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Cereal grain bread wheat (T. aestivum) is an important source of food and belongs to Poaceae family. Hypothetical proteins (HPs), i.e., proteins with unknown functions, share a substantial portion of wheat proteomes and play important roles in growth and physiology of plant system. Several functional annotations studies utilizing the protein sequences for characterization of role of individual protein in physiology of plant systems were being reported in recent past. In this study, an integrated pipeline of software/servers has been used for the identification and functional annotation of 124 unique HPs of T. aestivum considering available data in NCBI till date. All HPs were broadly annotated, out of which functions of 77 HPs were successfully assigned with high confidence level. Precisely functional annotation of remaining 47 HPs is also characterized with low confidence. Several latest versions of protein family databases, pathways information, genomics context methods and in silico tools were utilized to identify and assign function for individual HPs. Annotation result of several HPs mainly belongs to cellular protein, metabolic enzymes, binding proteins, transmembrane proteins, transcription factors and photosystem regulator proteins. Subsequently, functional analysis has revealed the role of few HPs in abiotic stress, which were further verified by phylogenetic analysis. The functionally associated proteins with each of above-mentioned abiotic stress-related proteins were identified through protein-protein interaction network analysis. The outcome of this study may be helpful for formulating general set pipeline/protocols for a better understanding of the role of HPs in physiological development of various plant systems.