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Protein

NEDD8

Gene

NEDD8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Ubiquitin-like protein which plays an important role in cell cycle control and embryogenesis. Covalent attachment to its substrates requires prior activation by the E1 complex UBE1C-APPBP1 and linkage to the E2 enzyme UBE2M. Attachment of NEDD8 to cullins activates their associated E3 ubiquitin ligase activity, and thus promotes polyubiquitination and proteasomal degradation of cyclins and other regulatory proteins.3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei8 – 81Interaction with UBE1C
Sitei44 – 441Interaction with UBE1C

GO - Molecular functioni

  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  • anatomical structure morphogenesis Source: ProtInc
  • cellular protein modification process Source: ProtInc
  • protein localization Source: Ensembl
  • protein neddylation Source: MGI
  • proteolysis Source: ProtInc
  • regulation of transcription from RNA polymerase II promoter Source: Ensembl
  • response to organic cyclic compound Source: Ensembl
  • transforming growth factor beta receptor signaling pathway Source: Reactome
  • ubiquitin-dependent protein catabolic process Source: ProtInc
Complete GO annotation...

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiREACT_120850. TGF-beta receptor signaling activates SMADs.

Names & Taxonomyi

Protein namesi
Recommended name:
NEDD8
Alternative name(s):
Neddylin
Neural precursor cell expressed developmentally down-regulated protein 8
Short name:
NEDD-8
Ubiquitin-like protein Nedd8
Gene namesi
Name:NEDD8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:7732. NEDD8.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • nucleus Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi72 – 721A → R: Prevents adenylation by UBE1C. 1 Publication

Organism-specific databases

PharmGKBiPA31537.

Polymorphism and mutation databases

BioMutaiNEDD8.
DMDMi2833270.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 7676NEDD8PRO_0000042767Add
BLAST
Propeptidei77 – 815PRO_0000042768

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei48 – 481N6-acetyllysineBy similarity
Cross-linki76 – 76Glycyl lysine isopeptide (Gly-Lys) (interchain with K-? in acceptor proteins)

Post-translational modificationi

Cleavage of precursor form by UCHL3 or SENP8 is necessary for function.

Keywords - PTMi

Acetylation, Isopeptide bond

Proteomic databases

MaxQBiQ15843.
PaxDbiQ15843.
PeptideAtlasiQ15843.
PRIDEiQ15843.

PTM databases

PhosphoSiteiQ15843.

Miscellaneous databases

PMAP-CutDBQ15843.

Expressioni

Tissue specificityi

Highly expressed in heart, skeletal muscle, spleen, thymus, prostate, testis, ovary, colon and leukocytes.2 Publications

Gene expression databases

BgeeiQ15843.
CleanExiHS_NEDD8.
ExpressionAtlasiQ15843. baseline and differential.
GenevisibleiQ15843. HS.

Organism-specific databases

HPAiCAB004082.

Interactioni

Subunit structurei

Directly interacts with NUB1 and AHR. Covalently attached to cullins and p53.8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BTRCQ9Y2972EBI-716247,EBI-307461
CUL1Q136168EBI-716247,EBI-359390
RPL11P629134EBI-716247,EBI-354380
RPL7P181242EBI-716247,EBI-350806
RPS20P608662EBI-716247,EBI-353105
RPS3P233962EBI-716247,EBI-351193
RPS7P620812EBI-716247,EBI-354360
STON2Q8WXE92EBI-716247,EBI-539742
UBE2MP610813EBI-716247,EBI-1041660

Protein-protein interaction databases

BioGridi110815. 1055 interactions.
DIPiDIP-29266N.
IntActiQ15843. 89 interactions.
MINTiMINT-268324.
STRINGi9606.ENSP00000250495.

Structurei

Secondary structure

1
81
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi2 – 65Combined sources
Beta strandi8 – 103Combined sources
Beta strandi12 – 165Combined sources
Helixi23 – 3412Combined sources
Helixi38 – 403Combined sources
Beta strandi41 – 455Combined sources
Beta strandi52 – 554Combined sources
Helixi56 – 594Combined sources
Beta strandi66 – 716Combined sources
Beta strandi73 – 753Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1NDDX-ray1.60A/B/C/D1-76[»]
1R4MX-ray3.00I/J/K/L1-76[»]
1R4NX-ray3.60I/J/K/L1-76[»]
1XT9X-ray2.20B1-76[»]
2BKRX-ray1.90B1-76[»]
2KO3NMR-A1-76[»]
2NVUX-ray2.80I/J1-76[»]
3DBHX-ray2.85I/J/K/L1-76[»]
3DBLX-ray2.90I/J/K/L1-76[»]
3DBRX-ray3.05I/J/K/L1-76[»]
3DQVX-ray3.00A/B1-76[»]
3GZNX-ray3.00I/J1-76[»]
4F8CX-ray1.95B/D1-81[»]
4FBJX-ray1.60B1-81[»]
4HCPX-ray2.52B1-76[»]
4P5OX-ray3.11H/K1-76[»]
ProteinModelPortaliQ15843.
SMRiQ15843. Positions 1-76.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ15843.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni70 – 723Interaction with UBE1C

Sequence similaritiesi

Belongs to the ubiquitin family.Curated

Phylogenomic databases

eggNOGiCOG5272.
GeneTreeiENSGT00660000095622.
HOGENOMiHOG000233942.
HOVERGENiHBG000057.
InParanoidiQ15843.
KOiK12158.
OMAiKLAPPRH.
OrthoDBiEOG7JDR1W.
PhylomeDBiQ15843.
TreeFamiTF300072.

Family and domain databases

InterProiIPR019956. Ubiquitin.
IPR000626. Ubiquitin-like.
IPR029071. Ubiquitin-rel_dom.
IPR019954. Ubiquitin_CS.
[Graphical view]
PfamiPF00240. ubiquitin. 1 hit.
[Graphical view]
PRINTSiPR00348. UBIQUITIN.
SMARTiSM00213. UBQ. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
PROSITEiPS00299. UBIQUITIN_1. 1 hit.
PS50053. UBIQUITIN_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q15843-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLIKVKTLTG KEIEIDIEPT DKVERIKERV EEKEGIPPQQ QRLIYSGKQM
60 70 80
NDEKTAADYK ILGGSVLHLV LALRGGGGLR Q
Length:81
Mass (Da):9,072
Last modified:November 1, 1996 - v1
Checksum:iDC2FE102BE4725D2
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti15 – 151I → V in CAG28590 (Ref. 2) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D23662 mRNA. Translation: BAA04889.1.
CR407662 mRNA. Translation: CAG28590.1.
BC104200 mRNA. Translation: AAI04201.1.
BC104201 mRNA. Translation: AAI04202.1.
BC104664 mRNA. Translation: AAI04665.1.
CCDSiCCDS9621.1.
RefSeqiNP_006147.1. NM_006156.2.
UniGeneiHs.531064.

Genome annotation databases

EnsembliENST00000250495; ENSP00000250495; ENSG00000129559.
GeneIDi4738.
KEGGihsa:4738.
UCSCiuc001wnn.2. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D23662 mRNA. Translation: BAA04889.1.
CR407662 mRNA. Translation: CAG28590.1.
BC104200 mRNA. Translation: AAI04201.1.
BC104201 mRNA. Translation: AAI04202.1.
BC104664 mRNA. Translation: AAI04665.1.
CCDSiCCDS9621.1.
RefSeqiNP_006147.1. NM_006156.2.
UniGeneiHs.531064.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1NDDX-ray1.60A/B/C/D1-76[»]
1R4MX-ray3.00I/J/K/L1-76[»]
1R4NX-ray3.60I/J/K/L1-76[»]
1XT9X-ray2.20B1-76[»]
2BKRX-ray1.90B1-76[»]
2KO3NMR-A1-76[»]
2NVUX-ray2.80I/J1-76[»]
3DBHX-ray2.85I/J/K/L1-76[»]
3DBLX-ray2.90I/J/K/L1-76[»]
3DBRX-ray3.05I/J/K/L1-76[»]
3DQVX-ray3.00A/B1-76[»]
3GZNX-ray3.00I/J1-76[»]
4F8CX-ray1.95B/D1-81[»]
4FBJX-ray1.60B1-81[»]
4HCPX-ray2.52B1-76[»]
4P5OX-ray3.11H/K1-76[»]
ProteinModelPortaliQ15843.
SMRiQ15843. Positions 1-76.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110815. 1055 interactions.
DIPiDIP-29266N.
IntActiQ15843. 89 interactions.
MINTiMINT-268324.
STRINGi9606.ENSP00000250495.

PTM databases

PhosphoSiteiQ15843.

Polymorphism and mutation databases

BioMutaiNEDD8.
DMDMi2833270.

Proteomic databases

MaxQBiQ15843.
PaxDbiQ15843.
PeptideAtlasiQ15843.
PRIDEiQ15843.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000250495; ENSP00000250495; ENSG00000129559.
GeneIDi4738.
KEGGihsa:4738.
UCSCiuc001wnn.2. human.

Organism-specific databases

CTDi4738.
GeneCardsiGC14M024686.
HGNCiHGNC:7732. NEDD8.
HPAiCAB004082.
MIMi603171. gene.
neXtProtiNX_Q15843.
PharmGKBiPA31537.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5272.
GeneTreeiENSGT00660000095622.
HOGENOMiHOG000233942.
HOVERGENiHBG000057.
InParanoidiQ15843.
KOiK12158.
OMAiKLAPPRH.
OrthoDBiEOG7JDR1W.
PhylomeDBiQ15843.
TreeFamiTF300072.

Enzyme and pathway databases

ReactomeiREACT_120850. TGF-beta receptor signaling activates SMADs.

Miscellaneous databases

EvolutionaryTraceiQ15843.
GeneWikiiNEDD8.
GenomeRNAii4738.
NextBioi18272.
PMAP-CutDBQ15843.
PROiQ15843.
SOURCEiSearch...

Gene expression databases

BgeeiQ15843.
CleanExiHS_NEDD8.
ExpressionAtlasiQ15843. baseline and differential.
GenevisibleiQ15843. HS.

Family and domain databases

InterProiIPR019956. Ubiquitin.
IPR000626. Ubiquitin-like.
IPR029071. Ubiquitin-rel_dom.
IPR019954. Ubiquitin_CS.
[Graphical view]
PfamiPF00240. ubiquitin. 1 hit.
[Graphical view]
PRINTSiPR00348. UBIQUITIN.
SMARTiSM00213. UBQ. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
PROSITEiPS00299. UBIQUITIN_1. 1 hit.
PS50053. UBIQUITIN_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBUNIT.
    Tissue: Fibrosarcoma.
  2. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
    Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  4. "Conjugation of the ubiquitin-like protein NEDD8 to cullin-2 is linked to von Hippel-Lindau tumor suppressor function."
    Liakopoulos D., Buesgen T., Brychzy A., Jentsch S., Pause A.
    Proc. Natl. Acad. Sci. U.S.A. 96:5510-5515(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 1-21, FUNCTION, SUBUNIT.
  5. "Characterization of NEDD8, a developmentally down-regulated ubiquitin-like protein."
    Kamitani T., Kito K., Nguyen H.P., Yeh E.T.H.
    J. Biol. Chem. 272:28557-28562(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION, CLEAVAGE SITE.
  6. Cited for: CLEAVAGE BY UCHL3.
  7. "Covalent modification of all members of human cullin family proteins by NEDD8."
    Hori T., Osaka F., Chiba T., Miyamoto C., Okabayashi K., Shimbara N., Kato S., Tanaka K.
    Oncogene 18:6829-6834(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBUNIT, TISSUE SPECIFICITY.
  8. "NUB1, a NEDD8-interacting protein, is induced by interferon and down-regulates the NEDD8 expression."
    Kito K., Yeh E.T.H., Kamitani T.
    J. Biol. Chem. 276:20603-20609(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH NUB1.
  9. "The NEDD8 pathway is essential for SCF(beta -TrCP)-mediated ubiquitination and processing of the NF-kappa B precursor p105."
    Amir R.E., Iwai K., Ciechanover A.
    J. Biol. Chem. 277:23253-23259(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  10. "Interaction with Nedd8, a ubiquitin-like protein, enhances the transcriptional activity of the aryl hydrocarbon receptor."
    Antenos M., Casper R.F., Brown T.J.
    J. Biol. Chem. 277:44028-44034(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH AHR.
  11. "NEDP1, a highly conserved cysteine protease that deneddylates cullins."
    Mendoza H.M., Shen L.-N., Botting C., Lewis A., Chen J., Ink B., Hay R.T.
    J. Biol. Chem. 278:25637-25643(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: CLEAVAGE BY SENP8.
  12. "DEN1 is a dual function protease capable of processing the C-terminus of Nedd8 and deconjugating hyper-neddylated CUL1."
    Wu K., Yamoah K., Dolios G., Gan-Erdene T., Tan P., Chen A., Lee C.-G., Wei N., Wilkinson K.D., Wang R., Pan Z.-Q.
    J. Biol. Chem. 278:28882-28891(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: CLEAVAGE BY SENP8.
  13. "Mdm2-mediated NEDD8 conjugation of p53 inhibits its transcriptional activity."
    Xirodimas D.P., Saville M.K., Bourdon J.-C., Hay R.T., Lane D.P.
    Cell 118:83-97(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT.
  14. "Crystal structure of the human ubiquitin-like protein NEDD8 and interactions with ubiquitin pathway enzymes."
    Whitby F.G., Xia G., Pickart C.M., Hill C.P.
    J. Biol. Chem. 273:34983-34991(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
  15. "The structure of the APPBP1-UBA3-NEDD8-ATP complex reveals the basis for selective ubiquitin-like protein activation by an E1."
    Walden H., Podgorski M.S., Huang D.T., Miller D.W., Howard R.J., Minor D.L. Jr., Holton J.M., Schulman B.A.
    Mol. Cell 12:1427-1437(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 1-76 IN COMPLEX WITH UBE1C; APPBP1 AND ATP, MUTAGENESIS OF ALA-72.
  16. "Structure of a complex between Nedd8 and the Ulp/Senp protease family member Den1."
    Reverter D., Wu K., Erdene T.G., Pan Z.-Q., Wilkinson K.D., Lima C.D.
    J. Mol. Biol. 345:141-151(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-76 IN COMPLEX WITH SENP8.

Entry informationi

Entry nameiNEDD8_HUMAN
AccessioniPrimary (citable) accession number: Q15843
Secondary accession number(s): Q3SXN8, Q6LES6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: June 24, 2015
This is version 142 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.