The insoluble TGFBIp fraction of the cornea is covalently linked via a disulfide bond to type XII collagen

Biochemistry. 2013 Apr 23;52(16):2821-7. doi: 10.1021/bi400212m. Epub 2013 Apr 15.


TGFBIp, also known as keratoepithelin and βig-h3, is among the most abundant proteins in the human cornea, and approximately 60% is associated with the insoluble fraction following extraction in sodium dodecyl sulfate (SDS) sample buffer. TGFBIp is of particular interest because a wide range of mutations causes amyloid or fuchsinophilic crystalloid deposits in the cornea leading to visual impairment. We show that the SDS-insoluble fraction of TGFBIp from porcine and human corneas is covalently linked via a reducible bond to the NC3 domain of type XII collagen in a TGFBIp:type XII collagen stoichiometric ratio of 2:1. Because type XII collagen is anchored to striated collagen fibers of the extracellular matrix, its interaction with TGFBIp is likely to provide anchoring for cells to the extracellular matrix through the integrin binding capability of TGFBIp. Furthermore, the TGFBIp-type XII collagen molecule will affect our understanding of the molecular pathogenesis of the TGFBI-linked corneal dystrophies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Collagen Type XII / chemistry*
  • Collagen Type XII / metabolism*
  • Cornea / chemistry*
  • Disulfides / chemistry
  • Disulfides / metabolism
  • Extracellular Matrix / metabolism
  • Extracellular Matrix Proteins / chemistry*
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Humans
  • Molecular Weight
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Solubility
  • Swine
  • Transforming Growth Factor beta / chemistry*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism


  • Collagen Type XII
  • Disulfides
  • Extracellular Matrix Proteins
  • Recombinant Proteins
  • Transforming Growth Factor beta
  • betaIG-H3 protein