FIBULIN-2 (FBLN2) - HUMAN CDNA SEQUENCE, MESSENGER-RNA EXPRESSION, AND MAPPING OF THE GENE ON HUMAN AND MOUSE CHROMOSOMES

Fibulin-2 is a new extracellular matrix protein that we recently ident ified by characterizing mouse cDNA clones. Fibulin-2 mRNA is prominent ly expressed in mouse heart tissue and is present in low amounts in ot her tissues. In this study, we isolated and sequenced a 4.1-kb human f ibulin-2 cDNA, which encoded a mature protein of 1157 amino acids prec eded by a 27-residue signal sequence, The predicted polypeptide contai ns three consecutive anaphylatoxin-related segments (domain I) in its central region followed by 10 EGF-like repeats (domain II), 9 of which have a consensus sequence for calcium binding. The 408-residue N-term inal region consists of two separate subdomains, a cysteine-rich segme nt of 150 residues (Na subdomain) and a cysteine-free segment with a s tretch of acidic amino acids (Nb subdomain). The 115-residue C-termina l segment (domain III) is similar to the C variant of fibulin-1. The a mino acid sequences of the human and mouse fibulin-2 share similar to 90% identity in domains Na, I, II, and III but only 62% identity in do main Nb. The human cDNA lacks an EGF like repeat, which is alternative ly spliced in the mouse cDNA clones, and a potential cell-binding Arg- Gly-Asp sequence found in the Nb domain of the mouse counterpart. Nort hern blot analysis of mRNA from various human tissues reveals an abund ant 4.5-kb transcript in heart, placenta, and ovary tissue. The expres sion pattern differs from that of fibulin-1. The fibulin-2 gene was lo calized by in situ hybridization to the p24-p25 region of human chromo some 3 and to the band D-E of mouse chromosome 6. (C) 1994 Academic Pr ess, Inc.