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Q15843

- NEDD8_HUMAN

UniProt

Q15843 - NEDD8_HUMAN

Protein

NEDD8

Gene

NEDD8

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
  1. 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

    1. protein binding Source: IntAct
    2. ubiquitin protein ligase binding Source: UniProtKB

    GO - Biological processi

    1. anatomical structure morphogenesis Source: ProtInc
    2. cellular protein modification process Source: ProtInc
    3. protein localization Source: Ensembl
    4. protein neddylation Source: MGI
    5. proteolysis Source: ProtInc
    6. regulation of transcription from RNA polymerase II promoter Source: Ensembl
    7. response to organic cyclic compound Source: Ensembl
    8. transforming growth factor beta receptor signaling pathway Source: Reactome
    9. ubiquitin-dependent protein catabolic process Source: ProtInc

    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: Chromosome 14

    Organism-specific databases

    HGNCiHGNC:7732. NEDD8.

    Subcellular locationi

    Nucleus 1 Publication
    Note: Mainly nuclear.

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. extracellular vesicular exosome Source: UniProt
    3. nucleus Source: ProtInc

    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.

    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

    ArrayExpressiQ15843.
    BgeeiQ15843.
    CleanExiHS_NEDD8.
    GenevestigatoriQ15843.

    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
    CUL1Q136165EBI-716247,EBI-359390
    RPL11P629134EBI-716247,EBI-354380
    RPL7P181242EBI-716247,EBI-350806
    RPS20P608662EBI-716247,EBI-353105
    RPS3P233962EBI-716247,EBI-351193
    RPS7P620812EBI-716247,EBI-354360
    UBE2MP610812EBI-716247,EBI-1041660

    Protein-protein interaction databases

    BioGridi110815. 752 interactions.
    DIPiDIP-29266N.
    IntActiQ15843. 88 interactions.
    MINTiMINT-268324.
    STRINGi9606.ENSP00000250495.

    Structurei

    Secondary structure

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

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    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[»]
    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.
    HOGENOMiHOG000233942.
    HOVERGENiHBG000057.
    InParanoidiQ15843.
    KOiK12158.
    OMAiHPAINSR.
    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

    MLIKVKTLTG KEIEIDIEPT DKVERIKERV EEKEGIPPQQ QRLIYSGKQM   50
    NDEKTAADYK ILGGSVLHLV LALRGGGGLR Q 81
    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. 1 PublicationCurated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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.

    Polymorphism databases

    DMDMi2833270.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS9621.1.
    RefSeqi NP_006147.1. NM_006156.2.
    UniGenei Hs.531064.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    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 [» ]
    3GZN X-ray 3.00 I/J 1-76 [» ]
    4F8C X-ray 1.95 B/D 1-81 [» ]
    4FBJ X-ray 1.60 B 1-81 [» ]
    4HCP X-ray 2.52 B 1-76 [» ]
    ProteinModelPortali Q15843.
    SMRi Q15843. Positions 1-76.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110815. 752 interactions.
    DIPi DIP-29266N.
    IntActi Q15843. 88 interactions.
    MINTi MINT-268324.
    STRINGi 9606.ENSP00000250495.

    PTM databases

    PhosphoSitei Q15843.

    Polymorphism databases

    DMDMi 2833270.

    Proteomic databases

    MaxQBi Q15843.
    PaxDbi Q15843.
    PeptideAtlasi Q15843.
    PRIDEi Q15843.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000250495 ; ENSP00000250495 ; ENSG00000129559 .
    GeneIDi 4738.
    KEGGi hsa:4738.
    UCSCi uc001wnn.2. human.

    Organism-specific databases

    CTDi 4738.
    GeneCardsi GC14M024686.
    HGNCi HGNC:7732. NEDD8.
    HPAi CAB004082.
    MIMi 603171. gene.
    neXtProti NX_Q15843.
    PharmGKBi PA31537.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5272.
    HOGENOMi HOG000233942.
    HOVERGENi HBG000057.
    InParanoidi Q15843.
    KOi K12158.
    OMAi HPAINSR.
    OrthoDBi EOG7JDR1W.
    PhylomeDBi Q15843.
    TreeFami TF300072.

    Enzyme and pathway databases

    Reactomei REACT_120850. TGF-beta receptor signaling activates SMADs.

    Miscellaneous databases

    EvolutionaryTracei Q15843.
    GeneWikii NEDD8.
    GenomeRNAii 4738.
    NextBioi 18272.
    PMAP-CutDB Q15843.
    PROi Q15843.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q15843.
    Bgeei Q15843.
    CleanExi HS_NEDD8.
    Genevestigatori Q15843.

    Family and domain databases

    InterProi IPR019956. Ubiquitin.
    IPR000626. Ubiquitin-like.
    IPR029071. Ubiquitin-rel_dom.
    IPR019954. Ubiquitin_CS.
    [Graphical view ]
    Pfami PF00240. ubiquitin. 1 hit.
    [Graphical view ]
    PRINTSi PR00348. UBIQUITIN.
    SMARTi SM00213. UBQ. 1 hit.
    [Graphical view ]
    SUPFAMi SSF54236. SSF54236. 1 hit.
    PROSITEi PS00299. UBIQUITIN_1. 1 hit.
    PS50053. UBIQUITIN_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 134 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