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FLASH GENE
Symbol CAD contributors: mct - updated : 15-01-2019
HGNC name carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase
HGNC id 1424
Corresponding disease
EIEE50 epileptic encephalopathy, early infantile, 50
Location 2p23.3      Physical location : 27.440.257 - 27.466.653
Synonym name
  • CAD trifunctional protein of pyrimidine biosynthesis
  • multifunctional protein CAD
  • Synonym symbol(s) GATD4, EIEE50
    EC.number 2.1.3.2/ 3.5.2.3/ 6.3.5.5
    DNA
    TYPE functioning gene
    STRUCTURE 26.40 kb     44 Exon(s)    1 Copie(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    DPYSL5 2p23-p21 dihydropyrimidinase-like 5 MAPRE3 2p23.3-p23.1 microtubule-associated protein, RP/EB family, member 3 FLJ20254 2p23.3 hypothetical protein FLJ20254 FLJ21839 2p23.3 hypothetical protein FLJ21839 EMILIN1 2p23.3-p23.2 elastin microfibril interfacer 1 KHK 2p23.3-p23.2 ketohexokinase (fructokinase) CGREF1 2p23.3 cell growth regulator with EF hand domain 1 ABHD1 2p23.3 abhydrolase domain containing 1 PREB 2p23 prolactin regulatory element binding MGC44505 2p23.3 hypothetical protein MGC44505 LOC391360 2 similar to class II basic helix-loop-helix protein TCF23 SLC5A6 2p23 solute carrier family 5 (sodium-dependent vitamin transporter), member 6 APR-3 2p23.3 solute carrier family 5 (sodium-dependent vitamin transporter), member 6 CAD 2p22-p21 carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase SLC30A3 2p23.3 solute carrier family 30 (zinc transporter), member 3 FLJ40417 2p23.3 gamma cysteine string protein RNF30 2p23.3 ring finger protein 30 UCN 2p23-p21 urocortin MPV17 2p23 MpV17 transgene, murine homolog, glomerulosclerosis GTF3C2 2p23.3 general transcription factor IIIC, polypeptide 2, beta 110kDa EIF2B4 2p23.3 eukaryotic translation initiation factor 2B, subunit 4 delta, 67kDa SNX17 2p23-p22 sorting nexin 17 ZNF513 2p23.3 zinc finger protein 513 PPM1G 2p33.3 protein phosphatase 1G (formerly 2C), magnesium-dependent, gamma isoform NRBP 2p23 nuclear receptor binding protein KCP3 SLB 2p23.3 selective LIM binding factor, rat homolog FRCP1 GCKR 2p23.3-p23.2 glucokinase (hexokinase 4) regulatory protein DKFZp434G118 ZNF512 2p23 zinc finger protein 512
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    44 - 7108 243 2225 - 2017 28552578
    43 - 6942 - 2162 - 2017 28552578
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node   highly
    Visualeye   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    cell lineage
    cell lines cell lines deficient in MLH1 or MSH6
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a dihydroorotase (DHO) and aspartate transcarbamoylase (ATC) domains
  • conjugated PhosphoP
    mono polymer homomer , hexamer
    HOMOLOGY
    interspecies homolog to C.elegans D2085.1
    Homologene
    FAMILY
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text nuclear import of CAD appears to promote optimal cell growth
    basic FUNCTION
  • catalyzing the first steps of the pyrimidine de novo biosynthesis among them, Cpsase is the rate-limiting step in this pathway
  • multifunctional protein that initiates and regulates de novo pyrimidine biosynthesis
  • aspartate transcarbamylase (atcase)
  • dihydroorotase (dhoase)
  • glutamine amidotransferase (gatase)
  • gatase and cpsase form together the glutamine-dependent cpase activity (gd-cpasase)
  • required for de novo pyrimidine nucleotide synthesis
  • multifunctional polypeptide that catalyzes the first three reactions of de novo pyrimidine biosynthesis: glutamine-dependent carbamyl phosphate synthetase, aspartate transcarbamylase and dihydroorotase (DHO)
  • CAD enzymatic activity decreased in the cells depleted of amino acids and serum, in which the mTOR activity is suppressed
  • up-regulation of CAD is essential for normal and tumour cell proliferation
  • CAD is a downstream effector of RHEB, suggesting a possible role of RHEB in regulating de novo pyrimidine nucleotide synthesis
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism purine/pyrimidine
    signaling
    pyrimidine nucleotide metabolism
    a component
    INTERACTION
    DNA
    RNA
    small molecule cofactor,
    zinc Zn2+ for dhoase activity
    protein
  • NOD2-interacting protein (negative regulator of NOD2)
  • MLST8 bridges between CAD and MTOR, and plays a role in the signaling mechanism where CAD is regulated in the MTOR pathway through the association with MLST8
  • RHEB proteins binds to CAD protein (RHEB and RHEBL1 binds CAD in a GTP- and effector domain-dependent manner)
  • cell & other
    REGULATION
    activated by EGF-dependent and phosphorylation
    PRPP for Cpsase activity
    inhibited by UMP for Cpsase activity
    repressed by 12-O-tetradecanoylphorbol-13-acetate and trans-retinoic acid and dibutyrol cyclic AMP
    by HIF-1alpha, which represents a functional link between hypoxia and cell-cycle arrest
    Other regulated by mitogen-activated protein kinase (MAPK) cascade
    regulated by allostery
    ASSOCIATED DISORDERS
    corresponding disease(s) EIEE50
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in the intestinal epithelium of patients with Crohn disease compared with controls
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • potential predictive marker of prostate cancer relapse
  • Therapy target
    SystemTypeDisorderPubmed
    immunologyinflammatory 
    potential therapeutic target for Crohn disease
    ANIMAL & CELL MODELS