SKP1 (S-phase kinase protein1) is an essential regulatory component of SCF (Skp1-cullin-F-box) E3 ubiquitin ligases involved in maintenance of cellular protein homeostasis through ubiquitin mediated proteasome system (UPS). UPS play a key role in stress response and grain yield. Earlier, we isolated TaSKP1-6B-4, highly induced in flag leaf tissues (Accession No. KJ830759.1) of developing wheat caryopses under heat stress. To further assess the functional role of SKP1, genetic variability analysis was carried out in a panel of 25 contrasting germplasm through extensive phenotyping and transcript profiling of TaSKP1-6B-4 during anthesis under ambient and terminal heat stress (THS) in field experiments for two consecutive years. The analysis of variance revealed significant variations for all the traits studied. Higher H2(%), GCV, PCV, GA and GA% mean observed in tiller number per plant (23.81, 17.65, 5.71, 28, 30.86%) and grain number per head (30.27, 82.79, 60.16, 105.00, 108.64%) under THS over ambient temperature. Higher fold induction of TaSKP1-6B-4 transcripts was recorded in 10 genotypes viz. HD2967 (9.9), IC145456 (6.18) in flag leaf; while C-306 (15.88), RAJ3765 (8.37) in ear head. Allele mining of SKP1-6B-4 showed genotypic sequence variations. Whole genome wide search of SKP1 gene family identified 95 SKP1 genes which were structurally characterized. Grain yield, leaf senescence and other agronomic-morpho-physiological parameters combined with transcript profiling, cvHD2967, was found to be the best positively responsive to THS which by pedigree was not heat tolerant. We report a novel 2 year comprehensive field based analysis on collective genetic variability and SKP1/UPS modulation under a natural environmental setting. The data reveals potential functional role of UPS under THS and tolerant cultivars can be further utilized for clarifying the role of UPS mechanistically at the molecular level and for developing terminal heat stress tolerant wheat.