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Q15843 (NEDD8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
NEDD8
Alternative name(s):
Neddylin
Neural precursor cell expressed developmentally down-regulated protein 8
Short name=NEDD-8
Ubiquitin-like protein Nedd8
Gene names
Name:NEDD8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length81 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4 Ref.7 Ref.9

Subunit structure

Directly interacts with NUB1 and AHR. Covalently attached to cullins and p53. Ref.1 Ref.4 Ref.7 Ref.8 Ref.10 Ref.13

Subcellular location

Nucleus. Note: Mainly nuclear. Ref.5

Tissue specificity

Highly expressed in heart, skeletal muscle, spleen, thymus, prostate, testis, ovary, colon and leukocytes. Ref.5 Ref.7

Post-translational modification

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

Sequence similarities

Belongs to the ubiquitin family.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 7676NEDD8
PRO_0000042767
Propeptide77 – 815
PRO_0000042768

Regions

Region70 – 723Interaction with UBE1C

Sites

Site81Interaction with UBE1C
Site441Interaction with UBE1C

Amino acid modifications

Modified residue481N6-acetyllysine By similarity
Cross-link76Glycyl lysine isopeptide (Gly-Lys) (interchain with K-? in acceptor proteins)

Experimental info

Mutagenesis721A → R: Prevents adenylation by UBE1C. Ref.15
Sequence conflict151I → V in CAG28590. Ref.2

Secondary structure

................. 81
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q15843 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: DC2FE102BE4725D2

FASTA819,072
        10         20         30         40         50         60 
MLIKVKTLTG KEIEIDIEPT DKVERIKERV EEKEGIPPQQ QRLIYSGKQM NDEKTAADYK 

        70         80 
ILGGSVLHLV LALRGGGGLR Q 

« Hide

References

« Hide 'large scale' references
[1]"A new NEDD8-ligating system for cullin-4A."
Osaka F., Kawasaki H., Aida N., Saeki M., Chiba T., Kawashima S., Tanaka K., Kato S.
Genes Dev. 12:2263-2268(1998) [PubMed] [Europe PMC] [Abstract]
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]"Cleavage of the C-terminus of NEDD8 by UCH-L3."
Wada H., Kito K., Caskey L.S., Yeh E.T.H., Kamitani T.
Biochem. Biophys. Res. Commun. 251:688-692(1998) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_006147.1. NM_006156.2.
UniGeneHs.531064.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalQ15843.
SMRQ15843. Positions 1-76.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110815. 389 interactions.
DIPDIP-29266N.
IntActQ15843. 88 interactions.
MINTMINT-268324.
STRING9606.ENSP00000250495.

PTM databases

PhosphoSiteQ15843.

Polymorphism databases

DMDM2833270.

Proteomic databases

PaxDbQ15843.
PeptideAtlasQ15843.
PRIDEQ15843.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000250495; ENSP00000250495; ENSG00000129559.
GeneID4738.
KEGGhsa:4738.
UCSCuc001wnn.2. human.

Organism-specific databases

CTD4738.
GeneCardsGC14M024686.
HGNCHGNC:7732. NEDD8.
HPACAB004082.
MIM603171. gene.
neXtProtNX_Q15843.
PharmGKBPA31537.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5272.
HOGENOMHOG000233942.
HOVERGENHBG000057.
InParanoidQ15843.
KOK12158.
OMAEPTDKVD.
OrthoDBEOG7JDR1W.
PhylomeDBQ15843.
TreeFamTF300072.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.

Gene expression databases

ArrayExpressQ15843.
BgeeQ15843.
CleanExHS_NEDD8.
GenevestigatorQ15843.

Family and domain databases

InterProIPR019956. Ubiquitin.
IPR000626. Ubiquitin-like.
IPR019954. Ubiquitin_CS.
[Graphical view]
PfamPF00240. ubiquitin. 1 hit.
[Graphical view]
PRINTSPR00348. UBIQUITIN.
SMARTSM00213. UBQ. 1 hit.
[Graphical view]
PROSITEPS00299. UBIQUITIN_1. 1 hit.
PS50053. UBIQUITIN_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ15843.
GeneWikiNEDD8.
GenomeRNAi4738.
NextBio18272.
PMAP-CutDBQ15843.
PROQ15843.
SOURCESearch...

Entry information

Entry nameNEDD8_HUMAN
AccessionPrimary (citable) accession number: Q15843
Secondary accession number(s): Q3SXN8, Q6LES6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM