Genomic organisation, alternative splicing and primary structure of human matrilin‐41

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Abstract
We have recently cloned a cDNA for mouse matrilin‐4. By sequence comparison we identified the 12 kb long human matrilin‐4 gene as a part of a high‐throughput genomic sequence (HS453C12) in the databases. Additionally we found a human matrilin‐4 expressed sequence tag (H54037) in the database that had been mapped to chromosome 20q13.1–2. The gene contains 10 exons and, like the matrilin‐1 gene, the human matrilin‐4 gene contains an AT‐AC intron between the two exons en coding the coiled‐coil domain. The cDNA sequence of human matrilin‐4 was determined by sequencing of RT‐PCR products obtained from mRNA of the human embryonic kidney cell line HEK 293. At the amino acid level it showed an overall sequence identity to the mature mouse matrilin‐4 of 91% with a maximum of 97% in the second vWFA‐like module. Alternative splicing leads to three different mRNAs. They all encode the putative signal peptide, the two vWFA‐like domains and the potential coiled‐coil α‐helical oligomerisation domain but differ in that either one, two or three EGF‐like domains are retained in the mature mRNA. Due to a G to A mutation at the splice donor site of intron C, the third exon encodes an untranslated pseudo‐exon specifying the first EGF‐like domain when compared to mouse matrilin‐4.