MultifacetedProtDB collects multifunctional proteins from UniProt/SwissProt (Release 2023-03). It includes 241 human proteins already present in existing datasets (MoonDB, MoonProt and MultitaskProtDB II), which when restricted to humans collect 47, 103, and 185 proteins, respectively.

Other proteins are derived from recent literature. Enzymes with multiple EC codes are included. The final dataset contains 1103 multifunctional proteins, of which 812 are enzymes. MultifacetedProtDB increases by four times the number of multifunctional proteins reported in currently available resources.

Table 1: Statistics of MultifacetedProtDB

	Proteins	PDB	Reactome paths^	Reactome roots^	InterPro	Pfam	Diseases
Enzymes	812	10,469 entries 520 proteins	662 leaf nodes 163 internal nodes∗ 698 proteins	27	1,943 entries 812 proteins	761 entries 807 proteins	619 MONDO diseases 172 ICD10 categories 16 ICD10 chapters 321 proteins
Non enzymes	291	2,840 entries	465 leaf nodes 106 internal nodes∗	25	784 entries 291 proteins	314 entries 287 proteins	309 MONDO diseases 117 ICD10 categories 13 ICD10 chapters 110 proteins
All proteins	1103	13,147 entries 743 proteins	849 leaf nodes 198 internal nodes∗ 950 proteins	27	2,626 entries 1103 proteins	1,045 entries 1094 proteins	895 MONDO diseases 213 ICD10 categories 17 ICD10 chapters 431 proteins

^ Reactome entries related to “Disease” and “Drug ADME” are not considered when counting the number of Reactome pathways and roots

^∗ "internal nodes" represent the intermediate nodes within the Reactome hierarchy.

Table 2: Statistics of Enzymatic Proteins in MultifacetedProtDB

	Enzymes	PDB	Reactome paths^	Reactome roots^	InterPro	Pfam	Diseases
Enzymes	812	10,469 entries 520 enzymes	662 leaf nodes 163 internal nodes∗ 698 enzymes	27	1,943 entries 812 enzymes	761 entries 807 enzymes	619 MONDO diseases 172 ICD10 categories 16 ICD10 chapters 321 enzymes
Enzymes with only 1 EC	144	3,315 entries	287 leaf nodes 82 internal nodes∗ 135 enzymes	23	623 entries 144 enzymes	213 entries 142 enzymes	173 MONDO diseases 89 ICD10 categories 13 ICD10 chapters 82 enzymes
Enzymes with Multiple ECs with different 1st levels	136	1,472 entries 88 proteins	149 leaf nodes 27 internal nodes∗ 112 enzymes	18	527 entries 136 enzymes	200 entries 136 enzymes	123 MONDO diseases 74 ICD10 categories 12 ICD10 chapters 56 enzymes
Enzymes with Multiple ECs with different figures other than the 1st	532	5,750 entries 312 enzymes	488 leaf nodes 107 internal nodes∗ 451 enzymes	27	1,110 entries 532 enzymes	440 entries 529 enzymes	349 MONDO diseases 161 ICD10 categories 15 ICD10 chapters 183 enzymes

^ Reactome entries related to “Disease” and “Drug ADME” are not considered when counting the number of Reactome pathways and roots

^∗ "internal nodes" represent the intermediate nodes within the Reactome hierarchy.