Assembly of collagen fibrils and other multimeric structures (Homo sapiens)

From WikiPathways

Jump to: navigation, search
2, 97, 3613, 3525530, 31324, 2110, 22, 2816, 3712, 23, 29334207, 366, 27161520143, 3911, 24, 2617388, 343, 1425cytosolLAMC2 3x4Hyp-3Hyp-COL9A1 3x4Hyp-GalHyl-COL9A1 Collagen type I fibril 3x4Hyp-GalHyl-COL6A1 5Hyl-COL9A1 Collagen type IVnetworksCOL9A1 3x4Hyp-COL9A3 Collagen type I fibril with hydroxylysyl-pyrrole cross-links LOX 3x4Hyp-COL10A1 COL10A1 MMP7 GalHyl-COL18A1(24-1754) 3x4Hyp-GlcGalHyl-COL9A3 Collagen type XI fibril LAMB3 3x4Hyp-COL6A2 3x4Hyp-3Hyp-COL1A2 GalHyl-COL9A2 Collagen type I fibre Collagen type VIIfibril:Laminin-3323x4Hyp-3Hyp-GlcGalHyl-COL9A3 4-Hyp Glu-Gal-Hyl-collagen alpha-1(XI) chain 3x4Hyp-GlcGalHyl-COL7A1 Collagen type XI fibril 3x4Hyp-GlcGalHyl-COL1A2 LOXL2 3x4Hyp-3Hyp-5Hyl-COL9A1 3x4Hyp-COL1A2 Collagen type V fibril 5Hyl-COL24A1(?-?) Sulfilimine-containing collagen type IV alpha3.alpha4.alpha5 network 3x4Hyp-3Hyp-GalHyl-COL24A1(?-?) 3x4Hyp-GalHyl-COL24A1(?-?) COL15A1(28-1388) 5Hyl-COL7A1(17-2821) 3x4Hyp-GlcGalHyl-COL10A1 3x4Hyp-5Hyl-COL27A1 COL9A2 3x4Hyp-GalHyl-COL2A1(182-1241) Collagen networksCollagen type XVIII3x4Hyp-5Hyl-COL9A2 Collagen type IV alpha1.alpha1.alpha2 network 3x4Hyp-5Hyl-COL9A1 5Hyl-COL18A1(24-1754) GalHyl-COL15A1(28-1388) Collagen type Ifibrils withlysyl-pyridinolinecross-linksCollagentypeIfibrilswithhydroxylysyl-pyrrole cross-links3x4Hyp-3Hyp-COL8A2 3x4Hyp-COL27A1 3x4Hyp-GalHyl-COL9A2 ITGA6(24-1130) 3x4Hyp-3Hyp-GalHyl-COL8A1(28-744) 3x4Hyp-3Hyp-5Hyl-COL24A1(?-?) 3x4Hyp-3Hyp-COL7A1 Collagen type I fibril 3x4Hyp-3Hyp-GlcGalHyl-COL9A3 Collagen type I fibril with dehydro-lysinonorleucine Laminin-3323x4Hyp-GalHyl-COL9A1 5Hyl-COL8A2 4-Hyp 5-Gal-Hyl-collagen alpha-1(XI) chain Collagen type I fibril with deH-HLNL 3x4Hyp-GlcGalHyl-COL18A1(24-1754) TLL2 COL1A2 3x4Hyp-GlcGalHyl-COL3A1 Collagen type I fibril ITGA6(24-1130) 5Hyl-COL27A1 3x4Hyp-GalHyl-COL3A1 3x4Hyp-3Hyp-GalHyl-COL7A1 3x4Hyp-3Hyp-GalHyl-COL9A1 Collagen type I fibril Collagen type Ifibril3x4Hyp-3Hyp-GlcGalHyl-COL9A1 3x4Hyp-3Hyp-GalHyl-COL1A2 3x4Hyp-COL9A1 GlcGalHyl-COL10A1 GalHyl-COL7A1(2822-2944) 3x4Hyp-5Hyl-COL7A1 3x4Hyp-3Hyp-5Hyl-COL1A2 Collagen type Ifibril withallysinesCollagentypeIfibrilswithlysino-5-ketonorleucine cross-links3x4Hyp-COL9A2 3x4Hyp-COL24A1(?-?) Endostatin releasingproteasesCollagen type IXCollagen type III fibril 4-Hyp 5-Hyl-collagen alpha-1(XI) chain LOXL3 Collagen type I fibril with lysino-5-ketonorleucine cross-links Collagen type X:typeII fibrils5Hyl-COL3A1 LOXL1 5Hyl-COL10A1 CTSL(292-333) Collagen type XIfibrilGlcGalHyl-COL3A1(154-1241) GlcGalHyl-COL15A1(28-1388) Collagen alpha-5(VI) chains COL9A2 3x4Hyp-3Hyp-5Hyl-COL9A1 Collagen type I fibril Collagen type VIIhexamer3x4Hyp-3Hyp-GlcGalHyl-COL24A1(?-?) Collagen type II fibril Collagenalpha-1(VII) trimerLOXL2(?-774) Collagen type VII fibril 3x4Hyp-3Hyp-COL7A1(2822-2944) GlcGalHyl-COL9A3 BMP1 LOX Collagen typeI,II:XII,XIVfibrilsGalHyl-COL7A1 Collagen type III fibre 3x4Hyp-3Hyp-COL7A1 3,4-Hyp 5-Gal-Hyl-collagen alpha-2(XI) chain 3x4Hyp-3Hyp-COL8A1(28-744) Collagen type VIINC2 proteinases3x4Hyp-GlcGalHyl-COL2A1(182-1241) Cu2+ GalHyl-COL2A1(182-1241) Lysyl oxidasesCD151 3x4Hyp-COL3A1 GlcGalHyl-COL7A1(2822-2944) LAMC2 LOXL1(26-574) 3,4-Hyp 5-Gal-Hyl-collagen alpha-1(XI) chain Collagen type IV alpha1.alpha2.alpha5.alpha6 network Collagen type Ifibril with freehydroxylysines3x4Hyp-GalHyl-COL8A2 3x4Hyp-3Hyp-GlcGalHyl-COL1A2 TLL2 3x4Hyp-GalHyl-COL9A3 GlcGalHyl-COL18A1(24-1754) GalHyl-COL7A1 O2PXDN 3x4Hyp-3Hyp-GlcGalHyl-COL18A1(24-1754) BMP1 3x4Hyp-3Hyp-5Hyl-COL1A1 3x4Hyp-3Hyp-GlcGalHyl-COL9A2 3x4Hyp-COL9A1 LAMA3 Collagen type II fibril COL24A1(?-?) 3,4-Hyp 5-Hyl-collagen alpha-2(XI) chain Collagen type Xnetwork3x4Hyp-3Hyp-COL9A1 GlcGalHyl-COL9A3 GalHyl-COL3A1 Sulfilimine-containing collagen type IV alpha1.alpha1.alpha2 network COL18A1(1572-11754)Collagen type I fibril Collagen type I fibril with lysyl-pyridinoline cross-links 3x4Hyp-5Hyl-COL1A2 3x4Hyp-3Hyp-5Hyl-COL7A1(2822-2944) Collagen type X network 5Hyl-COL9A1 3x4Hyp-GlcGalHyl-COL6A2 3x4Hyp-GalHyl-COL9A3 3x4Hyp-3Hyp-5Hyl-COL15A1(28-1388) 3x4Hyp-COL7A1 3x4Hyp-3Hyp-GlcGalHyl-COL7A1 Prolysyl oxidasesCollagen type I fibril with lysyl-pyrrole cross-links 3x4Hyp-COL7A1(2822-2944) 3x4Hyp-GalHyl-COL8A1(28-744) 3x4Hyp-COL18A1(24-1754) 3x4Hyp-3Hyp-GalHyl-COL1A1 3,4-Hyp Glu-Gal-Hyl-collagen alpha-1(XI) chain LAMC2 LOX(22-168) 3x4Hyp-3Hyp-5Hyl-COL3A1 3x4Hyp-3Hyp-GalHyl-COL9A3 Collagen type I fibril 3x4Hyp-5Hyl-COL7A1(17-2821) LOXL3(26-?) Anchoring fibrilcomplexCollagen type Ifibrils withdeH-HLNLcross-linksGalHyl-COL8A1(28-744) MMP9 3x4Hyp-GlcGalHyl-COL8A1(28-744) COL8A2 3x4Hyp-3Hyp-GalHyl-COL7A1(17-2821) 4-Hyp 5-Gal-Hyl collagen alpha-2(XI) chain PCOLCE 3x4Hyp-5Hyl-COL3A1 3x4Hyp-GlcGalHyl-COL7A1(2822-2944) Collagen type Ifibril withhydroxyallysinesCollagen type XII fibril LOXL4(25-?) 3Hyp-4Hyp-COL9A3 LAMA3 TropocollagensLOXL3(?-753) 5-hydroxylysyl-collagen alpha-1(XI) chain 3x4Hyp-GlcGalHyl-COL9A2 3x4Hyp-3Hyp-GalHyl-COL7A1 LOXL2(?-774) 3x4Hyp-3Hyp-GalHyl-COL27A1 3x4Hyp-COL1A1 3x4Hyp-GalHyl-COL7A1 LAMA3 3x4Hyp-GlcGalHyl-COL24A1(?-?) 3x4Hyp-5Hyl-COL8A1(28-744) 3x4Hyp-GalHyl-COL18A1(24-1754) 5Hyl-COL8A1(28-744) GlcGalHyl-COL9A1 3x4Hyp-GlcGalHyl-COL6A1 COL7A1 MMP3(100-477) 5Hyl-COL7A1(2822-2944) 5-Gal-Hyl-collagen alpha-1(XI) chain 3x4Hyp-5Hyl-COL9A1 Collagen type IV alpha1.alpha2.alpha5.alpha6 network 5Hyl-COL9A2 Collagen type XXVII fibre LOXL4 3x4Hyp-3Hyp-GalHyl-COL3A1 3x4Hyp-3Hyp-GalHyl-COL10A1 3x4Hyp-3Hyp-COL9A2 H2OCollagen type IV networks TLL1 5Hyl-COL7A1 3x4Hyp-3Hyp-GalHyl-COL7A1(2822-2944) Collagen type IV alpha3.alpha4.alpha5 network 3x4Hyp-5Hyl-COL10A1 GalHyl-COL6A1 PXDN:Br-ProcollagenC-proteinases3x4Hyp-GalHyl-COL7A1(2822-2944) GlcGalHyl-COL7A1 3x4Hyp-3Hyp-5Hyl-COL7A1 Collagen type II fibril 3x4Hyp-3Hyp-5Hyl-COL6A2 3,4-Hyp Glu-Gal-Hyl-collagen alpha-2(XI) chain 3x4Hyp-GalHyl-COL1A2 3x4Hyp-3Hyp-COL24A1(?-?) 3x4Hyp-3Hyp-GalHyl-COL9A3 Collagen type XII fibril Collagen type IV alpha3.alpha4.alpha5 network Type I hemidesmosomecomplexCD151MMP13 GlcGalHyl-COL27A1 Glu-Gal-Hyl-collagen alpha-1(XI) chain GalHyl-COL6A2 3x4Hyp-COL8A1(?-744) 3x4Hyp-GalHyl-COL1A1 3x4Hyp-3Hyp-5Hyl-COL8A2 3x4Hyp-3Hyp-GlcGalHyl-COL7A1(2822-2944) GlcGalHyl-COL8A1(28-744) ITGB4 Collagen type II fibril Collagen type IVnetworks withsulfiliminecross-linksCollagen type IIfibrilCollagen type XII,XIV fibrils3x4Hyp-3Hyp-GlcGalHyl-COL7A1 LOXL4(?-756) GlcGalHyl-COL8A2 GlcGalHyl-COL2A1(182-1241) LOXL1(26-94) 3x4Hyp-3Hyp-5Hyl-COL7A1 5-hydroxylysyl-collagen alpha-2(XI) chain LAMA3 Collagen type X network CTSS Tropocollagen type IV LOX(22-417) 3x4Hyp-3Hyp-GalHyl-COL6A1 3x4Hyp-GalHyl-COL10A1 Sulfilimine-containing collagen type IV alpha1.alpha2.alpha5.alpha6 network Collagenalpha-1(VII) NC2regionLOXL2(26-?) 3x4Hyp-GlcGalHyl-COL8A2 Collagen type VI network Collagen type VII-NC2 hexamerCOL7A1 Collagen type XI fibre Collagen type I fibril 3x4Hyp-5Hyl-COL6A2 LOXL3(?-753) DST-3 Collagen type I fibril with deH-HLNL PLEC 3x4Hyp-GlcGalHyl-COL9A3 Collagen fibres3x4Hyp-3Hyp-GalHyl-COL6A2 CollagentypeIfibrilswithhydroxylysyl-pyridinoline cross-links3x4Hyp-3Hyp-GlcGalHyl-COL9A1 H2O2LOXL1 3x4Hyp-3Hyp-GlcGalHyl-COL3A1 Lysyl oxidasepropeptides3x4Hyp-5Hyl-COL15A1(28-1388) 5Hyl-COL6A2 GlcGalHyl-COL9A2 3x4Hyp-GlcGalHyl-COL9A2 BPAG1e:Plectin3x4Hyp-3Hyp-COL6A1 Collagen type XXIV fibre 3x4Hyp-3Hyp-GlcGalHyl-COL9A2 3x4Hyp-GalHyl-COL7A1 3x4Hyp-5Hyl-COL7A1(2822-2944) Collagen alpha-2(XI) chain 3x4Hyp-GlcGalHyl-COL9A1 GalHyl-COL9A1 3x4Hyp-COL9A3 3x4Hyp-5Hyl-COL24A1(?-?) Collagen type XIV CollagentypeIfibrilswithhydroxylysino-5-ketonorleucine crosslinks3,4-Hyp 5-Hyl-collagen alpha-1(XI) chain Collagen type VIIfibril3x4Hyp-3Hyp-GlcGalHyl-COL8A2 3x4Hyp-5Hyl-COL9A3 3x4Hyp-5Hyl-COL8A2 5Hyl-COL1A2 Collagen type Ifibrils withlysyl-pyrrolecross-linksCollagen type XIV Collagen type I fibril with hydroxylysino-5-ketonorleucine crosslinks 3x4Hyp-3Hyp-GlcGalHyl-COL15A1(28-1388) 3x4Hyp-GlcGalHyl-COL15A1(28-1388) GlcGalHyl-COL9A1 3x4Hyp-5Hyl-COL9A3 5Hyl-COL2A1(182-1241) Collagen alpha-6(VI) chains Collagen type V fibre LAMB3 GlcGalHyl-COL1A2 3x4Hyp-3Hyp-GlcGalHyl-COL2A1(182-1241) Collagen type XVII fibril Collagentype1fibrilscross-linkedbydehydro-lysinonorleucine crosslinks3x4Hyp-3Hyp-5Hyl-COL9A3 3x4Hyp-COL7A1 3x4Hyp-3Hyp-GalHyl-COL18A1(24-1754) 3x4Hyp-COL7A1(17-2821) 3x4Hyp-3Hyp-5Hyl-COL2A1(182-1241) 3x4Hyp-5Hyl-COL1A1 CTSL(114-288) GlcGalHyl-COL1A1 3x4Hyp-3Hyp-5Hyl-COL9A3 LAMB3 3x4Hyp-GlcGalHyl-COL7A1 5Hyl-COL9A3 3x4Hyp-3Hyp-GalHyl-COL8A2 5Hyl-COL1A1 3,4-hydroxyprolyl-collagen alpha-1(XI) chain Collagen type I fibril 3x4Hyp-3Hyp-5Hyl-COL9A2 3x4Hyp-GalHyl-COL27A1 Collagen type XXIV fibril LAMC2 Collagen type I, IIfibrilsGlu-Gal-Hyl collagen alpha-2(XI) chain Network formingtropocollagens3x4Hyp-5Hyl-COL6A1 COL18A1(24-1754) COL9A3 COL3A1 5Hyl-COL9A2 3x4Hyp-3Hyp-5Hyl-COL7A1(17-2821) 3x4Hyp-GlcGalHyl-COL7A1(17-2821) Collagen type I fibril 4-Hyp 5-Hyl collagen alpha-2(XI) chain COL6A1 3x4Hyp-3Hyp-5Hyl-COL10A1 COL15A1(?-1211)Collagen alpha-1(XI) chain COL6A2 3x4Hyp-3Hyp-COL1A1 GlcGalHyl-COL6A1 3x4Hyp-3Hyp-GalHyl-COL15A1(28-1388) 3x4Hyp-3Hyp-GlcGalHyl-COL10A1 GalHyl-COL9A1 3x4Hyp-3Hyp-GalHyl-COL9A1 Collagen type VIII network 3x4Hyp-3Hyp-5Hyl-COL9A2 3x4Hyp-GalHyl-COL15A1(28-1388) DST-3 Collagen alpha-3(VI) chains 3x4Hyp-3Hyp-5Hyl-COL6A1 CTSB(80-126) 3x4Hyp-GalHyl-COL9A2 3x4Hyp-GalHyl-COL6A2 3x4Hyp-GlcGalHyl-COL1A1 5Hyl-COL6A1 GalHyl-COL27A1 GalHyl-COL24A1(?-?) 3Hyp-4Hyp-COL9A3 5Hyl-COL15A1(28-1388) 4-hydroxyprolyl collagen alpha-1(XI) chain 3x4Hyp-3Hyp-5Hyl-COL18A1(24-1754) 3x4Hyp-3Hyp-GalHyl-COL9A2 3x4Hyp-COL8A2 COL7A1(17-2821) GalHyl-COL1A2 3x4Hyp-3Hyp-GlcGalHyl-COL1A1 LAMB3 Collagen type XVCollagen type IV alpha1.alpha1.alpha2 network CollagentypeIfibrilswithhistidino-hydroxylysinoleucine cross-links3x4Hyp-5Hyl-COL9A2 COL1A1 3x4Hyp-GlcGalHyl-COL27A1 CTSL2 5-Gal-Hyl collagen alpha-2(XI) chain GlcGalHyl-COL24A1(?-?) 3x4Hyp-COL6A1 H2OTLL1 3x4Hyp-3Hyp-COL6A2 Collagen type XVIIfibril:Integrinalpha6beta4Collagen type I fibril with hydroxylysyl-pyridinoline cross-links 3x4Hyp-GalHyl-COL7A1(17-2821) 3x4Hyp-3Hyp-COL18A1(24-1754) Collagen type I fibril 4-Hyp Glu-Gal-Hyl collagen alpha-2(XI) chain GalHyl-COL10A1 5Hyl-COL7A1 3x4Hyp-3Hyp-GalHyl-COL2A1(182-1241) 3x4Hyp-COL15A1(28-1388) Collagen type I fibril Collagen type II fibril 3x4Hyp-3Hyp-GlcGalHyl-COL8A1(28-744) 3x4Hyp-3Hyp-COL15A1(28-1388) GalHyl-COL8A2 Collagen fibrils3x4Hyp-3Hyp-COL27A1 Collagen type VII fibril COL9A1 3x4Hyp-3Hyp-GlcGalHyl-COL6A2 3x4Hyp-3Hyp-GlcGalHyl-COL6A1 Collagen type II fibre 3x4Hyp-3Hyp-COL10A1 MMP20 Collagen type XVII fibril Lysyl oxidases:Cu2+GalHyl-COL1A1 3x4Hyp-3Hyp-GalHyl-COL9A2 LOXL4(?-756) COL9A3 Collagen type XIfibril:Collagentype II fibrilGlcGalHyl-COL6A2 Collagen type II fibril 3x4Hyp-5Hyl-COL18A1(24-1754) 3x4Hyp-3Hyp-GlcGalHyl-COL27A1 GalHyl-COL9A3 3x4Hyp-3Hyp-COL9A2 4-hydroxyprolyl collagen alpha-2(XI) chain COL18A1(?-1571)3,4-hydroxyprolyl collagen alpha-2(XI) chain 3x4Hyp-3Hyp-COL2A1(182-1241) H2O23x4Hyp-3Hyp-5Hyl-COL27A1 GlcGalHyl-COL7A1(17-2821) COL15A1(1212-1388)COL7A1(2822-2944) Tropocollagen type V 3x4Hyp-3Hyp-5Hyl-COL8A1(28-744) COL8A1(28-744) GlcGalHyl-COL9A2 5Hyl-COL9A3 3x4Hyp-COL2A1(182-1241) 3x4Hyp-3Hyp-GlcGalHyl-COL7A1(17-2821) 3x4Hyp-3Hyp-COL3A1 GalHyl-COL7A1(17-2821) GalHyl-COL9A2 3x4Hyp-GlcGalHyl-COL9A1 Collagen type VII fibril GlcGalHyl-COL7A1 Collagen type I fibril Collagen type IIfibril:Collagentype IXITGB4 3x4Hyp-COL9A2 Br- 3x4Hyp-3Hyp-COL7A1(17-2821) 3x4Hyp-5Hyl-COL2A1(182-1241) GalHyl-COL9A3 COL27A1 COL2A1(182-1241) Collagen type XXVII fibril NH33x4Hyp-5Hyl-COL7A1 PLEC 1, 1819


Collagen trimers in triple-helical form, referred to as procollagen or collagen molecules, are exported from the ER and trafficked through the Golgi network before secretion into the extracellular space. For fibrillar collagens namely types I, II, III, V, XI, XXIV and XXVII (Gordon & Hahn 2010, Ricard-Blum 2011) secretion is concomitant with processing of the N and C terminal collagen propeptides. These processed molecules are known as tropocollagens, considered to be the units of higher order collagen structures. They form within the extracellular space via a process that can proceed spontaneously, but in the cellular environment is regulated by many collagen binding proteins such as the FACIT (Fibril Associated Collagens with Interrupted Triple helices) family collagens and Small Leucine-Rich Proteoglycans (SLRPs). The architecture formed ultimately depends on the collagen subtype and the cellular conditions. Structures include the well-known fibrils and fibres formed by the major structural collagens type I and II plus several different types of supramolecular assembly (Bruckner 2010). The mechanical and physical properties of tissues depend on the spatial arrangement and composition of these collagen-containing structures (Kadler et al. 1996, Shoulders & Raines 2009, Birk & Bruckner 2011).

Fibrillar collagen structures are frequently heterotypic, composed of a major collagen type in association with smaller amounts of other types, e.g. type I collagen fibrils are associated with types III and V, while type II fibrils frequently contain types IX and XI (Wess 2005). Fibres composed exclusively of a single collagen type probably do not exist, as type I and II fibrils require collagens V and XI respectively as nucleators (Kadler et al. 2008, Wenstrup et al. 2011). Much of the structural understanding of collagen fibrils has been obtained with fibril-forming collagens, particularly type I, but some central features are believed to apply to at least the other fibrillar collagen subtypes (Wess 2005). Fibril diameter and length varies considerably, depending on the tissue and collagen types (Fang et al. 2012). The reasons for this are poorly understood (Wess 2005).

Some tissues such as skin have fibres that are approximately the same diameter while others such as tendon or cartilage have a bimodal distribution of thick and thin fibrils. Mature type I collagen fibrils in tendon are up to 1 cm in length, with a diameter of approx. 500 nm. An individual fibrillar collagen triple helix is less than 1.5 nm in diameter and around 300 nm long; collagen molecules must assemble to give rise to the higher-order fibril structure, a process known as fibrillogenesis, prevented by the presence of C-terminal propeptides (Kadler et al. 1987). In electron micrographs, fibrils have a banded appearance, due to regular gaps where fewer collagen molecules overlap, which occur because the fibrils are aligned in a quarter-stagger arrangement (Hodge & Petruska 1963). Collagen microfibrils are believed to have a quasi-hexagonal unit cell, with tropocollagen arranged to form supertwisted, right-handed microfibrils that interdigitate with neighbouring microfibrils, leading to a spiral-like structure for the mature collagen fibril (Orgel et al. 2006, Holmes & Kadler 2006).

Neighbouring tropocollagen monomers interact with each other and are cross-linked covalently by lysyl oxidase (Orgel et al. 2000, Maki 2006). Mature collagen fibrils are stabilized by lysyl oxidase-mediated cross-links. Hydroxylysyl pyridinoline and lysyl pyridinoline cross-links form between (hydroxy) lysine and hydroxylysine residues in bone and cartilage (Eyre et al. 1984). Arginoline cross-links can form in cartilage (Eyre et al. 2010); mature bovine articular cartilage contains roughly equimolar amounts of arginoline and hydroxylysyl pyridinoline based on peptide yields. Mature collagen fibrils in skin are stabilized by the lysyl oxidase-mediated cross-link histidinohydroxylysinonorleucine (Yamauch et al. 1987). Due to the quarter-staggered arrangement of collagen molecules in a fibril, telopeptides most often interact with the triple helix of a neighbouring collagen molecule in the fibril, except for collagen molecules in register staggered by 4D from another collagen molecule. Fibril aggregation in vitro can be unipolar or bipolar, influenced by temperature and levels of C-proteinase, suggesting a role for the N- and C- propeptides in regulation of the aggregation process (Kadler et al. 1996). In vivo, collagen molecules at the fibril surface may retain their N-propeptides, suggesting that this may limit further accretion, or alternatively represents a transient stage in a model whereby fibrils grow in diameter through a cycle of deposition, cleavage and further deposition (Chapman 1989).

In vivo, fibrils are often composed from more than one type of collagen. Type III collagen is found associated with type I collagen in dermal fibrils, with the collagen III on the periphery, suggesting a regulatory role (Fleischmajer et al. 1990). Type V collagen associates with type I collagen fibrils, where it may limit fibril diameter (Birk et al. 1990, White et al. 1997). Type IX associates with the surface of narrow diameter collagen II fibrils in cartilage and the cornea (Wu et al. 1992, Eyre et al. 2004). Highly specific patterns of crosslinking sites suggest that collagen IX functions in interfibrillar networking (Wess 2005). Type XII and XIV collagens are localized near the surface of banded collagen I fibrils (Nishiyama et al. 1994). Certain fibril-associated collagens with interrupted triple helices (FACITs) associate with the surface of collagen fibrils, where they may serve to limit fibril fusion and thereby regulate fibril diameter (Gordon & Hahn 2010). Collagen XV, a member of the multiplexin family, is almost exclusively associated with the fibrillar collagen network, in very close proximity to the basement membrane. In human tissues collagen XV is seen linking banded collagen fibers subjacent to the basement membrane (Amenta et al. 2005). Type XIV collagen, SLRPs and discoidin domain receptors also regulate fibrillogenesis (Ansorge et al. 2009, Kalamajski et al. 2010, Flynn et al. 2010).

Collagen IX is cross-linked to the surface of collagen type II fibrils (Eyre et al. 1987). Type XII and XIV collagens are found in association with type I (Walchli et al. 1994) and type II (Watt et al. 1992, Eyre 2002) fibrils in cartilage. They are thought to associate non-covalently via their COL1/NC1 domains (Watt et al. 1992, Eyre 2002).

Some non-fibrillar collagens form supramolecular assemblies that are distinct from typical fibrils. Collagen VII forms anchoring fibrils, composed of antiparallel dimers that connect the dermis to the epidermis (Bruckner-Tuderman 2009). During fibrillogenesis, the nascent type VII procollagen molecules dimerize in an antiparallel manner. The C-propeptides are then removed by Bone morphogenetic protein 1 (Rattenholl et al. 2002) and the processed antiparallel dimers aggregate laterally. Collagens VIII and X form hexagonal networks and collagen VI forms beaded filament (Gordon & Hahn 2010, Ricard-Blum et al. 2011). View original pathway at:Reactome.


Pathway is converted from Reactome ID: 2022090
Reactome version: 66
Reactome Author 
Reactome Author: Jupe, Steve

Quality Tags

Ontology Terms



View all...
  1. Huber S, van der Rest M, Bruckner P, Rodriguez E, Winterhalter KH, Vaughan L.; ''Identification of the type IX collagen polypeptide chains. The alpha 2(IX) polypeptide carries the chondroitin sulfate chain(s).''; PubMed Europe PMC Scholia
  2. Orgel JP, San Antonio JD, Antipova O.; ''Molecular and structural mapping of collagen fibril interactions.''; PubMed Europe PMC Scholia
  3. Reiser K, McCormick RJ, Rucker RB.; ''Enzymatic and nonenzymatic cross-linking of collagen and elastin.''; PubMed Europe PMC Scholia
  4. Pinnell SR, Martin GR.; ''The cross-linking of collagen and elastin: enzymatic conversion of lysine in peptide linkage to alpha-aminoadipic-delta-semialdehyde (allysine) by an extract from bone.''; PubMed Europe PMC Scholia
  5. Schmid TM, Linsenmayer TF.; ''Immunoelectron microscopy of type X collagen: supramolecular forms within embryonic chick cartilage.''; PubMed Europe PMC Scholia
  6. Sasaki T, Larsson H, Tisi D, Claesson-Welsh L, Hohenester E, Timpl R.; ''Endostatins derived from collagens XV and XVIII differ in structural and binding properties, tissue distribution and anti-angiogenic activity.''; PubMed Europe PMC Scholia
  7. Kuypers R, Tyler M, Kurth LB, Jenkins ID, Horgan DJ.; ''Identification of the loci of the collagen-associated Ehrlich chromogen in type I collagen confirms its role as a trivalent cross-link.''; PubMed Europe PMC Scholia
  8. Uzel MI, Scott IC, Babakhanlou-Chase H, Palamakumbura AH, Pappano WN, Hong HH, Greenspan DS, Trackman PC.; ''Multiple bone morphogenetic protein 1-related mammalian metalloproteinases process pro-lysyl oxidase at the correct physiological site and control lysyl oxidase activation in mouse embryo fibroblast cultures.''; PubMed Europe PMC Scholia
  9. Kadler KE, Holmes DF, Trotter JA, Chapman JA.; ''Collagen fibril formation.''; PubMed Europe PMC Scholia
  10. Koster J, Geerts D, Favre B, Borradori L, Sonnenberg A.; ''Analysis of the interactions between BP180, BP230, plectin and the integrin alpha6beta4 important for hemidesmosome assembly.''; PubMed Europe PMC Scholia
  11. Fujimoto D, Moriguchi T.; ''Pyridinoline, a non-reducible crosslink of collagen. Quantitative determination, distribution, and isolation of a crosslinked peptide.''; PubMed Europe PMC Scholia
  12. Brittingham R, Uitto J, Fertala A.; ''High-affinity binding of the NC1 domain of collagen VII to laminin 5 and collagen IV.''; PubMed Europe PMC Scholia
  13. Wälchli C, Koch M, Chiquet M, Odermatt BF, Trueb B.; ''Tissue-specific expression of the fibril-associated collagens XII and XIV.''; PubMed Europe PMC Scholia
  14. Bailey AJ, Peach CM.; ''Isolation and structural identification of a labile intermolecular crosslink in collagen.''; PubMed Europe PMC Scholia
  15. Gordon MK, Hahn RA.; ''Collagens.''; PubMed Europe PMC Scholia
  16. Wess TJ.; ''Collagen fibril form and function.''; PubMed Europe PMC Scholia
  17. Robins SP, Bailey AJ.; ''The chemistry of the collagen cross-links. The mechanism of stabilization of the reducible intermediate cross-links.''; PubMed Europe PMC Scholia
  18. Olsen BR.; ''Collagen IX.''; PubMed Europe PMC Scholia
  19. Hurskainen M, Ruggiero F, Hägg P, Pihlajaniemi T, Huhtala P.; ''Recombinant human collagen XV regulates cell adhesion and migration.''; PubMed Europe PMC Scholia
  20. Rattenholl A, Pappano WN, Koch M, Keene DR, Kadler KE, Sasaki T, Timpl R, Burgeson RE, Greenspan DS, Bruckner-Tuderman L.; ''Proteinases of the bone morphogenetic protein-1 family convert procollagen VII to mature anchoring fibril collagen.''; PubMed Europe PMC Scholia
  21. Siegel RC.; ''Lysyl oxidase.''; PubMed Europe PMC Scholia
  22. Karamatic Crew V, Burton N, Kagan A, Green CA, Levene C, Flinter F, Brady RL, Daniels G, Anstee DJ.; ''CD151, the first member of the tetraspanin (TM4) superfamily detected on erythrocytes, is essential for the correct assembly of human basement membranes in kidney and skin.''; PubMed Europe PMC Scholia
  23. Villone D, Fritsch A, Koch M, Bruckner-Tuderman L, Hansen U, Bruckner P.; ''Supramolecular interactions in the dermo-epidermal junction zone: anchoring fibril-collagen VII tightly binds to banded collagen fibrils.''; PubMed Europe PMC Scholia
  24. Stone PJ, Bryan-Rhadfi J, Shaw HA, Franzblau C.; ''Isolation of hydroxylysyl pyridinoline, a mature collagen crosslink from neonatal rat aorta smooth muscle cell cultures.''; PubMed Europe PMC Scholia
  25. Eyre DR, Pietka T, Weis MA, Wu JJ.; ''Covalent cross-linking of the NC1 domain of collagen type IX to collagen type II in cartilage.''; PubMed Europe PMC Scholia
  26. Henkel W, Glanville RW, Greifendorf D.; ''Characterisation of a type-I collagen trimeric cross-linked peptide from calf aorta and its cross-linked structure. Detection of pyridinoline by time-of-flight secondary ion-mass spectroscopy and evidence for a new cross-link.''; PubMed Europe PMC Scholia
  27. O'Reilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS, Flynn E, Birkhead JR, Olsen BR, Folkman J.; ''Endostatin: an endogenous inhibitor of angiogenesis and tumor growth.''; PubMed Europe PMC Scholia
  28. Hopkinson SB, Findlay K, deHart GW, Jones JC.; ''Interaction of BP180 (type XVII collagen) and alpha6 integrin is necessary for stabilization of hemidesmosome structure.''; PubMed Europe PMC Scholia
  29. Nakashima Y, Kariya Y, Yasuda C, Miyazaki K.; ''Regulation of cell adhesion and type VII collagen binding by the beta3 chain short arm of laminin-5: effect of its proteolytic cleavage.''; PubMed Europe PMC Scholia
  30. Vanacore R, Ham AJ, Voehler M, Sanders CR, Conrads TP, Veenstra TD, Sharpless KB, Dawson PE, Hudson BG.; ''A sulfilimine bond identified in collagen IV.''; PubMed Europe PMC Scholia
  31. Bhave G, Cummings CF, Vanacore RM, Kumagai-Cresse C, Ero-Tolliver IA, Rafi M, Kang JS, Pedchenko V, Fessler LI, Fessler JH, Hudson BG.; ''Peroxidasin forms sulfilimine chemical bonds using hypohalous acids in tissue genesis.''; PubMed Europe PMC Scholia
  32. Siegel RC, Fu JC, Uto N, Horiuchi K, Fujimoto D.; ''Collagen cross-linking: lysyl oxidase dependent synthesis of pyridinoline in vitro: confirmation that pyridinoline is derived from collagen.''; PubMed Europe PMC Scholia
  33. Okada K, Kondo A, Ishikawa O, Miyachi Y.; ''Histidinohydroxylysinonorleucine, a trifunctional cross-link of type I collagen, in sun-exposed and sun-protected human skin.''; PubMed Europe PMC Scholia
  34. Panchenko MV, Stetler-Stevenson WG, Trubetskoy OV, Gacheru SN, Kagan HM.; ''Metalloproteinase activity secreted by fibrogenic cells in the processing of prolysyl oxidase. Potential role of procollagen C-proteinase.''; PubMed Europe PMC Scholia
  35. Watt SL, Lunstrum GP, McDonough AM, Keene DR, Burgeson RE, Morris NP.; ''Characterization of collagen types XII and XIV from fetal bovine cartilage.''; PubMed Europe PMC Scholia
  36. Banse X, Sims TJ, Bailey AJ.; ''Mechanical properties of adult vertebral cancellous bone: correlation with collagen intermolecular cross-links.''; PubMed Europe PMC Scholia
  37. Hashizume H, Hitomi J, Ushiki T.; ''Growth of collagen fibrils produced by human osteosarcoma cells: high-resolution scanning electron microscopy.''; PubMed Europe PMC Scholia
  38. Morris NP, Keene DR, Glanville RW, Bentz H, Burgeson RE.; ''The tissue form of type VII collagen is an antiparallel dimer.''; PubMed Europe PMC Scholia
  39. Lehto M, Sims TJ, Bailey AJ.; ''Skeletal muscle injury--molecular changes in the collagen during healing.''; PubMed Europe PMC Scholia


View all...
101223view11:11, 1 November 2018ReactomeTeamreactome version 66
100761view20:37, 31 October 2018ReactomeTeamreactome version 65
100305view19:14, 31 October 2018ReactomeTeamreactome version 64
99852view15:58, 31 October 2018ReactomeTeamreactome version 63
99409view14:34, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93410view11:22, 9 August 2017ReactomeTeamreactome version 61
86500view09:19, 11 July 2016ReactomeTeamreactome version 56
83231view10:26, 18 November 2015ReactomeTeamVersion54
81628view13:10, 21 August 2015ReactomeTeamVersion53
77089view08:38, 17 July 2014ReactomeTeamFixed remaining interactions
76795view12:17, 16 July 2014ReactomeTeamFixed remaining interactions
76118view10:18, 11 June 2014ReactomeTeamRe-fixing comment source
75830view11:39, 10 June 2014ReactomeTeamReactome 48 Update
75191view09:40, 9 May 2014Anwesha
74835view10:06, 30 April 2014ReactomeTeamNew pathway

External references


View all...
NameTypeDatabase referenceComment
3,4-Hyp 5-Gal-Hyl-collagen alpha-1(XI) chain ProteinP12107 (Uniprot-TrEMBL)
3,4-Hyp 5-Gal-Hyl-collagen alpha-2(XI) chain ProteinP13942 (Uniprot-TrEMBL)
3,4-Hyp 5-Hyl-collagen alpha-1(XI) chain ProteinP12107 (Uniprot-TrEMBL)
3,4-Hyp 5-Hyl-collagen alpha-2(XI) chain ProteinP13942 (Uniprot-TrEMBL)
3,4-Hyp Glu-Gal-Hyl-collagen alpha-1(XI) chain ProteinP12107 (Uniprot-TrEMBL)
3,4-Hyp Glu-Gal-Hyl-collagen alpha-2(XI) chain ProteinP13942 (Uniprot-TrEMBL)
3,4-hydroxyprolyl collagen alpha-2(XI) chain ProteinP13942 (Uniprot-TrEMBL)
3,4-hydroxyprolyl-collagen alpha-1(XI) chain ProteinP12107 (Uniprot-TrEMBL)
3Hyp-4Hyp-COL9A3 ProteinQ14050 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL10A1 ProteinQ03692 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL15A1(28-1388) ProteinP39059 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL18A1(24-1754) ProteinP39060 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL1A1 ProteinP02452 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL1A2 ProteinP08123 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL24A1(?-?) ProteinQ17RW2 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL27A1 ProteinQ8IZC6 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL2A1(182-1241) ProteinP02458 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL3A1 ProteinP02461 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL6A1 ProteinP12109 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL6A2 ProteinP12110 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL7A1 ProteinQ02388 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL7A1(17-2821) ProteinQ02388 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL7A1(2822-2944) ProteinQ02388 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL8A1(28-744) ProteinP27658 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL8A2 ProteinP25067 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL9A1 ProteinP20849 (Uniprot-TrEMBL)
3x4Hyp-3Hyp-5Hyl-COL9A2 ProteinQ14055 (Uniprot-TrEMBL)