Reviewed, UniProtKB/Swiss-Prot Q15843 (NEDD8_HUMAN)

Names and origin

Protein names

Recommended name:
    NEDD8
Alternative name(s):
    Ubiquitin-like protein Nedd8
    Neddylin
    Neural precursor cell expressed developmentally down-regulated protein 8
      Short name=NEDD-8

Gene names

Name:

NEDD8

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	81 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.4 Ref.7 Ref.1 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.7 Ref.5
Post-translational modification	Cleavage of precursor form by UCHL3 or SENP8 is necessary for function.
Sequence similarities	Belongs to the ubiquitin family.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Nucleus
PTM	Acetylation Isopeptide bond
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	anatomical structure morphogenesis Ref.1 Traceable author statement. Source: ProtInc protein neddylation Inferred from direct assay. Source: MGI ubiquitin-dependent protein catabolic process Ref.5 Traceable author statement. Source: ProtInc
Cellular component	nucleus Ref.5 Traceable author statement. Source: ProtInc
Molecular function	protein binding Ref.18 Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CDK2	P24941	1	EBI-716247,EBI-375096
FBXO4	Q9UKT5	1	EBI-716247,EBI-960409
MAGED1	Q9Y5V3	1	EBI-716247,EBI-716006
SENP8	Q96LD8	1	EBI-716247,EBI-1041210
TFE3	P19532	1	EBI-716247,EBI-1048957
UBE2M	P61081	1	EBI-716247,EBI-1041660
VHL	P40337	1	EBI-716247,EBI-301246

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 76

76

NEDD8

PRO_0000042767

Propeptide

77 – 81

5

PRO_0000042768

Regions

Region

70 – 72

3

Interaction with UBE1C

Sites

Site

8

1

Interaction with UBE1C

Site

44

1

Interaction with UBE1C

Amino acid modifications

Modified residue

48

1

N6-acetyllysine Ref.15

Cross-link

76

Glycyl lysine isopeptide (Gly-Lys) (interchain with K-? in acceptor proteins)

Experimental info

Mutagenesis

72

1

A → R: Prevents adenylation by UBE1C. Ref.17

Sequence conflict

15

1

I → V in CAG28590. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

81

Helix Strand Turn

Details...

Beta strand

2 – 6

5

Beta strand

12 – 16

5

Helix

23 – 34

12

Helix

38 – 40

3

Beta strand

41 – 45

5

Helix

56 – 59

4

Beta strand

66 – 71

6

Sequences

	Sequence		Length	Mass (Da)
	Q15843-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: DC2FE102BE4725D2	FASTA	81	9,072
	10 20 30 40 50 60 MLIKVKTLTG KEIEIDIEPT DKVERIKERV EEKEGIPPQQ QRLIYSGKQM NDEKTAADYK 70 80 ILGGSVLHLV LALRGGGGLR Q

References

	« Hide 'large scale' referencesShow '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: 9694792] [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: 15489334] [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: 10318914] [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: 9353319] [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: 9790970] [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: 10597293] [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: 11259415] [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: 11953428] [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: 12215427] [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: 12730221] [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: 12759363] [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: 15242646] [Abstract] Cited for: SUBUNIT.
[14]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[15]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-48, MASS SPECTROMETRY.
[16]	"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: 9857030] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS).
[17]	"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: 14690597] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 1-76 IN COMPLEX WITH UBE1C; APPBP1 AND ATP, MUTAGENESIS OF ALA-72.
[18]	"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: 15567417] [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.

IPI

IPI00020008.

RefSeq

NP_006147.1.

UniGene

Hs.531064

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1NDD	X-ray	1.60	A/B/C/D	1-76	[»]
1R4M	X-ray	3.00	I/J/K/L	1-76	[»]
1R4N	X-ray	3.60	I/J/K/L	1-76	[»]
1XT9	X-ray	2.20	B	1-76	[»]
2BKR	X-ray	1.90	B	1-76	[»]
2KO3	NMR	-	A	1-76	[»]
2NVU	X-ray	2.80	I/J	1-76	[»]
3DBH	X-ray	2.85	I/J/K/L	1-76	[»]
3DBL	X-ray	2.90	I/J/K/L	1-76	[»]
3DBR	X-ray	3.05	I/J/K/L	1-76	[»]
3DQV	X-ray	3.00	A/B	1-76	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29266N.

IntAct

Q15843. 17 interactions.

STRING

Q15843.

PTM databases

PhosphoSite

Q15843.

Proteomic databases

PeptideAtlas

Q15843.

PRIDE

Q15843.

Genome annotation databases

Ensembl

ENST00000250495; ENSP00000250495; ENSG00000129559; Homo sapiens. [Genome view]

GeneID

4738.

KEGG

hsa:4738.

UCSC

uc001wnn.2. human.

Organism-specific databases

CTD

4738.

GeneCards

GC14M023755.

H-InvDB

HIX0026702.

HGNC

HGNC:7732. NEDD8.

HPA

CAB004082.

MIM

603171. gene.

PharmGKB

PA31537.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG21659.

HOGENOM

HBG713462.

HOVERGEN

Q15843.

InParanoid

Q15843.

OMA

DYKVQGG.

OrthoDB

EOG9XSP86.

PhylomeDB

Q15843.

Gene expression databases

ArrayExpress

Q15843.

Bgee

Q15843.

CleanEx

HS_NEDD8.

Genevestigator

Q15843.

GermOnline

ENSG00000129559. Homo sapiens.

Family and domain databases

InterPro

IPR000626. Ubiquitin.
IPR019954. Ubiquitin_CS.
IPR019956. Ubiquitin_subgroup.
IPR019955. Ubiquitin_supergroup.
[Graphical view]

Pfam

PF00240. ubiquitin. 1 hit.
[Graphical view]

PRINTS

PR00348. UBIQUITIN.

SMART

SM00213. UBQ. 1 hit.
[Graphical view]

PROSITE

PS00299. UBIQUITIN_1. 1 hit.
PS50053. UBIQUITIN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

18272.

PMAP-CutDB

Q15843.

SOURCE

Search...

Entry information

Entry name

NEDD8_HUMAN

Accession

Primary (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:	January 19, 2010
This is version 91 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.