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-τ) by the conceptus (trophoblast and embryo) and the actions of this cytokine on the uterine endometrium. A novel 17-kDa uterine protein that is regulated by IFN-τ during early pregnancy and crossreacts with ubiquitin antiserum on Western blots, has been named bovine ubiquitin cross-reactive protein (bUCRP). We suspected that bUCRP might be structurally related to ubiquitin, and to a human UCRP (ISG15 product) that has 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 bUCRP. Nucleotide sequence of the bUCRP cDNA shared 70% identity with hUCRP and 30% identity with a tandem ubiquitin repeat. Computer translation revealed that bUCRP shared the Leu-Arg-Gly-Gly (LRGG) C-terminal sequence with ubiquitin and hUCRP that has been implicated in the modulation of intracellular proteins. However, some ubiquitin residues known to function in the ligation (Arg-54) to targeted proteins and in the processing of conjugates through the proteasome (His-68), have been lost through mutation in bUCRP. Lys-48, known to function in formation of ubiquitin polymers, was present in hUCRP, but mutated to Arg in bUCRP. Because bUCRP is secreted and retains the LRGG sequence, it may have both intracellular and secreted endocrine roles in maintaining pregnancy. Bovine UCRP also may have very different intracellular roles when compared with ubiquitin and hUCRP because of mutations in residues known to form polymers and to target proteins to degradation.