Identification of a distinct type IV collagen alpha chain with restricted kidney distribution and assignment of its gene to the locus of X chromosome-linked Alport syndrome.

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Abstract
We have identified and extensively characterized a type IV collagen .alpha. chain, referred to as .alpha.5(IV). Four overlapping cDNA clones isolated contain an open reading frame for 543 amino acid residues of the carboxyl-terminal end of a collagenous domain, a 229-residue carboxyl-terminal noncollagenous domain, and 1201 base pairs coding for a 3'' untranslated region. The collagenous Gly-Xaa-Yaa repeat sequence has five imperfections that coincide with those in the corresponding region of the .alpha.1(IV) chain. The noncollagenous domain has 12 conserved cysteine residues and 83% and 63% sequence identity with the noncollagenous domains of the .alpha.1(IV) and .alpha.2(IV) chains, respectively. The .alpha.5(IV) chain has less sequence identity with the putative bovine .alpha.3(IV) and .alpha.4(IV) chains. Antiserum against an .alpha.5(IV) synthetic peptide stained a polypepide chain of about 185 kDa by immunoblot analysis and immunolocalization of the chain in human kidney was almost completely restricted to the glomerulus. The gene was assigned to the Xq22 locus by somatic cell hybrids and in situ hybridization. This may be identical or close to the locus of the X chromosome-linked Alport syndrome that is believed to be a type IV collagen disease.