Experimental characterization of amino acid functions of Domains of Unknown Function (DUF) proteins is expensive, and time-consuming which could be complemented by computational methods. Cysteine, being the second most reactive amino acid at the catalytic sites of enzymes, was selected for functional annotation and characterization on DUF proteins. Earlier we reported functional annotation of Cysteine on DUF proteins belonging to the COX-II family. However, holistic characterization of Cysteine functions on DUF proteins was not known, to the best of our knowledge. Here, we annotated and characterized Cysteine post-translational modifications (PTMs) based on biochemical pathways, diseases, taxonomy, and protein microenvironment. The information on uncharacterized DUF proteins was initially obtained from the literature and the sequence, structure, pathways, taxonomy, and disease information were retrieved from the SCOP database using DUF IDs. Protein microenvironments (MENV) around Cysteine were computed using protein structures. The Cysteine PTMs were predicted using the in-house Cysteine-function prediction server, DeepCys (https:/deepcys.bits-hyderabad.ac.in). The information was consolidated in the database ([http://cysduf.bits-hyderabad.ac.in/](http://cysduf.bits-hyderabad.ac.in/) ), retrievable in downloadable formats (CSV, JSON, or TXT) using the following inputs, DUF ID, PFAM ID, or PDB ID. For the first time, we annotated Cysteine PTMs in DUF proteins belonging to seven different biochemical pathways. For the first time, the Cysteine PTMs in DUF proteins were elucidated in Viruses, namely, SARS-COV2. The nature of MENV around Cysteine from DUF proteins (reported for the first time) was mainly buried and hydrophobic in nature; however, in viruses, a significant number of Cysteine residues were embedded in the exposed and hydrophilic microenvironment.