BioPAX pathway converted from "Transport and synthesis of PAPS" in the Reactome database. Transport and synthesis of PAPS 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> SLC26A1,2 cotransport SO4(2-), H+ from extracellular region to cytosol 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> Reactome DB_ID: 427648 1 extracellular region GO 0005576 sulfate [ChEBI:16189] sulfate Reactome http://www.reactome.org ChEBI 16189 Reactome DB_ID: 351626 2 hydron [ChEBI:15378] hydron ChEBI 15378 Reactome DB_ID: 70106 2 cytosol GO 0005829 Reactome DB_ID: 174375 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10830707 plasma membrane GO 0005886 SLC26A1,2 [plasma membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity SLC26A1 [plasma membrane] SLC26A2 [plasma membrane] SLC26A1 [plasma membrane] SLC26A2 [plasma membrane] Schizosaccharomyces pombe NCBI Taxonomy 4896 UniProt Q9URY8 UniProt O74377 GO 0015116 GO molecular function 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 by electronic annotation IEA GO IEA 2.7.7.4 PAPSS1,2 transfer SO4(2-) group to ATP to form APS PAPSS1,2 transfer SO4(2-) group to ATP to form APS ATP + sulfate => adenylyl sulfate (APS) + pyrophosphate Activation of inorganic sulfate forms APS 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> Reactome DB_ID: 113592 1 ATP(4-) [ChEBI:30616] ATP(4-) Adenosine 5'-triphosphate atp ATP ChEBI 30616 Reactome DB_ID: 174375 1 Reactome DB_ID: 174370 1 5'-adenylyl sulfate(2-) [ChEBI:58243] 5'-adenylyl sulfate(2-) adenosine 5'-phosphosulfate 5'-O-[(sulfonatooxy)phosphinato]adenosine 5'-adenylyl sulfate dianion ChEBI 58243 Reactome DB_ID: 111294 1 diphosphate(3-) [ChEBI:33019] diphosphate(3-) ChEBI 33019 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10827537 UniProt:Q9P7G9 met14 UniProt Q9P7G9 Chain Coordinates 1 EQUAL 624 EQUAL GO 0004781 GO molecular function 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 inferred by electronic annotation IEA GO IEA 2.7.1.25 PAPSS1,2 transfer PO4(2-) group from ATP to APS to form PAPS PAPSS1,2 transfer PO4(2-) group from ATP to APS to form PAPS adenylyl sulfate (APS) + ATP => PAPS + ADP 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> Reactome DB_ID: 174370 1 Reactome DB_ID: 113592 1 Reactome DB_ID: 158471 1 3'-phosphonato-5'-adenylyl sulfate(4-) [ChEBI:58339] 3'-phosphonato-5'-adenylyl sulfate(4-) ChEBI 58339 Reactome DB_ID: 29370 1 ADP(3-) [ChEBI:456216] ADP(3-) ADP trianion 5&apos;-O-[(phosphonatooxy)phosphinato]adenosine ADP ChEBI 456216 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10827537 1 EQUAL 624 EQUAL GO 0004020 GO molecular function 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). inferred by electronic annotation IEA GO IEA 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 GO 0050428 GO biological process 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 inferred by electronic annotation IEA GO IEA