E3 ISG15--protein ligase HERC5 (EC 2.3.2.-) (Cyclin-E-binding protein 1) (HECT domain and RCC1-like domain-containing protein 5)
1_MERRS 6_ RRKSR 11_ RNGRS 16_ TAGKA 21_ AATQP 26_ AKSPG 31_ AQLWL 36_ FPSAA 41_ GLHRA 46_ LLRRV 51_ EVTRQ 56_ LCCSP 61_ GRLAV 66_ LERGG 71_ AGVQV 76_ HQLLA 81_ GSGGA 86_ RTPKC 91_ IKLGK 96_ NMKIH 101_ SVDQG 106_ AEHML 111_ ILSSD 116_ GKPFE 121_ YDNYS 126_ MKHLR 131_ FESIL 136_ QEKKI 141_ IQITC 146_ GDYHS 151_ LALSK 156_ GGELF 161_ AWGQN 166_ LHGQL 171_ GVGRK 176_ FPSTT 181_ TPQIV 186_ EHLAG 191_ VPLAQ 196_ ISAGE 201_ AHSMA 206_ LSMSG 211_ NIYSW 216_ GKNEC 221_ GQLGL 226_ GHTES 231_ KDDPS 236_ LIEGL 241_ DNQKV 246_ EFVAC 251_ GGSHS 256_ ALLTQ 261_ DGLLF 266_ TFGAG 271_ KHGQL 276_ GHNST 281_ QNELR 286_ PCLVA 291_ ELVGY 296_ RVTQI 301_ ACGRW 306_ HTLAY 311_ VSDLG 316_ KVFSF 321_ GSGKD 326_ GQLGN 331_ GGTRD 336_ QLMPL 341_ PVKVS 346_ SSEEL 351_ KLESH 356_ TSEKE 361_ LIMIA 366_ GGNQS 371_ ILLWI 376_ KKENS 381_ YVNLK 386_ RTIPT 391_ LNEGT 396_ VKRWI 401_ ADVET 406_ KRWQS 411_ TKREI 416_ QEIFS 421_ SPACL 426_ TGSFL 431_ RKRRT 436_ TEMMP 441_ VYLDL 446_ NKARN 451_ IFKEL 456_ TQKDW 461_ ITNMI 466_ TTCLK 471_ DNLLK 476_ RLPFH 481_ SPPQE 486_ ALEIF 491_ FLLPE 496_ CPMMH 501_ ISNNW 506_ ESLVV 511_ PFAKV 516_ VCKMS 521_ DQSSL 526_ VLEEY 531_ WATLQ 536_ ESTFS 541_ KLVQM 546_ FKTAV 551_ ICQLD 556_ YWDES 561_ AEENG 566_ NVQAL 571_ LEMLK 576_ KLHRV 581_ NQVKC 586_ QLPES 591_ IFQVD 596_ ELLHR 601_ LNFFV 606_ EVCRR 611_ YLWKM 616_ TVDAS 621_ ENVQC 626_ CVIFS 631_ HFPFI 636_ FNNLS 641_ KIKLL 646_ HTDTL 651_ LKIES 656_ KKHKA 661_ YLRSA 666_ AIEEE 671_ RESEF 676_ ALRPT 681_ FDLTV 686_ RRNHL 691_ IEDVL 696_ NQLSQ 701_ FENED 706_ LRKEL 711_ WVSFS 716_ GEIGY 721_ DLGGV 726_ KKEFF 731_ YCLFA 736_ EMIQP 741_ EYGMF 746_ MYPEG 751_ ASCMW 756_ FPVKP 761_ KFEKK 766_ RYFFF 771_ GVLCG 776_ LSLFN 781_ CNVAN 786_ LPFPL 791_ ALFKK 796_ LLDQM 801_ PSLED 806_ LKELS 811_ PDLGK 816_ NLQTL 821_ LDDEG 826_ DNFEE 831_ VFYIH 836_ FNVHW 841_ DRNDT 846_ NLIPN 851_ GSSIT 856_ VNQTN 861_ KRDYV 866_ SKYIN 871_ YIFND 876_ SVKAV 881_ YEEFR 886_ RGFYK 891_ MCDED 896_ IIKLF 901_ HPEEL 906_ KDVIV 911_ GNTDY 916_ DWKTF 921_ EKNAR 926_ YEPGY 931_ NSSHP 936_ TIVMF 941_ WKAFH 946_ KLTLE 951_ EKKKF 956_ LVFLT 961_ GTDRL 966_ QMKDL 971_ NNMKI 976_ TFCCP 981_ ESWNE 986_ RDPIR 991_ ALTCF 996_ SVLFL 1001_ PKYST 1006_ METVE 1011_ EALQE 1016_AINNN
1: Major E3 ligase for ISG15 conjugation (PubMed:26355087, PubMed:27534820, PubMed:27564865, PubMed:34572049, PubMed:37279284). Acts as a positive regulator of innate antiviral response in cells induced by interferon. Functions as part of the ISGylation machinery that recognizes target proteins in a broad and relatively non-specific manner. Catalyzes ISGylation of IRF3 which results in sustained activation, it attenuates IRF3-PIN1 interaction, which antagonizes IRF3 ubiquitination and degradation, and boosts the antiviral response. Mediates ISGylation of the phosphatase PTEN leading to its degradation, thus alleviating its suppression of the PI3K-AKT signaling pathway and promoting the production of cytokines that facilitate bacterial clearance (PubMed:37279284). Interferes with the function of key viral structural proteins such as ebolavirus structural protein VP40 or HIV-1 protein GAG (PubMed:22093708, PubMed:34572049). Catalyzes ISGylation of influenza A viral NS1 which attenuates virulence; ISGylated NS1 fails to form homodimers and thus to interact with its RNA targets. Catalyzes ISGylation of papillomavirus type 16 L1 protein which results in dominant-negative effect on virus infectivity. Physically associated with polyribosomes, broadly modifies newly synthesized proteins in a cotranslational manner. In an interferon-stimulated cell, newly translated viral proteins are primary targets of ISG15. Promotes parkin/PRKN ubiquitin E3 ligase activity by suppressing the intramolecular interaction that maintains its autoinhibited conformation (PubMed:27534820)
2: (Microbial infection) Functions as an E3 ligase for ISGylation of hepatitis B virus protein X leading to enhanced viral replication due to increased interferon resistance