Adenine (T3D4279)

General Function:

Metal ion binding

Specific Function:

Catalyzes the ATP-dependent carboxylation of acetyl-CoA to malonyl-CoA. Carries out three functions: biotin carboxyl carrier protein, biotin carboxylase and carboxyltransferase. Involved in inhibition of fatty acid and glucose oxidation and enhancement of fat storage (By similarity). May play a role in regulation of mitochondrial fatty acid oxidation through malonyl-CoA-dependent inhibition of carnitine palmitoyltransferase 1 (By similarity).

Gene Name:

ACACB

Uniprot ID:

O00763

Molecular Weight:

276538.575 Da

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. [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. [17016423 ]
3. Rasmussen JT, Rosendal J, Knudsen J: Interaction of acyl-CoA binding protein (ACBP) on processes for which acyl-CoA is a substrate, product or inhibitor. Biochem J. 1993 Jun 15;292 ( Pt 3):907-13. [8318018 ]
4. Witters LA, Mendel DB, Colliton JW: Modulation of acetyl-CoA carboxylase by inhibitors of IMP dehydrogenase: implications for insulin regulation. Arch Biochem Biophys. 1987 Jan;252(1):130-5. [2880560 ]
5. Itani SI, Saha AK, Kurowski TG, Coffin HR, Tornheim K, Ruderman NB: Glucose autoregulates its uptake in skeletal muscle: involvement of AMP-activated protein kinase. Diabetes. 2003 Jul;52(7):1635-40. [12829626 ]
6. 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. [10592235 ]

General Function:

Amp binding

Specific Function:

Catalyzes a salvage reaction resulting in the formation of AMP, that is energically less costly than de novo synthesis.

Gene Name:

APRT

Uniprot ID:

P07741

Molecular Weight:

19607.535 Da

References

1. Barrett C, Alley J, Pulido JC, Spurling H, Li P, Parsons T, Mallender WD, Bembenek ME: Configuration of a scintillation proximity assay for the activity assessment of recombinant human adenine phosphoribosyltransferase. Assay Drug Dev Technol. 2006 Dec;4(6):661-9. [17199504 ]
2. Di Pietro V, Perruzza I, Amorini AM, Balducci A, Ceccarelli L, Lazzarino G, Barsotti P, Giardina B, Tavazzi B: Clinical, biochemical and molecular diagnosis of a compound homozygote for the 254 bp deletion-8 bp insertion of the APRT gene suffering from severe renal failure. Clin Biochem. 2007 Jan;40(1-2):73-80. Epub 2006 Oct 19. [17126311 ]
3. Katahira R, Ashihara H: Profiles of purine biosynthesis, salvage and degradation in disks of potato (Solanum tuberosum L.) tubers. Planta. 2006 Dec;225(1):115-26. Epub 2006 Jul 15. [16845529 ]
4. Katahira R, Ashihara H: Role of adenosine salvage in wound-induced adenylate biosynthesis in potato tuber slices. Plant Physiol Biochem. 2006 Oct;44(10):551-5. Epub 2006 Oct 9. [17064924 ]
5. Boitz JM, Ullman B: Leishmania donovani singly deficient in HGPRT, APRT or XPRT are viable in vitro and within mammalian macrophages. Mol Biochem Parasitol. 2006 Jul;148(1):24-30. Epub 2006 Mar 15. [16597468 ]
6. 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. [10592235 ]

General Function:

Non-membrane spanning protein tyrosine phosphatase activity

Specific Function:

Acts on tyrosine phosphorylated proteins, low-MW aryl phosphates and natural and synthetic acyl phosphates. Isoform 3 does not possess phosphatase activity.

Gene Name:

ACP1

Uniprot ID:

P24666

Molecular Weight:

18042.315 Da

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. [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. [17016423 ]
3. Wang S, Stauffacher CV, Van Etten RL: Structural and mechanistic basis for the activation of a low-molecular weight protein tyrosine phosphatase by adenine. Biochemistry. 2000 Feb 15;39(6):1234-42. [10684601 ]
4. Magherini F, Gamberi T, Paoli P, Marchetta M, Biagini M, Raugei G, Camici G, Ramponi G, Modesti A: The in vivo tyrosine phosphorylation level of yeast immunophilin Fpr3 is influenced by the LMW-PTP Ltp1. Biochem Biophys Res Commun. 2004 Aug 20;321(2):424-31. [15358193 ]
5. Ostanin K, Pokalsky C, Wang S, Van Etten RL: Cloning and characterization of a Saccharomyces cerevisiae gene encoding the low molecular weight protein-tyrosine phosphatase. J Biol Chem. 1995 Aug 4;270(31):18491-9. [7629177 ]
6. 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. [10592235 ]

General Function:

Used for biological information storage.

Specific Function:

DNA contains the instructions needed for an organism to develop, survive and reproduce.

Molecular Weight:

2.15 x 10¹² Da

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. [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. [17016423 ]
3. Simon R, Heithoff DM, Mahan MJ, Samuel CE: Comparison of tissue-selective proinflammatory gene induction in mice infected with wild-type, DNA adenine methylase-deficient, and flagellin-deficient Salmonella enterica. Infect Immun. 2007 Dec;75(12):5627-39. Epub 2007 Sep 24. [17893133 ]
4. Ichida H, Maeda K, Ichise H, Matsuyama T, Abe T, Yoneyama K, Koba T: In silico restriction landmark genome scanning analysis of Xanthomonas oryzae pathovar oryzae MAFF 311018. Biochem Biophys Res Commun. 2007 Nov 23;363(3):852-6. Epub 2007 Sep 24. [17904519 ]
5. Mamdouh W, Dong M, Kelly RE, Kantorovich LN, Besenbacher F: Coexistence of homochiral and heterochiral adenine domains at the liquid/solid interface. J Phys Chem B. 2007 Oct 25;111(42):12048-52. Epub 2007 Oct 5. [17918893 ]

General Function:

S-methyl-5-thioadenosine phosphorylase activity

Specific Function:

Catalyzes the reversible phosphorylation of S-methyl-5'-thioadenosine (MTA) to adenine and 5-methylthioribose-1-phosphate. Involved in the breakdown of MTA, a major by-product of polyamine biosynthesis. Responsible for the first step in the methionine salvage pathway after MTA has been generated from S-adenosylmethionine. Has broad substrate specificity with 6-aminopurine nucleosides as preferred substrates.

Gene Name:

MTAP

Uniprot ID:

Q13126

Molecular Weight:

31235.76 Da

References

1. Chow WA, Bedell V, Gaytan P, Borden E, Goldblum J, Hicks D, Slovak ML: Methylthioadenosine phosphorylase gene deletions are frequently detected by fluorescence in situ hybridization in conventional chondrosarcomas. Cancer Genet Cytogenet. 2006 Apr 15;166(2):95-100. [16631464 ]
2. Chattopadhyay S, Zhao R, Tsai E, Schramm VL, Goldman ID: The effect of a novel transition state inhibitor of methylthioadenosine phosphorylase on pemetrexed activity. Mol Cancer Ther. 2006 Oct;5(10):2549-55. [17041099 ]
3. Singh V, Schramm VL: Transition-state structure of human 5'-methylthioadenosine phosphorylase. J Am Chem Soc. 2006 Nov 15;128(45):14691-6. [17090056 ]

General Function:

Rna polymerase ii carboxy-terminal domain kinase activity

Specific Function:

Plays a key role in the control of the eukaryotic cell cycle by modulating the centrosome cycle as well as mitotic onset; promotes G2-M transition, and regulates G1 progress and G1-S transition via association with multiple interphase cyclins. Required in higher cells for entry into S-phase and mitosis. Phosphorylates PARVA/actopaxin, APC, AMPH, APC, BARD1, Bcl-xL/BCL2L1, BRCA2, CALD1, CASP8, CDC7, CDC20, CDC25A, CDC25C, CC2D1A, CSNK2 proteins/CKII, FZR1/CDH1, CDK7, CEBPB, CHAMP1, DMD/dystrophin, EEF1 proteins/EF-1, EZH2, KIF11/EG5, EGFR, FANCG, FOS, GFAP, GOLGA2/GM130, GRASP1, UBE2A/hHR6A, HIST1H1 proteins/histone H1, HMGA1, HIVEP3/KRC, LMNA, LMNB, LMNC, LBR, LATS1, MAP1B, MAP4, MARCKS, MCM2, MCM4, MKLP1, MYB, NEFH, NFIC, NPC/nuclear pore complex, PITPNM1/NIR2, NPM1, NCL, NUCKS1, NPM1/numatrin, ORC1, PRKAR2A, EEF1E1/p18, EIF3F/p47, p53/TP53, NONO/p54NRB, PAPOLA, PLEC/plectin, RB1, UL40/R2, RAB4A, RAP1GAP, RCC1, RPS6KB1/S6K1, KHDRBS1/SAM68, ESPL1, SKI, BIRC5/survivin, STIP1, TEX14, beta-tubulins, MAPT/TAU, NEDD1, VIM/vimentin, TK1, FOXO1, RUNX1/AML1, SIRT2 and RUNX2. CDK1/CDC2-cyclin-B controls pronuclear union in interphase fertilized eggs. Essential for early stages of embryonic development. During G2 and early mitosis, CDC25A/B/C-mediated dephosphorylation activates CDK1/cyclin complexes which phosphorylate several substrates that trigger at least centrosome separation, Golgi dynamics, nuclear envelope breakdown and chromosome condensation. Once chromosomes are condensed and aligned at the metaphase plate, CDK1 activity is switched off by WEE1- and PKMYT1-mediated phosphorylation to allow sister chromatid separation, chromosome decondensation, reformation of the nuclear envelope and cytokinesis. Inactivated by PKR/EIF2AK2- and WEE1-mediated phosphorylation upon DNA damage to stop cell cycle and genome replication at the G2 checkpoint thus facilitating DNA repair. Reactivated after successful DNA repair through WIP1-dependent signaling leading to CDC25A/B/C-mediated dephosphorylation and restoring cell cycle progression. In proliferating cells, CDK1-mediated FOXO1 phosphorylation at the G2-M phase represses FOXO1 interaction with 14-3-3 proteins and thereby promotes FOXO1 nuclear accumulation and transcription factor activity, leading to cell death of postmitotic neurons. The phosphorylation of beta-tubulins regulates microtubule dynamics during mitosis. NEDD1 phosphorylation promotes PLK1-mediated NEDD1 phosphorylation and subsequent targeting of the gamma-tubulin ring complex (gTuRC) to the centrosome, an important step for spindle formation. In addition, CC2D1A phosphorylation regulates CC2D1A spindle pole localization and association with SCC1/RAD21 and centriole cohesion during mitosis. The phosphorylation of Bcl-xL/BCL2L1 after prolongated G2 arrest upon DNA damage triggers apoptosis. In contrast, CASP8 phosphorylation during mitosis prevents its activation by proteolysis and subsequent apoptosis. This phosphorylation occurs in cancer cell lines, as well as in primary breast tissues and lymphocytes. EZH2 phosphorylation promotes H3K27me3 maintenance and epigenetic gene silencing. CALD1 phosphorylation promotes Schwann cell migration during peripheral nerve regeneration.

Gene Name:

CDK1

Uniprot ID:

P06493

Molecular Weight:

34095.14 Da

References

1. Havlicek L, Hanus J, Vesely J, Leclerc S, Meijer L, Shaw G, Strnad M: Cytokinin-derived cyclin-dependent kinase inhibitors: synthesis and cdc2 inhibitory activity of olomoucine and related compounds. J Med Chem. 1997 Feb 14;40(4):408-12. [9046330 ]

General Function:

Utp binding

Specific Function:

Molecular chaperone that promotes the maturation, structural maintenance and proper regulation of specific target proteins involved for instance in cell cycle control and signal transduction. Undergoes a functional cycle that is linked to its ATPase activity. This cycle probably induces conformational changes in the client proteins, thereby causing their activation. Interacts dynamically with various co-chaperones that modulate its substrate recognition, ATPase cycle and chaperone function.

Gene Name:

HSP90AB1

Uniprot ID:

P08238

Molecular Weight:

83263.475 Da

References

1. Brough PA, Barril X, Borgognoni J, Chene P, Davies NG, Davis B, Drysdale MJ, Dymock B, Eccles SA, Garcia-Echeverria C, Fromont C, Hayes A, Hubbard RE, Jordan AM, Jensen MR, Massey A, Merrett A, Padfield A, Parsons R, Radimerski T, Raynaud FI, Robertson A, Roughley SD, Schoepfer J, Simmonite H, Sharp SY, Surgenor A, Valenti M, Walls S, Webb P, Wood M, Workman P, Wright L: Combining hit identification strategies: fragment-based and in silico approaches to orally active 2-aminothieno[2,3-d]pyrimidine inhibitors of the Hsp90 molecular chaperone. J Med Chem. 2009 Aug 13;52(15):4794-809. doi: 10.1021/jm900357y. [19610616 ]

General Function:

Protein serine/threonine kinase activity

Specific Function:

Serine/arginine-rich protein-specific kinase which specifically phosphorylates its substrates at serine residues located in regions rich in arginine/serine dipeptides, known as RS domains and is involved in the phosphorylation of SR splicing factors and the regulation of splicing. Promotes neuronal apoptosis by up-regulating cyclin-D1 (CCND1) expression. This is done by the phosphorylation of SRSF2, leading to the suppression of p53/TP53 phosphorylation thereby relieving the repressive effect of p53/TP53 on cyclin-D1 (CCND1) expression. Phosphorylates ACIN1, and redistributes it from the nuclear speckles to the nucleoplasm, resulting in cyclin A1 but not cyclin A2 up-regulation. Plays an essential role in spliceosomal B complex formation via the phosphorylation of DDX23/PRP28. Can mediate hepatitis B virus (HBV) core protein phosphorylation. Plays a negative role in the regulation of HBV replication through a mechanism not involving the phosphorylation of the core protein but by reducing the packaging efficiency of the pregenomic RNA (pgRNA) without affecting the formation of the viral core particles.

Gene Name:

SRPK2

Uniprot ID:

P78362

Molecular Weight:

77525.955 Da

References

1. 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. [10592235 ]

General Function:

Xanthine oxidase activity

Specific Function:

Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro).

Gene Name:

XDH

Uniprot ID:

P47989

Molecular Weight:

146422.99 Da

References

1. Hsieh JF, Wu SH, Yang YL, Choong KF, Chen ST: The screening and characterization of 6-aminopurine-based xanthine oxidase inhibitors. Bioorg Med Chem. 2007 May 15;15(10):3450-6. Epub 2007 Mar 12. [17379526 ]

General Function:

Not Available

Specific Function:

Not Available

Gene Name:

PECR

Uniprot ID:

Q9BY49

Molecular Weight:

32544.11 Da