Q15843 · NEDD8_HUMAN
- ProteinNEDD8
- GeneNEDD8
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids
- Protein existenceEvidence at protein level
- Annotation score5/5
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:10318914, PubMed:10597293, PubMed:11953428, PubMed:14690597, PubMed:15242646, PubMed:9694792).
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).
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).
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).
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).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 8 | Interaction with UBE1C | ||||
Sequence: L | ||||||
Site | 44 | Interaction with UBE1C | ||||
Sequence: I |
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | extracellular exosome | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Molecular Function | protein tag activity | |
Molecular Function | ubiquitin protein ligase binding | |
Biological Process | anatomical structure morphogenesis | |
Biological Process | modification-dependent protein catabolic process | |
Biological Process | protein localization | |
Biological Process | protein modification process | |
Biological Process | protein neddylation | |
Biological Process | proteolysis | |
Biological Process | regulation of proteolysis | |
Biological Process | regulation of transcription by RNA polymerase II | |
Biological Process | ubiquitin-dependent protein catabolic process |
Keywords
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameNEDD8
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ15843
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 7-9 | Decreased interaction with B.pseudomallei Cif protein, leading to decreased deamidation. | ||||
Sequence: TLT → ALA | ||||||
Mutagenesis | 11 | Decreased interaction with B.pseudomallei Cif protein, leading to decreased deamidation. | ||||
Sequence: K → A | ||||||
Mutagenesis | 31 | Decreased interaction with B.pseudomallei Cif protein, leading to slightly decreased deamidation. | ||||
Sequence: E → Q | ||||||
Mutagenesis | 40 | Impaired ability to activate cullin-RING-based E3 ubiquitin-protein ligase complexes. | ||||
Sequence: Q → E | ||||||
Mutagenesis | 68 | Decreased interaction with B.pseudomallei Cif protein, leading to slightly decreased deamidation. | ||||
Sequence: H → A | ||||||
Mutagenesis | 72 | Prevents adenylation by UBE1C. | ||||
Sequence: A → R |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 56 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, cross-link, propeptide.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000042767 | 1-76 | NEDD8 | |||
Sequence: MLIKVKTLTGKEIEIDIEPTDKVERIKERVEEKEGIPPQQQRLIYSGKQMNDEKTAADYKILGGSVLHLVLALRGG | ||||||
Modified residue | 40 | (Microbial infection) Deamidated glutamine | ||||
Sequence: Q | ||||||
Modified residue | 48 | N6-acetyllysine | ||||
Sequence: K | ||||||
Cross-link | 76 | Glycyl lysine isopeptide (Gly-Lys) (interchain with K-? in acceptor proteins) | ||||
Sequence: G | ||||||
Propeptide | PRO_0000042768 | 77-81 | ||||
Sequence: GGLRQ |
Post-translational modification
Cleavage of precursor form by UCHL3 or SENP8 is necessary for function.
(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:23175788, PubMed:23589306, PubMed:26632597).
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).
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).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in heart, skeletal muscle, spleen, thymus, prostate, testis, ovary, colon and leukocytes.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with AHR; interaction is direct (PubMed:12215427).
Interacts with NUB1; interaction is direct (PubMed:11259415).
Interacts with ESR1 (By similarity).
Interacts with NUB1; interaction is direct (PubMed:11259415).
Interacts with ESR1 (By similarity).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q15843 | BTRC Q9Y297 | 2 | EBI-716247, EBI-307461 | |
BINARY | Q15843 | CUL1 Q13616 | 23 | EBI-716247, EBI-359390 | |
BINARY | Q15843 | GSN P06396 | 3 | EBI-716247, EBI-351506 | |
BINARY | Q15843 | KHNYN O15037 | 13 | EBI-716247, EBI-6148525 | |
BINARY | Q15843 | POLI Q9UNA4 | 2 | EBI-716247, EBI-741774 | |
BINARY | Q15843 | PPP2R2A P63151 | 3 | EBI-716247, EBI-1048931 | |
BINARY | Q15843 | RAD23A P54725 | 2 | EBI-716247, EBI-746453 | |
BINARY | Q15843 | RPL11 P62913 | 5 | EBI-716247, EBI-354380 | |
BINARY | Q15843 | RPL7 P18124 | 2 | EBI-716247, EBI-350806 | |
BINARY | Q15843 | RPS20 P60866 | 3 | EBI-716247, EBI-353105 | |
BINARY | Q15843 | RPS3 P23396 | 3 | EBI-716247, EBI-351193 | |
BINARY | Q15843 | RPS7 P62081 | 2 | EBI-716247, EBI-354360 | |
BINARY | Q15843 | S100B P04271 | 3 | EBI-716247, EBI-458391 | |
BINARY | Q15843 | STON2 Q8WXE9 | 2 | EBI-716247, EBI-539742 | |
BINARY | Q15843 | TUBB P07437 | 4 | EBI-716247, EBI-350864 | |
BINARY | Q15843 | UBE2K P61086 | 3 | EBI-716247, EBI-473850 | |
BINARY | Q15843 | UBE2M P61081 | 10 | EBI-716247, EBI-1041660 | |
BINARY | Q15843 | UBXN7 O94888 | 2 | EBI-716247, EBI-1993627 | |
BINARY | Q15843 | UCHL1 P09936 | 4 | EBI-716247, EBI-714860 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 70-72 | Interaction with UBE1C | ||||
Sequence: VLA |
Sequence similarities
Belongs to the ubiquitin family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
- Length81
- Mass (Da)9,072
- Last updated1996-11-01 v1
- ChecksumDC2FE102BE4725D2
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
F8VSA6 | F8VSA6_HUMAN | NEDD8 | 50 |
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 15 | in Ref. 2; CAG28590 | ||||
Sequence: I → V |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
D23662 EMBL· GenBank· DDBJ | BAA04889.1 EMBL· GenBank· DDBJ | mRNA | ||
CR407662 EMBL· GenBank· DDBJ | CAG28590.1 EMBL· GenBank· DDBJ | mRNA | ||
BC104200 EMBL· GenBank· DDBJ | AAI04201.1 EMBL· GenBank· DDBJ | mRNA | ||
BC104201 EMBL· GenBank· DDBJ | AAI04202.1 EMBL· GenBank· DDBJ | mRNA | ||
BC104664 EMBL· GenBank· DDBJ | AAI04665.1 EMBL· GenBank· DDBJ | mRNA |