BioPAX pathway converted from "Transport and synthesis of PAPS" in the Reactome database. Transport and synthesis of PAPS This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> LEFT-TO-RIGHT SLC26A1,2 cotransport SO4(2-), H+ from extracellular region to cytosol This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> SO4(2-) inorganic sulfate sulfate Sulphate Reactome DB_ID: 427648 extracellular region GENE ONTOLOGY GO:0005576 sulfate [ChEBI:16189] sulfate ChEBI CHEBI:16189 Reactome Database ID Release 81 427648 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=427648 Reactome R-ALL-427648 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-427648.3 Reactome http://www.reactome.org H+ hydron Reactome DB_ID: 351626 hydron [ChEBI:15378] hydron ChEBI CHEBI:15378 Reactome Database ID Release 81 351626 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=351626 Reactome R-ALL-351626 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-351626.4 COMPOUND C00080 additional information MI MI:0361 2 H+ proton hydron Reactome DB_ID: 70106 cytosol GENE ONTOLOGY GO:0005829 Reactome Database ID Release 81 70106 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=70106 Reactome R-ALL-70106 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-70106.4 COMPOUND C00080 2 SO4(2-) inorganic sulfate sulfate Sulphate Reactome DB_ID: 174375 Reactome Database ID Release 81 174375 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174375 Reactome R-ALL-174375 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-174375.3 ACTIVATION Converted from EntitySet in Reactome SLC26A1,2 Sulfate transporters Reactome DB_ID: 10830707 Converted from EntitySet in Reactome Homologues of SLC26A1 Reactome DB_ID: 10830699 O74377 SLC26A1 Reactome DB_ID: 10830692 plasma membrane GENE ONTOLOGY GO:0005886 UniProt:O74377 Schizosaccharomyces pombe NCBI Taxonomy 4896 UniProt O74377 1 EQUAL 701 EQUAL Reactome Database ID Release 81 10830692 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10830692 Reactome R-SPO-427580 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SPO-427580.1 Q9URY8 SLC26A1 Reactome DB_ID: 10830697 UniProt:Q9URY8 UniProt Q9URY8 1 EQUAL 701 EQUAL Reactome Database ID Release 81 10830697 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10830697 Reactome R-SPO-427580-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SPO-427580-2.1 Reactome Database ID Release 81 10830699 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10830699 Reactome R-SPO-427580-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SPO-427580-3.1 Converted from EntitySet in Reactome Homologues of SLC26A2 Reactome DB_ID: 10830705 O74377 SLC26A2 Reactome DB_ID: 10830701 1 EQUAL 739 EQUAL Reactome Database ID Release 81 10830701 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10830701 Reactome R-SPO-427669 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SPO-427669.1 Q9URY8 SLC26A2 Reactome DB_ID: 10830703 1 EQUAL 739 EQUAL Reactome Database ID Release 81 10830703 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10830703 Reactome R-SPO-427669-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SPO-427669-2.1 Reactome Database ID Release 81 10830705 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10830705 Reactome R-SPO-427669-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SPO-427669-3.1 Reactome Database ID Release 81 10830707 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10830707 Reactome R-SPO-427632 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SPO-427632.1 GENE ONTOLOGY GO:0015116 gene ontology term for cellular function MI MI:0355 Same Catalyst Activity Reactome Database ID Release 81 10830708 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10830708 Reactome Database ID Release 81 10830710 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10830710 Reactome R-SPO-427555 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SPO-427555.1 The SLC26A1 and 2 genes encode proteins that facilitate sulfate (SO4(2-)) uptake into cells (Alper & Sharma 2013). The mechanism by which these transporters work is unclear but may be enhanced by extracellular halides or acidic pH environments, cotransporting protons electroneutrally. Both can transport SO4(2-) (as well as oxalate and Cl-) across the basolateral membrane of epithelial cells. SLC26A1 encodes the sulfate anion transporter 1 (SAT1) (Regeer et al. 2003) and is most abundantly expressed in the liver and kidney, with lower levels expressed in many other parts of the body. SLC26A2 is ubiquitously expressed and encodes a sulfate transporter (Diastrophic dysplasia protein, DTD, DTDST) (Hastbacka et al. 1994). This transporter provides sulfate for sulfation of glycosaminoglycan chains in proteoglycans needed for cartilage development. Defects in SLC26A2 are implicated in the pathogenesis of several human chondrodysplasias. 23506885 Pubmed 2013 The SLC26 gene family of anion transporters and channels Alper, Seth L Sharma, Alok K Mol. Aspects Med. 34:494-515 7923357 Pubmed 1994 The diastrophic dysplasia gene encodes a novel sulfate transporter: positional cloning by fine-structure linkage disequilibrium mapping de la Chapelle, A Mahtani, MM Clines, G Reeve-Daly, MP Daly, M Hamilton, BA Kusumi, K Trivedi, B Weaver, A Cell 78:1073-87 12713736 Pubmed 2003 Characterization of the human sulfate anion transporter (hsat-1) protein and gene (SAT1; SLC26A1) Regeer, RR Lee, A Markovich, D DNA Cell Biol 22:107-17 inferred from electronic annotation EVIDENCE CODE ECO:0000203 LEFT-TO-RIGHT 2.7.7.4 Activation of inorganic sulfate forms APS PAPSS1,2 transfer SO4(2-) group to ATP to form APS ATP + sulfate => adenylyl sulfate (APS) + pyrophosphate This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> ATP Adenosine 5'-triphosphate ATP(4-) Reactome DB_ID: 113592 ATP(4-) [ChEBI:30616] ATP(4-) ATP atp Adenosine 5'-triphosphate ChEBI CHEBI:30616 Reactome Database ID Release 81 113592 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=113592 Reactome R-ALL-113592 5 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113592.5 COMPOUND C00002 APS Adenosine 5'-phosphosulfate 5'-adenylyl sulfate Reactome DB_ID: 174370 5'-adenylyl sulfate(2-) [ChEBI:58243] 5'-adenylyl sulfate(2-) 5'-O-[(sulfonatooxy)phosphinato]adenosine adenosine 5'-phosphosulfate 5'-adenylyl sulfate dianion ChEBI CHEBI:58243 Reactome Database ID Release 81 174370 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=174370 Reactome R-ALL-174370 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-174370.4 PPi pyrophosphate diphosphoric acid pyrophosphoric acid diphosphate Reactome DB_ID: 111294 diphosphate(3-) [ChEBI:33019] diphosphate(3-) ChEBI CHEBI:33019 Reactome Database ID Release 81 111294 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=111294 Reactome R-ALL-111294 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-111294.4 COMPOUND C00013 ACTIVATION met14 PAPSS1 Q9P7G9 Reactome DB_ID: 10827537 UniProt:Q9P7G9 met14 UniProt Q9P7G9 1 EQUAL 624 EQUAL Reactome Database ID Release 81 10827537 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10827537 Reactome R-SPO-174387 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SPO-174387.1 GENE ONTOLOGY GO:0004781 Reactome Database ID Release 81 10827559 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10827559 Reactome Database ID Release 81 10827561 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10827561 Reactome R-SPO-174392 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SPO-174392.1 In the first step of PAPS biosynthesis, ATP and sulfate react to form adenylyl sulfate (APS) and pyrophosphate (PPi), catalyzed by the ATP sulfurylase domains of the bifunctional enzymes PAPS synthases 1 and 2 (PAPSS1 and 2). PAPSS2 is essential for the sulfation of glycosaminoglycan chains in proteoglycans, a necessary post translational modification. Defective PAPSS2 results in undersulfation of the glycosaminoglycan chains in proteoglycans which causes spondyloepimetaphyseal dysplasia Pakistani type (SEMD PA; MIM:612847), a bone disease characterized by epiphyseal dysplasia with mild metaphyseal abnormalities. Mutations resulting in SEMD PA include S438*, T48R and R329* (Ahmad et al. 1998, ul Haque et al. 1998, Noordam et al. 2009). 9771708 Pubmed 1998 Mutations in orthologous genes in human spondyloepimetaphyseal dysplasia and the brachymorphic mouse ul Haque, MF King, LM Krakow, D Cantor, RM Rusiniak, ME Swank, RT Superti-Furga, A Haque, S Abbas, H Ahmad, W Ahmad, M Cohn, DH Nat Genet 20:157-62 9576487 Pubmed 1998 Sulfation in high endothelial venules: cloning and expression of the human PAPS synthetase Girard, JP Baekkevold, ES Amalric, F FASEB J 12:603-12 9668121 Pubmed 1998 Molecular cloning, expression, and characterization of human bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase and its functional domains Venkatachalam, KV Akita, H Strott, CA J Biol Chem 273:19311-20 LEFT-TO-RIGHT 2.7.1.25 adenylyl sulfate (APS) + ATP => PAPS + ADP PAPSS1,2 transfer PO4(2-) group from ATP to APS to form PAPS APS reacts with another ATP molecule to form PAPS This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> PAPS 3'-phospho-5'-adenylyl sulfate Reactome DB_ID: 158471 3'-phosphonato-5'-adenylyl sulfate(4-) [ChEBI:58339] 3'-phosphonato-5'-adenylyl sulfate(4-) ChEBI CHEBI:58339 Reactome Database ID Release 81 158471 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=158471 Reactome R-ALL-158471 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-158471.4 COMPOUND C00053 ADP Adenosine 5'-diphosphate ADP(3-) Reactome DB_ID: 29370 ADP(3-) [ChEBI:456216] ADP(3-) ADP 5&apos;-O-[(phosphonatooxy)phosphinato]adenosine ADP trianion ChEBI CHEBI:456216 Reactome Database ID Release 81 29370 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=29370 Reactome R-ALL-29370 5 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29370.5 COMPOUND C00008 ACTIVATION GENE ONTOLOGY GO:0004020 Reactome Database ID Release 81 10827540 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10827540 Reactome Database ID Release 81 10827542 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10827542 Reactome R-SPO-174389 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SPO-174389.1 In the second step of PAPS biosynthesis, adenylyl sulfate (APS) is phosphorylated to 3'-phosphoadenylyl sulfate (PAPS), catalyzed by the APS kinase domains of the bifunctional enzymes PAPS synthases 1 and 2 (PAPSS1 and 2). PAPSS2 is essential for the sulfation of glycosaminoglycan chains of proteoglycans, a necessary post-translational modification. Defective PAPSS2 results in undersulfation of proteoglycans which causes spondyloepimetaphyseal dysplasia Pakistani type (SEMD-PA; MIM:612847), a bone disease characterized by epiphyseal dysplasia with mild metaphyseal abnormalities. Mutations resulting in SEMD-PA include S438*, T48R and R329* (Ahmad et al. 1998, ul Haque et al. 1998, Noordam et al. 2009). Reactome Database ID Release 81 10846890 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10846890 Reactome R-SPO-174362 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-SPO-174362.1 GENE ONTOLOGY GO:0050428 gene ontology term for cellular process MI MI:0359 PAPS (3'-phosphoadenosine-5'-phosphosulfate), which functions as a sulfate donor in the cell, is synthesized from sulfate and two molecules of ATP in a two-step process (Robbins & Lipmann 1958) catalyzed in vertebrates by a bifunctional enzyme (Venkatachalam et al. 1998). PAPS synthesis takes place in the cytosol, and it is either consumed there in the sulfonation of a variety of hormones and xenobiotics, or it is transported to the Golgi apparatus and consumed in the synthesis of proteoglycans like chondroitin sulfate. Two isoforms of the human bifunctional enzyme are known, mutations in one of which are associated with defects in proteoglycan biosynthesis (Girard et al. 1998, ul Haque et al. 1998). 13575436 Pubmed 1958 Separation of the two enzymatic phases in active sulfate synthesis Robbins, PW Lipmann, F J Biol Chem 233:681-5