| IED ID | IndEnz0002012902 |
| Enzyme Type ID | protease012902 |
| Protein Name |
NEDD8 Neddylin Neural precursor cell expressed developmentally down-regulated protein 8 NEDD-8 Ubiquitin-like protein Nedd8 |
| Gene Name | NEDD8 |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MLIKVKTLTGKEIEIDIEPTDKVERIKERVEEKEGIPPQQQRLIYSGKQMNDEKTAADYKILGGSVLHLVLALRGGGGLRQ |
| Enzyme Length | 81 |
| Uniprot Accession Number | Q15843 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Ubiquitin-like protein which plays an important role in cell cycle control and embryogenesis via its conjugation to a limited number of cellular proteins, such as cullins or p53/TP53 (PubMed:9694792, PubMed:10318914, PubMed:10597293, PubMed:11953428, PubMed:15242646, PubMed:14690597). 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:9694792, PubMed:10318914, PubMed:10597293, PubMed:11953428, PubMed:20688984). 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). {ECO:0000269|PubMed:10318914, ECO:0000269|PubMed:10597293, ECO:0000269|PubMed:11953428, ECO:0000269|PubMed:14690597, ECO:0000269|PubMed:15242646, ECO:0000269|PubMed:20688984, ECO:0000269|PubMed:9694792}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Beta strand (7); Chain (1); Cross-link (1); Helix (3); Modified residue (2); Mutagenesis (6); Propeptide (1); Region (1); Sequence conflict (1); Site (2) |
| Keywords | 3D-structure;Acetylation;Direct protein sequencing;Isopeptide bond;Nucleus;Reference proteome;Ubl conjugation pathway |
| Interact With | Q9Y297; Q13616; P06396; O15037; Q9UNA4; P63151; P54725; P62913; P18124; P60866; P23396; P62081; P04271; Q8WXE9; P07437; P61086; P61081; O94888; P09936 |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:9353319}. Note=Mainly nuclear. {ECO:0000269|PubMed:9353319}. |
| Modified Residue | MOD_RES 40; /note="(Microbial infection) Deamidated glutamine"; /evidence="ECO:0000269|PubMed:20688984, ECO:0000269|PubMed:21903097, ECO:0000269|PubMed:23175788, ECO:0000269|PubMed:23589306, ECO:0000269|PubMed:26632597"; MOD_RES 48; /note="N6-acetyllysine"; /evidence="ECO:0000250|UniProtKB:P29595" |
| Post Translational Modification | PTM: Cleavage of precursor form by UCHL3 or SENP8 is necessary for function. {ECO:0000269|PubMed:12730221, ECO:0000269|PubMed:12759363, ECO:0000269|PubMed:9353319, ECO:0000269|PubMed:9790970}.; PTM: (Microbial infection) Deamidated at Gln-40 by bacterial cyclomodulin Cif produced by enteropathogenic E.coli, Y.pseudotuberculosis or B.pseudomallei, leading to impair NEDD8 ability to activate cullin-RING-based E3 ubiquitin-protein ligase complexes (CRL complexes) (PubMed:20688984, PubMed:21903097, PubMed:23589306, PubMed:26632597, PubMed:23175788). 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 evidences (PubMed:20850415, PubMed:21903097). {ECO:0000269|PubMed:20688984, ECO:0000269|PubMed:20850415, ECO:0000269|PubMed:21903097, ECO:0000269|PubMed:23175788, ECO:0000269|PubMed:23589306, ECO:0000269|PubMed:26632597}. |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (2); Electron microscopy (6); X-ray crystallography (15) |
| Cross Reference PDB | 1NDD; 1R4M; 1R4N; 1XT9; 2BKR; 2KO3; 2N7K; 2NVU; 3DBH; 3DBL; 3DBR; 3DQV; 3GZN; 4F8C; 4FBJ; 4HCP; 4P5O; 6R7F; 6R7I; 6TTU; 7B5L; 7B5N; 7ONI; |
| Mapped Pubmed ID | 10535940; 10823831; 10878807; 10944113; 10973499; 11024059; 11069780; 11292861; 11292862; 11358837; 11454738; 11504942; 11585840; 12101228; 12186903; 12504025; 12526791; 12538644; 12554766; 12646924; 12740388; 12816948; 12821933; 14676825; 14757770; 15361859; 15537541; 15574592; 15694336; 15775960; 16111684; 16169070; 16171779; 16401342; 16547496; 16647857; 16707496; 16735510; 16861300; 16943200; 16979187; 17098746; 17119158; 17132228; 17183367; 17220875; 17318178; 17332328; 17353931; 17660949; 17935801; 18093314; 18096514; 18206966; 18264111; 18274552; 18323857; 18652489; 18723677; 18805092; 18826954; 18851830; 18926707; 19250909; 19281774; 19615732; 19617556; 19713960; 19748355; 19762596; 19762597; 19782077; 19784069; 20129059; 20603103; 21102408; 21169563; 21193393; 21316600; 21399617; 21447816; 21474709; 21822215; 21863050; 21940857; 22004789; 22069333; 22081073; 22095636; 22190034; 22306028; 22370482; 22466964; 22502714; 22537386; 22584050; 22612509; 22653443; 22767593; 22836579; 22895816; 22959436; 23001041; 23105008; 23201271; 23209320; 23246961; 23290524; 23300442; 23333871; 23394999; 23401859; 23453757; 23535662; 23535663; 23583660; 23812220; 24019527; 24076655; 24245672; 24634510; 24793695; 24793696; 24811749; 24949976; 25229838; 25314029; 25349211; 25416956; 25452302; 25531226; 25655932; 25782162; 25918018; 26003431; 26344709; 26364603; 26460955; 26906416; 27030794; 27086113; 27222660; 27381497; 27565346; 27756846; 27901050; 27906189; 28082425; 28169289; 28475037; 28535453; 28536428; 28569775; 28592528; 28831681; 29301501; 30407690; 30563767; 30857167; 31002342; 31208947; 31243299; 31444342; 31545502; 31577950; 31882005; 32051583; 32457294; 32819610; 33097763; 33288957; 33420360; 33536622; 34518685; 34642328; 9122164; 9891082; |
| Motif | |
| Gene Encoded By | |
| Mass | 9,072 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |