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FLASH GENE
Symbol KLHL12 contributors: mct - updated : 02-02-2018
HGNC name kelch-like 12 (Drosophila)
HGNC id 19360
Location 1q32.1      Physical location : 202.860.229 - 202.896.371
Synonym name
  • kelch-like protein C3IP1
  • CUL3-interacting protein 1
  • DKIR homolog
  • Synonym symbol(s) C3IP1, DKIR, FLJ27152
    DNA
    TYPE functioning gene
    STRUCTURE 37.55 kb     12 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    12 - 3364 - 606 - 2016 27716508
    10 - 3081 - 467 - 2016 27716508
    12 - 3384 - 568 - 2016 27716508
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivesalivary gland    
    Endocrinethyroid    
    Reproductivemale systemtestis   
    Respiratorylung    
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose   
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • one BTB/POZ domain
  • six kelch repeat motifs
  • HOMOLOGY
    Homologene
    FAMILY
    CATEGORY regulatory
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    text inner surface of cytoplasmic bridges or ring canals present in egg chambers
    basic FUNCTION
  • may be involved in the regulation of cytoplasm flow from nurse cells to the oocyte during oogenesis
  • negatively regulating the Wnt-beta-catenin pathway by targeting Dishevelled for degradation
  • functions as an adaptor between the D4 receptor and CUL3, and targets the D4 receptor to the E3 ligase complex by a direct and simultaneous interaction with the D4 receptor (DRD4) and CUL3, which gives rise to ubiquitination of the D4 receptor (DRD4)
  • KLHL12 is a novel interaction partner of the DRD4 that functions as an adaptor in a CUL3-based E3 ubiquitin ligase complex to target the receptor for ubiquitination
  • CUL3-KLHL12 catalyses the monoubiquitylation of the COPII-component SEC31 and drives the assembly of large COPII coats
  • ubiquitylation by CUL3-KLHL12 is essential for collagen export, yet less important for the transport of small cargo
  • KLHL12 plays a critical role in facilitating the ER exit and secretion of APOB100-VLDL particles, suggesting that KLHL12 modulation would influence plasma lipid levels
  • CELLULAR PROCESS cell organization/biogenesis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • KLHL12 does also interact with ARRB2 but this has no effect on the ubiquitination or localization of ARRB2 nor on the internalization of the DRD4
  • specifically interacts with the polymorphic repeats of the DRD4 and enhances its ubiquitination, which, however, has no influence on receptor degradation and promotes ubiquitination of the DRD4 on non-lysine residues
  • KLHL12 strongly promotes ubiquitination of the two- and four-repeat variant but has hardly any effect on ubiquitination of the seven-repeat DRD4
  • ARRB1, ARRB2 bind constitutively to the most common DRD4 polymorphic variants and to KLHL12 and all three proteins can interact within a single macromolecular complex
  • interaction between the Kelch domain of KLHL12 and the C-terminal domain of KHSRP contributed to KHSRP ubiquitination
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    ANIMAL & CELL MODELS