Menadione (T3D2704)

General Function:

Protein tyrosine phosphatase activity

Specific Function:

Tyrosine protein phosphatase which functions as a dosage-dependent inducer of mitotic progression. Required for G2/M phases of the cell cycle progression and abscission during cytokinesis in a ECT2-dependent manner. Directly dephosphorylates CDK1 and stimulates its kinase activity. The three isoforms seem to have a different level of activity.

Gene Name:

CDC25B

Uniprot ID:

P30305

Molecular Weight:

64986.745 Da

References

1. Sarkis M, Tran DN, Kolb S, Miteva MA, Villoutreix BO, Garbay C, Braud E: Design and synthesis of novel bis-thiazolone derivatives as micromolar CDC25 phosphatase inhibitors: effect of dimerisation on phosphatase inhibition. Bioorg Med Chem Lett. 2012 Dec 15;22(24):7345-50. doi: 10.1016/j.bmcl.2012.10.072. Epub 2012 Oct 22. [23141909 ]
2. Cao S, Murphy BT, Foster C, Lazo JS, Kingston DG: Bioactivities of simplified adociaquinone B and naphthoquinone derivatives against Cdc25B, MKP-1, and MKP-3 phosphatases. Bioorg Med Chem. 2009 Mar 15;17(6):2276-81. doi: 10.1016/j.bmc.2008.10.090. Epub 2008 Nov 8. [19028102 ]

General Function:

Ww domain binding

Specific Function:

Functions as a dosage-dependent inducer in mitotic control. Tyrosine protein phosphatase required for progression of the cell cycle. When phosphorylated, highly effective in activating G2 cells into prophase. Directly dephosphorylates CDK1 and activates its kinase activity.

Gene Name:

CDC25C

Uniprot ID:

P30307

Molecular Weight:

53364.17 Da

References

1. Contour-Galcera MO, Lavergne O, Brezak MC, Ducommun B, Prevost G: Synthesis of small molecule CDC25 phosphatases inhibitors. Bioorg Med Chem Lett. 2004 Dec 6;14(23):5809-12. [15501045 ]
2. Lavergne O, Fernandes AC, Brehu L, Sidhu A, Brezak MC, Prevost G, Ducommun B, Contour-Galcera MO: Synthesis and biological evaluation of novel heterocyclic quinones as inhibitors of the dual specificity protein phosphatase CDC25C. Bioorg Med Chem Lett. 2006 Jan 1;16(1):171-5. Epub 2005 Oct 10. [16216500 ]

General Function:

Xanthine dehydrogenase activity

Specific Function:

Oxidase with broad substrate specificity, oxidizing aromatic azaheterocycles, such as N1-methylnicotinamide and N-methylphthalazinium, as well as aldehydes, such as benzaldehyde, retinal, pyridoxal, and vanillin. Plays a key role in the metabolism of xenobiotics and drugs containing aromatic azaheterocyclic substituents. Participates in the bioactivation of prodrugs such as famciclovir, catalyzing the oxidation step from 6-deoxypenciclovir to penciclovir, which is a potent antiviral agent. Is probably involved in the regulation of reactive oxygen species homeostasis. May be a prominent source of superoxide generation via the one-electron reduction of molecular oxygen. Also may catalyze nitric oxide (NO) production via the reduction of nitrite to NO with NADH or aldehyde as electron donor. May play a role in adipogenesis.

Gene Name:

AOX1

Uniprot ID:

Q06278

Molecular Weight:

147916.735 Da

References

1. Pryde DC, Dalvie D, Hu Q, Jones P, Obach RS, Tran TD: Aldehyde oxidase: an enzyme of emerging importance in drug discovery. J Med Chem. 2010 Dec 23;53(24):8441-60. doi: 10.1021/jm100888d. Epub 2010 Sep 20. [20853847 ]

General Function:

Serotonin binding

Specific Function:

Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine.

Gene Name:

MAOA

Uniprot ID:

P21397

Molecular Weight:

59681.27 Da

References

1. Coelho Cerqueira E, Netz PA, Diniz C, Petry do Canto V, Follmer C: Molecular insights into human monoamine oxidase (MAO) inhibition by 1,4-naphthoquinone: evidences for menadione (vitamin K3) acting as a competitive and reversible inhibitor of MAO. Bioorg Med Chem. 2011 Dec 15;19(24):7416-24. doi: 10.1016/j.bmc.2011.10.049. Epub 2011 Oct 20. [22071524 ]

General Function:

Primary amine oxidase activity

Specific Function:

Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine.

Gene Name:

MAOB

Uniprot ID:

P27338

Molecular Weight:

58762.475 Da

References

1. Coelho Cerqueira E, Netz PA, Diniz C, Petry do Canto V, Follmer C: Molecular insights into human monoamine oxidase (MAO) inhibition by 1,4-naphthoquinone: evidences for menadione (vitamin K3) acting as a competitive and reversible inhibitor of MAO. Bioorg Med Chem. 2011 Dec 15;19(24):7416-24. doi: 10.1016/j.bmc.2011.10.049. Epub 2011 Oct 20. [22071524 ]

General Function:

Nadp binding

Specific Function:

Maintains high levels of reduced glutathione in the cytosol.

Gene Name:

GSR

Uniprot ID:

P00390

Molecular Weight:

56256.565 Da

References

1. Biot C, Bauer H, Schirmer RH, Davioud-Charvet E: 5-substituted tetrazoles as bioisosteres of carboxylic acids. Bioisosterism and mechanistic studies on glutathione reductase inhibitors as antimalarials. J Med Chem. 2004 Nov 18;47(24):5972-83. [15537352 ]

General Function:

Structural molecule activity

Specific Function:

Constitutes 1-2% of the total bone protein. It binds strongly to apatite and calcium.

Gene Name:

BGLAP

Uniprot ID:

P02818

Molecular Weight:

10962.445 Da

References

1. Price PA: Role of vitamin-K-dependent proteins in bone metabolism. Annu Rev Nutr. 1988;8:565-83. [3060178 ]

General Function:

Lipid binding

Specific Function:

Modulator of adipocyte lipid metabolism. Coats lipid storage droplets to protect them from breakdown by hormone-sensitive lipase (HSL). Its absence may result in leanness. Plays a role in unilocular lipid droplet formation by activating CIDEC. Their interaction promotes lipid droplet enlargement and directional net neutral lipid transfer. May modulate lipolysis and triglyceride levels.

Gene Name:

PLIN1

Uniprot ID:

O60240

Molecular Weight:

55989.785 Da

References

1. Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]

General Function:

Not Available

Specific Function:

Lipid droplet-associated protein that maintains the balance between lipogenesis and lipolysis and also regulates fatty acid oxidation in oxidative tissues. Recruits mitochondria to the surface of lipid droplets and is involved in lipid droplet homeostasis by regulating both the storage of fatty acids in the form of triglycerides and the release of fatty acids for mitochondrial fatty acid oxidation. In lipid droplet triacylglycerol hydrolysis, plays a role as a scaffolding protein for three major key lipolytic players: ABHD5, PNPLA2 and LIPE. Reduces the triacylglycerol hydrolase activity of PNPLA2 by recruiting and sequestering PNPLA2 to lipid droplets. Phosphorylation by PKA enables lipolysis probably by promoting release of ABHD5 from the perilipin scaffold and by facilitating interaction of ABHD5 with PNPLA2. Also increases lipolysis through interaction with LIPE and upon PKA-mediated phosphorylation of LIPE (By similarity).

Gene Name:

PLIN5

Uniprot ID:

Q00G26

Molecular Weight:

50790.96 Da

References

1. Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]

General Function:

Protein-glutamine gamma-glutamyltransferase activity

Specific Function:

Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins.

Gene Name:

TGM2

Uniprot ID:

P21980

Molecular Weight:

77328.21 Da

References

1. Lai TS, Liu Y, Tucker T, Daniel KR, Sane DC, Toone E, Burke JR, Strittmatter WJ, Greenberg CS: Identification of chemical inhibitors to human tissue transglutaminase by screening existing drug libraries. Chem Biol. 2008 Sep 22;15(9):969-78. doi: 10.1016/j.chembiol.2008.07.015. [18804034 ]

General Function:

Ubiquitin-specific protease activity

Specific Function:

Ubiquitin-protein hydrolase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins. This enzyme is a thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of ubiquitin. Also binds to free monoubiquitin and may prevent its degradation in lysosomes. The homodimer may have ATP-independent ubiquitin ligase activity.

Gene Name:

UCHL1

Uniprot ID:

P09936

Molecular Weight:

24824.17 Da

References

1. Love KR, Catic A, Schlieker C, Ploegh HL: Mechanisms, biology and inhibitors of deubiquitinating enzymes. Nat Chem Biol. 2007 Nov;3(11):697-705. [17948018 ]

General Function:

Ubiquitin-specific protease activity

Specific Function:

Deubiquitinating enzyme (DUB) that controls levels of cellular ubiquitin through processing of ubiquitin precursors and ubiquitinated proteins. Thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal glycine of either ubiquitin or NEDD8. Has a 10-fold preference for Arg and Lys at position P3", and exhibits a preference towards 'Lys-48'-linked Ubiquitin chains. Deubiquitinates ENAC in apical compartments, thereby regulating apical membrane recycling. Indirectly increases the phosphorylation of IGFIR, AKT and FOXO1 and promotes insulin-signaling and insulin-induced adipogenesis. Required for stress-response retinal, skeletal muscle and germ cell maintenance. May be involved in working memory. Can hydrolyze UBB(+1), a mutated form of ubiquitin which is not effectively degraded by the proteasome and is associated with neurogenerative disorders.

Gene Name:

UCHL3

Uniprot ID:

P15374

Molecular Weight:

26182.385 Da

References

1. Love KR, Catic A, Schlieker C, Ploegh HL: Mechanisms, biology and inhibitors of deubiquitinating enzymes. Nat Chem Biol. 2007 Nov;3(11):697-705. [17948018 ]

General Function:

Serine-type endopeptidase activity

Specific Function:

Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipids, and factor VIIIa.

Gene Name:

F9

Uniprot ID:

P00740

Molecular Weight:

51778.11 Da

General Function:

Serine-type peptidase activity

Specific Function:

Initiates the extrinsic pathway of blood coagulation. Serine protease that circulates in the blood in a zymogen form. Factor VII is converted to factor VIIa by factor Xa, factor XIIa, factor IXa, or thrombin by minor proteolysis. In the presence of tissue factor and calcium ions, factor VIIa then converts factor X to factor Xa by limited proteolysis. Factor VIIa will also convert factor IX to factor IXa in the presence of tissue factor and calcium.

Gene Name:

F7

Uniprot ID:

P08709

Molecular Weight:

51593.465 Da

General Function:

Serine-type endopeptidase activity

Specific Function:

Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.

Gene Name:

F10

Uniprot ID:

P00742

Molecular Weight:

54731.255 Da

General Function:

Superoxide dismutase activity

Specific Function:

The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinons involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis.

Gene Name:

NQO1

Uniprot ID:

P15559

Molecular Weight:

30867.405 Da

General Function:

Thrombospondin receptor activity

Specific Function:

Thrombin, which cleaves bonds after Arg and Lys, converts fibrinogen to fibrin and activates factors V, VII, VIII, XIII, and, in complex with thrombomodulin, protein C. Functions in blood homeostasis, inflammation and wound healing.

Gene Name:

F2

Uniprot ID:

P00734

Molecular Weight:

70036.295 Da

General Function:

Nadph dehydrogenase (quinone) activity

Specific Function:

The enzyme apparently serves as a quinone reductase in connection with conjugation reactions of hydroquinones involved in detoxification pathways as well as in biosynthetic processes such as the vitamin K-dependent gamma-carboxylation of glutamate residues in prothrombin synthesis.

Gene Name:

NQO2

Uniprot ID:

P16083

Molecular Weight:

25918.4 Da

General Function:

Vitamin-k-epoxide reductase (warfarin-sensitive) activity

Specific Function:

Involved in vitamin K metabolism. Catalytic subunit of the vitamin K epoxide reductase (VKOR) complex which reduces inactive vitamin K 2,3-epoxide to active vitamin K. Vitamin K is required for the gamma-carboxylation of various proteins, including clotting factors, and is required for normal blood coagulation, but also for normal bone development.

Gene Name:

VKORC1

Uniprot ID:

Q9BQB6

Molecular Weight:

18234.3 Da

General Function:

Vitamin-k-epoxide reductase (warfarin-sensitive) activity

Specific Function:

Involved in vitamin K metabolism. Can reduce inactive vitamin K 2,3-epoxide to active vitamin K (in vitro), and may contribute to vitamin K-mediated protection against oxidative stress. Plays a role in vitamin K-dependent gamma-carboxylation of Glu residues in target proteins.

Gene Name:

VKORC1L1

Uniprot ID:

Q8N0U8

Molecular Weight:

19835.425 Da

General Function:

Gamma-glutamyl carboxylase activity

Specific Function:

Mediates the vitamin K-dependent carboxylation of glutamate residues to calcium-binding gamma-carboxyglutamate (Gla) residues with the concomitant conversion of the reduced hydroquinone form of vitamin K to vitamin K epoxide.

Gene Name:

GGCX

Uniprot ID:

P38435

Molecular Weight:

87560.065 Da

General Function:

Serine-type endopeptidase activity

Specific Function:

Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts a protective effect on the endothelial cell barrier function (PubMed:25651845).

Gene Name:

PROC

Uniprot ID:

P04070

Molecular Weight:

52070.82 Da

General Function:

Endopeptidase inhibitor activity

Specific Function:

Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis.

Gene Name:

PROS1

Uniprot ID:

P07225

Molecular Weight:

75121.905 Da

General Function:

Serine-type endopeptidase activity

Specific Function:

Appears to assist hemostasis by binding thrombin and promoting its association with phospholipid vesicles. Inhibits activity of the coagulation protease factor Xa in the presence of SERPINA10, calcium and phospholipids.

Gene Name:

PROZ

Uniprot ID:

P22891

Molecular Weight:

44743.605 Da