COMPLEMENTARY DEOXYRIBONUCLEIC-ACID SEQUENCE ENCODING BOVINE UBIQUITIN CROSS-REACTIVE PROTEIN - A COMPARISON WITH UBIQUITIN AND A 15-KDA UBIQUITIN HOMOLOG

Pregnancy in the cow depends on secretion of interferon-tau (IFN-tau) by the conceptus (trophoblast and embryo) and the actions of this cyto kine on the uterine endometrium. A novel 17-kDa uterine protein that i s regulated by IFN-tau during early pregnancy and cross-reacts with ub iquitin antiserum on Western blots, has been named bovine ubiquitin cr oss-reactive protein (bUCRP). We suspected that bUCRP might be structu rally related to ubiquitin, and to a human UCRP (ISG15 product) that h as been described in several cell lines to be regulated by Type I IFNs . In this study, immunoscreening of a bovine endometrial cDNA library with ubiquitin antiserum resulted in the isolation of cDNAs encoding b UCRP. Nucleotide sequence of the bUCRP cDNA shared 70 % identity with hUCRP and 30% identity with a tandem ubiquitin repeat. Computer transl ation revealed that bUCRP shared the Leu-Arg-Gly-Gly (LRGG) C-terminal sequence with ubiquitin and hUCRP that has been implicated in the mod ulation of intracellular proteins. However, some ubiquitin residues kn own to function in the ligation (Arg-54) to targeted proteins and in t he processing of conjugates through the proteasome (His-68), have been lost through mutation in bUCRP. Lys-48, known to function in formatio n of ubiquitin polymers, was present in hUCRP, but mutated to Arg in b UCRP. Because bUCRP is secreted and retains the LRGG sequence, it may have both intracellular and secreted endocrine roles in maintaining pr egnancy. Bovine UCRP also may have very different intracellular roles when compared with ubiquitin and hUCRP because of mutations in residue s known to form polymers and to target proteins to degradation.