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FLASH GENE
Symbol CUL1 contributors: mct/pgu - updated : 20-02-2018
HGNC name cullin 1
HGNC id 2551
Location 7q36.1      Physical location : 148.395.932 - 148.498.201
Synonym symbol(s) LIN-19, MGC149835, MGC149834, CUL-1
DNA
TYPE functioning gene
STRUCTURE 102.27 kb     22 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Physical map
LOC392145 7 similar to Mtr3 (mRNA transport regulator 3)-homolog; Mtr3 (mRNA transport regulator 3)-homolog (yeast) LOC392146 7 similar to 60S ribosomal protein L32 C7orf33 7q36.1 chromosome 7 open reading frame 33 LOC392147 7 similar to Huntingtin interacting protein K CUL1 7q35-q36 cullin 1 EZH2 7q35 enhancer of zeste homolog 2 (Drosophila) RNY5 7q36 RNA, Y5 small cytoplasmic (associated with Ro protein) ERP70 7q35 protein disulfide isomerase related protein (calcium-binding protein, intestinal-related) DKFZp762I137 7q36.1 hypothetical protein DKFZp762I137 LOC155054 7q36.1 hypothetical protein LOC155054 ZNF398 7q36.1 zinc finger protein 398 ZNF282 7q35-q36 zinc finger protein 282 ZNF212 7q36.1 zinc finger protein 212 LOC389594 7 similar to KIAA1285 protein NPM1P12 7q35 nucleophosmin 1 (nucleolar phosphoprotein B23, numatrin) pseudogene 12 KIAA1285 7q36.1 nucleophosmin 1 (nucleolar phosphoprotein B23, numatrin) pseudogene 12 FLJ31413 7q36.1 hypothetical protein FLJ31413 LOC392148 7 similar to KIAA1285 protein FLJ12700 7q36.1 hypothetical protein FLJ12700 KIAA1862 7q36 KIAA1862 protein EZI 7q36.1 likely ortholog of mouse zinc finger protein EZI FLJ36112 7q36.1 hypothetical protein FLJ36112 C7orf32 7q36.1 chromosome 7 open reading frame 32 LOC389595 7 hypothetical gene supported by AK127966 MGC3036 7q31-q35 hypothetical protein MGC3036 C7orf29 7q35 chromosome 7 open reading frame 29 RARRES2 7q35 retinoic acid receptor responder (tazarotene induced) 2
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
22 - 3226 - 776 - 2009 19679553
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestiveliver    
Endocrinepancreas    
Nervousbrain    
 spinal cord    
Reproductivemale systemprostate   
Respiratorylung    
Urinarykidney    
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Muscularstriatumcardiac  
Muscularstriatumskeletal  
Nervouscentral   
cells
SystemCellPubmedSpeciesStageRna symbol
 digestive
cell lineage
cell lines osteosarcoma, acute lymphoblastic leukemia, b-lymphoblastoid and cervical epitheloid carcinoma
fluid/secretion
at STAGE
cell cycle     cell cycle, checkpoint, G1S
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a globular segment binding RBX1
  • a stalk bound to SKP1-F-box protein
  • a conserved C terminal sequence required for nuclear accumulation
  • conjugated Other
    mono polymer heteromer , dimer
    HOMOLOGY
    interspecies homolog to C.elegans CUL 1
    ortholog to murine Cul1
    ortholog to rattus Cul1_predicted
    Homologene
    FAMILY
  • cullin family
  • CATEGORY chaperone/stress , regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • acting as a negative regulator of the cell cycle
  • targeting protein for ubiquitin dependent proteolysis
  • may function as a tumor suppressor by regulating PLK4 protein levels and thereby restraining excessive daughter centriole formation at maternal centrioles
  • matrix degrading enzyme known to be involved in the remodelling of extracellular matrix proteins
  • play a key role in tumour progression and its presence is associated with poor clinical outcome for several different types of tumours
  • scaffold protein in cullin-based ubiquitin ligases, playing an important role in early embryonic development
  • promotes likely trophoblast cell invasion and dysregulation of CUL1 expression may be associated with preeclampsia
  • is a scaffold protein of the ubiquitin E3 ligase SKP1/CUL1/RBX1/F-box protein complex, which ubiquitinates a broad range of proteins involved in cell-cycle progression, signal transduction, and transcription
  • is a scaffold protein of the ubiquitin E3 ligase SKP1/CUL1/RBX1/F-box protein complex, which ubiquitinates a broad range of proteins involved in cell-cycle progression, signal transduction, and transcription
  • unneddylated CUL1 is another central player involved in maintenance of the adaptor module pool through the formation of CUL1-SKP1-F-box complexes and promotion of rapid SCF (SKP1-CUL1-F-box protein) assembly
  • CELLULAR PROCESS cell cycle, division
    cell cycle, checkpoint
    cell life, proliferation/growth
    cell life, cell death/apoptosis
    protein, ubiquitin dependent proteolysis
    cell migration & motility
    PHYSIOLOGICAL PROCESS
    text G1/S transition
    PATHWAY
    metabolism
    signaling
    a component
  • constituent of a core ubiquitin-ligase SCF (SKP1, CUL1, SKP2), RRX1 with CIP1/WAF1, CDC34 and cyclin D(CCND)
  • hyper-neddylated
  • complex between GLMN, RBX1, and a fragment of CUL1
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • targeting G1 cell cycle regulators (NAF1, CDC34, CCND) for ubiquitin-dependent proteolysis required with RBX1 for nuclear localization of NEDD8
  • EIF3E and the COP9 signalosome play opposing roles in regulation of cullin neddylation
  • binds to the components of the neddylation pathway (DCUN1D1, UBE2M, and CAND1)
  • binding CAND1
  • interacting with PLK4 (is critical for the degradation of active PLK4 following deregulation of cyclin E/cyclin-dependent kinase 2 activity, as is frequently observed in human cancer cells, as well as for baseline PLK4 protein stability)
  • critical for the ubiquitin-dependent suppression of the KDM4A-dependent faster S phase progression
  • DRG2 was a substrate of a SKP1-CUL1-F-box E3 ligase complex and inhibition the function of Cullin1 prevented the degradation of DRG2 during apoptosis
  • SF3B3 overexpression reduces the binding of adaptor protein SKP1 and substrate receptor SKP2 to CUL1, whereas it has no effect on CAND1 binding to CUL1
  • CUL1 promoted MTOR activity and cap-dependent translation by enhancing the ubiquitination and degradation of DEPTOR
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    significantly associated with high-grade tumours and poor prognosis
    tumoral     --over  
    in renal cell carcinoma (RCC)
    tumoral     --over  
    in melanoma, enhancing melanoma cell proliferation by promoting G1-S phase transition
    tumoral     --over  
    positively associated with lymph node metastasis and tumor diameter
    tumoral     --over  
    significantly increased in human glioma, and it may be involved in proliferation, migration and invasion of glioma cells
    Susceptibility
  • may affect the susceptibility of rheumatoid arthritis (RA) via altering lymphocyte signal transduction
  • Variant & Polymorphism other
  • possible role of CUL1 variation(s) in RA and its response to methotrexate
  • Candidate gene
    Marker
  • its expression may therefore be crucial for the prediction of disease outcome in breast cancer patients
  • CUL1 may be an important prognosis marker for human hepatocellular carcinoma (HCC)
  • may serve as promising prognostic markers in colorectal cancer (CRC) patients
  • Therapy target
    SystemTypeDisorderPubmed
    cancerurinary 
    CUL1 may constitute a potential therapeutic target in enal cell carcinoma (RCC)
    ANIMAL & CELL MODELS
  • dysregulation of cyclin E and early embryonic lethality in CUL1-/-
  • cul1-/- sequestrate and inactivate Skp1 leading to genetic instability and neoplastic transformation