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FLASH GENE
Symbol DHODH contributors: mct - updated : 25-10-2016
HGNC name dihydroorotate dehydrogenase
HGNC id 2867
Corresponding disease
POADS post axial acrofacial dysostosis
Location 16q22.2      Physical location : 72.042.642 - 72.058.954
Synonym name
  • dihydroorotate oxidase
  • human complement of yeast URA1
    • Synonym symbol(s) DHOdehase, POADS, URA1
    EC.number 1.3.3.1/ 1.3.5.2
    DNA
    TYPE functioning gene
    STRUCTURE 16.31 kb     9 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked   status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 splicing 2080 - 395 - 2000 10727948
  • a 20 aa signal peptide (2.2 kda)
  • a 375 aa mature peptide (40.7 kda)
    • 7 splicing 1778 - 197 - 2000 10727948
  • a 10 aa signal peptide (1.3 kda)
  • a 187 aa mature peptide (20.7 kda)
  • lacking 2 consective exons in the 3' coding region compared to variant 1, taht producing a frameshift
    		•
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousbrainforebraincerebral cortex highly Homo sapiens
     brainlimbic systemhippocampus highly Homo sapiens
     plexus choroid   highly Homo sapiens
     spinal cord   highly Homo sapiens
    Respiratorylung   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • peptide N-t(DH) represents the N-terminal microdomain of this enzyme, responsible for anchoring it to the inner mitochondrial membrane
    • HOMOLOGY
    Homologene
    FAMILY dihydroorotate dehydrogenase family
    CATEGORY enzyme , transport
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,inner
    intracellular,cytoplasm,organelle,mitochondria,interspace
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    text
  • localized at mitochondria among enzymes of the de novo pyrimidine biosynthesis pathway
    • basic FUNCTION
  • catalyzes the fourth enzymatic step, the ubiquinone-mediated oxidation of dihydroorotate to orotate, in de novo pyrimidine biosynthesis
  • catalyzes the only redox reaction in the pathway for pyrimidine biosynthesis
  • enzyme associated with the mitochondrial electron transport chain and required for de novo pyrimidine synthesis
  • flavin-dependent mitochondrial enzyme that catalyzes fourth reaction of pyrimidine de-novo synthesis
  • pyrimidine biosynthesis pathway is coupled to the mitochondrial RC (respiratory chain) via DHODH
  • mediates the fourth step of de novo pyrimidine biosynthesis and is a proven drug target for inducing immunosuppression in therapy of human disease as well as a rapidly emerging drug target for treatment of malaria
  • role of DHODH as a metabolic regulator of differentiation and point to its inhibition as a strategy for overcoming differentiation blockade in Acute Myeloid Leukemia
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS electron transport
    PATHWAY
    metabolism energetic , purine/pyrimidine
    signaling
    nucleotide biosynthesis, UMP biosynthesis
    a component
    INTERACTION
    DNA
    RNA
    small molecule cofactor,
    binds 1 FAD per subunit
    protein
    cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) POADS
    related resource MITOP database
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    DHODH depletion partially inhibited the RC complex III, decreased the mitochondrial membrane potential, and increased the generation of ROS (reactive oxygen species)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyautoimmunearticular
    therapeutic potential of DHODH inhibitors for treatment of autoimmune diseases
    immunologyinfectious 
    therapeutic potential of DHODH inhibitors for treatment of malaria
    cancer  
    therapeutic potential of DHODH inhibitors for treatment of cancer
    cancerskin 
    inhibition of DHODH may be a unique mechanism for modulating transcriptional elongation, and in combination with a BRAF(V600E) inhibitor, a treatment of melanoma
    cancerdigestivecolon
    DHODH and PCK1 are metabolic therapeutic targets in Colorectal metastatic progression
    ANIMAL & CELL MODELS