BioPAX pathway converted from "Purine salvage" in the Reactome database.

Purine salvage

Nucleosides and free bases generated by DNA and RNA breakdown are converted back to nucleotide monophosphates, allowing them to re-enter the pathway of purine biosynthesis and interconversiohn. Under normal conditions, DNA turnover is limited and deoxyribonucleotide salvage operates at a correspondingly low level (Watts 1974).

Authored: Jassal, B, 2003-07-17 08:31:43 Edited: D'Eustachio, P, 0000-00-00 00:00:00 deoxyadenosine or deoxyguanosine + ATP => dAMP or dGMP + ADP (DCK)

deoxyadenosine or deoxyguanosine + ATP => dAMP or dGMP + ADP (DCK)

Cytosolic deoxycytidine kinase (DCK) catalyzes the reactions of deoxyadenosine and deoxyguanosine with ATP to form the corresponding nucleotide monophosphates and AMP, The enzyme is a dimer (Bohman and Eriksson 1988; Datta et al. 1989). While the enzyme can be found in nuclei of cultured cells expressing high levels of a tagged recombinant protein, its normal location appears to be cytosolic (Hatzis et al. 1998).

ReactomeDB_ID: 113592

cytosol GO 0005829

ATP(4-) [ChEBI:30616]

ATP(4-)

腺苷5 '三磷酸 atp ATP Reactome //www.joaskin.com ChEBI 30616 Converted from EntitySet in Reactome

ReactomeDB_ID: 500201

dA, dG [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity dA [cytosol] dG [cytosol] ChEBI 17256 ChEBI 17172 Converted from EntitySet in Reactome

ReactomeDB_ID: 500199

dAMP, dGMP [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity 2'-deoxyguanosine 5'-monophosphate [cytosol] 2'-deoxyadenosine 5'-monophosphate [cytosol] ChEBI 16192 ChEBI 17713

ReactomeDB_ID: 29370

ADP(3-) [ChEBI:456216]

ADP(3-)

ADP trianion 5'-O-[(phosphonatooxy)phosphinato]adenosine ADP ChEBI 456216 PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

ReactomeDB_ID: 73516 DCK dimer [cytosol]

DCK dimer

deoxycytidine kinase holoenzyme

ReactomeDB_ID: 29926

magnesium(2+) [ChEBI:18420]

magnesium(2+)

ChEBI 18420

ReactomeDB_ID: 73515

UniProt:P27707 DCK

DCK

DCK 函数磷酸化deoxyribonucleosides deoxycytidine, deoxyguanosine and deoxyadenosine (PubMed:1996353, PubMed:12808445, PubMed:18377927, PubMed:19159229, PubMed:20614893). Has broad substrate specificity, and does not display selectivity based on the chirality of the substrate. It is also an essential enzyme for the phosphorylation of numerous nucleoside analogs widely employed as antiviral and chemotherapeutic agents (PubMed:12808445).SUBUNIT Homodimer.PTM Phosphorylated and activated in vitro upon phosphorylation at Ser-74 by CSNK1D/CK1.SIMILARITY Belongs to the DCK/DGK family.CAUTION Was shown to be phosphorylated and activated by CSNK1D/CK1 in vitro but probably not in vivo. Homo sapiens

NCBI Taxonomy 9606 UniProt P27707

Chain Coordinates

EQUAL

260

EQUAL

ReactomeDatabase ID Release 77 73516 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=73516 Reactome R-HSA-73516

Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-73516.1 GO 0019206

GO molecular function

ReactomeDatabase ID Release 77 73517 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=73517 ReactomeDatabase ID Release 77 109671 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=109671 Reactome R-HSA-109671

Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-109671.4 2539852 Pubmed 1989 Human T-lymphoblast deoxycytidine kinase: purification and properties Datta, NS Shewach, DS Hurley, MC Mitchell, BS Fox, IH Biochemistry 28:114-123 2844225 Pubmed 1988 Deoxycytidine kinase from human leukemic spleen: preparation and characterization of the homogeneous enzyme Bohman, C Eriksson, S Biochemistry 27:4258-4265 9804782 Pubmed 1998 The intracellular localization of deoxycytidine kinase Hatzis, P Al-Madhoon, AS Jullig, M Petrakis, TG Eriksson, S Talianidis, I J Biol Chem 273:30239-30243

2.4.2.7

Adenine + PRPP => AMP + PPi

Cytosolic APRT dimer catalyzes the reaction of adenine and 5-phospho-alpha-D-ribose 1-diphosphate to form AMP and pyrophosphate (Holden et al. 1979).

ReactomeDB_ID: 73566

5-O-phosphono-alpha-D-ribofuranosyl diphosphate [ChEBI:17111]

5-O-phosphono-alpha-D-ribofuranosyl diphosphate

ChEBI 17111

ReactomeDB_ID: 83951

亚丁湾ine [ChEBI:16708]

亚丁湾ine

6-aminopurine ChEBI 16708

ReactomeDB_ID: 111294

diphosphoric acid [ChEBI:29888]

diphosphoric acid

ChEBI 29888

ReactomeDB_ID: 76577

亚丁湾osine 5'-monophosphate [ChEBI:16027]

亚丁湾osine 5'-monophosphate

ChEBI 16027 PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

ReactomeDB_ID: 74211 APRT dimer [cytosol]

APRT dimer

ReactomeDB_ID: 50171

UniProt:P07741 APRT

APRT

APRT FUNCTION Catalyzes a salvage reaction resulting in the formation of AMP, that is energically less costly than de novo synthesis.PATHWAY Purine metabolism; AMP biosynthesis via salvage pathway; AMP from adenine: step 1/1.SUBUNIT Homodimer.SIMILARITY Belongs to the purine/pyrimidine phosphoribosyltransferase family. UniProt P07741

EQUAL

180

EQUAL

ReactomeDatabase ID Release 77 74211 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=74211 Reactome R-HSA-74211

Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-74211.2 GO 0003999

GO molecular function

ReactomeDatabase ID Release 77 74212 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=74212 ReactomeDatabase ID Release 77 74213 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=74213 Reactome R-HSA-74213

Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-74213.2 457664 Pubmed 1979 Human adenine phosphoribosyltransferase. Affinity purification, subunit structure, amino acid composition, and peptide mapping. Holden, JA Meredith, GS Kelley, WN J Biol Chem 254:6951-5

3.5.4.6

AMP + H2O => IMP + NH4+ (AMPD)

Cytosolic AMP deaminase (AMPD) catalyzes the hydrolysis of AMP to yield IMP and ammonia. Three isoforms of AMPD, E, L, and M, have been identified that differ in their expression patterns in the body. All occur as tetramers and all have qualitatively the same catalytic activity, however (Bausch-Jurken et al. 1992; Mahnke-Zizelman et al. 1998).

ReactomeDB_ID: 29356

water [ChEBI:15377]

water

ChEBI 15377

ReactomeDB_ID: 76577

ReactomeDB_ID: 29602

IMP [ChEBI:17202]

IMP

5'-Inosinate Inosine monophosphate Inosine 5'-phosphate Inosine 5'-monophosphate 5'-Inosine monophosphate 5'-Inosinic acid Inosinic acid ChEBI 17202

ReactomeDB_ID: 31633

ammonium [ChEBI:28938]

ammonium

ChEBI 28938 PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Converted from EntitySet in Reactome

ReactomeDB_ID: 500235

AMPD tetramers [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity GO 0003876

GO molecular function

ReactomeDatabase ID Release 77 76587 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=76587 ReactomeDatabase ID Release 77 76590 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=76590 Reactome R-HSA-76590

Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-76590.4 1429593 Pubmed 1992 Molecular cloning of AMP deaminase isoform L. Sequence and bacterial expression of human AMPD2 cDNA Bausch-Jurken, MT Mahnke-Zizelman, DK Morisaki T Sabina, RL J Biol Chem 267:22407-13 9857047 Pubmed 1998 Novel aspects of tetramer assembly and N-terminal domain structure and function are revealed by recombinant expression of human AMP deaminase isoforms Mahnke-Zizelman, DK Tullson, PC Sabina, RL J Biol Chem 273:35118-25

2.4.2.8

guanine or hypoxanthine + PRPP => GMP or IMP + PPi (HPRT1)

Cytosolic hypoxanthine-guanine phosphoribosyltransferase (HPRT1) tetramer catalyzes the reactions of guanine or hypoxanthine with PRPP to form GMP ir IMP and pyrophosphate (Holden and Kelley 1978; Jolly et al. 1983).

Converted from EntitySet in Reactome

ReactomeDB_ID: 500259

Gua, Hyp [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Hyp [cytosol] Gua [cytosol] ChEBI 17368 ChEBI 16235

ReactomeDB_ID: 73566

ReactomeDB_ID: 111294

Converted from EntitySet in Reactome

ReactomeDB_ID: 500260

GMP, IMP [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity GMP [cytosol] IMP [cytosol] ChEBI 17345 PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

ReactomeDB_ID: 74208 HGPRT tetramer [cytosol]

HGPRT tetramer

ReactomeDB_ID: 29926

ReactomeDB_ID: 56639

UniProt:P00492 HPRT1

HPRT1

HPRT1 HPRT FUNCTION Converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate. Transfers the 5-phosphoribosyl group from 5-phosphoribosylpyrophosphate onto the purine. Plays a central role in the generation of purine nucleotides through the purine salvage pathway.PATHWAY Purine metabolism; IMP biosynthesis via salvage pathway; IMP from hypoxanthine: step 1/1.SUBUNIT Homotetramer.SIMILARITY Belongs to the purine/pyrimidine phosphoribosyltransferase family. UniProt P00492

EQUAL

218

EQUAL

ReactomeDatabase ID Release 77 74208 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=74208 Reactome R-HSA-74208

Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-74208.2 GO 0004422

GO molecular function

ReactomeDatabase ID Release 77 74210 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=74210 ReactomeDatabase ID Release 77 74215 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=74215 Reactome R-HSA-74215

Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-74215.4 6300847 Pubmed 1983 Isolation and characterization of a full-length expressible cDNA for human hypoxanthine phosphoribosyl transferase Jolly, DJ Okayama, H Berg, P Esty, AC Filpula, D Bohlen, P Johnson, GG Shively, JE Hunkapillar, T Friedmann, T Proc Natl Acad Sci U S A 80:477-81

dA, dG, or dI + ATP => dAMP, dGMP, or dIMP + ADP (DGUOK)

Mitochondrial deoxyguanosine kinase (DGUOK) catalyzes the reactions of deoxyadenosine, deoxyguanosine, and deoxyinosine with ATP to form the corresponding nucleotide monophosphates and ADP (Park and Ives 1988; Johansson and Karlson 1996). Crystallographic studies of the human enzyme have confirmed its dimeric structure and allowed identification of key amino acid residues responsible for its substrate specificity (Johansson et al. 2001).

Converted from EntitySet in Reactome

ReactomeDB_ID: 500224

mitochondrial matrix GO 0005759

dA, dG, dI [mitochondrial matrix] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity dI [mitochondrial matrix] dA [mitochondrial matrix] dG [mitochondrial matrix] ChEBI 28997

ReactomeDB_ID: 113593

ReactomeDB_ID: 113581

Converted from EntitySet in Reactome

ReactomeDB_ID: 500222

dAMP, dGMP, dIMP [mitochondrial matrix] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity 2'-deoxyadenosine 5'-monophosphate [mitochondrial matrix] 2'-deoxyguanosine 5'-monophosphate [mitochondrial matrix] dIMP [mitochondrial matrix] ChEBI 28806 PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

ReactomeDB_ID: 74205 DGUOK dimer [mitochondrial matrix]

DGUOK dimer

deoxyguanosine kinase holoenzyme

ReactomeDB_ID: 53573

UniProt:Q16854 DGUOK

DGUOK

DGUOK DGK FUNCTION Phosphorylates deoxyguanosine and deoxyadenosine in the mitochondrial matrix, with the highest efficiency for deoxyguanosine (PubMed:8692979, PubMed:8706825, PubMed:11687801, PubMed:17073823, PubMed:23043144). In non-replicating cells, where cytosolic dNTP synthesis is down-regulated, mtDNA synthesis depends solely on DGUOK and TK2. Phosphorylates certain nucleoside analogs (By similarity). Widely used as target of antiviral and chemotherapeutic agents.SUBUNIT Homodimer.TISSUE SPECIFICITY Ubiquitous. Highest expression in muscle, brain, liver and lymphoid tissues.SIMILARITY Belongs to the DCK/DGK family. UniProt Q16854

EQUAL

277

EQUAL

ReactomeDatabase ID Release 77 74205 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=74205 Reactome R-HSA-74205

Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-74205.2 ReactomeDatabase ID Release 77 74206 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=74206 ReactomeDatabase ID Release 77 74207 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=74207 Reactome R-HSA-74207

Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-74207.4 2845866 Pubmed 1988 Properties of a highly purified mitochondrial deoxyguanosine kinase Park, I Ives, DH Arch Biochem Biophys 266:51-60 11427893 Pubmed 2001 Structural basis for substrate specificities of cellular deoxyribonucleoside kinases Johansson, K Ramaswamy,年代 Ljungcrantz, C Knecht, W Piskur, J Munch-Petersen, B Eriksson, S Eklund, Hans Nat Struct Biol 8:616-620 8692979 Pubmed 1996 Cloning and expression of human deoxyguanosine kinase cDNA Johansson, M Karlsson, A Proc Natl Acad Sci USA 93:7258-7262

3.5.4.4

N6-methyl-AMP + H2O => IMP + methylamine

Deamination of N6-methyl-AMP to form IMP Cytosolic ADAL (Adenosine DeAminase-Like) catalyzes the reaction of N6-methyl-AMP and water to form IMP and methylamine. The active form of the enzyme is a protein monomer complexed with a zinc ion (Murakami et al. 2011).

Authored: D'Eustachio, P, 2012-03-14 Reviewed: Jassal, B, 2012-03-16 Edited: D'Eustachio, P, 2012-03-16

ReactomeDB_ID: 29356

ReactomeDB_ID: 2161190

N(6)-methyl-AMP [ChEBI:40196]

N(6)-methyl-AMP

ChEBI 40196

ReactomeDB_ID: 2161177

methylamine [ChEBI:16830]

methylamine

ChEBI 16830

ReactomeDB_ID: 29602

PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

ReactomeDB_ID: 2161178 ADAL:Zn [cytosol]

ADAL:Zn

ReactomeDB_ID: 2161180

UniProt:Q6DHV7 ADAL

ADAL

ADAL ADAL1 FUNCTION Catalyzes the hydrolysis of the free cytosolic methylated adenosine nucleotide N(6)-methyl-AMP (N6-mAMP) to produce inositol monophosphate (IMP) and methylamine (PubMed:21755941, PubMed:29884623). Is required for the catabolism of cytosolic N6-mAMP, which is derived from the degradation of mRNA containing N6-methylated adenine (m6A) (PubMed:21755941, PubMed:29884623). Catalyzes the removal of different alkyl groups not only from N6-substituted purine or 2-aminopurine nucleoside monophosphates but also from O6-substituted compounds in vitro (PubMed:21755941).SUBUNIT Monomer.SIMILARITY Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family. UniProt Q6DHV7

EQUAL

355

EQUAL

ReactomeDB_ID: 29426

zinc(2+) [ChEBI:29105]

zinc(2+)

ChEBI 29105 ReactomeDatabase ID Release 77 2161178 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=2161178 Reactome R-HSA-2161178

Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2161178.1 GO 0004000

GO molecular function

ReactomeDatabase ID Release 77 2161186 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=2161186 ReactomeDatabase ID Release 77 2161187 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=2161187 Reactome R-HSA-2161187

Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2161187.2 21755941 Pubmed 2011 Adenosine deaminase-like protein 1 (ADAL1): characterization and substrate specificity in the hydrolysis of N(6)- or O(6)-substituted purine or 2-aminopurine nucleoside monophosphates Murakami, E Bao, H Mosley, RT Du, J Sofia, MJ Furman, PA J Med Chem 54:5902-14

2.7.1.20

(2'-deoxy)adenosine + ATP => (d)AMP + ADP (ADK)

胞质腺苷酸激酶(理应)催化的意图ctions of adenosine and deoxyadenosine with ATP to yield the corresponding nucleotide monophosphates and ADP (Andres and Fox 1979). The enzyme is substantially more active on adenosine than deoxyadenosine in vitro (Hurley at al. 1985) though studies of cultured cells suggest that both reactions may be physiologically relevant (Hershfield et al. 1982). The enzyme is a monomer complexed with magnesium (Mathews et al. 1998).

Converted from EntitySet in Reactome

ReactomeDB_ID: 500173

Ade-Rib, dA [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity dA [cytosol] Ade-Rib [cytosol] ChEBI 16335

ReactomeDB_ID: 113592

Converted from EntitySet in Reactome

ReactomeDB_ID: 500088

(d)AMP [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity 2'-deoxyadenosine 5'-monophosphate [cytosol] AMP [cytosol]

ReactomeDB_ID: 29370

PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

ReactomeDB_ID: 76542 ADK [cytosol]

ADK

亚丁湾osine kinase holoenzyme

ReactomeDB_ID: 29926

ReactomeDB_ID: 49725

UniProt:P55263 ADK

ADK

ADK FUNCTION ATP dependent phosphorylation of adenosine and other related nucleoside analogs to monophosphate derivatives. Serves as a potential regulator of concentrations of extracellular adenosine and intracellular adenine nucleotides.PATHWAY Purine metabolism; AMP biosynthesis via salvage pathway; AMP from adenosine: step 1/1.SUBUNIT Monomer.TISSUE SPECIFICITY Widely expressed. Highest level in placenta, liver, muscle and kidney.SIMILARITY Belongs to the carbohydrate kinase PfkB family. UniProt P55263

EQUAL

362

EQUAL

ReactomeDatabase ID Release 77 76542 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=76542 Reactome R-HSA-76542

Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-76542.2 GO 0004001

GO molecular function

ReactomeDatabase ID Release 77 76547 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=76547 ReactomeDatabase ID Release 77 109624 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=109624 Reactome R-HSA-109624

Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-109624.4 2999129 Pubmed 1985 Regulation of deoxyadenosine and nucleoside analog phosphorylation by human placental adenosine kinase Hurley, MC Lin, B Fox, IH J Biol Chem 260:15675-15681 227870 Pubmed 1979 Purification and properties of human placental adenosine kinase Andres, CM Fox, IH J Biol Chem 254:11388-11393 6281270 Pubmed 1982 Effects of mutational loss of adenosine kinase and deoxycytidine kinase on deoxyATP accumulation and deoxyadenosine toxicity in cultured CEM human T-lymphoblastoid cells Hershfield, MS Fetter, JE Small, WC Bagnara, AS Williams, SR Ullman, B Martin, Jr, DW Wasson, DB Carson, DA J Biol Chem 257:6380-6386 9843365 Pubmed 1998 Structure of human adenosine kinase at 1.5 A resolution. Mathews, II Erion, MD Ealick, SE Biochemistry 37:15607-20

3.5.4.4

(2'-deoxy)adenosine + H2O => (2'-deoxy)inosine + NH4+ (ADA)

Cytosolic adenosine deaminase (ADA) catalyzes the hydrolysis of 2'deoxyadenosine and adenosine to yield deoxyinosine and inosine, respectively, plus ammonia (Akeson et al. 1988). Unpublished crystallographic data (PDB 3IAR) indicate that the human enzyme is a monomer.

Converted from EntitySet in Reactome

ReactomeDB_ID: 500173

ReactomeDB_ID: 29356

Converted from EntitySet in Reactome

ReactomeDB_ID: 500172

Ino, dI [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Ino [cytosol] dI [cytosol] ChEBI 17596

ReactomeDB_ID: 31633

PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

ReactomeDB_ID: 49701

UniProt:P00813 ADA

ADA

ADA1 ADA FUNCTION Catalyzes the hydrolytic deamination of adenosine and 2-deoxyadenosine (PubMed:8452534, PubMed:16670267). Plays an important role in purine metabolism and in adenosine homeostasis. Modulates signaling by extracellular adenosine, and so contributes indirectly to cellular signaling events. Acts as a positive regulator of T-cell coactivation, by binding DPP4 (PubMed:20959412). Its interaction with DPP4 regulates lymphocyte-epithelial cell adhesion (PubMed:11772392). Enhances dendritic cell immunogenicity by affecting dendritic cell costimulatory molecule expression and cytokines and chemokines secretion (By similarity). Enhances CD4+ T-cell differentiation and proliferation (PubMed:20959412). Acts as a positive modulator of adenosine receptors ADORA1 and ADORA2A, by enhancing their ligand affinity via conformational change (PubMed:23193172). Stimulates plasminogen activation (PubMed:15016824). Plays a role in male fertility (PubMed:21919946, PubMed:26166670). Plays a protective role in early postimplantation embryonic development (By similarity).ACTIVITY REGULATION Inhibited by Cu(2+) and Hg(2+), coformycin, deoxycoformycin (dCF), 2-deoxyadenosine, 6-methylaminopurine riboside, 2-3-iso-propylidene-adenosine and erythro-9-(2-hydroxy-3-nonyl)adenine.SUBUNIT Interacts with DPP4 (via extracellular domain) (PubMed:10951221, PubMed:14691230, PubMed:7907293, PubMed:8101391, PubMed:15016824). Interacts with PLG (via Kringle 4 domain); the interaction stimulates PLG activation when in complex with DPP4 (PubMed:15016824).TISSUE SPECIFICITY Found in all tissues, occurs in large amounts in T-lymphocytes (PubMed:20959412). Expressed at the time of weaning in gastrointestinal tissues.INDUCTION Up-regulated by hypoxia.POLYMORPHISM There is a common allele, ADA*2, also known as the ADA 2 allozyme. It is associated with the reduced metabolism of adenosine to inosine. It specifically enhances deep sleep and slow-wave activity (SWA) during sleep.SIMILARITY Belongs to the metallo-dependent hydrolases superfamily. Adenosine and AMP deaminases family. UniProt P00813

EQUAL

363

EQUAL

ReactomeDatabase ID Release 77 74234 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=74234 ReactomeDatabase ID Release 77 74241 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=74241 Reactome R-HSA-74241

Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-74241.4 3182793 Pubmed 1988 Mutant human adenosine deaminase alleles and their expression by transfection into fibroblasts Akeson, AL Wiginton, DA Dusing, MR States, JC Hutton, JJ J Biol Chem 263:16291-6

2.4.2.1

guanine + (deoxy)ribose 1-phosphate <=> (deoxy)guanosine + orthophosphate (NP)

Cytosolic nucleoside phosphorylase (NP) trimer catalyzes the reversible reaction of guanine with ribose 1-phosphate or deoxyribose 1-phosphate to form guanosine or deoxyguanosine and orthophosphate (Ealick et al. 1990; Wiginton et al. 1980). While NP is active with either ribose 1-phosphate or deoxyribose 1-phosphate in vitro, levels of deoxyribose 1-phosphate are normally low in vivo, limiting the extent of this reaction. NP deficiency in vivo is associated with defects in purine nucleotide salvage and leads to immunodeficiency (Williams et al. 1987).

Converted from EntitySet in Reactome

ReactomeDB_ID: 500244

R1P, dRibP [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity dRibP [cytosol] R1P [cytosol] ChEBI 28542 ChEBI 35425

ReactomeDB_ID: 83956

guanine [ChEBI:16235]

guanine

2-amino-6-hydroxypurine Converted from EntitySet in Reactome

ReactomeDB_ID: 500245

G, dG [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity dG [cytosol] Gua-Rib [cytosol] ChEBI 16750

ReactomeDB_ID: 29372

hydrogenphosphate [ChEBI:43474]

hydrogenphosphate

[PO3(OH)](2-) HYDROGENPHOSPHATE离子 hydrogen phosphate [P(OH)O3](2-) HPO4(2-) phosphate INORGANIC PHOSPHATE GROUP ChEBI 43474 PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

ReactomeDB_ID: 74237 NP trimer [cytosol]

NP trimer

nucleoside phosphorylase homotrimer PNPase homotrimer

ReactomeDB_ID: 61933

UniProt:P00491 PNP

PNP

NP PNP FUNCTION Catalyzes 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 (PubMed:9305964, PubMed:23438750). Preferentially acts on 6-oxopurine nucleosides including inosine and guanosine (PubMed:9305964).ACTIVITY REGULATION Inhibited by 5'-deaza-1'-aza-2c-deoxy-1'-(9-methylene)-Immucilin-G (DADMe-ImmG).PATHWAY Purine metabolism; purine nucleoside salvage.SUBUNIT Homotrimer.TISSUE SPECIFICITY Expressed in red blood cells; overexpressed in red blood cells (cytoplasm) of patients with hereditary non-spherocytic hemolytic anemia of unknown etiology.SIMILARITY Belongs to the PNP/MTAP phosphorylase family. UniProt P00491

EQUAL

289

EQUAL

ReactomeDatabase ID Release 77 74237 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=74237 Reactome R-HSA-74237

Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-74237.1 GO 0004731

GO molecular function

ReactomeDatabase ID Release 77 74238 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=74238 ReactomeDatabase ID Release 77 112034 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=112034 Reactome R-HSA-112034

Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-112034.4 3029074 Pubmed 1987 A human purine nucleoside phosphorylase deficiency caused by a single base change Williams, SR Gekeler, V McIvor, RS Martin, Jr, DW J Biol Chem 262:2332-2338 2104852 Pubmed 1990 Three-dimensional structure of human erythrocytic purine nucleoside phosphorylase at 3.2 A resolution Ealick, SE Rule, SA Carter, DC Greenhough, TJ Babu, YS Cook, WJ Habash, J Helliwell, JR Stoeckler, JD Parks, Jr, RE Chen, SF Bugg, CE J Biol Chem 265:1812-1820 6771276 Pubmed 1980 Characterization of purine nucleoside phosphorylase from human granulocytes and its metabolism of deoxyribonucleosides Wiginton, DA Coleman, MS Hutton, JJ J Biol Chem 255:6663-6669

2.4.2.1

hypoxanthine + (deoxy)ribose 1-phosphate <=> (deoxy)inosine + orthophosphate (NP)

Cytosolic nucleoside phosphorylase (NP) trimer catalyzes the reversible reaction of hypoxanthine with ribose 1-phosphate or deoxyribose 1-phosphate to form inosine or deoxyinosine and orthophosphate (Ealick et al. 1990; Wiginton et al. 1980). While NP is active with either ribose 1-phosphate or deoxyribose 1-phosphate in vitro, levels of deoxyribose 1-phosphate are normally low in vivo, limiting the extent of this reaction. NP deficiency in vivo is associated with defects in purine nucleotide salvage and leads to immunodeficiency (Williams et al. 1987).

ReactomeDB_ID: 113599

hypoxanthine [ChEBI:17368]

hypoxanthine

Converted from EntitySet in Reactome

ReactomeDB_ID: 500244

Converted from EntitySet in Reactome

ReactomeDB_ID: 500172

ReactomeDB_ID: 29372

PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

ReactomeDB_ID: 74237 ReactomeDatabase ID Release 77 112033 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=112033 Reactome R-HSA-112033

Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-112033.4

1.7.1.7

GMP + NADPH + H+ => IMP + NADP+ + NH4+ (GMPR,GMPR2)

Cytosolic GMP reductase (GMPR) catalyzes the reaction of GMP and NADPH + H+ to yield IMP and NADP+ + NH4+ (Spector et al. 1979; Deng et al. 2002). Two GMPR proteins have been identified, GMPR and GMPR2. Both proteins form homotetramers (GMPR - unpublished crstallographic data PDB 2BLE; GMPR2 - Li et al. 2006).

Authored: D'Eustachio, P, 2010-02-17 Reviewed: Graves, L, Rush, MG, 0000-00-00 00:00:00 Edited: D'Eustachio, P, 2010-02-18

ReactomeDB_ID: 29364

NADPH [ChEBI:16474]

NADPH

TPNH ChEBI 16474

ReactomeDB_ID: 113578

guanosine 5'-monophosphate [ChEBI:17345]

guanosine 5'-monophosphate

ReactomeDB_ID: 70106

hydron [ChEBI:15378]

hydron

ChEBI 15378

ReactomeDB_ID: 29366

NADP(+) [ChEBI:18009]

NADP(+)

ChEBI 18009

ReactomeDB_ID: 29602

ReactomeDB_ID: 31633

PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Converted from EntitySet in Reactome

ReactomeDB_ID: 514620

GMPR tetramers [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity GO 0003920

GO molecular function

ReactomeDatabase ID Release 77 514632 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=514632 ReactomeDatabase ID Release 77 514604 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=514604 Reactome R-HSA-514604

Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-514604.3 12009299 Pubmed 2002 NADPH-dependent GMP reductase isoenzyme of human (GMPR2). Expression, purification, and kinetic properties Deng, Y Wang, Z 应,K Gu, S Ji, C Huang, Y Gu, X Wang, Y Xu, Y Li, Y Xie, Y Mao, Y Int J Biochem Cell Biol 34:1035-50 218932 Pubmed 1979 Reaction mechanism and specificity of human GMP reductase. Substrates, inhibitors, activators, and inactivators Spector, T 琼斯,你 Miller, RL J Biol Chem 254:2308-15 16359702 Pubmed 2006 Crystal structure of human guanosine monophosphate reductase 2 (GMPR2) in complex with GMP Li, J Wei, Z Zheng, M Gu, X Deng, Y Qiu, R Chen, F Ji, C Gong, W Xie, Y Mao, Y J Mol Biol 355:980-8

ReactomeDatabase ID Release 77 74217 数据库标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser?DB=gk_current&ID=74217 Reactome R-HSA-74217

Reactome稳定的标识符。使用这个URL连接到the web page of this instance in Reactome: //www.joaskin.com/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-74217.4 4620886 Pubmed 1974 Molecular variation in relation to purine metabolism Watts, RW J Clin Pathol Suppl (R Coll Pathol) 8:48-63 GO 0043101

GO biological process