structure
Thumb
Synonyms
  1. 3-Carbamoylpyridine
  2. 3-Pyridinecarboxamide
  3. 3-Pyridinecarboxylic acid amide
  4. Acid amide
  5. Amid kyseliny nikotinove
  6. Amide PP
  7. Aminicotin
  8. Amixicotyn
  9. Amnicotin
  10. Austrovit PP
  11. b-Pyridinecarboxamide
  12. Benicot
  13. beta-Pyridinecarboxamide
  14. Delonin Amide
  15. Dipegyl
  16. Dipigyl
  17. Endobion
  18. Factor pp
  19. Hansamid
  20. Inovitan PP
  21. m-(Aminocarbonyl)pyridine
  22. Mediatric
  23. NAM
  24. Nandervit-N
  25. Niacevit
  26. Niacinamide
  27. Niamide
  28. Niavit PP
  29. Nicamide
  30. Nicamina
  31. Nicamindon
  32. Nicasir
  33. Nicobion
  34. Nicofort
  35. Nicogen
  36. Nicomidol
  37. Nicosan 2
  38. Nicosylamide
  39. Nicota
  40. Nicotamide
  41. Nicotilamide
  42. Nicotililamido
  43. Nicotinamida
  44. Nicotinamide
  45. Nicotinamidum
  46. Nicotine acid amide
  47. Nicotine amide
  48. Nicotinic acid amide
  49. Nicotinic amide
  50. Nicotinsaureamid
  51. Nicotol
  52. Nicotylamide
  53. Nicotylamidum
  54. Nicovel
  55. Nicovit
  56. Nicovitina
  57. Nicovitol
  58. Nicozymin
  59. Nictoamide
  60. Niko-tamin
  61. Nikotinamid
  62. Nikotinsaeureamid
  63. Niocinamide
  64. Niozymin
  65. Papulex
  66. Pelmin
  67. Pelmine
  68. Pelonin amide
  69. PP-Faktor
  70. Propamine A
  71. Pyridine-3-carboxylic acid amide
  72. Savacotyl
  73. Vi-Nicotyl
  74. Vi-noctyl
  75. Vitamin B3
  76. Vitamin PP
  77. Witamina PP
Chemical FormulaC6H6N2O
Average Molecular Weight122.1246
Monoisotopic Molecular Weight122.048012824
IUPAC Namepyridine-3-carboxamide
Traditional Namenicotinamide
CAS Registry Number98-92-0
SMILES
NC(=O)C1=CN=CC=C1
InChI Identifier
InChI=1S/C6H6N2O/c7-6(9)5-2-1-3-8-4-5/h1-4H,(H2,7,9)
InChI KeyDFPAKSUCGFBDDF-UHFFFAOYSA-N
Chemical Taxonomy
KingdomOrganic Compounds
Super ClassAromatic Heteromonocyclic Compounds
ClassPyridines and Derivatives
Sub ClassN/A
Other Descriptors
  • Pyridine alkaloids(KEGG)
  • Water-soluble vitamins(KEGG)
  • a vitamin(Cyc)
  • an aliphatic amide(Cyc)
  • pyridine alkaloid(ChEBI)
  • pyridinecarboxamide(ChEBI)
Substituents
  • Carboxamide Group
  • Primary Carboxylic Acid Amide
Direct ParentPyridines and Derivatives
Ontology
StatusDetected and Quantified
Origin
  • Endogenous
Biofunction
  • Component of Nicotinate and nicotinamide metabolism
ApplicationNot Available
Cellular locations
  • Extracellular
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point130 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility500 mg/mL at 25 °CNot Available
LogP-0.37HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility50.1ALOGPS
logP-0.45ALOGPS
logP-0.39ChemAxon
logS-0.39ALOGPS
pKa (Strongest Acidic)13.39ChemAxon
pKa (Strongest Basic)3.63ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area55.98 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity32.98 m3·mol-1ChemAxon
Polarizability11.71 Å3ChemAxon
Spectra
SpectraGC-MSMS/MSLC-MSMS1D NMR2D NMR
Biological Properties
Cellular Locations
  • Extracellular
Biofluid Locations
  • Blood
  • Urine
Tissue Location
  • Bladder
  • Fibroblasts
  • Neuron
  • Pancreas
  • Placenta
  • Prostate
  • Skin
  • Spleen
  • Stratum Corneum
Pathways
NameSMPDB LinkKEGG Link
Nicotinate and Nicotinamide MetabolismSMP00048map00760
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.03 +/- 0.01 uMAdult (>18 years old)BothNormal details
BloodDetected and Quantified0.44 +/- 0.0054 uMAdult (>18 years old)BothNormal details
UrineDetected and Quantified0.30 +/- 0.51 umol/mmol creatinineInfant (0-1 year old)BothNormal details
Abnormal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.29 +/- 0.24 uMAdult (>18 years old)Bothuremia details
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB02701
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDFDB012485
KNApSAcK IDC00000209
Chemspider ID911
KEGG Compound IDC00153
BioCyc IDNIACINAMIDE
BiGG ID34058
Wikipedia LinkNiacinamide
NuGOwiki LinkHMDB01406
Metagene LinkHMDB01406
METLIN ID1497
PubChem Compound936
PDB IDNCA
ChEBI ID17154
References
Synthesis ReferenceGalat, Alexander. Nicotinamide from nicotinonitrile by catalytic hydration. Journal of the American Chemical Society (1948), 70 3945.
Material Safety Data Sheet (MSDS)Download (PDF)
General References
  1. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. Pubmed: 19212411
  2. Rybak ME, Pfeiffer CM: Clinical analysis of vitamin B(6): determination of pyridoxal 5'-phosphate and 4-pyridoxic acid in human serum by reversed-phase high-performance liquid chromatography with chlorite postcolumn derivatization. Anal Biochem. 2004 Oct 15;333(2):336-44. Pubmed: 15450810
  3. Draelos ZD, Ertel K, Berge C: Niacinamide-containing facial moisturizer improves skin barrier and benefits subjects with rosacea. Cutis. 2005 Aug;76(2):135-41. Pubmed: 16209160
  4. Soma Y, Kashima M, Imaizumi A, Takahama H, Kawakami T, Mizoguchi M: Moisturizing effects of topical nicotinamide on atopic dry skin. Int J Dermatol. 2005 Mar;44(3):197-202. Pubmed: 15807725
  5. Final report of the safety assessment of niacinamide and niacin. Int J Toxicol. 2005;24 Suppl 5:1-31. Pubmed: 16596767
  6. Draelos ZD, Matsubara A, Smiles K: The effect of 2% niacinamide on facial sebum production. J Cosmet Laser Ther. 2006 Jun;8(2):96-101. Pubmed: 16766489
  7. Schulpis K, Spiropoulos A, Gavrili S, Karikas G, Grigori C, Vlachos G, Papassotiriou I: Maternal - neonatal folate and vitamin B12 serum concentrations in Greeks and in Albanian immigrants. J Hum Nutr Diet. 2004 Oct;17(5):443-8. Pubmed: 15357698
  8. Yang L, Yao Y, Shi Y, Wang X, Shi J: [Expression of nicotinamide edenine dinucleotide dehydrogenase gene in placenta of patients with pregnancy induced hypertension] Zhonghua Fu Chan Ke Za Zhi. 2002 Nov;37(11):660-2. Pubmed: 12487919
  9. Sonee M, Martens JR, Mukherjee SK: Nicotinamide protects HCN2 cells from the free radical generating toxin, tertiary butylhydroperoxide (t-BuOOH). Neurotox Res. 2002 Nov;4(7-8):595-599. Pubmed: 12709297
  10. Bayraktar F, Dereli D, Ozgen AG, Yilmaz C: Plasma homocysteine levels in polycystic ovary syndrome and congenital adrenal hyperplasia. Endocr J. 2004 Dec;51(6):601-8. Pubmed: 15644580
  11. Sonee M, Martens JR, Evers MR, Mukherjee SK: The effect of tertiary butylhydroperoxide and nicotinamide on human cortical neurons. Neurotoxicology. 2003 Jun;24(3):443-8. Pubmed: 12782109
  12. Anisimov AG, Bolotnikov IA: [Nicotinamide decreases DNA destabilization in K562 cells treated with AlF(-4)] Tsitologiia. 1997;39(9):822-8. Pubmed: 9518388
  13. Matuoka K, Chen KY, Takenawa T: Rapid reversion of aging phenotypes by nicotinamide through possible modulation of histone acetylation. Cell Mol Life Sci. 2001 Dec;58(14):2108-16. Pubmed: 11814060
  14. Bartalena L, Tanda ML, Piantanida E, Lai A: Oxidative stress and Graves' ophthalmopathy: in vitro studies and therapeutic implications. Biofactors. 2003;19(3-4):155-63. Pubmed: 14757966
  15. Bissett DL, Oblong JE, Berge CA: Niacinamide: A B vitamin that improves aging facial skin appearance. Dermatol Surg. 2005 Jul;31(7 Pt 2):860-5; discussion 865. Pubmed: 16029679
  16. Baeza N, Moriscot C, Figarella C, Guy-Crotte O, Vialettes B: Reg protein: a potential beta-cell-specific growth factor? Diabetes Metab. 1996 Jul;22(4):229-34. Pubmed: 8767167
  17. Hoskin PJ, Rojas AM, Phillips H, Saunders MI: Acute and late morbidity in the treatment of advanced bladder carcinoma with accelerated radiotherapy, carbogen, and nicotinamide. Cancer. 2005 Jun 1;103(11):2287-97. Pubmed: 15834926
  18. Rembold CM: Combination therapy of dyslipidemia in non-insulin-dependent diabetes mellitus and the metabolic syndrome. Curr Diab Rep. 2004 Oct;4(5):330-4. Pubmed: 15461896
  19. Kawasaki E, Abiru N, Eguchi K: Prevention of type 1 diabetes: from the view point of beta cell damage. Diabetes Res Clin Pract. 2004 Dec;66 Suppl 1:S27-32. Pubmed: 15563975

Enzymes

General function:
Involved in methyltransferase activity
Specific function:
Catalyzes the N-methylation of nicotinamide and other pyridines to form pyridinium ions. This activity is important for biotransformation of many drugs and xenobiotic compounds.
Gene Name:
NNMT
Uniprot ID:
P40261
Molecular weight:
29573.705
Reactions
S-Adenosylmethionine + Niacinamide → S-Adenosylhomocysteine + 1-Methylnicotinamidedetails
S-Adenosylmethionine + Niacinamide + Hydrogen Ion → S-Adenosylhomocysteine + 1-Methylnicotinamidedetails
General function:
Involved in NAD+ ADP-ribosyltransferase activity
Specific function:
Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates poly-ADP-ribosylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates poly-ADP-ribosylation of TERF1, thereby contributing to the regulation of telomere length. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles.
Gene Name:
TNKS2
Uniprot ID:
Q9H2K2
Molecular weight:
126916.895
Reactions
NAD + (ADP-D-ribosyl)(n)-acceptor → Niacinamide + (ADP-D-ribosyl)(n+1)-acceptordetails
General function:
Involved in zinc ion binding
Specific function:
NAD-dependent protein deacetylase. Has deacetylase activity towards histone H3K9Ac and H3K56Ac. Modulates acetylation of histone H3 in telomeric chromatin during the S-phase of the cell cycle. Deacetylates histone H3K9Ac at NF-kappa-B target promoters and may down-regulate the expression of a subset of NF-kappa-B target genes. Acts as a corepressor of the transcription factor HIF1A to control the expression of multiple glycolytic genes to regulate glucose homeostasis. Required for genomic stability. Regulates the production of TNF protein. Has a role in the regulation of life span (By similarity). Deacetylation of nucleosomes interferes with RELA binding to target DNA. May be required for the association of WRN with telomeres during S-phase and for normal telomere maintenance. Required for genomic stability. Required for normal IGF1 serum levels and normal glucose homeostasis. Modulates cellular senescence and apoptosis. On DNA damage, promotes DNA end resection via deacetylation of RBBP8. Has very weak deacetylase activity and can bind NAD(+) in the absence of acetylated substrate.
Gene Name:
SIRT6
Uniprot ID:
Q8N6T7
Molecular weight:
36064.295
Reactions
NAD + an acetylprotein → Niacinamide + O-acetyl-ADP-ribose + a proteindetails
General function:
Involved in NAD+ ADP-ribosyltransferase activity
Specific function:
Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. May link the DNA damage surveillance network to the mitotic fidelity checkpoint. Negatively influences the G1/S cell cycle progression without interfering with centrosome duplication. Binds DNA. May be involved in the regulation of PRC2 and PRC3 complex-dependent gene silencing.
Gene Name:
PARP3
Uniprot ID:
Q9Y6F1
Molecular weight:
60845.685
Reactions
NAD + (ADP-D-ribosyl)(n)-acceptor → Niacinamide + (ADP-D-ribosyl)(n+1)-acceptordetails
General function:
Involved in NAD(P)+-protein-arginine ADP-ribosyltransferase activity
Specific function:
Not Available
Gene Name:
ART3
Uniprot ID:
Q13508
Molecular weight:
43922.97
Reactions
NAD + protein-L-arginine → Niacinamide + N(omega)-(ADP-D-ribosyl)-protein-L-argininedetails
NADP + protein-L-arginine → Niacinamide + N(omega)-((2'-phospho-ADP)-D-ribosyl)-protein-L-argininedetails
General function:
Involved in NAD(P)+-protein-arginine ADP-ribosyltransferase activity
Specific function:
Not Available
Gene Name:
ART5
Uniprot ID:
Q96L15
Molecular weight:
32053.48
Reactions
NAD + protein-L-arginine → Niacinamide + N(omega)-(ADP-D-ribosyl)-protein-L-argininedetails
NADP + protein-L-arginine → Niacinamide + N(omega)-((2'-phospho-ADP)-D-ribosyl)-protein-L-argininedetails
General function:
Involved in NAD(P)+-protein-arginine ADP-ribosyltransferase activity
Specific function:
Has ADP-ribosyltransferase activity toward GLP1R.
Gene Name:
ART1
Uniprot ID:
P52961
Molecular weight:
36334.32
Reactions
NAD + protein-L-arginine → Niacinamide + N(omega)-(ADP-D-ribosyl)-protein-L-argininedetails
NADP + protein-L-arginine → Niacinamide + N(omega)-((2'-phospho-ADP)-D-ribosyl)-protein-L-argininedetails
General function:
Involved in NAD+ ADP-ribosyltransferase activity
Specific function:
Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking. Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation (PARsylation) of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates PARsylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates PARsylation of TERF1, thereby contributing to the regulation of telomere length. Involved in centrosome maturation during prometaphase by mediating PARsylation of HEPACAM2/MIKI. May also regulate vesicle trafficking and modulate the subcellular distribution of SLC2A4/GLUT4-vesicles. May be involved in spindle pole assembly through PARsylation of NUMA1.
Gene Name:
TNKS
Uniprot ID:
O95271
Molecular weight:
142038.18
Reactions
NAD + (ADP-D-ribosyl)(n)-acceptor → Niacinamide + (ADP-D-ribosyl)(n+1)-acceptordetails
General function:
Involved in DNA binding
Specific function:
Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. Mediates the poly(ADP-ribosyl)ation of APLF and CHFR. Positively regulates the transcription of MTUS1 and negatively regulates the transcription of MTUS2/TIP150. With EEF1A1 and TXK, forms a complex that acts as a T-helper 1 (Th1) cell-specific transcription factor and binds the promoter of IFN-gamma to directly regulate its transcription, and is thus involved importantly in Th1 cytokine production.
Gene Name:
PARP1
Uniprot ID:
P09874
Molecular weight:
113082.945
Reactions
NAD + (ADP-D-ribosyl)(n)-acceptor → Niacinamide + (ADP-D-ribosyl)(n+1)-acceptordetails
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed: 11752352
General function:
Involved in NAD+ nucleosidase activity
Specific function:
Synthesizes cyclic ADP-ribose, a second messenger that elicits calcium release from intracellular stores. May be involved in pre-B-cell growth.
Gene Name:
BST1
Uniprot ID:
Q10588
Molecular weight:
35723.545
Reactions
NAD + Water → Adenosine diphosphate ribose + Niacinamidedetails
NADP + Water → Niacinamide + (E)-3-(2,3-Dihydroxyphenyl)-2-propenoic aciddetails
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
General function:
Involved in NAD+ ADP-ribosyltransferase activity
Specific function:
Involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks.
Gene Name:
PARP2
Uniprot ID:
Q9UGN5
Molecular weight:
64804.695
Reactions
NAD + (ADP-D-ribosyl)(n)-acceptor → Niacinamide + (ADP-D-ribosyl)(n+1)-acceptordetails
General function:
Involved in NAD+ nucleosidase activity
Specific function:
Synthesizes cyclic ADP-ribose, a second messenger for glucose-induced insulin secretion. Also has cADPr hydrolase activity. Also moonlights as a receptor in cells of the immune system.
Gene Name:
CD38
Uniprot ID:
P28907
Molecular weight:
34328.145
Reactions
NAD + Water → Adenosine diphosphate ribose + Niacinamidedetails
NADP + Water → Niacinamide + (E)-3-(2,3-Dihydroxyphenyl)-2-propenoic aciddetails
General function:
Involved in NAD(P)+-protein-arginine ADP-ribosyltransferase activity
Specific function:
Not Available
Gene Name:
ART4
Uniprot ID:
Q93070
Molecular weight:
35878.285
Reactions
NAD + protein-L-arginine → Niacinamide + N(omega)-(ADP-D-ribosyl)-protein-L-argininedetails
NADP + protein-L-arginine → Niacinamide + N(omega)-((2'-phospho-ADP)-D-ribosyl)-protein-L-argininedetails
General function:
Involved in NAD+ ADP-ribosyltransferase activity
Specific function:
Not Available
Gene Name:
PARP4
Uniprot ID:
Q9UKK3
Molecular weight:
192592.915
Reactions
NAD + (ADP-D-ribosyl)(n)-acceptor → Niacinamide + (ADP-D-ribosyl)(n+1)-acceptordetails
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed: 19934256
General function:
Involved in monooxygenase activity
Specific function:
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms.
Gene Name:
CYP2E1
Uniprot ID:
P05181
Molecular weight:
56848.42
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed: 19934256
General function:
Involved in monooxygenase activity
Specific function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular weight:
55768.94
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed: 19934256
General function:
Involved in oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
Specific function:
Not Available
Gene Name:
LDHA
Uniprot ID:
P00338
Molecular weight:
30204.975
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed: 10592235
General function:
Involved in purine-nucleoside phosphorylase activity
Specific function:
The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate.
Gene Name:
PNP
Uniprot ID:
P00491
Molecular weight:
32117.69
Reactions
Nicotinamide riboside + Phosphoric acid → Niacinamide + Ribose 1-phosphatedetails
General function:
Involved in nicotinate phosphoribosyltransferase activity
Specific function:
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 (By similarity).
Gene Name:
NAMPT
Uniprot ID:
P43490
Molecular weight:
55520.8
Reactions
beta-nicotinamide D-ribonucleotide + Pyrophosphate → Niacinamide + Phosphoribosyl pyrophosphatedetails
General function:
Involved in nucleotide binding
Specific function:
May play a role in cell proliferation. May be required for the maintenance of cell cycle progression.
Gene Name:
PARP10
Uniprot ID:
Q53GL7
Molecular weight:
109997.35
Reactions
NAD + (ADP-D-ribosyl)(n)-acceptor → Niacinamide + (ADP-D-ribosyl)(n+1)-acceptordetails
General function:
Involved in NAD+ ADP-ribosyltransferase activity
Specific function:
Not Available
Gene Name:
PARP11
Uniprot ID:
Q9NR21
Molecular weight:
39596.545
Reactions
NAD + (ADP-D-ribosyl)(n)-acceptor → Niacinamide + (ADP-D-ribosyl)(n+1)-acceptordetails
General function:
Involved in NAD+ ADP-ribosyltransferase activity
Specific function:
Not Available
Gene Name:
PARP12
Uniprot ID:
Q9H0J9
Molecular weight:
79063.08
Reactions
NAD + (ADP-D-ribosyl)(n)-acceptor → Niacinamide + (ADP-D-ribosyl)(n+1)-acceptordetails
General function:
Involved in NAD+ ADP-ribosyltransferase activity
Specific function:
Enhances STAT6-dependent transcription (By similarity). Has ADP-ribosyltransferase activity.
Gene Name:
PARP14
Uniprot ID:
Q460N5
Molecular weight:
202798.68
Reactions
NAD + (ADP-D-ribosyl)(n)-acceptor → Niacinamide + (ADP-D-ribosyl)(n+1)-acceptordetails
General function:
Involved in NAD+ ADP-ribosyltransferase activity
Specific function:
Transcriptional repressor. Has ADP-ribosyltransferase activity.
Gene Name:
PARP15
Uniprot ID:
Q460N3
Molecular weight:
74575.465
Reactions
NAD + (ADP-D-ribosyl)(n)-acceptor → Niacinamide + (ADP-D-ribosyl)(n+1)-acceptordetails
General function:
Involved in NAD+ ADP-ribosyltransferase activity
Specific function:
Mono-ADP-ribosyltransferase targeting the karyopherin KPNB1. Plays a role in unfolded protein response (UPR), by ADP-ribosylating and activating EIF2AK3 and ERN1, two important UPR effectors.
Gene Name:
PARP16
Uniprot ID:
Q8N5Y8
Molecular weight:
36469.41
Reactions
NAD + protein-L-arginine → Niacinamide + N(omega)-(ADP-D-ribosyl)-protein-L-argininedetails
General function:
Involved in NAD+ ADP-ribosyltransferase activity
Specific function:
Not Available
Gene Name:
PARP6
Uniprot ID:
Q2NL67
Molecular weight:
71114.175
Reactions
NAD + (ADP-D-ribosyl)(n)-acceptor → Niacinamide + (ADP-D-ribosyl)(n+1)-acceptordetails
General function:
Involved in NAD+ ADP-ribosyltransferase activity
Specific function:
Not Available
Gene Name:
PARP8
Uniprot ID:
Q8N3A8
Molecular weight:
95870.105
Reactions
NAD + (ADP-D-ribosyl)(n)-acceptor → Niacinamide + (ADP-D-ribosyl)(n+1)-acceptordetails
General function:
Involved in NAD+ ADP-ribosyltransferase activity
Specific function:
Involved in inducing the expression of IFN-gamma-responsive genes.
Gene Name:
PARP9
Uniprot ID:
Q8IXQ6
Molecular weight:
96342.655
Reactions
NAD + (ADP-D-ribosyl)(n)-acceptor → Niacinamide + (ADP-D-ribosyl)(n+1)-acceptordetails
General function:
Involved in NAD+ ADP-ribosyltransferase activity
Specific function:
Poly [ADP-ribose] polymerase using NAD(+) as a substrate to transfer ADP-ribose onto glutamic acid residues of a protein acceptor; repeated rounds of ADP-ribosylation leads to the formation of poly(ADPribose) chains on the protein, thereby altering the function of the target protein. May play a role in the adaptative response to chemical exposure (TCDD) and thereby mediates certain effects of the chemicals (By similarity).
Gene Name:
TIPARP
Uniprot ID:
Q7Z3E1
Molecular weight:
76226.74
Reactions
NAD + (ADP-D-ribosyl)(n)-acceptor → Niacinamide + (ADP-D-ribosyl)(n+1)-acceptordetails
General function:
Involved in zinc ion binding
Specific function:
NAD-dependent protein deacetylase that links transcriptional regulation directly to intracellular energetics and participates in the coordination of several separated cellular functions such as cell cycle, response to DNA damage, metobolism, apoptosis and autophagy. Can modulate chromatin function through deacetylation of histones and can promote alterations in the methylation of histones and DNA, leading to transcriptional repression. Deacetylates a broad range of transcription factors and coregulators, thereby regulating target gene expression positively and negatively. Serves as a sensor of the cytosolic ratio of NAD(+)/NADH which is altered by glucose deprivation and metabolic changes associated with caloric restriction. Is essential in skeletal muscle cell differentiation and in response to low nutrients mediates the inhibitory effect on skeletal myoblast differentiation which also involves 5'-AMP-activated protein kinase (AMPK) and nicotinamide phosphoribosyltransferase (NAMPT). Component of the eNoSC (energy-dependent nucleolar silencing) complex, a complex that mediates silencing of rDNA in response to intracellular energy status and acts by recruiting histone-modifying enzymes. The eNoSC complex is able to sense the energy status of cell: upon glucose starvation, elevation of NAD(+)/NADP(+) ratio activates SIRT1, leading to histone H3 deacetylation followed by dimethylation of H3 at 'Lys-9' (H3K9me2) by SUV39H1 and the formation of silent chromatin in the rDNA locus. Deacetylates 'Lys-266' of SUV39H1, leading to its activation. Inhibits skeletal muscle differentiation by deacetylating PCAF and MYOD1. Deacetylates H2A and 'Lys-26' of HIST1H1E. Deacetylates 'Lys-16' of histone H4 (in vitro). Involved in NR0B2/SHP corepression function through chromatin remodeling: Recruited to LRH1 target gene promoters by NR0B2/SHP thereby stimulating histone H3 and H4 deacetylation leading to transcriptional repression. Proposed to contribute to genomic integrity via positive regulation of telomere length; however, reports on localization to pericentromeric heterochromatin are conflicting. Proposed to play a role in constitutive heterochromatin (CH) formation and/or maintenance through regulation of the available pool of nuclear SUV39H1. Upon oxidative/metabolic stress decreases SUV39H1 degradation by inhibiting SUV39H1 polyubiquitination by MDM2. This increase in SUV39H1 levels enhances SUV39H1 turnover in CH, which in turn seems to accelerate renewal of the heterochromatin which correlates with greater genomic integrity during stress response. Deacetylates 'Lys-382' of p53/TP53 and impairs its ability to induce transcription-dependent proapoptotic program and modulate cell senescence. Deacetylates TAF1B and thereby represses rDNA transcription by the RNA polymerase I. Deacetylates MYC, promotes the association of MYC with MAX and decreases MYC stability leading to compromised transformational capability. Deacetylates FOXO3 in response to oxidative stress thereby increasing its ability to induce cell cycle arrest and resistance to oxidative stress but inhibiting FOXO3-mediated induction of apoptosis transcriptional activity; also leading to FOXO3 ubiquitination and protesomal degradation. Appears to have a similar effect on MLLT7/FOXO4 in regulation of transcriptional activity and apoptosis. Deacetylates DNMT1; thereby impairs DNMT1 methyltransferase-independent transcription repressor activity, modulates DNMT1 cell cycle regulatory function and DNMT1-mediated gene silencing. Deacetylates RELA/NF-kappa-B p65 thereby inhibiting its transactivating potential and augments apoptosis in response to TNF-alpha. Deacetylates HIF1A, KAT5/TIP60, RB1 and HIC1. Deacetylates FOXO1 resulting in its nuclear retention and enhancement of its transcriptional activity leading to increased gluconeogenesis in liver. Inhibits E2F1 transcriptional activity and apoptotic function, possibly by deacetylation. Involved in HES1- and HEY2-mediated transcriptional repression. In cooperation with MYCN seems to be involved in transcriptional repression of DUSP6/MAPK3 leading to MYCN stabilization by phosphorylation at 'Ser-62'. Deacetylates MEF2D. Required for antagonist-mediated transcription suppression of AR-dependent genes which may be linked to local deacetylation of histone H3. Represses HNF1A-mediated transcription. Required for the repression of ESRRG by CREBZF. Modulates AP-1 transcription factor activity. Deacetylates NR1H3 AND NR1H2 and deacetylation of NR1H3 at 'Lys-434' positively regulates transcription of NR1H3:RXR target genes, promotes NR1H3 proteosomal degradation and results in cholesterol efflux; a promoter clearing mechanism after reach round of transcription is proposed. Involved in lipid metabolism. Implicated in regulation of adipogenesis and fat mobilization in white adipocytes by repression of PPARG which probably involves association with NCOR1 and SMRT/NCOR2. Deacetylates ACSS2 leading to its activation, and HMGCS1. Involved in liver and muscle metabolism. Through deacteylation and activation of PPARGC1A is required to activate fatty acid oxidation in skeletel muscle under low-glucose conditions and is involved in glucose homeostasis. Involved in regulation of PPARA and fatty acid beta-oxidation in liver. Involved in positive regulation of insulin secretion in pancreatic beta cells in response to glucose; the function seems to imply transcriptional repression of UCP2. Proposed to deacetylate IRS2 thereby facilitating its insuline-induced tyrosine phosphorylation. Deacetylates SREBF1 isoform SREBP-1C thereby decreasing its stability and transactivation in lipogenic gene expression. Involved in DNA damage response by repressing genes which are involved in DNA repair, such as XPC and TP73, deacetylating XRCC6/Ku70, and faciliting recruitment of additional factors to sites of damaged DNA, such as SIRT1-deacetylated NBN can recruit ATM to initiate DNA repair and SIRT1-deacetylated XPA interacts with RPA2. Also involved in DNA repair of DNA double-strand breaks by homologous recombination and specifically single-strand annealing independently of XRCC6/Ku70 and NBN. Transcriptional suppression of XPC probably involves an E2F4:RBL2 suppressor complex and protein kinase B (AKT) signaling. Transcriptional suppression of TP73 probably involves E2F4 and PCAF. Deacetylates WRN thereby regulating its helicase and exonuclease activities and regulates WRN nuclear translocation in response to DNA damage. Deacetylates APEX1 at 'Lys-6' and 'Lys-7' and stimulates cellular AP endonuclease activity by promoting the association of APEX1 to XRCC1. Increases p53/TP53-mediated transcription-independent apoptosis by blocking nuclear translocation of cytoplasmic p53/TP53 and probably redirecting it to mitochondria. Deacetylates XRCC6/Ku70 at 'Lys-539' and 'Lys-542' causing it to sequester BAX away from mitochondria thereby inhibiting stress-induced apoptosis. Is involved in autophagy, presumably by deacetylating ATG5, ATG7 and MAP1LC3B/ATG8. Deacetylates AKT1 which leads to enhanced binding of AKT1 and PDK1 to PIP3 and promotes their activation. Proposed to play role in regulation of STK11/LBK1-dependent AMPK signaling pathways implicated in cellular senescence which seems to involve the regulation of the acetylation status of STK11/LBK1. Can deacetylate STK11/LBK1 and thereby increase its activity, cytoplasmic localization and association with STRAD; however, the relevance of such activity in normal cells is unclear. In endothelial cells is shown to inhibit STK11/LBK1 activity and to promote its degradation. Deacetylates SMAD7 at 'Lys-64' and 'Lys-70' thereby promoting its degradation. Deacetylates CIITA and augments its MHC class II transacivation and contributes to its stability. Deacteylates MECOM/EVI1. Isoform 2 is shown to deacetylate 'Lys-382' of p53/TP53, however with lower activity than isoform 1. In combination, the two isoforms exert an additive effect. Isoform 2 regulates p53/TP53 expression and cellular stress response and is in turn repressed by p53/TP53 presenting a SIRT1 isoform-dependent auto-regulatory loop. In case of HIV-1 infection, interacts with and deacetylates the viral Tat protein. The viral Tat protein inhibits SIRT1 deacetylation activity toward RELA/NF-kappa-B p65, thereby potentiates its transcriptional activity and SIRT1 is proposed to contribute to T-cell hyperactivation during infection. SirtT1 75 kDa fragment: catalytically inactive 75SirT1 may be involved in regulation of apoptosis. May be involved in protecting chondrocytes from apoptotic death by associating with cytochrome C and interfering with apoptosome assembly.
Gene Name:
SIRT1
Uniprot ID:
Q96EB6
Molecular weight:
50496.105
Reactions
NAD + an acetylprotein → Niacinamide + O-acetyl-ADP-ribose + a proteindetails
General function:
Involved in zinc ion binding
Specific function:
NAD-dependent protein deacetylase, which deacetylates internal lysines on histone and non-histone proteins. Deacetylates 'Lys-40' of alpha-tubulin. Involved in the control of mitotic exit in the cell cycle, probably via its role in the regulation of cytoskeleton. Deacetylates PCK1, opposing proteasomal degradation. Deacetylates 'Lys-310' of RELA.
Gene Name:
SIRT2
Uniprot ID:
Q8IXJ6
Molecular weight:
26711.565
Reactions
NAD + an acetylprotein → Niacinamide + O-acetyl-ADP-ribose + a proteindetails
General function:
Involved in zinc ion binding
Specific function:
NAD-dependent protein deacetylase. Activates mitochondrial target proteins, including ACSS1, IDH2 and GDH by deacetylating key lysine residues. Contributes to the regulation of the cellular energy metabolism. Important for regulating tissue-specific ATP levels.
Gene Name:
SIRT3
Uniprot ID:
Q9NTG7
Molecular weight:
28566.64
Reactions
NAD + an acetylprotein → Niacinamide + O-acetyl-ADP-ribose + a proteindetails
General function:
Involved in zinc ion binding
Specific function:
NAD-dependent protein ADP-ribosyl transferase. Catalyzes the transfer of ADP-ribosyl groups onto target proteins, including mitochondrial GLUD1. Inhibits GLUD1 enzyme activity. Down-regulates insulin secretion. Has no detectable protein deacetylase activity.
Gene Name:
SIRT4
Uniprot ID:
Q9Y6E7
Molecular weight:
35187.205
Reactions
NAD + a protein → Niacinamide + an N-(ADP-D-ribosyl)-proteindetails
NAD + an acetylprotein → Niacinamide + O-acetyl-ADP-ribose + a proteindetails
General function:
Involved in zinc ion binding
Specific function:
NAD-dependent lysine demalonylase and desuccinylase that specifically removes malonyl and succinyl groups on target proteins. Activates CPS1 and contributes to the regulation of blood ammonia levels during prolonged fasting: acts by mediating desuccinylation of CPS1, thereby increasing CPS1 activity in response to elevated NAD levels during fasting. Has weak NAD-dependent protein deacetylase activity; however this activity may not be physiologically relevant in vivo. Can deacetylate cytochrome c (CYCS) and a number of other proteins in vitro.
Gene Name:
SIRT5
Uniprot ID:
Q9NXA8
Molecular weight:
31993.505
Reactions
NAD + a malonylprotein → Niacinamide + O-malonyl-ADP-ribose + a proteindetails
NAD + a succinylprotein → Niacinamide + O-succinyl-ADP-ribose + a proteindetails
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed: 17139284
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed: 17016423
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed: 10592235
General function:
Involved in zinc ion binding
Specific function:
NAD-dependent protein deacetylase that specifically mediates deacetylation of histone H3 at 'Lys-18' (H3K18Ac). In contrast to other histone deacetylases, displays selectivity for a single histone mark, H3K18Ac, directly linked to control of gene expression. H3K18Ac is mainly present around the transcription start site of genes and has been linked to activation of nuclear hormone receptors. SIRT7 thereby acts as a transcription repressor. Moreover, H3K18 hypoacetylation has been reported as a marker of malignancy in various cancers and seems to maintain the transformed phenotype of cancer cells. These data suggest that SIRT7 may play a key role in oncogenic transformation by suppresses expression of tumor suppressor genes by locus-specific deacetylation of H3K18Ac at promoter regions. Also required to restore the transcription of ribosomal RNA (rRNA) at the exit from mitosis: promotes the association of RNA polymerase I with the rDNA promoter region and coding region. Stimulates transcription activity of the RNA polymerase I complex. May also deacetylate p53/TP53 and promotes cell survival, however such data need additional confirmation.
Gene Name:
SIRT7
Uniprot ID:
Q9NRC8
Molecular weight:
44897.945
Reactions
NAD + an acetylprotein → Niacinamide + O-acetyl-ADP-ribose + a proteindetails
General function:
Involved in transferase activity, transferring phosphorus-containing groups
Specific function:
Catalyzes the last step of tRNA splicing, the transfer of the splice junction 2'-phosphate from ligated tRNA to NAD to produce ADP-ribose 1''-2'' cyclic phosphate (Probable).
Gene Name:
TRPT1
Uniprot ID:
Q86TN4
Molecular weight:
27741.69
Reactions
2'-phospho-[ligated tRNA] + NAD → mature tRNA + ADP ribose 1'',2''-phosphate + Niacinamide + Waterdetails