Function
E3 ubiquitin-protein ligase which accepts ubiquitin specifically from endoplasmic reticulum-associated UBC6 and UBC7 E2 ligases, and transfers it to substrates promoting their degradation. Mediates the degradation of a broad range of substrates, including endoplasmic reticulum membrane proteins (ERQC), soluble nuclear proteins and soluble cytoplasmic proteins (CytoQC). Component of the DOA10 ubiquitin ligase complex, which is part of the ERAD-C pathway responsible for the rapid degradation of membrane proteins with misfolded cytoplasmic domains. ERAD-C substrates are ubiquitinated through DOA10 in conjunction with the E2 ubiquitin-conjugating enzymes UBC6 and UBC7-CUE1. Ubiquitinated substrates are then removed to the cytosol via the action of the UFD1-NPL4-CDC48/p97 (UNC) AAA ATPase complex and targeted to the proteasome. Also recognizes the N-terminally acetylated residue of proteins as degradation signal (degron). N-terminally acetylated target proteins include MATALPHA2, TBF1, SLK19, YMR090W, HIS3, HSP104, UBP6 and ARO8.
Sequence
MDVDSDVNVSRLRDELHKVANEETDTATFNDDAPSGATCRICRGEATEDNPLFHPCKCRGSIKYMHESCLLEWVASKNIDISKPGADVKCDICHYPIQFKTIYAENMPEKIPFSLLLSKSILTFFEKARLALTIGLAAVLYIIGVPLVWNMFGKLYTMMLDGSSPYPGDFLKSLIYGYDQSATPELTTRAIFYQLLQNHSFTSLQFIMIVILHIALYFQYDMIVREDVFSKMVFHKIGPRLSPKDLKSRLKERFPMMDDRMVEYLAREMRAHDENRQEQGHDRLNMPAAAADNNNNVINPRNDNVPPQDPNDHRNFENLRHVDELDHDEATEEHENNDSDNSLPSGDDSSRILPGSSSDNEEDEEAEGQQQQQQPEEEADYRDHIEPNPIDMWANRRAQNEFDDLIAAQQNAINRPNAPVFIPPPAQNRAGNVDQDEQDFGAAVGVPPAQANPDDQGQGPLVINLKLKLLNVIAYFIIAVVFTAIYLAISYLFPTFIGFGLLKIYFGIFKVILRGLCHLYYLSGAHIAYNGLTKLVPKVDVAMSWISDHLIHDIIYLYNGYTENTMKHSIFIRALPALTTYLTSVSIVCASSNLVSRGYGRENGMSNPTRRLIFQILFALKCTFKVFTLFFIELAGFPILAGVMLDFSLFCPILASNSRMLWVPSICAIWPPFSLFVYWTIGTLYMYWFAKYIGMIRKNIIRPGVLFFIRSPEDPNIKILHDSLIHPMSIQLSRLCLSMFIYAIFIVLGFGFHTRIFFPFMLKSNLLSVPEAYKPTSIISWKFNTILLTLYFTKRILESSSYVKPLLERYWKTIFKLCSRKLRLSSFILGKDTPTERGHIVYRNLFYKYIAAKNAEWSNQELFTKPKTLEQAEELFGQVRDVHAYFVPDGVLMRVPSSDIVSRNYVQTMFVPVTKDDKLLKPLDLERIKERNKRAAGEFGYLDEQNTEYDQYYIVYVPPDFRLRYMTLLGLVWLFASILMLGVTFISQALINFVCSFGFLPVVKLLLGERNKVYVAWKELSDISYSYLNIYYVCVGSVCLSKIAKDILHFTEGQNTLDEHAVDENEVEEVEHDIPERDINNAPVNNINNVEEGQGIFMAIFNSIFDSMLVKYNLMVFIAIMIAVIRTMVSWVVLTDGILACYNYLTIRVFGNSSYTIGNSKWFKYDESLLFVVWIISSMVNFGTGYKSLKLFFRNRNTSKLNFLKTMALELFKQGFLHMVIYVLPIIILSLVFLRDVSTKQIIDISHGSRSFTLSLNESFPTWTRMQDIYFGLLIALESFTFFFQATVLFIQWFKSTVQNVKDEVYTKGRALENLPDES