Protein
E3 ubiquitin-protein ligase arkadia-A
Function
E3 ubiquitin-protein ligase required for mesoderm patterning during embryonic development by enhancing signaling of the subset of TGF-beta factors responsible for the formation of dorso-anterior tissues of Spemann's organizer (PubMed:11298453). Acts as an enhancer of the transcriptional responses of the smad2/smad3 effectors, which are activated downstream of BMP (By similarity). Acts by mediating ubiquitination and degradation of SMAD inhibitors such as smad7, inducing their proteasomal degradation and thereby enhancing the transcriptional activity of TGF-beta and BMP (By similarity). Specifically binds polysumoylated chains via SUMO interaction motifs (SIMs) and mediates ubiquitination of sumoylated substrates (By similarity). The regulation of the BMP-SMAD signaling is however independent of sumoylation and is not dependent of SUMO interaction motifs (SIMs) (By similarity).
Similarity
Belongs to the Arkadia family.
Sequence
VEMIASKVSNEFNHLCSDTNKQQSDLNSNGTEQDKSLVVHKKRKSQQAGTSYAQSCEVKEYQRLLRLQPKSDEDNDSSFSDCISSPSSSSHFGDSDTMTSDEDKDNPLSSVNSTPRTQSARAQKWPRPHTDSVSSLLMKRPCYQVSSLRRPLHRKRFVKNVSSQRTQKQKERIMLQRKKREVLARQKYALLPSSSSSSENDLSSESSSSSSTEGEEDLFVSPGENHQDGTTLPSGGMDEDVVVIEASSTPQVTANEEINVTSTDSEVEIVTVGETYRSRATLGHPRSHWGQNSQSGRTQEQRTRNRVSTIIQPLRQNTTEVVDLTVDEDDPTVVPTTSGRVESQPVSIVSSLTSTSEPASDSMSGLMGSAVPEIPAIPPNTVGTIADDSRTCTSGANADGGPPAMPRLPSCCPQHSPCGGSSQNHVLGHPHSSCFPPHSHHFPHHHHHHHHSSHPGVPLSPSFRDSHCTVERNAAVPPPCGVSSSSGSTYHDPQALPVDLSNNGIRSHGSVGFHSTSAFDPCCPGSSSRSTVYGHQATTSTAQTMAIDGYGSSMVAQAQPPPPLSSCRHYMHASYTSLPRPLHHQTSSCPHSNSASQPPPPPPPPPPPPMDYVIAHQVPFISPLPSLTSTHAVPPPPPSHHLSAAAAPLPQHLSTSHQSMSHHISATAPATQRLHAHEVIQRMEVQRRRMMQHPTRAHERPPPHPHRMHPNYGHGHHIHVPQTMSSHPRQGPERSAWEIAIETGVTAAPYQTGPLHTHLAPYHPPPRLHHLQIGALPLMVPDMAGYPHIRYISSGLDGRSFRVPFRGNFEELIHLEERLGNVNRGASQGTIERCTYPHKYKKVSTDWFSQRKLHSKQDGEEAPEEDTEEKCTICLSILEEGEDVRRLPCMHLFHQVCVDQWLITNKKCPICRVDIDTQLPTES