The Y chromosome is a type of sex chromosome existing primarily in male mammalian species. The Y chromosome passes through the male gamete and determines male sex in humans, non-human primates, and other mammals. The mammalian Y chromosome varies from the X chromosome and the rest of the chromosomes primarily by size and its male sex-determining/spermatogenesis function. In the Y chromosome, male sex-determining function is exclusively located on the short arm, while the spermatogenesis function is distributed widely on the short and long arm. Deletions or mutations particularly in the male-specific region of Y chromosome (MSY) may cause male infertility. During the last few decades, researchers put forth an enormous effort to discover Y chromosome specific genes, and their encoded RNAs and proteins in humans, primates, and rodents. As a result, most of the genes and encoded proteins responsible for male-sex determination, testis development, and spermatogenesis have been discovered in humans, however not well established in non-human primates and rodents. Also, there might be a percent of proteins missing in human Y chromosome. The aim of this study is to annotate the proteins that encoded on the Y chromosome of humans, chimpanzee, and mouse using extensive bioinformatics tools. The human (annotation release 107), chimpanzee (annotation release 103), and mouse (annotation release 105) proteins were first retrieved from the National Center for Biotechnology Information (NCBI) eukaryotic genome annotation resource database. Then, the annotated human proteins (66 proteins) were compared with the core databases of human proteome project such as neXtProt, PeptideAtlas, and the Human Protein Atlas. The X-homologous of human Y chromosome-encoded proteins were searched using the NCBI Protein BLAST program. The cellular pathways and protein-protein interactions involving human Y chromosome-encoded proteins were searched using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway mapping database, the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and the Pathway Studio software. Finally, the human Y chromosome-encoded protein homologs/orthologs in chimpanzee and mouse were analyzed using the NCBI bl2seq program. This analysis resulted a significant number of homologous/orthologous proteins between human, chimpanzee and mouse. Our findings provide the scientific community with updated information on the Y chromosome-encoded proteins in humans, chimpanzee, and mouse.