Updated project metadata. Systemic lupus erythematosus (SLE) is a complex autoimmune disease that affects multiple organs. Protein lysine modifications play important roles in gene regulation, transcription, metabolism and other biological processes. The lysine 2-hydroxyisobutyrylation(Khib) histone mark has recently been discovered as a novel protein modification. Utilizing antibody-based affinity enrichment and nano-HPLC/MS/MS analyses of Khib peptides, we identified 156 upregulated proteins(fold change>1.5),124 downregulated proteins(fold change<1/1.5), including 220 Khib sites that were upregulated and 187 Khib sites that were downregulated. Our data demonstrate that proteins with Khib sites were localized in the cytoplasm. Functional enrichment analysis revealed that proteins with Khib sites are broadly involved in a wide range of biological processes, cellular components and molecular functions. The 03010 Ribosome pathways may exert important influence on the SLE pathogenic mechanism, according to a KEGG analysis. The functional analysis of Khib is of value for important future investigations of SLE pathogenesis.