117314PathwayTenofovir Action Pathway (New)
Tenofovir is a nucleotide analog that has shown to be effective against HIV, herpes simplex virus-2, and hepatitis B virus.
When HIV infects a cell, the virus first binds and fuses with the cell, releasing its nucleocapsid containing its RNA and reverse transcriptase into the cytosol of the cell. The reverse transcriptase converts the viral RNA into viral DNA in the cytosol. The viral DNA goes to the nucleus through the nuclear pore complex where it undergoes the process of transcription. The new viral RNA formed from transcription is transported back to the cytosol through the nuclear pore complex and translation occurs to produce viral proteins. These viral proteins are assembled and new HIV viruses bud from the cell.
Tenofovir enters the cell via solute carrier family 22 member 8 and is converted into tenofovir monophosphate by adenylate kinase. Nucleoside diphosphate kinase then converts tenofovir monophosphate into tenofovir diphosphate.
Tenofovir diphosphate is an analog of deoxyadenosine triphosphate (dATP). Tenofovir diphosphate inhibits the activity of HIV-1 reverse transcriptase by competing with its substrate, dATP and by incorporation into viral DNA. Tenofovir diphosphate lacks the 3'-OH group which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation, therefore, once tenofovir diphosphate gets incorporated into DNA, this causes DNA chain termination, preventing the growth of viral DNA. Less viral proteins are therefore produced, and there is a reduction in new viruses being formed.
Drug ActionPW126444CenterPathwayVisualizationContext12672036002500#000099PathwayVisualization117149117314Tenofovir Pathway (New)
Tenofovir is a nucleotide analog that has shown to be effective against HIV, herpes simplex virus-2, and hepatitis B virus.
When HIV infects a cell, the virus first binds and fuses with the cell, releasing its nucleocapsid containing its RNA and reverse transcriptase into the cytosol of the cell. The reverse transcriptase converts the viral RNA into viral DNA in the cytosol. The viral DNA goes to the nucleus through the nuclear pore complex where it undergoes the process of transcription. The new viral RNA formed from transcription is transported back to the cytosol through the nuclear pore complex and translation occurs to produce viral proteins. These viral proteins are assembled and new HIV viruses bud from the cell.
Tenofovir enters the cell via solute carrier family 22 member 8 and is converted into tenofovir monophosphate by adenylate kinase. Nucleoside diphosphate kinase then converts tenofovir monophosphate into tenofovir diphosphate.
Tenofovir diphosphate is an analog of deoxyadenosine triphosphate (dATP). Tenofovir diphosphate inhibits the activity of HIV-1 reverse transcriptase by competing with its substrate, dATP and by incorporation into viral DNA. Tenofovir diphosphate lacks the 3'-OH group which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation, therefore, once tenofovir diphosphate gets incorporated into DNA, this causes DNA chain termination, preventing the growth of viral DNA. Less viral proteins are therefore produced, and there is a reduction in new viruses being formed.
Drug1336861Andrade, C. H., Freitas, L. M., & Oliveira, V. de. (2011). Twenty-six years of HIV science: An overview of anti-HIV drugs metabolism. Brazilian Journal of Pharmaceutical Sciences, 47(2), 209–230. https://doi.org/10.1590/s1984-82502011000200003117314Pathway336862Safrin S (2017). Antiviral agents. Katzung B.G.(Ed.), Basic & Clinical Pharmacology, 14e. McGraw-Hill. https://accessmedicine-mhmedical-com.login.ezproxy.library.ualberta.ca/content.aspx?bookid=2249§ionid=175223510117314Pathway336863Wishart DS, Feunang YD, Guo AC, Lo EJ, Marcu A, Grant JR, Sajed T, Johnson D, Li C, Sayeeda Z, Assempour N, Iynkkaran I, Liu Y, Maciejewski A, Gale N, Wilson A, Chin L, Cummings R, Le D, Pon A, Knox C, Wilson M: DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. doi: 10.1093/nar/gkx1037117314Pathway336864Ritter, James (2020). Rang and Dale’s Pharmacology (9th ed). Antiviral drugs. Retrieved from: https://www-clinicalkey-com.login.ezproxy.library.ualberta.ca/#!/browse/book/3-s2.0-C2016004202X117314Pathway1CellCL:00000002Platelet CL:00002335HepatocyteCL:00001823NeuronCL:00005404CardiomyocyteCL:00007468Beta cellCL:00006397Epithelial CellCL:000006618ErythrocyteCL:00002321Homo sapiens9606EukaryoteHuman2Bacteria2ProkaryoteBacteria3Escherichia coli562Prokaryote12Mus musculus10090EukaryoteMouse17Rattus norvegicus10116EukaryoteRat19Schizosaccharomyces pombe4896Eukaryote24Solanum lycopersicum4081EukaryoteTomato4Arabidopsis thaliana3702EukaryoteThale cress18Saccharomyces cerevisiae4932EukaryoteYeast21Xenopus laevis8355EukaryoteAfrican clawed frog6Caenorhabditis elegans6239EukaryoteRoundworm25Escherichia coli (strain K12)83333Prokaryote49Bathymodiolus platifrons220390EukaryoteDeep sea mussel23Pseudomonas aeruginosa287Prokaryote60Nitzschia sp.0001EukaryoteNitzschia45Bos taurus9913EukaryoteCattle10Drosophila melanogaster7227EukaryoteFruit fly138human0046323Eukaryote186Human immunodeficiency virus type 111676EukaryoteHIV-11CytosolGO:00058295CytoplasmGO:00057373Mitochondrial MatrixGO:000575914Mitochondrial Outer MembraneGO:00057412MitochondrionGO:000573915NucleusGO:00056344PeroxisomeGO:000577713Endoplasmic ReticulumGO:00057837Endoplasmic Reticulum MembraneGO:000578910Cell MembraneGO:000588627Peroxisome MembraneGO:000577831Periplasmic SpaceGO:000562011Extracellular SpaceGO:000561535ChloroplastGO:000950712Mitochondrial Inner MembraneGO:000574332Inner MembraneGO:007025819Sarcoplasmic ReticulumGO:001652925Golgi ApparatusGO:000579426Golgi Apparatus MembraneGO:000013949Nuclear EnvelopeGO:000563537Basolateral cell membraneGO:001632356Basal Cell MembraneGO:000992539Mitochondrial membraneGO:00319668Blood VesselBTO:000110274112Endothelium BTO:00003931LiverBTO:00007597297Nervous SystemBTO:000148418PancreasBTO:000098825IntestineBTO:00006485cardiocyteBTO:00015396KidneyBTO:000067171837Blood-Brain BarrierBTO:00062442111PW_BS000002918511PW_BS0000914311PW_BS0000048511PW_BS00000816212PW_BS000016221411PW_BS00002213121PW_BS0000133211515PW_BS0000325411PW_BS000005397113PW_BS0000393211PW_BS000003181311PW_BS000018101711PW_BS00001049711PW_BS00004914101PW_BS0000145811411PW_BS000058592711PW_BS00005927151PW_BS00002746114PW_BS00004629111PW_BS0000296618518PW_BS00006672513PW_BS000072612517PW_BS0000615181PW_BS000051231511PW_BS000023311511PW_BS000031541315PW_BS000054892PW_BS000089261115PW_BS000026711PW_BS000007971521PW_BS000097100521PW_BS0001001041431PW_BS000104101531PW_BS0001011115121PW_BS0001111122121PW_BS000112103331PW_BS000103117131PW_BS0001171181171PW_BS0001181203171PW_BS00012012915121PW_BS0001291321121PW_BS0001321333121PW_BS0001331355171PW_BS00013510813PW_BS00010814315191PW_BS0001431465191PW_BS000146107313PW_BS0001071471241PW_BS000147151141PW_BS0001511553241PW_BS0001551613181PW_BS00016116611PW_BS0001661783211PW_BS000178188118PW_BS0000241601181PW_BS00016019914181PW_BS000024205561PW_BS000024206261PW_BS00002421013181PW_BS0000242137181PW_BS0000242111018PW_BS0000241985181PW_BS0000242164181PW_BS0000242171518PW_BS00002421815181PW_BS0000241632181PW_BS000163222341PW_BS0000241901118PW_BS0000242253541PW_BS0000242771218PW_BS00002417018PW_BS0001702811251PW_BS0000241644PW_BS0001642851041PW_BS000024226441PW_BS0000242905491PW_BS0000242231241PW_BS0000243081011PW_BS000024315123PW_BS0000243221231PW_BS0000243183123PW_BS000024253541PW_BS00002413412121PW_BS00013432914121PW_BS0000283331212PW_BS0000283361121PW_BS00002833217121PW_BS000028350114121PW_BS00002812815121PW_BS0001283511512PW_BS00002835325127PW_BS00002833527121PW_BS0000281151012PW_BS00011513013121PW_BS0001303317121PW_BS0000283344121PW_BS0000283683601PW_BS000028184121PW_BS0000241192171PW_BS00011911PW_BS000001124151PW_BS000124943PW_BS000094388161PW_BS000112109323PW_BS000109122551PW_BS000122406351PW_BS000115407251PW_BS0001153821451PW_BS000100412125PW_BS000115429151PW_BS0001151231751PW_BS00012343311451PW_BS000115408451PW_BS0001154101551PW_BS0001151251351PW_BS000125383751PW_BS000100405105PW_BS0001154222751PW_BS000115435155PW_BS00011539914171PW_BS0001134461217PW_BS0001154641171PW_BS00011544717171PW_BS000115468114171PW_BS0001153744171PW_BS00005344415171PW_BS00011513613171PW_BS0001363987171PW_BS0001133761017PW_BS00005347225177PW_BS00011537527171PW_BS0000534701517PW_BS0001152975101PW_BS0000244793101PW_BS0001152991101PW_BS0000244812101PW_BS00011548414101PW_BS00011548515101PW_BS00011530013101PW_BS0000244957101PW_BS0001154781010PW_BS00011549127101PW_BS0001154991510PW_BS000115501361PW_BS0001153891461PW_BS0001125161561PW_BS0001153951361PW_BS000113390761PW_BS000112209106PW_BS0000245082761PW_BS000115517156PW_BS0001158911421PW_BS00055215111PW_BS000015471914PW_BS00004731323PW_BS000024215114PW_BS000021432511PW_BS000043562611PW_BS00005621425181PW_BS0000242491341PW_BS0000242881441PW_BS00002435625121PW_BS000028372102PW_BS0000284192551PW_BS00011545525171PW_BS0001154824101PW_BS00011549025101PW_BS000115502461PW_BS0001155072561PW_BS0001157684911PW_BS000517229371PW_BS00002483265611PW_BS00054886881011PW_BS0005525311015PW_BS0000536816561PW_BS0005101067371PW_BS0005783093911PW_BS00002483351381PW_BS00054810761118PW_BS00057882311861PW_BS0005488834TenofovirHMDB0014445Tenofovir is only found in individuals that have used or taken this drug. Tenofovir, marketed by Gilead Sciences under the trade name Viread®, belongs to a class of antiretroviral drugs known as nucleotide analogue reverse transcriptase inhibitors (nRTIs), which block reverse transcriptase, an enzyme crucial to viral production in HIV-infected people. [Wikipedia]Tenofovir inhibits the activity of HIV reverse transcriptase by competing with the natural substrate deoxyadenosine 5’-triphosphate and, after incorporation into DNA, by DNA chain termination. Specifically, the drugs are analogues of the naturally occurring deoxynucleotides needed to synthesize the viral DNA and they compete with the natural deoxynucleotides for incorporation into the growing viral DNA chain. However, unlike the natural deoxynucleotides substrates, NRTIs and NtRTIs (nucleoside/tide reverse transcriptase inhibitors) lack a 3'-hydroxyl group on the deoxyribose moiety. As a result, following incorporation of an NRTI or an NtRTI, the next incoming deoxynucleotide cannot form the next 5'-3' phosphodiester bond needed to extend the DNA chain. Thus, when an NRTI or NtRTI is incorporated, viral DNA synthesis is halted, a process known as chain termination. All NRTIs and NtRTIs are classified as competitive substrate inhibitors. 147127-20-646420563625408154DB00300C[C@H](CN1C=NC2=C1N=CN=C2N)OCP(O)(O)=OC9H14N5O4PInChI=1S/C9H14N5O4P/c1-6(18-5-19(15,16)17)2-14-4-13-7-8(10)11-3-12-9(7)14/h3-4,6H,2,5H2,1H3,(H2,10,11,12)(H2,15,16,17)/t6-/m1/s1SGOIRFVFHAKUTI-ZCFIWIBFSA-N({[(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)phosphonic acid287.2123287.078340473-2.193tenofovir0-1Tenofovir disoproxil;Tenofovir disoproxil fumarate;D,l-tenofovir;Tdf;Pmpa;(r)-pmpa;Anh. tenofovir;Anhydrous tenofovir;Tenofovir (anh.)PW_C008834TenFvr35522476791414Adenosine triphosphateHMDB0000538Adenosine triphosphate (ATP) is a nucleotide consisting of a purine base (adenine) attached to the first carbon atom of ribose (a pentose sugar). Three phosphate groups are esterified at the fifth carbon atom of the ribose. ATP is incorporated into nucleic acids by polymerases in the processes of DNA replication and transcription. ATP contributes to cellular energy charge and participates in overall energy balance, maintaining cellular homeostasis. ATP can act as an extracellular signaling molecule via interactions with specific purinergic receptors to mediate a wide variety of processes as diverse as neurotransmission, inflammation, apoptosis, and bone remodelling. Extracellular ATP and its metabolite adenosine have also been shown to exert a variety of effects on nearly every cell type in human skin, and ATP seems to play a direct role in triggering skin inflammatory, regenerative, and fibrotic responses to mechanical injury, an indirect role in melanocyte proliferation and apoptosis, and a complex role in Langerhans cell-directed adaptive immunity. During exercise, intracellular homeostasis depends on the matching of adenosine triphosphate (ATP) supply and ATP demand. Metabolites play a useful role in communicating the extent of ATP demand to the metabolic supply pathways. Effects as different as proliferation or differentiation, chemotaxis, release of cytokines or lysosomal constituents, and generation of reactive oxygen or nitrogen species are elicited upon stimulation of blood cells with extracellular ATP. The increased concentration of adenosine triphosphate (ATP) in erythrocytes from patients with chronic renal failure (CRF) has been observed in many studies but the mechanism leading to these abnormalities still is controversial. (PMID: 15490415, 15129319, 14707763, 14696970, 11157473).56-65-5C00002595715422ATP5742DB00171NC1=NC=NC2=C1N=CN2[C@@H]1O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1OC10H16N5O13P3InChI=1S/C10H16N5O13P3/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(17)6(16)4(26-10)1-25-30(21,22)28-31(23,24)27-29(18,19)20/h2-4,6-7,10,16-17H,1H2,(H,21,22)(H,23,24)(H2,11,12,13)(H2,18,19,20)/t4-,6-,7-,10-/m1/s1ZKHQWZAMYRWXGA-KQYNXXCUSA-N({[({[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}oxy)phosphonic acid507.181506.995745159-2.057adenosine triphosphate0-3FDB0218135'-(tetrahydrogen triphosphate) adenosine;5'-atp;Atp;Adenosine 5'-triphosphate;Adenosine 5'-triphosphorate;Adenosine 5'-triphosphoric acid;Adenosine triphosphate;Adenylpyrophosphorate;Adenylpyrophosphoric acid;Adephos;Adetol;Adynol;Atipi;Atriphos;Cardenosine;Fosfobion;Glucobasin;Myotriphos;Phosphobion;Striadyne;Triadenyl;Triphosphaden;Triphosphoric acid adenosine ester;Adenosine-5'-triphosphate;H4atp;Adenosine triphosphoric acid;Adenosine-5'-triphosphoric acidPW_C000414ATP9221460826616414224781373332799593439976321051821121021464921561421605824055924342727264628122930296631637236166136175143992344743147689148645450328950352651557520597521510052501045291101531311153461125390103540611754301185443120554212955561325569133560313556211085846143585414658761075897147592415160481556109161623016664931786839188687016069761997157205718420672092107225213722921172981987302216739021774082187432163748122274991908186225118472771190317012010281120391641217828512578226126912901326422315327308423263154262132242694318770282537721813477233329774683337763233678037332780413507816812878214351782403537841133578494115788501307886533178919334800283688004618480674119856291948261241132349411328238811628010911991412211999240612015440712024538212036241212124642912139212312139743312147140812197441012206512512207938312208340512240242212244443512291939912300944612381646412395144712395646812402937412452744412461613612463039812463437612494347212497237512501147012530429712537147912539229912551548112559548412612348512622030012623449512624047812654749112659649912691350112712338912773151612778139512779639012780120912811950812816751714077089140511Tenofovir MonophosphateHMDB0061280Tenofovir phosphate belongs to the class of organic compounds known as 6-aminopurines. These are purines that carry an amino group at position 6. Purine is a bicyclic aromatic compound made up of a pyrimidine ring fused to an imidazole ring. Tenofovir phosphate is slightly soluble (in water) and a moderately acidic compound (based on its pKa).63202844881605C[C@H](CN1C=NC2=C1N=CN=C2N)OCP(O)(=O)OP(O)(O)=OC9H15N5O7P2InChI=1S/C9H15N5O7P2/c1-6(20-5-22(15,16)21-23(17,18)19)2-14-4-13-7-8(10)11-3-12-9(7)14/h3-4,6H,2,5H2,1H3,(H,15,16)(H2,10,11,12)(H2,17,18,19)/t6-/m1/s1BQDRSOMUPPCKPB-ZCFIWIBFSA-N{[({[(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)(hydroxy)phosphoryl]oxy}phosphonic acid367.1922367.044670883-2.174({[(2R)-1-(6-aminopurin-9-yl)propan-2-yl]oxy}methyl(hydroxy)phosphoryl)oxyphosphonic acid0-2DBMET01176PW_C040511TnfvrMP355324769911034Adenosine diphosphateHMDB0001341Adenosine diphosphate, abbreviated ADP, is a nucleotide. It is an ester of pyrophosphoric acid with the nucleotide adenine. ADP consists of the pyrophosphate group, the pentose sugar ribose, and the nucleobase adenine. ADP is the product of ATP dephosphorylation by ATPases. ADP is converted back to ATP by ATP synthases.58-64-0C00008602216761ADP5800NC1=NC=NC2=C1N=CN2[C@@H]1O[C@H](COP(O)(=O)OP(O)(O)=O)[C@@H](O)[C@H]1OC10H15N5O10P2InChI=1S/C10H15N5O10P2/c11-8-5-9(13-2-12-8)15(3-14-5)10-7(17)6(16)4(24-10)1-23-27(21,22)25-26(18,19)20/h2-4,6-7,10,16-17H,1H2,(H,21,22)(H2,11,12,13)(H2,18,19,20)/t4-,6-,7-,10-/m1/s1XTWYTFMLZFPYCI-KQYNXXCUSA-N[({[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]phosphonic acid427.2011427.029414749-2.126adenosine-diphosphate0-2FDB021817Adp;Adenosindiphosphorsaeure;Adenosine 5'-pyrophosphate;Adenosine diphosphate;Adenosine pyrophosphate;Adenosine-5'-diphosphate;Adenosine-5-diphosphate;Adenosine-diphosphate;5'-adenylphosphoric acid;Adenosine 5'-diphosphate;H3adp;5'-adenylphosphate;Adenosine 5'-diphosphoric acid;Adenosine-5'-diphosphoric acidPW_C001034ADP23413484152248213801596315978310611415182190149210418211310216158240859243527272847273646285529316572363561440023447631477091503626515775208975217100531511153491125392103544612055441295572133562410857411175764101584914358561465878107589914759261516050155611116162311666495178670094684118868721607159205718720672082107226213723121173001987303216739121774102187433163748322281872251185127711905170120132811218028513262223153293084232831542398313426223224269631877029253770871327721613477306329774723337766333678039332780433507817012878215351782443537841433578495115787053317884913078920334800303688062211880651135806761199482712411328338811620410911994412211999440612015640712031838212036641212124842912139412312139943312147240812189938312197641012206412512208540512240542212244543512297339912301344612381846412395344712395846812403037412445239812452944412461513612463637612494747212497537512501247012533429712537347912549229912551748112564548412612548512621930012623549512624247812655049112659749912691550112773351612778039512779739012780320912812250812816851712831338940512Tenofovir DiphosphateHMDB0061281Tenofovir diphosphate belongs to the class of organic compounds known as 6-aminopurines. These are purines that carry an amino group at position 6. Purine is a bicyclic aromatic compound made up of a pyrimidine ring fused to an imidazole ring. Tenofovir diphosphate is slightly soluble (in water) and a moderately acidic compound (based on its pKa).54811804587147C[C@H](CN1C=NC2=C1N=CN=C2N)OCP(O)(=O)OP(O)(=O)OP(O)(O)=OC9H16N5O10P3InChI=1S/C9H16N5O10P3/c1-6(2-14-4-13-7-8(10)11-3-12-9(7)14)22-5-25(15,16)23-27(20,21)24-26(17,18)19/h3-4,6H,2,5H2,1H3,(H,15,16)(H,20,21)(H2,10,11,12)(H2,17,18,19)/t6-/m1/s1IACQCQDWSIQSRP-ZCFIWIBFSA-N[({[({[(2R)-1-(6-amino-9H-purin-9-yl)propan-2-yl]oxy}methyl)(hydroxy)phosphoryl]oxy}(hydroxy)phosphoryl)oxy]phosphonic acid447.1721447.011001293-2.175[({[(2R)-1-(6-aminopurin-9-yl)propan-2-yl]oxy}methyl(hydroxy)phosphoryl)oxy(hydroxy)phosphoryl]oxyphosphonic acid0-3DBMET01177PW_C040512TenfDP3556247739150382351597423MagnesiumHMDB0000547Magnesium salts are essential in nutrition, being required for the activity of many enzymes, especially those concerned with oxidative phosphorylation. Physiologically, it exists as an ion in the body. It is a component of both intra- and extracellular fluids and is excreted in the urine and feces. Deficiency causes irritability of the nervous system with tetany, vasodilatation, convulsions, tremors, depression, and psychotic behavior. Magnesium ion in large amounts is an ionic laxative, and magnesium sulfate (Epsom salts) is sometimes used for this purpose. So-called "milk of magnesia" is a water suspension of one of the few insoluble magnesium compounds, magnesium hydroxide; the undissolved particles give rise to its appearance and name. Milk of magnesia is a mild base, and is commonly used as an antacid.22537-22-0C003058881842013-HYDROXY-MAGNESIUM-PROTOPORP865DB01378[Mg++]MgInChI=1S/Mg/q+2JLVVSXFLKOJNIY-UHFFFAOYSA-Nmagnesium(2+) ion24.30523.9850418980magnesium(2+) ion22FDB003518Magnesium;Magnesium ions;Magnesium ion;Magnesium, doubly charged positive ion;Magnesium, ion (mg(2+));Mg(2+);Mg2+PW_C000423Mg2+8682274268164762727268115819188832293639983399221116746148349152943176414212410241159294223312629337374540314774914869544974565253104532911153561125376103590614759341516038155609416162501666484178659416468811606979199717020571942067227213723321172502147310216731319874732221176313211843210123122251232424912513288125812261272929015275285153373087713713377236329779373367839333478417335784891157852233178536356785741308002036880045184800483728062311880654135808651580965253818415193832383949002710859622311055939011568739811997440612007012212024738212070240712098140812118112412126542912131941912192412512208640512240842212275912012292139912330711912354637412383546412388945512447713612463737612497837512544729712559848412566947912577748112592148212594729912597349512600049012624347812655349112675330012712538912716450112738050212740738812745150712780420912812550812834739514077389142916dATPDeoxyadenosine triphosphate (dATP) is a purine nucleoside triphosphate used in cells for DNA synthesis. A nucleoside triphosphate is a molecule type that contains a nucleoside with three phosphates bound to it. dATP contains the sugar deoxyribose, a precursor in DNA synthesis whereby the two existing phosphate groups are cleaved with the remaining deoxyadenosine monophosphate being incorporated into DNA during replication. Due to its enzymatic incorporation into DNA, photoreactive dATP analogs such as N6-[4-azidobenzoyl–(2-aminoethyl)]-2′-deoxyadenosine-5′-triphosphate (AB-dATP) and N6-[4-[3-(trifluoromethyl)-diazirin-3-yl]benzoyl-(2-aminoethyl)]-2′-deoxyadenosine-5′-triphosphate (DB-dATP) have been used for DNA photoaffinity labeling.2532018361404[H][C@]1(O)C[C@@]([H])(O[C@]1([H])COP([O-])(=O)OP([O-])(=O)OP([O-])([O-])=O)N1C=NC2=C(N)N=CN=C12C10H12N5O12P3InChI=1S/C10H16N5O12P3/c11-9-8-10(13-3-12-9)15(4-14-8)7-1-5(16)6(25-7)2-24-29(20,21)27-30(22,23)26-28(17,18)19/h3-7,16H,1-2H2,(H,20,21)(H,22,23)(H2,11,12,13)(H2,17,18,19)/p-4/t5-,6+,7+/m0/s1SUYVUBYJARFZHO-RRKCRQDMSA-J({[(2R,3S,5R)-5-(6-amino-9H-purin-9-yl)-3-hydroxyoxolan-2-yl]methyl phosphonato}oxy)(phosphonatooxy)phosphinate487.152486.97172616-2.0522'-deoxyadenosine triphosphate-4-32'-deoxyatp, 2'-deoxyadenosine triphosphate, deoxy-atp, deoxyadenosine-triphosphate, 2'-deoxyadenosine-5'-triphosphatePW_C042916dATP612Viral ProteinsProteinComplexProteinComplexPW_EC00061223604Nuclear pore complex protein Nup98-Nup96P52948
Plays a role in the nuclear pore complex (NPC) assembly and/or maintenance. NUP98 and NUP96 are involved in the bidirectional transport across the NPC. May anchor NUP153 and TPR to the NPC. In cooperation with DHX9, plays a role in transcription and alternative splicing activation of a subset of genes (PubMed:28221134). Involved in the localization of DHX9 in discrete intranuclear foci (GLFG-body) (PubMed:28221134).
NUP9813.4.21.-1400412314100876823605Nuclear pore complex P529481140042235801Solute carrier family 22 member 8Q8TCC7SLC22A81845522914100330814126583214387951143927868143946531439526811439531067144293309533Adenylate kinase isoenzyme 1P00568Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. Small ubiquitous enzyme involved in energy metabolism and nucleotide synthesis that is essential for maintenance and cell growth.
HMDBP00562AK19q34.1BC00111612.7.4.3; 2.7.4.67242619078355424762314771911404148331430441076105Nucleoside diphosphate kinase AP15531Major role in the synthesis of nucleoside triphosphates other than ATP. Possesses nucleoside-diphosphate kinase, serine/threonine-specific protein kinase, geranyl and farnesyl pyrophosphate kinase, histidine protein kinase and 3'-5' exonuclease activities. Involved in cell proliferation, differentiation and development, signal transduction, G protein-coupled receptor endocytosis, and gene expression. Required for neural development including neural patterning and cell fate determination.
HMDBP00109NME117q21.3X1762012.7.4.67292633747355724108234320847653147759114351332108Nucleoside diphosphate kinase BP22392Major role in the synthesis of nucleoside triphosphates other than ATP. Negatively regulates Rho activity by interacting with AKAP13/LBC. Acts as a transcriptional activator of the MYC gene; binds DNA non-specifically (PubMed:8392752). Exhibits histidine protein kinase activity.
HMDBP00112NME217q21.3M3698112.7.4.6; 2.7.13.3728261519247663147769123596Reverse transcriptase proteinQ9WJQ2reverse transcriptase1861399422313994321400318232398Adenylate kinase 2, mitochondrialP54819Catalyzes the reversible transfer of the terminal phosphate group between ATP and AMP. This small ubiquitous enzyme involved in energy metabolism and nucleotide synthesis that is essential for maintenance and cell growth. Plays a key role in hematopoiesis.
HMDBP04072AK21p34U3994512.7.4.3725263555247633147729114237141096Solute carrier family 22 member 81PW_P001096125758011204Adenylate kinase isoenzyme 11PW_P000204222533206Nucleoside diphosphate kinase A1PW_P0002062241056934231207Nucleoside diphosphate kinase B1PW_P00020722510894423114533Reverse Transcriptase186PW_P0145332451423596205Adenylate kinase 2, mitochondrial1PW_P00020522323981808falsePW_R001808Right675488341Compoundfalse85524141Compoundtrue6755405111Compoundfalse855310341Compoundtrue154320415442052.7.4.31807falsePW_R001807Right6752405111Compoundfalse85544141Compoundtrue6753405121Compoundfalse855510341Compoundtrue15452062.7.4.6154620713934PW_T0139341435588341Compound152Right494410962021-12-06T02:38:45-07:002021-12-06T02:38:45-07:003083836InhibitionPW_I003836767140512Compound1767214533ProteinComplex14300ActivationPW_I004300859942916Compound1860014533ProteinComplex13145908883415157false25010010regular200190314590988342157false25090510regular2001903145913414242false47091010regular5030314591440511281false80090710regular20019031459151034243false735108710regular50303145916414242false104589710regular5030314591740512281false138090710regular20019031459181034243false1305108710regular5030314591942329false114092216regular10025314592042329false1155107716regular10025319295342916281false205090710regular200190243886121442false1380319212regular1507012147562360476876false1770143320subunitregular1507012147572360576false1045272820subunitregular150701214821580130876false2753958subunitregular15070121482353322false5459678subunitregular150701214824105217false1100100213subunitregular18085121482510822false111593212subunitregular1507012148262359622false17509678subunitregular150709565721096117149120929512148219565742041171492120929712148239565752061171492120929812148244603831459194299358Cofactor9565762071171492120929912148254603931459204299359Cofactor956577145331171492120930012148264299133M1825 1037 C1826 1093 1827 1123.1666870117188 1825 1169.1666870117188 5false18true1543.0713449077346,1016.3627876355049 1550,1029.6666870117188 1558.0571872830603,1017.0143459996495false4299134M1825 814.5 C1826 866.5 1825 924 1825 972 5false18falsefalse4299135M1846 1361.8333435058594 C1845 1438.8333435058594 1845 1544.8333435058594 1845 1590.8333435058594 83false14falsefalsetrue1542.5,1398.3429624490927 1550,1411.3333435058594 1557.5,1398.3429624490927false4299136M1326 1678.8333129882812 C1370 1678.8333129882812 1731 1674.8333129882812 1769 1675.8333129882812 218false18trueM 1168.9903810567666 1496.8333129882812 L 1156 1504.3333129882812 L 1168.9903810567666 1511.8333129882812false4299137M1292 1842.5 C1305 1870.5 1361 1991.5 1377 2024.5 218false18trueM 1149.58403510137 1816.5831231661625 L 1162 1825 L 1163.081246709313 1810.0390205683718false4299138M1455 2541.5 C1456 2579.5 1456 2630.5 1456 2705.5 218false18trueM 1093.5 2493.0096189432334 L 1101 2506 L 1108.5 2493.0096189432334false4299139M938 2765.166748046875 C1009 2765.166748046875 1326 2764.166748046875 1385 2764.166748046875 83false18trueM 734.9903810567666 2553.166748046875 L 722 2560.666748046875 L 734.9903810567666 2568.166748046875false4299140M988 3227.166748046875 C1031 3226.166748046875 1334 3227.5 1380 3227.5 218false20trueM 1112.0096189432334 2905.5 L 1125 2898 L 1112.0096189432334 2890.5false4299141M867 2891.166748046875 C867 2940.166748046875 867 2988.166748046875 867 3059.166748046875 218false18trueM 644.844329429519 2763.4835625939295 L 652 2776.666748046875 L 659.8391382198117 2763.878162825253false4299344M350 290 C350 320 350 365 350 395 83false184299345M350 905 C350 875 350 495 350 465 83false18trueM 25.946855044164835 13.26155629629604 L 11 12 L 17.380887721185843 25.575134323078345false4299350M450 1000 C480 1000 515 1002 545 1002 5false184299351M495 940 C495 981 515 1002 545 1002 5false184299352M800 1002 C770 1002 725 1002 695 1002 5false18trueM 109.94685504416483 288.261556296296 L 95 287 L 101.38088772118584 300.5751343230783false4299353M760 1087 C759 1041 725 1002 695 1002 5false18trueM 109.94685504416483 288.261556296296 L 95 287 L 101.38088772118584 300.5751343230783false4299354M1000 1002 C1030 1002 1160 1002 1190 1002 5false104299355M1070 927 C1077 997 1160 1002 1190 1002 5false104299356M1380 1002 C1350 1002 1220 1002 1190 1002 5false11trueM 109.94685504416483 288.261556296296 L 95 287 L 101.38088772118584 300.5751343230783false4299357M1330 1087 C1324 1022 1220 1002 1190 1002 5false11trueM 109.94685504416483 288.261556296296 L 95 287 L 101.38088772118584 300.5751343230783false4299358M1115 617 L1115 667 L1165 617 z10true184299359M1115 737 L1115 787 L1165 737 z10true184299360M1580 1002 C1610 1002 1612.5 862 1642.5 862 148true184299361M1750 1002 C1720 1002 1610 1002 1580 1002 148false18falsetrueM 466.565967322979 198.6864219732177 L 458 211 L 449.434032677021 223.31357802678234373644M2050 1002 C2020 1002 1930 1002 1900 1002 149true184373645M1900 1002 C1930 1002 2020 1002 2050 1002 149false18trueM 746.9468550441649 279.261556296296 L 732 278 L 738.3808877211858 291.5751343230783false92403711714918082375726731459094299350Left375726831459134299351Left375726931459144299352Right375727031459154299353Right877637154395657492403811714918072375727131459144299354Left375727231459164299355Left375727331459174299356Right375727431459184299357Right877638154595657587763915469565761033491393411714920827831459084299344Left20827931459094299345Right4915995657249441199238361171492323831459174299360Left157099565774299361Right1438643001171492461031929534373644Left185409565774373645Right77114429913377115429913477116429913577117429913677118429913777119429913877120429913977121429914077122429914169224388553812147565539121475747506924518992.22.2031432726747507018255691.31.30212571145475071183011511.01.0061267815447507217155711.31.30212571145475073176511561.01.00412678154475074118515621.91.9076678154475075178016011.01.00812678154475076184516061.01.00812678154475077168515730.80.80752400274475078114520010.40.408412000184547507932526590.40.40104217851645475080140027021.31.30812571145475081148526971.31.3081257114547508284526691.31.30121257114547508375526691.31.301212571145475084129031140.80.8025240027447508617569431.31.302047102101484348163110941.01.0025240027448434934521471.91.9-1052328036048435015211150.60.6021327487014843517105351.01.0021490240472807M127 524.5 C127 474.5 177 424.5 227 424.5 C848 424.5 1654 424.5 2275 424.5 C2325 424.5 2375 474.5 2375 524.5 C2375 1388.5 2375 2512.5 2375 3376.5 C2375 3426.5 2325 3476.5 2275 3476.5 C1654 3476.5 848 3476.5 227 3476.5 C177 3476.5 127 3426.5 127 3376.5 C127 2512.5 127 1388.5 127 524.5 1true60.00.0472808M1079 1570.5 C1079 1520.5 1129 1470.5 1179 1470.5 C1434 1470.5 1767 1470.5 2022 1470.5 C2072 1470.5 2122 1520.5 2122 1570.5 C2122 1980.5 2122 2514.5 2122 2924.5 C2122 2974.5 2072 3024.5 2022 3024.5 C1767 3024.5 1434 3024.5 1179 3024.5 C1129 3024.5 1079 2974.5 1079 2924.5 C1079 2514.5 1079 1980.5 1079 1570.5 93true60.00.0885161235HIV Infected Cell555324202.22.220015885162235Integration14101620201.31.320015885163235Nucleus11751393201.91.920015885164235Viral RNA1650735201.61.620015885165235Viral DNA16651271201.61.62001588516615Less Viral DNA is transported into the nucleus, therefore, less viral DNA is integrated into the host DNA.13651746202.22.216015885167235Transcription13452307201.91.920015885168235Translation6153259201.91.92001588516915Less viral proteins produced, fewer viruses can form.16543093202.52.516015885170235Cytosol3251203202.22.22001588517215Tenofovir diphosphate inhibits the activity of reverse transcriptase by competing with its substrate dATP.1946537202.22.216015885173235Extracellular Space545150202.22.220015885259235Viral mRNA13352849201.61.62001588526015Tenofovir diphosphate gets incorporated into viral DNA, but since it lacks the 3'-OH group which is needed to form the 5′ to 3′ phosphodiester linkage essential for DNA chain elongation, this causes DNA chain termination, preventing the growth of viral DNA.11851083202.22.216015885261235Viral mRNA7352853201.31.320015885262235Viral DNA17281721201.31.3200152815626912147105014432149305239#FFF9C9410991609