ID Q9UII4; PN E3 ISG15--protein ligase HERC5; GN HERC5; OS 9606; SL Nucleus Position: SL-0198; SL Comments: Cytoplasm, perinuclear region {ECO:0000269|PubMed:20542004}. Note=Associated with the polyribosomes, probably via the 60S subunit. DR UNIPROT: Q9UII4; DR UNIPROT: B2RTQ1; DR UNIPROT: Q69G20; DR Pfam: PF00632; DR Pfam: PF00415; DR PROSITE: PS50237; DR PROSITE: PS00626; DR PROSITE: PS50012; DR OMIM: 608242; DR DisGeNET: 51191; DE Function: Major E3 ligase for ISG15 conjugation. 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. 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. {ECO:0000269|PubMed:16407192, ECO:0000269|PubMed:16815975, ECO:0000269|PubMed:16884686, ECO:0000269|PubMed:20133869, ECO:0000269|PubMed:20308324, ECO:0000269|PubMed:20385878, ECO:0000269|PubMed:20542004}. DE Reference Proteome: Yes; DE Interaction: P59595; IntAct: EBI-27129966; Score: 0.35 DE Interaction: Q8K4B0; IntAct: EBI-11126052; Score: 0.35 DE Interaction: Q9UKV8; IntAct: EBI-7642941; Score: 0.35 DE Interaction: P51965; IntAct: EBI-2339545; Score: 0.37 DE Interaction: Q96LR5; IntAct: EBI-2339579; Score: 0.37 DE Interaction: Q969T4; IntAct: EBI-2339769; Score: 0.37 DE Interaction: Q8WVJ2; IntAct: EBI-9484933; Score: 0.40 DE Interaction: Q12952; IntAct: EBI-11321256; Score: 0.35 DE Interaction: Q08050; IntAct: EBI-11321374; Score: 0.35 DE Interaction: P05412; IntAct: EBI-11324725; Score: 0.35 DE Interaction: Q9JJR9; IntAct: EBI-11017700; Score: 0.35 DE Interaction: P33981; IntAct: EBI-11027245; Score: 0.35 DE Interaction: P27635; IntAct: EBI-11035646; Score: 0.35 DE Interaction: F8VQC1; IntAct: EBI-11054725; Score: 0.35 DE Interaction: Q99PL5; IntAct: EBI-11066888; Score: 0.35 DE Interaction: Q00839; IntAct: EBI-11088773; Score: 0.35 DE Interaction: P37840; IntAct: EBI-11113842; Score: 0.35 DE Interaction: Q8TF76; IntAct: EBI-11146909; Score: 0.35 DE Interaction: Q76RH4; IntAct: EBI-14063348; Score: 0.35 DE Interaction: Q9GZY0; IntAct: EBI-21528397; Score: 0.35 DE Interaction: O43159; IntAct: EBI-21627620; Score: 0.35 DE Interaction: Q9P031; IntAct: EBI-21664473; Score: 0.35 DE Interaction: P15880; IntAct: EBI-21677299; Score: 0.35 DE Interaction: Q9BSG1; IntAct: EBI-21680046; Score: 0.35 DE Interaction: Q8WYQ5; IntAct: EBI-21679517; Score: 0.35 DE Interaction: Q5T3I0; IntAct: EBI-21681508; Score: 0.35 DE Interaction: Q07020; IntAct: EBI-21680991; Score: 0.35 DE Interaction: A2RU67; IntAct: EBI-21694732; Score: 0.35 DE Interaction: P50914; IntAct: EBI-21741266; Score: 0.35 DE Interaction: Q9Y3C1; IntAct: EBI-21875103; Score: 0.35 DE Interaction: P03495; IntAct: EBI-15833966; Score: 0.54 DE Interaction: A2A935; IntAct: EBI-21022882; Score: 0.35 DE Interaction: P14404; IntAct: EBI-21026252; Score: 0.35 DE Interaction: Q99558; IntAct: EBI-21261374; Score: 0.35 DE Interaction: Q4FZB7; IntAct: EBI-25485626; Score: 0.40 DE Interaction: A0A0F6B063; IntAct: EBI-27033283; Score: 0.35 DE Interaction: P0DTC9; IntAct: EBI-27102259; Score: 0.53 DE Interaction: P15130; IntAct: EBI-27131516; Score: 0.35 DE Interaction: Q0ZME3; IntAct: EBI-27131755; Score: 0.35 DE Interaction: Q6Q1R8; IntAct: EBI-27132003; Score: 0.35 DE Interaction: K9N4V7; IntAct: EBI-27132270; Score: 0.35 DE Interaction: P33469; IntAct: EBI-27132272; Score: 0.35 DE Interaction: P46108; IntAct: EBI-30821447; Score: 0.44 GO GO:0005737; GO GO:0005829; GO GO:0048471; GO GO:0030332; GO GO:0042296; GO GO:0003723; GO GO:0061630; GO GO:0004842; GO GO:0051607; GO GO:0045087; GO GO:0032020; GO GO:0016567; GO GO:0000079; GO GO:0050688; GO GO:0006511; TP Membrane Topology: Unknown; Source: UniProt - Sequence Analysis; SQ MERRSRRKSRRNGRSTAGKAAATQPAKSPGAQLWLFPSAAGLHRALLRRVEVTRQLCCSPGRLAVLERGGAGVQVHQLLA SQ GSGGARTPKCIKLGKNMKIHSVDQGAEHMLILSSDGKPFEYDNYSMKHLRFESILQEKKIIQITCGDYHSLALSKGGELF SQ AWGQNLHGQLGVGRKFPSTTTPQIVEHLAGVPLAQISAGEAHSMALSMSGNIYSWGKNECGQLGLGHTESKDDPSLIEGL SQ DNQKVEFVACGGSHSALLTQDGLLFTFGAGKHGQLGHNSTQNELRPCLVAELVGYRVTQIACGRWHTLAYVSDLGKVFSF SQ GSGKDGQLGNGGTRDQLMPLPVKVSSSEELKLESHTSEKELIMIAGGNQSILLWIKKENSYVNLKRTIPTLNEGTVKRWI SQ ADVETKRWQSTKREIQEIFSSPACLTGSFLRKRRTTEMMPVYLDLNKARNIFKELTQKDWITNMITTCLKDNLLKRLPFH SQ SPPQEALEIFFLLPECPMMHISNNWESLVVPFAKVVCKMSDQSSLVLEEYWATLQESTFSKLVQMFKTAVICQLDYWDES SQ AEENGNVQALLEMLKKLHRVNQVKCQLPESIFQVDELLHRLNFFVEVCRRYLWKMTVDASENVQCCVIFSHFPFIFNNLS SQ KIKLLHTDTLLKIESKKHKAYLRSAAIEEERESEFALRPTFDLTVRRNHLIEDVLNQLSQFENEDLRKELWVSFSGEIGY SQ DLGGVKKEFFYCLFAEMIQPEYGMFMYPEGASCMWFPVKPKFEKKRYFFFGVLCGLSLFNCNVANLPFPLALFKKLLDQM SQ PSLEDLKELSPDLGKNLQTLLDDEGDNFEEVFYIHFNVHWDRNDTNLIPNGSSITVNQTNKRDYVSKYINYIFNDSVKAV SQ YEEFRRGFYKMCDEDIIKLFHPEELKDVIVGNTDYDWKTFEKNARYEPGYNSSHPTIVMFWKAFHKLTLEEKKKFLVFLT SQ GTDRLQMKDLNNMKITFCCPESWNERDPIRALTCFSVLFLPKYSTMETVEEALQEAINNNRGFG //