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FLASH GENE
Symbol NEDD8 contributors: mct/npt/shn - updated : 31-01-2023
HGNC name neural precursor cell expressed, developmentally down-regulated 8
HGNC id 7732
DNA
TYPE functioning gene
STRUCTURE 15.52 kb     4 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
Map cen - D14S581 - D14S64 - NEDD8 - D14S264 - D14S1041 - qter
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
4 - 625 8.9 81 - 2005 15567417
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly Homo sapiens
Digestiveintestinesmall intestine  lowly Homo sapiens
 intestinelarge intestinecolon lowly Homo sapiens
 liver   lowly Homo sapiens
Endocrinepancreas   lowly Homo sapiens
Nervousbrain   lowly Homo sapiens
Reproductivefemale systemovary  lowly Homo sapiens
 female systemplacenta  lowly Homo sapiens
Respiratorylung   lowly Homo sapiens
Urinarykidney   lowly Homo sapiens
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumskeletal highly Homo sapiens
cell lineage neural precursor cells
cell lines
fluid/secretion
at STAGE
physiological period embryo, fetal
Text moderately in umbilical cord
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a cullin binding domain associating with NEDD8 (CUBAN domain), poly-ubiquitinated in cells
  • HOMOLOGY
    interspecies ortholog to Nedd8, Rattus norvegicus
    ortholog to Nedd8, Mus musculus
    ortholog to nedd8, Danio rerio
    Homologene
    FAMILY
  • ubiquitin family
  • CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • acting as an ubiquitin-like protein playing an important role in cell cycle control and embryogenesis
  • regulating cell-cycle progression (targeting of katanin for degradation during transition from meiosis to mitosis)
  • involved in protecting a subset of ribosomal proteins from destabilization
  • interplay between NEDD8 and ubiquitin pathways operating in diverse cellular stress conditions
  • NEDD8 modification potentiates parkin E3 ligase activity
  • conserved role for NEDD8 in linking cullin-RING ubiquitin ligases (CRLs) ubiquitin ligase function to the VCP pathway
  • modifies cullin-RING ubiquitin E3 ligases
  • role of NEDD8 in regulating transcription factor stability and function
  • may play an important role in the control of proliferation and differentiation of human placenta throughout pregnancy
  • role of NEDD8 in regulating CASP1 activation following inflammasome activation, presumably via augmenting autoprocessing/cleavage of pro-caspase-1 into its corresponding catalytically active subunits
  • ubiquitin-like protein that activates the largest ubiquitin E3 ligase family, the cullin-RING ligases
  • eukaryotic cell biology depends on cullin-RING E3 ligase (CRL)-catalysed protein ubiquitylation, which is tightly controlled by the modification of cullin with NEDD8
  • highly conserved ubiquitin-like modifier that has recently been identified as a key regulator of cellular redox homeostasis
  • role of NEDD8-dependent ERBB2 neddylation promotes tumor growth in breast cancer
  • CELLULAR PROCESS cell cycle, progression
    protein, ubiquitin dependent proteolysis
    PHYSIOLOGICAL PROCESS development
    text
  • embryogenesis
  • morphogenesis
  • PATHWAY
    metabolism
    signaling
  • NEDD8 pathway has a critical role in mediating the ubiquitination of numerous substrates involved in cell cycle progression, such as regulators of cell cycle and prosurvival signaling pathways
  • a component
  • covalently conjugating to cullin 2 through the complex VHL-elongin B and elongin C
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ubiquitin C-terminal hydrolase, UCH-L3
  • culin 1, CUL1
  • NEDD8 Ultimate Buster-1, NUB1
  • ROC1-CUL1
  • aryl hydrocarbon receptor, AhR
  • negative regulator of ubiquitin-like proteins 1 like, NUB1L
  • ubiquitin-like protein FAT10
  • Ulp/Senp protease family member Den1
  • breast cancer-associated protein 3, BCA3
  • Cullin3, Cul3
  • crucial regulator of RPL11 signalling to TP53
  • NEDD8 is an ancillary player to regulate the stability of HIF1A
  • PRKN and PINK1 are NEDD8 conjugated
  • UBXD7, associate only with the active, NEDD8- or Rub1-modified form of cullins
  • E2F1 is a substrate for NEDD8 post-translational modification (NEDDylation results in decreased E2F1 stability, lower transcriptional activity and slower cell growth)
  • NEDD8 is conjugated to RCAN1 (RCAN1-1S) via three lysine residues, K96, K104, and K107 (neddylation enhances RCAN1 protein stability without affecting its cellular location)
  • plays an important role in the ubiquitination of SCNN1A in alveolar epithelial cells
  • NUB1L directly interacted with NEDD8, but not with ubiquitin, on the key residue Asn-51 of NEDD8 and with VCP on its positively charged VCP binding motif
  • COPS5 acts potentially as a positive regulator of IFN responses by stabilizing IFNR through antagonizing the NEDD8 pathway
  • physically SMURF1 interacts with NEDD8 and UBE2M, forms a NEDD8-thioester intermediate, and then catalyses its own neddylation on multiple lysine residues
  • MDM2 binds to and is involved in conjugating either ubiquitin or NEDD8 to TP53
  • NEDD8 targets ubiquitin ligase SMURF2 for neddylation and promote its degradation
  • KHNYN has a stark preference for NEDD8
  • NEDD8 acts as a nexus that binds disparate cullin elements and the RING-activated ubiquitin-linked UBE2D1
  • HSPA4 chaperone is sensor of the NEDD8 cycle upon DNA damage
  • with ubiquitin function as covalent modifiers of other proteins but are also themselves subject to post-translational modifications including phosphorylation
  • ERBB2 directly interacts with NEDD8 and NAE1, whereas ERBB2 protein expression is decreased by neddylation depletion
  • cell & other
    REGULATION
    activated by ubiquitin-activating (E1) enzyme
    Other modified by CUL1
    cleavage of precursor form by UCHL3 or SENP8 is necessary for function
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in colorectal cancers, the elevated expression of NEDD8, correlates with cancer progression and poor prognosis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    NEDD8 conjugation process could be a potential target for cancer therapy
    ANIMAL & CELL MODELS