Domain-Aware Multi-View Contrastive Representation Learning for Protein Subcellular Localization Prediction

Protein subcellular localization prediction is essential for understanding protein function and cellular organization. However, existing methods exhibit two major limitations: (1) they overlook the critical role of evolutionarily conserved protein domains, which are fundamental functional and structural units that significantly influence functions and subcellular localization, and (2) they rarely learn residue order and backbone coordinates simultaneously, neglecting the complementary information inherent in multi-modal representations. In this paper, we propose a novel Domain-Aware Multi-View Contrastive Representation Learning for Protein Subcellular Localization prediction, named DMVCL. Firstly, it devises domain-sequence/structure attention modules, which identify functionally significant regions in protein structures/sequences that critically determine subcellular localization. Secondly, it introduces a multi-view contrastive learning framework that unites inter-view and intra-view objectives. Inter-view contrastive learning aligns protein sequences with their corresponding structures by maximizing mutual information, thereby capturing the consistency of protein residue order and backbone coordinates. Intra-view contrastive learning enhances the representation discriminability of each modality by explicitly separating proteins with no common location and attracting those with any shared localization. Extensive experiments demonstrate that DMVCL significantly outperforms existing baselines. Ablation studies and visualizations further highlight the contributions of domain-sequence/structure attention and multi-view contrastive learning in achieving superior predictive performance.