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FLASH GENE
Symbol CPS1 contributors: mct - updated : 20-01-2016
HGNC name carbamoyl-phosphate synthetase 1, mitochondrial
HGNC id 2323
Corresponding disease
CPS1D carbamoyl phosphate synthetase I deficiency
Location 2q34      Physical location : 211.342.408 - 211.543.829
Synonym name
  • ammonia mitochondrial
  • CPSase I
  • Synonym symbol(s) CPSASE1, PHN
    EC.number 6.3.4.16
    DNA
    TYPE functioning gene
    STRUCTURE 201.43 kb     38 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked Y status confirmed
    Map cen - D2S116 - D2S2068 - D2S355 - D2S1408 - D2S157 ,D2S371 - CPS1 - ACADL ACADL - MAP2 - ERBB4 - D2S317 ,D2S1749 - D2S254 - D2S334 - D2S128 - D2S143 - qter
    Authors Summar (98),LDB (98)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    39 - 5738 160.5 1506 - 2003 12655559
  • precursor
  • 38 - 5770 160.5 1500 - 2003 12655559
  • precursor
  • 28 - 4794 115.9 1049 in human testis 2010 20800523
  • differs in the 5'UTR and may not be localized to the mitochondrion
  • containing the catalytic and regulatory domains of the human liver CPS1
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine    Homo sapiens
     liver   predominantly Homo sapiens
    Lymphoid/Immunespleen   highly
    Urinarykidney   moderately Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveenterocyte Homo sapiens
    Digestivehepatocyte Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal signal peptide of 38 AAs, required for importing the protein into the mitochondria and is cleaved off by specific proteases after translocation
  • MGS a glutamine amido transferase-like
  • two ATP binding sites
  • a synthetase domain
  • structural domain I, II and III with unknown function, that are likely essentially involved in the preservation of the correct tertiary structure of the CPS1 monomer
  • UFSD, which is in the middle of the 1462-AA multidomain CPS1 protein, plays a key integrating role for creating the CPS1 multidomain architecture leading us to propose here a denomination of "Integrating Domain" for this CPS1 region
  • a binding site for NBAS consists of a pocket that is located between the central beta-sheet and two alpha-helices (liver-specific, intramitochondrial, rate-limiting enzyme in the urea cycle)
  • mono polymer homomer , dimer
    HOMOLOGY
    interspecies ortholog to murine Cps1
    Homologene
    FAMILY carbamoyl phosphate synthetase family
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria,inner
    intracellular,cytoplasm,organelle,mitochondria,matrix
    intracellular,cytoplasm,organelle,membrane
    intracellular,nucleus,nucleolus
    basic FUNCTION
  • playing an important role in removing excess ammonia from the cell
  • mitochondrial matrix enzyme that catalyzes the first step of the urea cycle, synthesis of carbamoylphosphate from bicarbonate, ATP, and ammonia
  • plays a paramount role in liver ureagenesis since it catalyzes the first and rate-limiting step of the urea cycle, the major pathway for nitrogen disposal (
  • liver-specific, intramitochondrial, rate-limiting enzyme in the urea cycle
  • responsible for ammonia removal in the urea cycle, and nitration of CPS1 with attenuated function might be involved in some diseases and drug-induced toxicities associated with mitochondrial dysfunction
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS detoxification
    PATHWAY
    metabolism aminoacid
    signaling
    urea biosynthesis
    a component
    INTERACTION
    DNA
    RNA
    small molecule cofactor,
  • ATP
  • cofactor N-acetylglutamate (NAG)
  • protein
  • interacting with SIRT5
  • interaction with NBAS (unable to hydrolyze glutamine, CPS1 exhibits an increased affinity for ammonia, and has an absolute requirement for NBAS to attain the active conformation)
  • NAGS produces a unique cofactor, NAG, that is essential for the catalytic function of the first and rate-limiting enzyme of ureagenesis, CPS1
  • by binding at the C-terminal domain of CPS1, N-acetyl-L-glutamate (NAG) triggers long-range conformational changes affecting the two distant phosphorylation domains
  • cell & other
    REGULATION
    activated by n-acetylglutamate (allosteric activator)
    Other deacetylated by SIRT5 that upregulates its activity (Nakagawa 2009)
    ASSOCIATED DISORDERS
    corresponding disease(s) CPS1D
    related resource MITOP database
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    silenced or down-regulated in liver tumor tissues compared with the matched noncancerous tissues
    tumoral     --low  
    complete loss in the invasive small-intestinal adenocarcinoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • CPS1 gene hypermethylation of the two CpG dinucleotides is a potential biomarker for hepatocellular carcinoma (
  • may be a useful prognostic biomarker in human and mouse liver injury
  • Therapy target
    ANIMAL & CELL MODELS