Table 3.
Identification of tissue- and tumor-selective E3 ligases
| Highly expressed E3 ligases in normal tissues | Lowly expressed E3 ligases in normal tissues | E3 ligases highly expressed in tumors but lowly expressed in most normal tissues |
|---|---|---|
| BCL6 | ARMC5 | ASB2 |
| BTBD2 | ASB7 | ASB4 |
| CPSF1 | ATRX | ASB5 |
| FBXL5 | CBLL1 | ASB9 |
| FBXW5 | CNOT4 | ASB11 |
| PJA2 | FBXL4 | ASB15 |
| PRPF19 | FBXO3 | ASB16 |
| RBCK1 | FBXO22 | BIRC3 |
| RING1 | FBXO33 | BIRC7 |
| RNF5 | FBXO42 | DPF1 |
| RNF10 | HERC4 | ENC1 |
| RNF11 | KBTBD4 | FBXL13 |
| RNF114 | KBTBD6 | FBXL16 |
| RNF126 | KCTD21 | FBXO2 |
| RNF167 | KDM2B | FBXO32 |
| RNF181 | KLHL8 | FBXO40 |
| RNF187 | KLHL9 | FBXO41 |
| SPSB3 | KLHL15 | HECW1 |
| STUB1 | KLHL18 | HERC5 |
| TRIM8 | KLHL20 | KCNA1 |
| TRIM28 | KLHL26 | KCNA7 |
| WSB1 | LTN1 | KCNB2 |
| ZFAND3 | MDM2 | KCNC1 |
| ZFAND5 | MIB1 | KCNC2 |
| MYNN | KCNC3 | |
| PCGF1 | KCND2 | |
| PEX2 | KCNG1 | |
| RC3H1 | KCNS1 | |
| RC3H2 | KCNV1 | |
| RCHY1 | KCTD4 | |
| RNF2 | KCTD16 | |
| RNF111 | KLHL1 | |
| RNF121 | KLHL6 | |
| SMURF2 | KLHL30 | |
| SOCS4 | KLHL31 | |
| SPOPL | KLHL34 | |
| TRAF3 | MARCH4’ | |
| TRAF6 | MARCH10’ | |
| TRIM23 | MARCH11’ | |
| TRIM68 | MKRN3 | |
| UBE3B | NEURL3 | |
| UBOX5 | OTUD7A | |
| UBR1 | RAPSN | |
| VPS8 | RFPL4B | |
| WDSUB1 | RNF17 | |
| XIAP | RNF39 | |
| ZBTB2 | RNF157 | |
| ZBTB5 | RNF175 | |
| ZBTB11 | RNF182 | |
| ZBTB14 | RNF183 | |
| ZBTB25 | RNF186 | |
| ZBTB33 | SKP2 | |
| ZBTB45 | SOCS7 | |
| ZBTB49 | SPSB4 | |
| ZNF131 | TRIM7 | |
| TRIM9 | ||
| TRIM10 | ||
| TRIM15 | ||
| TRIM17 | ||
| TRIM31 | ||
| TRIM36 | ||
| TRIM46 | ||
| TRIM50 | ||
| TRIM54 | ||
| TRIM63 | ||
| TRIM67 | ||
| TRIM72 | ||
| TRIML1 | ||
| ZBTB32 |
Note: The original RNA-sequencing (RNA-seq) data of normal tissues used for the analyses were obtained from the GTEx Portal (https://www.gtexportal.org) in 2017. RNA-seq data of the tissues with same origin and similar gene expression pattern were averaged to represent one tissue. For example, there are 11 brain tissues as shown in Figure 3, we calculated the average of gene expression level in the 11 brain tissues to represent the brain tissue. In the final analysis, 31 tissues were used to identify the normal tissue specific/selective E3 ligases. The criteria of classification for E3 ligases are: 1) Not expressed in normal tissues – RPKM (Reads Per Kilobase of exon model per Million mapped reads) <1 in all 31 tissues; 2) Tissue specific – RPKM is 5-fold higher in one tissue than all other tissues; 3) Tissue enriched – RPKM is 2.5-fold higher in one tissue than in all other tissues; 4) Group enriched – RPKM is 2.5-fold higher in a group of 2-7 tissues than all other tissues; 5) Expressed low in all tissues – RPKM ≥1 and <10 in all 31 tissues and; 6) Expressed high in all tissues – RPKM ≥10 in all 31 tissues; and 7) Mixed – The remaining genes detected in 1–31 tissues with RPKM>1 and are not in the above categories. In the table, only type 5) Expressed low in all tissues (left column) and 6) Expressed high in all tissues (top column) were listed. Tumor-selective/specific E3 ligases (right column) were identified by overlapping the E3 ligases highly expressed in tumors with those of E3 ligases not or lowly expressed in all normal tissues or selectively expressed in limited normal tissues. The RNA-seq data of 12 cancer types were downloaded from the Cancer Genome Atlas (TCGA) (http://cancergenome.nih.gov). The criteria for determination of tumor-specific/selective E3 ligases are: 1) Log fold change of tumor-RPKM/normal tissue- RPKM> 1.5; 2) Statistical significance of p<0.05 when comparing the gene expression in tumors to their corresponding normal tissues. RPKM, Fragments Per Kilobase of exon model per Million mapped fragments.