{"metadata":{"accession":"Q8IWV8","id":"UBR2_HUMAN","source_organism":{"taxId":"9606","scientificName":"Homo sapiens","fullName":"Homo sapiens (Human)"},"name":"E3 ubiquitin-protein ligase UBR2","description":["E3 ubiquitin-protein ligase which is a component of the N-end rule pathway (PubMed:15548684, PubMed:20835242, PubMed:28392261). Recognizes and binds to proteins bearing specific N-terminal residues (N-degrons) that are destabilizing according to the N-end rule, leading to their ubiquitination and subsequent degradation (PubMed:20835242, PubMed:28392261). Recognizes both type-1 and type-2 N-degrons, containing positively charged amino acids (Arg, Lys and His) and bulky and hydrophobic amino acids, respectively (PubMed:20835242, PubMed:28392261). Does not ubiquitinate proteins that are acetylated at the N-terminus (PubMed:20835242). In contrast, it strongly binds methylated N-degrons (PubMed:28392261). Plays a critical role in chromatin inactivation and chromosome-wide transcriptional silencing during meiosis via ubiquitination of histone H2A (By similarity). Binds leucine and is a negative regulator of the leucine-mTOR signaling pathway, thereby controlling cell growth (PubMed:20298436). Required for spermatogenesis, promotes, with Tex19.1, SPO11-dependent recombination foci to accumulate and drive robust homologous chromosome synapsis (By similarity). Polyubiquitinates LINE-1 retrotransposon encoded, LIRE1, which induces degradation, inhibiting LINE-1 retrotransposon mobilization (By similarity). Catalyzes ubiquitination and degradation of the N-terminal part of NLRP1 following NLRP1 activation by pathogens and other damage-associated signals: ubiquitination promotes degradation of the N-terminal part and subsequent release of the cleaved C-terminal part of NLRP1, which polymerizes and forms the NLRP1 inflammasome followed by host cell pyroptosis (By similarity). Plays a role in T-cell receptor signaling by inducing 'Lys-63'-linked ubiquitination of lymphocyte cell-specific kinase LCK (PubMed:38225265). This activity is regulated by DUSP22, which induces 'Lys-48'-linked ubiquitination of UBR2, leading to its proteasomal degradation by SCF E3 ubiquitin-protein ligase complex (PubMed:38225265)"],"length":1755,"sequence":"MASELEPEVQAIDRSLLECSAEEIAGKWLQATDLTREVYQHLAHYVPKIYCRGPNPFPQKEDMLAQHVLLGPMEWYLCGEDPAFGFPKLEQANKPSHLCGRVFKVGEPTYSCRDCAVDPTCVLCMECFLGSIHRDHRYRMTTSGGGGFCDCGDTEAWKEGPYCQKHELNTSEIEEEEDPLVHLSEDVIARTYNIFAITFRYAVEILTWEKESELPADLEMVEKSDTYYCMLFNDEVHTYEQVIYTLQKAVNCTQKEAIGFATTVDRDGRRSVRYGDFQYCEQAKSVIVRNTSRQTKPLKVQVMHSSIVAHQNFGLKLLSWLGSIIGYSDGLRRILCQVGLQEGPDGENSSLVDRLMLSDSKLWKGARSVYHQLFMSSLLMDLKYKKLFAVRFAKNYQQLQRDFMEDDHERAVSVTALSVQFFTAPTLARMLITEENLMSIIIKTFMDHLRHRDAQGRFQFERYTALQAFKFRRVQSLILDLKYVLISKPTEWSDELRQKFLEGFDAFLELLKCMQGMDPITRQVGQHIEMEPEWEAAFTLQMKLTHVISMMQDWCASDEKVLIEAYKKCLAVLMQCHGGYTDGEQPITLSICGHSVETIRYCVSQEKVSIHLPVSRLLAGLHVLLSKSEVAYKFPELLPLSELSPPMLIEHPLRCLVLCAQVHAGMWRRNGFSLVNQIYYYHNVKCRREMFDKDVVMLQTGVSMMDPNHFLMIMLSRFELYQIFSTPDYGKRFSSEITHKDVVQQNNTLIEEMLYLIIMLVGERFSPGVGQVNATDEIKREIIHQLSIKPMAHSELVKSLPEDENKETGMESVIEAVAHFKKPGLTGRGMYELKPECAKEFNLYFYHFSRAEQSKAEEAQRKLKRQNREDTALPPPVLPPFCPLFASLVNILQSDVMLCIMGTILQWAVEHNGYAWSESMLQRVLHLIGMALQEEKQHLENVTEEHVVTFTFTQKISKPGEAPKNSPSILAMLETLQNAPYLEVHKDMIRWILKTFNAVKKMRESSPTSPVAETEGTIMEESSRDKDKAERKRKAEIARLRREKIMAQMSEMQRHFIDENKELFQQTLELDASTSAVLDHSPVASDMTLTALGPAQTQVPEQRQFVTCILCQEEQEVKVESRAMVLAAFVQRSTVLSKNRSKFIQDPEKYDPLFMHPDLSCGTHTSSCGHIMHAHCWQRYFDSVQAKEQRRQQRLRLHTSYDVENGEFLCPLCECLSNTVIPLLLPPRNIFNNRLNFSDQPNLTQWIRTISQQIKALQFLRKEESTPNNASTKNSENVDELQLPEGFRPDFRPKIPYSESIKEMLTTFGTATYKVGLKVHPNEEDPRVPIMCWGSCAYTIQSIERILSDEDKPLFGPLPCRLDDCLRSLTRFAAAHWTVASVSVVQGHFCKLFASLVPNDSHEELPCILDIDMFHLLVGLVLAFPALQCQDFSGISLGTGDLHIFHLVTMAHIIQILLTSCTEENGMDQENPPCEEESAVLALYKTLHQYTGSALKEIPSGWHLWRSVRAGIMPFLKCSALFFHYLNGVPSPPDIQVPGTSHFEHLCSYLSLPNNLICLFQENSEIMNSLIESWCRNSEVKRYLEGERDAIRYPRESNKLINLPEDYSSLINQASNFSCPKSGGDKSRAPTLCLVCGSLLCSQSYCCQTELEGEDVGACTAHTYSCGSGVGIFLRVRECQVLFLAGKTKGCFYSPPYLDDYGETDQGLRRGNPLHLCKERFKKIQKLWHQHSVTEEIGHAQEANQTLVGIDWQHL","proteome":"UP000005640","gene":"UBR2","go_terms":[{"identifier":"GO:0008270","name":"zinc ion binding","category":{"code":"F","name":"molecular_function"}},{"identifier":"GO:0061630","name":"ubiquitin protein ligase activity","category":{"code":"F","name":"molecular_function"}},{"identifier":"GO:0071596","name":"ubiquitin-dependent protein catabolic process via the N-end rule pathway","category":{"code":"P","name":"biological_process"}},{"identifier":"GO:0030163","name":"protein catabolic process","category":{"code":"P","name":"biological_process"}}],"protein_evidence":1,"source_database":"reviewed","is_fragment":false,"in_alphafold":true,"in_bfvd":false,"ida_accession":"5696b282a9e71c88df01beac41c868c8241dad06","counters":{"domain_architectures":3585,"entries":23,"isoforms":4,"proteomes":1,"sets":3,"structures":9,"taxa":1,"dbEntries":{"smart":1,"profile":1,"cdd":2,"cathgene3d":3,"ssf":2,"pfam":4,"panther":1,"interpro":9},"proteome":1,"taxonomy":1,"similar_proteins":3585}}}