BioPAX pathway converted from "Collagen prolyl 3-hydroxylase converts 4-Hyp collagen to 3,4-Hyp collagen" in the Reactome database.1.14.11.7Collagen prolyl 3-hydroxylase converts 4-Hyp collagen to 3,4-Hyp collagenCollagen prolyl 3-hydroxylase converts 4-Hyp collagen to 3,4-Hyp collagenCollagen contains (2S,3S)-3-hydroxyproline (3-Hyp), though much less abundantly than 4-Hyp (Rhodes and Miller 1978). The 3-Hyp content of collagen is much more variable than that of 4-Hyp, varying between collagen types, tissues, developmental stages and pathological states (Kivirikko et al. 1992). It is more prevalent in type IV and V collagens at 10-15 3-Hyp residues (Bentz et al. 1983) than in Type I-III fibrillar collagens which have a single 3-Hyp residue per chain; the alpha-1 chain of type I collagen has 3-Hyp at residue 986 (Fietzek et al. 1972, Marini et al. 2007). 3-Hyp is formed from Pro in the Xaa position of Xaa-Hyp-Gly triplets (Gryder et al. 1975, Kivirikko et al. 1992). It is likely that 4-Hyp is a requirement at the second position of the triplet as 4-Hyp rich substrates are more active than 4-Hyp poor (Adams & Frank 1980). 3-Hyp has a modest effect on triple-helix stability (Jenkins et al. 2003; Mizuno et al. 2008). 3-Hyp may adjust the stability of basement membranes to enable formation of the meshwork structure, or serve as a ligand for other proteins. It is suggested to have a role in the self-assembly of collagen supramolecular structures (Weis et al. 2010). <br>3-Hyp is formed by prolyl 3-hydroxylase (P3H; EC 1.14.11.7), which has 3 isoforms in vertebrates. All contain an ER-retention signal but vary in their tissue expression (Vranka et al. 2009). P3H can hydroxylate prolines that precede 4-Hyp residues (Tryggvason et al. 1976) but not those that precede an unhydroxylated proline (Kivirikko & Myllla 1982, Myllyharju 2005). Like P4H, P3H requires molecular oxygen, alpha-ketoglutarate, iron(II), and ascorbate for activity. P3H1 is homologous to mammalian leprecan or growth suppressor 1 (Gros1), and forms a 3-prolyl hydroxylation complex with cartilage-associated protein (CRTAP) and a peptidyl-prolyl cis-trans isomerase, cyclophilin B (CypB), which is encoded by the PPIB gene (Vranka et al. 2004). Lack of 3-Hyp in Type I and II collagens leads to an osteogenesis imperfecta (OI)-like disease, as demonstrated by CRTAP and PPIB knock-out mice (Morello et al. 2006, Choi et al. 2009) and by mutations in human LEPRE1 (which encodes P3H1), CRTAP, and PPIB (Barnes et al. 2006, Cabral et al. 2007, van Dijk et al. 2009). The P3H1/CRTAP/CypB complex has also been shown to have chaperone activity (Ishikawa et al. 2009). P3H2 hydroxylates peptides derived from Type IV collagen more efficiently than Type I peptides and is localized to tissues that are rich in basement membrane (Tiainen et al. 2008). The effect of prolyl 3-hydroxylation on basement membrane collagens remains unknown.<br><br> In this generalized reaction, all collagen subtypes are represented as having one 3-Hyp residue. Authored: Jupe, S, 2010-07-20Reviewed: Canty-Laird, EG, 2012-05-24Edited: Jupe, S, 2012-05-14Reactome DB_ID: 89482331endoplasmic reticulum lumenGO0005788Prolyl 3-hydroxylases:Fe2+:4-Hyp collagen propeptides [endoplasmic reticulum lumen]Prolyl 3-hydroxylases:Fe2+:4-Hyp collagen propeptidesReactome DB_ID: 19811601Prolyl 3-hydroxylases:Fe2+ [endoplasmic reticulum lumen]Prolyl 3-hydroxylases:Fe2+Reactome DB_ID: 16507741iron(2+) [ChEBI:29033]iron(2+)FE (II) IONFe(2+)Fe(II)Ferrous ionFe2+iron ion(2+)Reactomehttp://www.reactome.orgChEBI29033Reactome DB_ID: 19811461L-ascorbic acid [ChEBI:29073]L-ascorbic acidChEBI29073Converted from EntitySet in ReactomeReactome DB_ID: 19802361Prolyl 3-hydroxylases [endoplasmic reticulum lumen]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityLEPREL1 [endoplasmic reticulum lumen]UniProtQ8IVL5Homo sapiensNCBI Taxonomy9606Reactome Database ID Release 751981160Database 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=1981160ReactomeR-HSA-19811601Reactome 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-HSA-1981160.1Converted from EntitySet in ReactomeReactome DB_ID: 165076714-Hyp collagen propeptides [endoplasmic reticulum lumen]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome Database ID Release 758948233Database 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=8948233ReactomeR-HSA-89482331Reactome 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-HSA-8948233.1Reactome DB_ID: 165077912-oxoglutarate(2-) [ChEBI:16810]2-oxoglutarate(2-)2-ketoglutaratealpha-ketoglutarate2-oxopentanedioic acid, ion(2-)2-oxoglutarateChEBI16810Reactome DB_ID: 1135341dioxygen [ChEBI:15379]dioxygenChEBI15379Reactome DB_ID: 20224261Prolyl 3-hydroxylases:Fe2+:3,4-Hyp collagen propeptides [endoplasmic reticulum lumen]Prolyl 3-hydroxylases:Fe2+:3,4-Hyp collagen propeptidesReactome DB_ID: 19811601Converted from EntitySet in ReactomeReactome DB_ID: 202249213,4-Hyp collagen propeptides [endoplasmic reticulum lumen]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityReactome Database ID Release 752022426Database 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=2022426ReactomeR-HSA-20224262Reactome 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-HSA-2022426.2Reactome DB_ID: 1597511carbon dioxide [ChEBI:16526]carbon dioxideChEBI16526Reactome DB_ID: 16507691succinate(2-) [ChEBI:30031]succinate(2-)succinate(-)OOC-CH2-CH2-COO(-)butanedioic acid, ion(2-)butanedioateChEBI30031PHYSIOL-LEFT-TO-RIGHTACTIVATIONReactome DB_ID: 8948233GO0019797GO molecular functionReactome Database ID Release 751980260Database 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=1980260Reactome Database ID Release 751980233Database 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=1980233ReactomeR-HSA-19802332Reactome 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-HSA-1980233.219419969Pubmed2009Biochemical characterization of the prolyl 3-hydroxylase 1.cartilage-associated protein.cyclophilin B complexIshikawa, YWirz, JVranka, JANagata, KBächinger, HPJ Biol Chem 284:17641-73-540-23272-9ISBN2005Intracellular Post Translational Modifications of CollagensMyllyharju, JCollagen: primer in structure, processing and assembly (Book)17277775Pubmed2007Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfectaCabral, WAChang, WBarnes, AMWeis, MScott, MALeikin, SMakareeva, EKuznetsova, NVRosenbaum, KNTifft, CJBulas, DIKozma, CSmith, PAEyre, DRMarini, JCNat Genet 39:359-6519652424Pubmed2009Expression of prolyl 3-hydroxylase genes in embryonic and adult mouse tissuesVranka, JStadler, HSBächinger, HPCell Struct Funct 34:97-10412785781Pubmed2003Effect of 3-hydroxyproline residues on collagen stabilityJenkins, CLBretscher, LEGuzei, IARaines, RTJ Am Chem Soc 125:6422-717055431Pubmed2006CRTAP is required for prolyl 3- hydroxylation and mutations cause recessive osteogenesis imperfectaMorello, RBertin, TKChen, YHicks, JTonachini, LMonticone, MCastagnola, PRauch, FGlorieux, FHVranka, JBächinger, HPPace, JMSchwarze, UByers, PHWeis, MFernandes, RJEyre, DRYao, ZBoyce, BFLee, BCell 127:291-30419781681Pubmed2009PPIB mutations cause severe osteogenesis imperfectavan Dijk, FSNesbitt, IMZwikstra, EHNikkels, PGPiersma, SRFratantoni, SAJimenez, CRHuizer, MMorsman, ACCobben, JMvan Roij, MHElting, MWVerbeke, JIWijnaendts, LCShaw, NJHögler, WMcKeown, CSistermans, EADalton, AMeijers-Heijboer, HPals, GAm J Hum Genet 85:521-715044469Pubmed2004Prolyl 3-hydroxylase 1, enzyme characterization and identification of a novel family of enzymesVranka, JASakai, LYBächinger, HPJ Biol Chem 279:23615-2119997487Pubmed2009Severe osteogenesis imperfecta in cyclophilin B-deficient miceChoi, JWSutor, SLLindquist, LEvans, GLMadden, BJBergen HR, 3rdHefferan, TEYaszemski, MJBram, RJPLoS Genet 5:e100075018487197Pubmed2008Characterization of recombinant human prolyl 3-hydroxylase isoenzyme 2, an enzyme modifying the basement membrane collagen IVTiainen, PPasanen, ASormunen, RMyllyharju, JJ Biol Chem 283:19432-96574478Pubmed1983Isolation and partial characterization of a new human collagen with an extended triple-helical structural domainBentz, HMorris, NPMurray, LWSakai, LYHollister, DWBurgeson, REProc Natl Acad Sci U S A 80:3168-726250440Pubmed1980Metabolism of proline and the hydroxyprolinesAdams, ElijahFrank, LeonardAnnu Rev Biochem 49:1005-61164442Pubmed1975Sequence position of 3-hydroxyproline in basement membrane collagen. Isolation of glycyl-3-hydroxyprolyl-4-hydroxyproline from swine kidneyGryder, RMLamon, MAdams, ElijahJ Biol Chem 250:2470-4194596Pubmed1976Separation of prolyl 3-hydroxylase and 4-hydroxylase activities and the 4-hydroxyproline requirement for synthesis of 3-hydroxyprolineTryggvason, KRisteli, JKivirikko, KIBiochem Biophys Res Commun 76:275-816210830Pubmed1982Posttranslational enzymes in the biosynthesis of collagen: intracellular enzymesKivirikko, KIMyllylä, RMethods Enzymol 82:245-3044343807Pubmed1972The covalent structure of collagen. Amino-acid sequence of peptide 1-CB6-C2Fietzek, PPRexrodt, FWWendt, PStark, MKühn, KEur J Biochem 30:163-81992Hydroxylation of proline and lysine residues in collagens and other animal and plant proteins.Kivirikko, KIMyllylä, RPihlajaniemi, TPost-translational modification of proteins (Book): 1-5117192541Pubmed2006Deficiency of cartilage-associated protein in recessive lethal osteogenesis imperfectaBarnes, AMChang, WMorello, RCabral, WAWeis, MEyre, DRLeikin, SMakareeva, EKuznetsova, NUveges, TEAshok, AFlor, AWMulvihill, JJWilson, PLSundaram, UTLee, BMarini, JCN Engl J Med 355:2757-64687595Pubmed1978Physicochemical characterization and molecular organization of the collagen A and B chainsRhodes, RKMiller, EJBiochemistry 17:3442-819021759Pubmed2008Effect of the -Gly-3(S)-hydroxyprolyl-4(R)-hydroxyprolyl- tripeptide unit on the stability of collagen model peptidesMizuno, KPeyton, DHHayashi, TEngel, JBächinger, HPFEBS J 275:5830-4017630507Pubmed2007Components of the collagen prolyl 3-hydroxylation complex are crucial for normal bone developmentMarini, JCCabral, WABarnes, AMChang, WCell Cycle 6:1675-8119940144Pubmed2010Location of 3-hydroxyproline residues in collagen types I, II, III, and V/XI implies a role in fibril supramolecular assemblyWeis, MAHudson, DMKim, LScott, MWu, JJEyre, DRJ Biol Chem 285:2580-90