Humans and Acanthamoeba Polyphaga Mimivirus share numerous homologous genes, including collagens and collagen-modifying enzymes. To explore the homology, a genome-wide comparison was performed between human and mimivirus using DELTA-BLAST (Domain Enhanced Lookup Time Accelerated BLAST) and identified 190 new mimiviral proteins that share homology with 1236 human proteins. To gain functional insights into mimiviral proteins, the human protein homologs were organized into Gene Ontology (GO) and REACTOME pathways to build a functional network. Collagen and collagen-modifying enzymes form the largest subnetwork with most nodes. Further analysis of this subnetwork identified a putative collagen glycosyltransferase R699. Protein expression test suggested that R699 is highly expressed in E coli, unlike the human collagen-modifying enzymes. Enzymatic activity assays showed that R699 catalyzes the conversion of galactosyl-hydroxylysine to glucosyl-galactosyl-hydroxylysine on collagen using UDP-glucose as a sugar donor, suggesting R699 is a mimiviral collagen galactosylhydroxylysyl glucosyltransferase (GGT). Structural study of R699 produced the first crystal structure of a collagen GGT with uridine diphosphate glucose (UDP-Glc). Sugar moiety of the UDP-Glc resides in a previously unrecognized pocket. Mn2+ coordination and nucleoside-diphosphate binding site are conserved among GGT family members and critical for R699's collagen GGT activity. To facilitate further analysis of human and mimiviral homologous proteins, we presented an interactive and searchable genome-wide comparison app for quickly browsing of human and Acanthamoeba Polyphaga Mimivirus homologs, which is available at RRID Resource ID: SCR_022140 or guolab.shinyapps.io/app-mimivirus-publication/.