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FLASH GENE
Symbol DCUN1D1 contributors: mct/npt/pgu - updated : 10-06-2020
HGNC name DCN1, defective in cullin neddylation 1, domain containing 1 (S. cerevisiae)
HGNC id 18184
Location 3q26.33      Physical location : 182.660.558 - 182.698.326
Synonym name
  • defective in cullin neddylation protein 1-like protein 1
  • DCN1-like protein 1
  • squamous cell carcinoma-related oncogene
  • RP42 homolog
  • Synonym symbol(s) RP42, SCRO, DCUN1L1, Tes3, SCCRO, DCNL1, DCN1
    DNA
    TYPE functioning gene
    STRUCTURE 48.29 kb     7 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    7 - 7849 30.1 259 - 2008 18826954
    7 - 6895 - 244 - 2008 18826954
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineadrenal gland   highly
    Lymphoid/Immunelymph node   highly
    Reproductivemale systemtestis  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal ubiquitin-associated (UBA) domain, that preferentially binds to polyubiquitin chains in a linkage-independent manner, and functions as a negative regulator of DCUN1D1 function
  • HOMOLOGY
    Homologene
    FAMILY
    CATEGORY protooncogene
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • component of the HH signaling pathway involved in the malignant transformation of squamous cell lineage
  • important component of the neddylation E3 complex that functions to recruit charged E2 and is involved in the release of inhibitory effects of CAND1 on cullin-RING ligase E3 complex assembly and activity
  • induces extracellular matrix invasion by activating matrix metalloproteinase 2 in squamous cell carcinoma
  • involved in protein degradation
  • possible role in the pathogenesis of gliomas and other human cancers
  • has broader, pleiotropic effects that are essential for cullin neddylation
  • has an essential role in neddylation, involving nuclear localization of neddylation components and recruitment and proper positioning of UBC12
  • DCUN1D1 expression may play a role in tumor progression and development of brain metastasis in patients with Non-small cell lung carcinoma (NSCLC)
  • DCUN1D1 functions as a substrate sensor and activator of CUL2-RING ligase
  • oncogenic activity of DCUN1D1 requires its potentiating neddylation domain, which regulates its E3 activity for neddylation
  • specific role of the DCUN1D1-UBE2M interaction for cellular neddylation of cullin 3
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    HH signaling pathway
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • regulates GLI1--a key regulator of the hedgehog (HH) pathway
  • binds to the components of the neddylation pathway (Cullin-RBX1, UBE2M, and CAND1)
  • molecular suppression of DCUN1D1 attenuates CUL2 neddylation
  • DCUN1D1 via its DAD patch binds to CUL2 but is also able to bind VHL independent of CUL2 and the DAD patch
  • expression of SQSTM1 inhibits the interaction of DCUN1D1 with CUL2 and attenuates the neddylation of CUL2, and thus downregulates the VHL E3 ligase complex activity (PMUID: 26743088)
  • the effects of DCUN1D1 on spermatogenesis likely involve its regulation of cullin-RING-ligase (CRL)-type ubiquitin E3 activity during spermiogenesis through its role in promoting CUL3 neddylation
  • interactions of DCUN1D1 with UBE2M
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   amplification   gain of function
    activated by amplification in squamous cell carcinomas
    tumoral     --over  
    associated with invasive progression and poor outcomes in non-small cell lung cancer
    Susceptibility to frontotemporal lobar degeneration (FTLD)
    Variant & Polymorphism SNP
  • GG genotype of the DCUN1D1 rs4859147 SNP represents a risk factor for the development of FTLD, increasing the risk of about fourfold
  • Candidate gene
    Marker potential marker for metastatic progression in affected cancers
    Therapy target
    ANIMAL & CELL MODELS
  • infertility in Dcun1d1-/- mice is secondary to primary defects in spermatogenesis