A locus containing 14 genes, encoding protein domains that have homology with whey acidic protein (WAP), has been identified in a region of 678kb on human chromosome 20q12-13.1. Among them are genes of the known or postulated protease inhibitors elafin, secretory leucocyte protease inhibitor, human epididymis gene product 4, eppin, and huWAP2. Nucleotide sequences of full-length transcripts were obtained from cDNA fragments generated by rapid amplification of cDNA ends. Characteristic features of the genes are that the upstream promoter regions are devoid of TATA-boxes and that the coding nucleotides are divided into distinct exons for the signal peptide and for each WAP domain. In most cases, there is also a separate exon encompassing a few terminal codons and the 3′ untranslated nucleotides. There are also examples of mixed type inhibitors, that encode inhibitor domains of both WAP and Kunitz types. Several of the genes appear to be expressed ubiquitously, but, in most cases, the highest transcript levels are found in epididymis followed by testis and trachea. Some of the genes also display high transcript levels in neural tissues. Potential biological roles of protein products could be in host defence against invading micro-organisms or in the regulation of endogenous proteolytic enzymes, of which those originating from the kallikrein gene locus on chromosome 19 are of particular interest.
- serine protease
The nucleotide sequences reported in this paper have been submitted to the GenBank®, EMBL, DDBJ and GSDB Nucleotide Sequence databases under accession numbers AY038181 for WAP1, AF411861 for WAP6, AF492015 for WAP8a, AF492016 for WAP8b, AY047610 for WAP9, AY038182 for WAP10, AY047609 for WAP11, AF454506 for WAP12a, AF454507 for WAP12b, AF454505 for WAP13 and AF488306 for WAP14.
Abbreviations used: APRT, adenine phosphoribosyltransferase; EST, expressed sequence tag; HE4, human epididymis gene product 4; PSA, prostate-specific antigen; RACE, rapid amplification of cDNA ends; RT-PCR, reverse transcriptase-PCR; SLPI, secretory leucocyte protease inhibitor; WAP, whey acidic protein.
- The Biochemical Society, London ©2002