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Attachment of NEDD8 to cullins is critical for the recruitment of E2 to the cullin-RING-based E3 ubiquitin-protein ligase complex, thus facilitating polyubiquitination and proteasomal degradation of cyclins and other regulatory proteins (PubMed:10318914, PubMed:10597293, PubMed:11953428, PubMed:20688984, PubMed:9694792, PubMed:38605244, PubMed:38316879). Attachment of NEDD8 to p53/TP53 inhibits p53/TP53 transcriptional activity (PubMed:15242646). Covalent attachment to its substrates requires prior activation by the E1 complex UBE1C-APPBP1 and linkage to the E2 enzyme UBE2M (PubMed:14690597). Neddylates EGFR resulting in protein stabilization and translocation to the cell membrane (PubMed:28891468)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q71UE8"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11259415"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12215427"}],"value":"Interacts with AHR; interaction is direct (PubMed:12215427). Interacts with NUB1; interaction is direct (PubMed:11259415). 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Deamidation occurs on NEDD8-modified cullins (PubMed:20850415, PubMed:21903097). NEDD8 deamidation prevents switching from the inactive to active state by maintaining the 'closed' structure of the CRL complexes (PubMed:23589306, PubMed:26632597). Deamidation may also impair its deconjugation by the COP9 signalosome; However this result needs additional evidence (PubMed:20850415, PubMed:21903097)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Belongs to the ubiquitin family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":76,"modifier":"EXACT"}},"description":"Ubiquitin-like protein NEDD8","featureId":"PRO_0000042767"},{"type":"Propeptide","location":{"start":{"value":77,"modifier":"EXACT"},"end":{"value":81,"modifier":"EXACT"}},"description":"","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9353319"}],"featureId":"PRO_0000042768"},{"type":"Region","location":{"start":{"value":70,"modifier":"EXACT"},"end":{"value":72,"modifier":"EXACT"}},"description":"Interaction with UBE1C","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14690597"}]},{"type":"Site","location":{"start":{"value":8,"modifier":"EXACT"},"end":{"value":8,"modifier":"EXACT"}},"description":"Interaction with UBE1C","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14690597"}]},{"type":"Site","location":{"start":{"value":44,"modifier":"EXACT"},"end":{"value":44,"modifier":"EXACT"}},"description":"Interaction with UBE1C","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14690597"}]},{"type":"Modified residue","location":{"start":{"value":40,"modifier":"EXACT"},"end":{"value":40,"modifier":"EXACT"}},"description":"(Microbial infection) Deamidated glutamine","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20688984"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21903097"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23175788"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23589306"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26632597"}]},{"type":"Modified residue","location":{"start":{"value":48,"modifier":"EXACT"},"end":{"value":48,"modifier":"EXACT"}},"description":"N6-acetyllysine","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P29595"}]},{"type":"Cross-link","location":{"start":{"value":76,"modifier":"EXACT"},"end":{"value":76,"modifier":"EXACT"}},"description":"Glycyl lysine isopeptide (Gly-Lys) (interchain with K-? in acceptor proteins)","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38316879"}]},{"type":"Mutagenesis","location":{"start":{"value":7,"modifier":"EXACT"},"end":{"value":9,"modifier":"EXACT"}},"description":"Decreased interaction with B.pseudomallei Cif protein, leading to decreased deamidation.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23175788"}],"alternativeSequence":{"originalSequence":"TLT","alternativeSequences":["ALA"]}},{"type":"Mutagenesis","location":{"start":{"value":11,"modifier":"EXACT"},"end":{"value":11,"modifier":"EXACT"}},"description":"Decreased interaction with B.pseudomallei Cif protein, leading to decreased deamidation.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23175788"}],"alternativeSequence":{"originalSequence":"K","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":31,"modifier":"EXACT"},"end":{"value":31,"modifier":"EXACT"}},"description":"Decreased interaction with B.pseudomallei Cif protein, leading to slightly decreased deamidation.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23175788"}],"alternativeSequence":{"originalSequence":"E","alternativeSequences":["Q"]}},{"type":"Mutagenesis","location":{"start":{"value":40,"modifier":"EXACT"},"end":{"value":40,"modifier":"EXACT"}},"description":"Impaired ability to activate cullin-RING-based E3 ubiquitin-protein ligase complexes.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20688984"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21903097"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23589306"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26632597"}],"alternativeSequence":{"originalSequence":"Q","alternativeSequences":["E"]}},{"type":"Mutagenesis","location":{"start":{"value":68,"modifier":"EXACT"},"end":{"value":68,"modifier":"EXACT"}},"description":"Decreased interaction with B.pseudomallei Cif protein, leading to slightly decreased deamidation.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23175788"}],"alternativeSequence":{"originalSequence":"H","alternativeSequences":["A"]}},{"type":"Mutagenesis","location":{"start":{"value":72,"modifier":"EXACT"},"end":{"value":72,"modifier":"EXACT"}},"description":"Prevents adenylation by UBE1C.","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"14690597"}],"alternativeSequence":{"originalSequence":"A","alternativeSequences":["R"]}},{"type":"Sequence conflict","location":{"start":{"value":15,"modifier":"EXACT"},"end":{"value":15,"modifier":"EXACT"}},"description":"in Ref. 2; 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