DegronMD: protein-targeted degradation, mutation and drug response to degrons

Degron muatation that destroys and perturbs UPS signals

Mutations can alter degrons by abolishing motifs or adjacent key PTMs, which affects specific E3 ligase-substrate binding efficiency, and correspondingly cause rewiring of UPS signaling. Loss of-function mutations occurring in the degrons of several oncoproteins, such as the transcription factors MYC and NRF2, and in various mitogenic receptors, such as NOTCH1 and several receptor tyrosine kinases are found in many cancers and are considered one of the most abundant mutations driving carcinogenesis. Thus, a comprehensive mutational landscape on degrome is urgent to illuminate their quantitative influence on degrons. We systematically investigated and quantified the impact of missense mutations on the functionality of a degron. As a result, 89,318 actionable mutations were identified that directly destroys UPS signaling. The remaining mutations would indirectly perturb E3-degron network. The functional outcomes were annotated into five types: altering degron motif, blocking phosphorylation signal, blocking ubiquitination signal, and substituting flanking lysine, rewiring degron network. A full list of degron regulatory network-rewiring mutations can be accessed here.


Uniprot ID Gene name Degron number Mutation number Network rewiring Altering degron motif Blocking phosphorylation Blocking ubiquitination Substituting flanking lysine Details
A0AUZ9KANSL1L223172004More >>
A0AV02SLC12A8117143000More >>
A0AV96RBM47137274600More >>
A0AVI2FER1L51312000More >>
A0AVK6E2F871227943000More >>
A0FGR9ESYT31751001More >>
A0JLT2MED192725000More >>
A0JNW5UHRF1BP1L2422418000More >>
A0MZ66SHTN11101000More >>
A0PJK1SLC5A101954000More >>
A0PJW8DAPL111494100More >>
A0PJX4SHISA3352484000More >>
A0PJY2FEZF1126179000More >>
A0PK05TMEM72113112000More >>
A1A4G5LNP1118135000More >>
A1A4S6ARHGAP102291613000More >>
A1A4V9CCDC1891110000More >>
A1A519FAM170A148417000More >>
A1A5C7SLC22A232281214002More >>
A1E959ODAM132266000More >>
A1IGU5ARHGEF373906327000More >>
A1KXE4FAM168B1971100More >>
A1KZ92PXDNL2877512000More >>
A1L020MEX3A111101000More >>
A1L167UBE2QL1111110000More >>
A1L168C20orf2021842200More >>
A1L170C1orf226225149002More >>
A1L1A6IGSF23117140003More >>
A1L390PLEKHG33502819300More >>
A1L443NUTM2F1660000More >>
A1L4H1SSC5D1615911047002More >>
A1L4K1FSD2238308000More >>
A1X283SH3PXD2B2452814300More >>
A2A368MAGEB161271710000More >>
A2A3K4PTPDC111495000More >>
A2A3L6TTC242502619005More >>
A2AJT9BCLAF32550000More >>
A2CJ06DYTN3734620007More >>
A2IDD5CCDC781523000More >>
A2RRP1NBAS115123000More >>
A2RU30TESPA12572828001More >>
A2RU54HMX2122157000More >>
A2RUB1MEIOC2651000More >>
A2RUB6CCDC662331914000More >>
A2RUR9CCDC144A1512002More >>
A2RUS2DENND3121133230More >>
A2VDJ0TMEM131L1211000More >>
A3KMH1VWA83342113000More >>
A3KN83SBNO1910070171300More >>
A4D0V7CPED1127234000More >>
A4D161FAM221A337307000More >>
A4D1E1ZNF804B1503317000More >>
A4D1E9GTPBP101642000More >>
A4D263SPATA483251213000More >>
A4FU28CTAGE91972000More >>
A4FU49SH3D2111789000More >>
A4FU69EFCAB5116151000More >>
A4UGR9XIRP293602325714057More >>
A5LHX3PSMB1111073000More >>
A5PKW4PSD2564214000More >>
A5PL33KRBA15634219200More >>
A5PLL1ANKRD34B2332112000More >>
A5PLN9TRAPPC13112102000More >>
A5YKK6CNOT13402810101More >>
A6H8M9CDHR4120173000More >>
A6H8Y1BDP18805024312More >>
A6H8Z2FAM221B322148000More >>
A6NC57ANKRD62242279006More >>
A6NC98CCDC88B349409000More >>
A6NCI8C2orf783553916000More >>
A6NCL1GMNC176751000More >>
A6NCS4NKX2-61430001More >>
A6ND36FAM83G321147000More >>
A6NDA9LRIT2130219000More >>
A6NDB9PALM331686200More >>
A6NDK9GOLGA6C1110000More >>
A6NDN3GOLGA6B1752000More >>
A6NDS4TBC1D3B1220000More >>
A6NDV4TMEM8B232284000More >>
A6NE01FAM186A4291511003More >>
A6NEE1PLEKHD1120191000More >>
A6NEH6TMEM247136360000More >>
A6NEL2SOWAHB116133000More >>
A6NER0TBC1D3F11091000More >>
A6NES4MROH2A1514000More >>
A6NEV1PRR23A121813000More >>
A6NFA0FAM205C1110000More >>
A6NFA1TRABD2B211101000More >>
A6NFK2GRXCR2211101000More >>
A6NFN3RBFOX311055000More >>
A6NFR6C5orf60336288000More >>
A6NGB9WIPF3225241000More >>
A6NGG8PCARE1734000More >>
A6NGH7CCDC160225194002More >>
A6NGN9IGLON5119145000More >>
A6NGY1FRG2C250424004More >>
A6NGY3C5orf52113130000More >>
A6NHC0CAPN81211000More >>
A6NHP3SPDYE2B1651000More >>
A6NHQ2FBLL11990000More >>
A6NHR9SMCHD1224175200More >>
A6NHS7MANSC4226260000More >>
A6NI15MSGN1125167002More >>
A6NI28ARHGAP424442813102More >>
A6NI47POTEM1311001More >>
A6NI56CCDC154121156000More >>
A6NI79CCDC69126251000More >>
A6NI86GOLGA6L101110000More >>
A6NI87CBY31110000More >>
A6NIN4RNF2271413000More >>
A6NIR3AGAP5217134000More >>
A6NIY4SPDYE51110000More >>
A6NJB7PRR19226242000More >>
A6NJG2SOWAHD1523000More >>
A6NJG6ARGFX1281711000More >>
A6NJJ6C19orf6721165000More >>
A6NJT0UNCX1330000More >>
A6NJV1FAM166C1110000More >>
A6NJW9CD8B21220000More >>
A6NK53ZNF23311495000More >>
A6NK58LIPT21752000More >>
A6NKB5PCNX2420812000More >>
A6NKC9SH2D7228217000More >>
A6NKD9CCDC85C21182100More >>
A6NKF2ARID3C1422814000More >>
A6NKL6TMEM200C511710512000More >>
A6NKT7RGPD358856181112More >>
A6NL88SHISA7236306000More >>
A6NLJ0C2CD4B2330000More >>
A6NLU5VSTM2B120137000More >>
A6NM11LRRC37A2420153200More >>
A6NM62LRRC532660000More >>
A6NMB9FIGNL22422000More >>
A6NMD0IFITM101651000More >>
A6NMK8INSYN2B218124002More >>
A6NMS7LRRC37A31181002More >>
A6NMT0DBX16825032000More >>
A6NMZ2SNTN128226000More >>
A6NNA2SRRM32502921000More >>
A6NNA5DRGX115122001More >>
A6NNE9MARCHF111101000More >>
A6NNL0NUTM2B1633000More >>
A6NNM3RIMBP3B1110000More >>
A6NNT2C16orf961642000More >>
A6NNY8USP27X1512002More >>
A6NP61ZAR1L1281261000More >>
A6QL63BTBD11118153000More >>
A6QL64ANKRD36222202000More >>
A6XGL0YJEFN3124183300More >>
A7E2F4GOLGA8A120137000More >>
A7E2V4ZSWIM8328215200More >>
A7E2Y1MYH7B118153000More >>
A7KAX9ARHGAP3210159109337010More >>
A7MBM2DISP22433310000More >>
A7MCY6TBKBP1116124000More >>
A7MD48SRRM451197736105More >>
A7XYQ1SOBP2271512000More >>
A8CG34POM121C131149513402More >>
A8K0R7ZNF839224182004More >>
A8K4G0CD300LB129272000More >>
A8K5M9C15orf622550000More >>
A8K7I4CLCA11391821000More >>
A8K8P3SFI11853000More >>
A8K979ERI2212111000More >>
A8MPS7YDJC11037000More >>
A8MQ03CYSRT11330000More >>
A8MQ27NEURL1B3251411000More >>
A8MT33SYCE1L1990000More >>
A8MTA8FAM166B11358000More >>
A8MTB9CEACAM182736112000More >>
A8MTJ6FOXI31101000More >>
A8MTL3RNF212B2312000More >>
A8MTQ0NOTO11192000More >>
A8MTZ7C12orf71112120000More >>
A8MU46SMTNL1117143000More >>
A8MU93C17orf10021475200More >>
A8MUV8ZNF72711061003More >>
A8MUX0KRTAP16-11734000More >>
A8MV65VGLL3126206000More >>
A8MVS5C19orf3821899000More >>
A8MVW0FAM171A211190200More >>
A8MVW5HEPACAM2122138100More >>
A8MVX0ARHGEF3321064000More >>
A8MW92PHF20L13503217001More >>
A8MW99MEI4122202000More >>
A8MWE9EFCAB8216106000More >>
A8MXT2MAGEB171101000More >>
A8MXY4ZNF991312011000More >>
A8MYU2KCNU1115114000More >>
A8MYV0DCDC2C323174200More >>
A8MZG2C16orf90117134000More >>
A8TX70COL6A5112111000More >>
B1AK53ESPN229243200More >>
B1AKI9ISM11281711000More >>
B2RTY4MYO9A5988414000More >>
B2RXF5ZBTB421743000More >>
B2RXH2KDM4E1954000More >>
B2RXH4BTBD18415114000More >>
B4DS77SHISA91880000More >>
B6SEH8ERVV-11321000More >>
B7Z6K7ZNF814115411000More >>
B8ZZ34SHISA82220000More >>
C9J069AJM11404000More >>
C9J202ALG1L2120182000More >>
C9J3V5TEX222953001More >>
C9JE40PATL21633000More >>
C9JH25PRRT42291811000More >>
C9JI98TMEM2381110000More >>
C9JLJ4USP17L131100001More >>
C9JN71ZNF87811358000More >>
C9JQI7TMEM232121152004More >>
C9JTQ0ANKRD631651000More >>
C9JUS6ADM51770000More >>
D6REC4CFAP991110000More >>
D6RGH6MCIDAS1220000More >>
D6RGX4FAM90A262734000More >>
D6RIA3C4orf542220000More >>
E2RYF6MUC229584513000More >>
E5RJ46C8orf871936000More >>
E7ERA6RNF22321192000More >>
E7EW31PROB1415114000More >>
E9PAV3NACA1529723063004More >>
F2Z3F1C5orf671330000More >>
F5H4B4FAM227A119104104More >>
H0YL09UBE2Q2L1110000More >>
H3BV60TGFBR3L1211000More >>
H7BZ55CROCC2311101000More >>
I3L273GFY1100001More >>
O00115DNASE2110100000More >>
O00116AGPS11382102More >>
O00124UBXN81550000More >>
O00139KIF2A2342210200More >>
O00151PDLIM1139255900More >>
O00159MYO1C11293000More >>
O00160MYO1F1321715000More >>
O00167EYA2256524000More >>
O00182LGALS91532000More >>
O00189AP4M111889010More >>
O00192ARVCF122193000More >>
O00203AP3B1116124000More >>
O00212RHOD118140103More >>
O00221NFKBIE328198100More >>
O00257CBX4116142000More >>
O00267SUPT5H130199200More >>
O00268TAF4355486100More >>
O00287RFXAP11390004More >>
O00291HIP1118153000More >>
O00292LEFTY22392910000More >>
O00295TULP211679000More >>
O00299CLIC1115105000More >>
O00303EIF3F118126000More >>
O00305CACNB4116115000More >>
O00330PDHX125154024More >>
O00358FOXE11550000More >>
O00399DCTN61981000More >>
O00401WASL112111000More >>
O00409FOXN32301510005More >>
O00418EEF2K114100400More >>
O00425IGF2BP34713732020More >>
O00429DNM1L127913500More >>
O00443PIK3C2A2442114216More >>
O00444PLK45826912100More >>
O00458IFRD1115114000More >>
O00459PIK3R211255020More >>
O00468AGRN237307000More >>
O00472ELL21532000More >>
O00478BTN3A32372412001More >>
O00482NR5A23433110200More >>
O00488ZNF59311165000More >>
O00499BIN1232257000More >>
O00512BCL95644516300More >>
O00515LAD13633822300More >>
O00519FAAH120191000More >>
O00533CHL1140346000More >>
O00534VWA5A124204000More >>
O00548DLL11231011200More >>
O00555CACNA1A2981000More >>
O00562PITPNM13524012000More >>
O00566MPHOSPH1011192000More >>
O00567NOP56224138201More >>
O00571DDX3X227179100More >>
O00592PODXL10178119401603More >>
O00625PIR111110000More >>
O00629KPNA4218135000More >>
O00712NFIB128222400More >>
O00743PPP6C122616000More >>
O00750PIK3C2B2412021000More >>
O00754MAN2B1113121000More >>
O00763ACACB61348249102More >>
O00764PDXK11082000More >>
O00767SCD115103020More >>
O14490DLGAP1717511647606More >>
O14492SH2B23281513000More >>
O14497ARID1A1113710331003More >>
O14498ISLR116133000More >>
O14511NRG23423111000More >>
O14513NCKAP51126320852003More >>
O14514ADGRB12743000More >>
O14523C2CD2L5443013100More >>
O14524NEMP11202000More >>
O14526FCHO1317107000More >>
O14529CUX2120200000More >>
O14544SOCS611190020More >>
O14559ARHGAP336826913000More >>
O14562UBFD1116124000More >>
O14578CIT3462714203More >>
O14579COPE1980010More >>
O14594NCAN5433211000More >>
O14613CDC42EP211064000More >>
O14618CCS129209000More >>
O14639ABLIM13463410200More >>
O14640DVL11990000More >>
O14641DVL24463214000More >>
O14645DNALI1117104003More >>
O14646CHD1431245200More >>
O14647CHD2345258507More >>
O14654IRS43453014100More >>
O14668PRRG1244316700More >>
O14669PRRG2110100000More >>
O14672ADAM10222183001More >>
O14681EI2411483300More >>
O14686KMT2D16249175621101More >>
O14715RGPD8530169500More >>
O14730RIOK311764700More >>
O14737PDCD52301712010More >>
O14745SLC9A3R15542924010More >>
O14746TERT220173000More >>
O14757CHEK11843001More >>
O14770MEIS2128244000More >>
O14771ZNF213126215000More >>
O14773TPP1123185000More >>
O14776TCERG17714427000More >>
O14782KIF3C128270001More >>
O14791APOL1122183100More >>
O14793MSTN115105000More >>
O14795UNC13B257498000More >>
O14798TNFRSF10C21174000More >>
O14813PHOX2A115105000More >>
O14815CAPN9112111000More >>
O14827RASGRF2114120200More >>
O14828SCAMP3119172000More >>
O14830PPEF21761000More >>
O14836TNFRSF13B116151000More >>
O14874BCKDK120155000More >>
O14893GEMIN21550000More >>
O14901KLF11240307201More >>
O14917PCDH174138102191007More >>
O14920IKBKB119126010More >>
O14924RGS12118180000More >>
O14936CASK117125000More >>
O14939PLD21852100More >>
O14950MYL12B11578000More >>
O14958CASQ2130228000More >>
O14964HGS35227101410More >>
O14965AURKA223154400More >>
O14966RAB291110000More >>
O14974PPP1R12A81327844901More >>
O14975SLC27A2124186000More >>
O14976GAK3624812200More >>
O14978ZNF263125167200More >>
O14981BTAF1218142200More >>
O14986PIP5K1B123212000More >>
O14994SYN3132284000More >>
O15013ARHGEF104564212002More >>
O15014ZNF6094543511503More >>
O15015ZNF6462381721000More >>
O15016TRIM664644816000More >>
O15018PDZD2193272247615012More >>
O15020SPTBN2350446000More >>
O15021MAST45704321600More >>
O15027SEC16A1120513166602More >>
O15031PLXNB2120128000More >>
O15034RIMBP23554411000More >>
O15037KHNYN1330000More >>
O15040TECPR23644321000More >>
O15042U2SURP3322111000More >>
O15047SETD1A81309626800More >>
O15049N4BP33534310000More >>
O15050TRANK11221010101More >>
O15054KDM6B91348743301More >>
O15055PER23765323000More >>
O15056SYNJ2113103000More >>
O15060ZBTB391440000More >>
O15061SYNM4593424100More >>
O15062ZBTB5323176000More >>
O15067PFAS124177000More >>
O15068MCF2L2745021300More >>
O15069NACAD7825923000More >>
O15072ADAMTS3114140000More >>
O15075DCLK12734018708More >>
O15078CEP290218161010More >>
O15083ERC21880000More >>
O15085ARHGEF11713571481600More >>
O15090ZNF5361291413200More >>
O15111CHUK113121000More >>
O15117FYB12880000More >>
O15127SCAMP2225223000More >>
O15146MUSK1211110000More >>
O15151MDM4134283030More >>
O15156ZBTB7B226260000More >>
O15162PLSCR1245369000More >>
O15164TRIM2411746700More >>
O15165LDLRAD4245414000More >>
O15169AXIN1123194000More >>
O15178TBXT2844000More >>
O15195VILL120182000More >>
O15197EPHB62453410100More >>
O15209ZBTB22229254000More >>
O15211RGL2115123000More >>
O15226NKRF239301080More >>
O15230LAMA54796514000More >>
O15231ZNF185131237100More >>
O15232MATN3110100000More >>
O15234CASC3321145020More >>
O15235MRPS12133294000More >>
O15247CLIC2125205000More >>
O15254ACOX3127196020More >>
O15259NPHP11954000More >>
O15264MAPK13122166000More >>
O15265ATXN7798848204More >>
O15266SHOX1301911000More >>
O15270SPTLC214613201210More >>
O15304SIVA111137100More >>
O15344MID11981000More >>
O15350TP73356466301More >>
O15353FOXN1232257000More >>
O15357INPPL1133245400More >>
O15360FANCA11071020More >>
O15370SOX121330000More >>
O15372EIF3H126731402More >>
O15379HDAC3119163000More >>
O15389SIGLEC5125135304More >>
O15391YY2357459102More >>
O15393TMPRSS21770000More >>
O15400STX7114113000More >>
O15405TOX32463115000More >>
O15409FOXP21523220000More >>
O15417TNRC181014711226702More >>
O15427SLC16A31927000More >>
O15440ABCC52342110300More >>
O15442MPPED12695712000More >>
O15444CCL25115121200More >>
O15446POLR1G1110000More >>
O15457MSH4250419000More >>
O15460P4HA2135350000More >>
O15479MAGEB2245369000More >>
O15480MAGEB3236282006More >>
O15481MAGEB44847014000More >>
O15484CAPN5239334200More >>
O15504NUP421512200More >>
O15516CLOCK114103100More >>
O15523DDX3Y11091000More >>
O15524SOCS1122193000More >>
O15530PDPK1120163100More >>
O15534PER15735122000More >>
O15550KDM6A239309000More >>
O15553MEFV41138624003More >>
O43143DHX15234256300More >>
O43147SGSM2114122000More >>
O43148RNMT1422000More >>
O43149ZZEF15572329302More >>
O43150ASAP2129263000More >>
O43151TET381197542200More >>
O43155FLRT23957223000More >>
O43157PLXNB16895534000More >>
O43159RRP82382711000More >>
O43164PJA2222157000More >>
O43166SIPA1L1611271291101More >>
O43167ZBTB24114104000More >>
O43172PRPF41770000More >>
O43175PHGDH113103000More >>
O43182ARHGAP61981000More >>
O43187IRAK2121138000More >>
O43189PHF1225214000More >>
O43237DYNC1LI2226215000More >>
O43242PSMD31862000More >>
O43247TEX331803005More >>
O43251RBFOX2115123000More >>
O43264ZW1011779010More >>
O43272PRODH1826000More >>
O43278SPINT1218126000More >>
O43281EFS3503119000More >>
O43283MAP3K133513514200More >>
O43290SART11523000More >>
O43293DAPK31220000More >>
O43294TGFB1I14634218003More >>
O43298ZBTB43116142000More >>
O43303CCP11031199126002More >>
O43304SEC14L52422418000More >>
O43307ARHGEF91962001More >>
O43310CTIF11683005More >>
O43312MTSS14834930301More >>
O43313ATMIN113121000More >>
O43314PPIP5K26834825802More >>
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O43379WDR625806118100More >>
O43390HNRNPR130237000More >>
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O43424GRID22553219103More >>
O43426SYNJ15724820202More >>
O43432EIF4G33765917000More >>
O43439CBFA2T2225187000More >>
O43451MGAM2402812000More >>
O43464HTRA2217152000More >>
O43474KLF4226224000More >>
O43491EPB41L25623918401More >>
O43493TGOLN2410841382306More >>
O43497CACNA1G226251000More >>
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O43520ATP8B1246415000More >>
O43525KCNQ331006530500More >>
O43526KCNQ2241308300More >>
O43541SMAD611394000More >>
O43543XRCC211071200More >>
O43556SGCE1231010111More >>
O43559FRS32302010000More >>
O43561LAT335228500More >>
O43581SYT712587406More >>
O43586PSTPIP14896620300More >>
O43593HR2351817000More >>
O43597SPRY2122126400More >>
O43602DCX123155003More >>
O43609SPRY12372314000More >>
O43610SPRY32584018000More >>
O43613HCRTR1116142000More >>
O43638FOXS13564511000More >>
O43660PLRG11770000More >>
O43663PRC1239336000More >>
O43670ZNF2076845727000More >>
O43676NDUFB3115132000More >>
O43683BUB14452021400More >>
O43687AKAP7136304002More >>
O43719HTATSF11291513100More >>
O43734TRAF3IP21742100More >>
O43736ITM2A118143001More >>
O43760SYNGR2113112000More >>
O43765SGTA128226000More >>
O43776NARS11211000More >>
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