Northern blot analysis indicated that the mRNA for human properdin is approximately 1.5 kb long and that its level in U-937 cells is increased by pretreating the cells with phorbol12-myristate 13-acetate (PMA). Using a human genomic probe clones coding for human properdin were isolated from a hgtlO cDNA library derived from PMA-treated U-937 cells. The sequence of the 1474-bp cDNA insert of the longest clone revealed an open reading frame of 1326 bp coding for the entire 442 amino acids of the mature form of human properdin and 67 bp coding for 22 amino acids of typical, but incomplete leader sequence. Polymerase chain reaction "RACE" experiments identified the start site ATG and revealed the complete, 27-amino acid-long, leader peptide sequence. Within the 81-bp 3' non-translated extension a polyadenylation signal was identified 41 bp downstream from the stop codon,TAA, and 12 bp upstream of a 19 nucleotide long poly(A) tail.The amino acid sequence of human properdin is clearly divided into three distinct regions: a 49 residue-long N-terminal region, a 32 residue-long C-terminal region and a middle region, covering residues 50 to 411, composed of six tandemly repeated thrompospondin repeat (TSR) motifs of the type first described in the adhesive glycoprotein thrombospondin and also known to be present in the C6, C7, C8a, CSP and C9 terminal components of complement. Human and mouse properdin sequences show a high (-76%) degree of identity with almost complete conservation of the relatively large number of Cys (44) and Trp (20) residues.