Carbamoyl-phosphate synthase [ammonia], mitochondrial · UniProt P31327
CPS1 is a mitochondrial matrix enzyme that catalyzes the first, committed step of the urea cycle, phosphorylating bicarbonate and condensing it with ammonia to form carbamoyl phosphate in a reaction strictly dependent on the allosteric activator N-acetyl-L-glutamate (NAG) (PMID:23649895, PMID:25410056). Recombinant human enzyme reconstitution established its multidomain architecture and confirmed that NAG—and its therapeutic analogue N-carbamoyl-L-glutamate (NCG)—together with MgATP both activate and stabilize the enzyme against proteolytic and thermal inactivation (PMID:23649895, PMID:28007335). Structure-function analysis of clinical mutations defines how disease arises: mutations in the central 'Integrating Domain' (the former unknown-function subdomain) compromise interdomain contacts, solubility, and folding, while residues such as V1013 near the carbamate tunnel abolish catalysis and NAG-site mutations alter activator affinity, rationalizing why some patients respond to NCG and others do not (PMID:20578160, PMID:24813853, PMID:25410056, PMID:28007335). Enzyme activity is tuned by competing post-translational modifications: O-GlcNAcylation on specific threonines acts as a nutrient-sensing switch that enhances catalytic efficiency for ammonia and ureagenesis (PMID:36064721, PMID:35285892), whereas K1168 acetylation impairs ATP binding and lowers activity (PMID:41720236); under acute liver injury, GSDME-driven loss of ISG15 leads to deISGylation of CPS1 and its K48-ubiquitin-mediated degradation, causing ammonia-clearance failure (PMID:38417117). Beyond detoxification, CPS1 supplies carbamoyl phosphate for an unconventional ammonia-to-pyrimidine biosynthetic route in KRAS/LKB1-mutant lung cancer, where its loss depletes pyrimidines, stalls replication, and triggers DNA damage (PMID:28538732), and a CPS1-selective allosteric inhibitor that blocks ATP hydrolysis suppresses both urea synthesis and pyrimidine production (PMID:32017919). CPS1 expression is constrained by multiple transcriptional and epigenetic controls—promoter CpG methylation silences it in hepatocellular carcinoma (PMID:21281797), C/EBPα/β drive clock-dependent induction (PMID:26075008), and the histone demethylase JMJD1C represses it via reduced H3K36me3 (PMID:38650379). CPS1 additionally exerts non-enzymatic roles, including induction of M2 monocyte polarization that protects against liver injury after its release into blood (PMID:30979808), and metabolic-signaling roles spanning fumarate-driven EMT in lung cancer metastasis (PMID:41356199) and glucagon-induced hepatic gluconeogenesis through CaMKII/FOXO1 (PMID:39193349).
Establishing the chromosomal locus of CPS1 provided the genetic anchor needed to link the gene to inherited urea cycle disorders.
Evidence FISH physical mapping and CEPH family linkage analysis
It was unknown why CPS1 is lost in liver cancer; demonstrating promoter/intronic CpG hypermethylation and 5-azacytidine rescue showed that epigenetic silencing, not mutation, downregulates CPS1 in hepatocellular carcinoma.
Evidence Bisulfite sequencing, demethylation rescue, and promoter-reporter mutagenesis in HCC cells
To explain how patient mutations cause enzyme failure, recombinant CPS1 reconstitution mapped nine clinical mutations onto solubility, stability, and NAG-affinity defects, validating the C-terminal NAG allosteric site structurally.
Evidence Baculovirus/insect-cell expression, kinetics, and structure-function analysis using the C-terminal domain crystal structure
Demonstrating that recombinant human CPS1 reproduces native kinetics, and that NAG/NCG plus MgATP protect it from inactivation, established a faithful in vitro system and revealed an activator-linked stabilizing/chaperone effect.
Evidence Recombinant expression, enzymatic kinetics, thermal stability, and site-limited proteolysis
Systematic reconstitution of clinical mutations resolved the dominant disease mechanism—misfolding via disrupted interdomain contacts in the central Integrating Domain, and catalytic abolition by residues near the carbamate tunnel.
Evidence Recombinant expression of 18 mutants (Integrating Domain) and partial-reaction assays of the V1013del founder mutation, with structural modelling
To explain divergent clinical NCG responses, kinetic competition assays showed NCG sub-optimally activates CPS1 and competes with NAG, helping mutants lacking NAG occupancy but harming mutants with scarce functional enzyme.
Evidence Purified recombinant wild-type and mutant CPS1 competition kinetics and stability assays
It was assumed CPS1 functions only in ammonia detoxification; showing that KRAS/LKB1-mutant lung cancer cells use CPS1 to channel nitrogen into pyrimidines redefined it as a biosynthetic enzyme whose loss causes replication stress.
Evidence siRNA silencing, metabolomics, isotope tracing, and pyrimidine rescue in KL cell lines, xenografts, and patient tumors
The discovery that secreted CPS1 induces M2 monocyte polarization and protects against liver injury independent of enzymatic activity revealed an unexpected extracellular, non-catalytic function.
Evidence Bile/blood proteomics, recombinant CPS1 administration, macrophage-depletion, and APAP/FasL injury models in mice
Identifying a druggable allosteric pocket and a CPS1-selective inhibitor (H3B-120) that blocks ATP hydrolysis established that CPS1 enzymatic output is pharmacologically targetable in both urea and pyrimidine pathways.
Evidence In vitro enzymatic assays, structure-based drug design, cellular pathway assays, and CPS2 counterscreening
Resolving how nutrient state tunes ureagenesis, two studies showed O-GlcNAcylation on specific threonines as a regulatory switch—enhancing ammonia catalysis in one context and acting as an aging/high-glucose-driven nutrient sensor that limits activity in another.
Evidence MS site-mapping, enzyme kinetics, OGT liver knockout, OGA inhibition, and dietary interventions in mouse disease models
Linking inflammatory cell death to ammonia toxicity, GSDME-driven ISG15 loss was shown to deISGylate CPS1 and route it to K48-ubiquitin degradation, identifying a stability-control axis that fails in acute liver injury.
Evidence GSDME knockout/rescue mice, ISG15 loss-of-function, K48-ubiquitination pulldown/MS, and APAP injury model
A second epigenetic repressor of CPS1 was identified: JMJD1C reduces H3K36me3 at the CPS1 locus to silence it in PNH clones, with knockdown restoring CPS1 and impairing clone proliferation.
Evidence ChIP for H3K36me3, JMJD1C knockdown, and proliferation/apoptosis assays in PIG-A knockout cells and PNH model
Beyond catalysis, CPS1 was shown to drive metabolic-signaling programs—fumarate-mediated TET2 inhibition driving miR-200a-linked EMT and metastasis, and a CaMKII/FOXO1 axis controlling glucagon-induced gluconeogenesis—plus circRNA-mediated regulation of its activity in fatty liver and an mTORC1-activating arginine route in ovarian follicle activation.
Evidence Knockdown/overexpression, omics, metabolomics, TET2 activity and pathway readouts across lung cancer, hepatocyte, MAFLD, and ovarian tissue models
PMID:39193349 PMID:41224057 PMID:41356199 PMID:42111264
Acetylation at K1168 was added to the CPS1 PTM map, shown to impair ATP binding and reduce activity, complementing the activating O-GlcNAcylation switch.
Evidence Quantitative acetylomics, K1168R/K1168Kac mutagenesis, ATP-binding and activity assays, and in silico docking under PFOA/PFO4DA exposure
| Year | Finding | Method | Journal | Conf | PMIDs |
|---|---|---|---|---|---|
| 2017 | CPS1 expression in KRAS/LKB1-mutant (KL) lung cancer cells is suppressed by LKB1 through AMPK. CPS1 enables an unconventional pathway of nitrogen flow from ammonia into pyrimidines: silencing CPS1 in KL cells depletes pyrimidines (reducing the pyrimidine-to-purine ratio), compromises S-phase progression, and induces DNA-polymerase stalling and DNA damage. Exogenous pyrimidines reverse the DNA damage and rescue growth, establishing that the role of CPS1 is pyrimidine supply rather than ammonia detoxification in this context. | siRNA silencing, metabolomics, isotope tracing, cell death/growth assays, exogenous pyrimidine rescue, genetic epistasis (KRAS/LKB1 mutant cell lines and patient tumors) | Nature | High | 28538732 |
| 2011 | CPS1 expression in human hepatocellular carcinoma cells is silenced by DNA methylation. Two CpG dinucleotides near the transcription start site and a CpG-rich region in the first intron are hypermethylated in HCC cells; site-directed mutagenesis of these CpG dinucleotides reduced CPS1 promoter activity. Treatment with the demethylating agent 5-azacytidine restored CPS1 expression. | Bisulfite sequencing, 5-azacytidine demethylation, promoter-reporter assays with site-directed mutagenesis of CpG sites | The American journal of pathology | Medium | 21281797 |
| 2020 | Small-molecule inhibitors (including H3B-120) bind to a previously unknown allosteric pocket on CPS1 and block ATP hydrolysis in the first step of carbamoyl phosphate synthesis. These inhibitors are selective for CPS1 over CPS2 and are active in cellular assays, blocking both urea synthesis and pyrimidine biosynthesis. | Biochemical in vitro CPS1 enzymatic assay, structure-based drug design, cellular urea synthesis and pyrimidine pathway assays, selectivity counterscreening against CPS2 | Cell chemical biology | High | 32017919 |
| 2019 | CPS1 is constitutively secreted into bile by hepatocytes, likely as a soluble protein, and is released into blood during acute liver injury. In blood, CPS1 is rapidly sequestered by circulating monocytes, inducing their M2 polarization and homing to the liver independent of CPS1 enzymatic activity. Recombinant CPS1 (but not control transferrin) increases hepatic macrophage numbers and phagocytic activity, and protects mice from Fas-ligand- or acetaminophen-induced liver injury; protection is absent in macrophage-deficient mice. | Mouse/human bile proteomics, sedimentation analysis, recombinant CPS1 administration, monocyte uptake assays, macrophage polarization assays, macrophage-depletion experiments, acetaminophen and FasL liver injury models | Proceedings of the National Academy of Sciences of the United States of America | High | 30979808 |
| 2022 | O-GlcNAcylation of CPS1 on specific threonine residues increases the catalytic efficiency of CPS1 for ammonia, thereby enhancing ureagenesis. Pharmacological inhibition of O-GlcNAcase (which removes O-GlcNAc from proteins) reduced systemic ammonia in both genetic (propionic acidemia) and acquired (thioacetamide-induced acute liver failure) mouse models. | Mass spectrometry identification of O-GlcNAcylation sites, enzymatic kinetics of O-GlcNAcylated vs. unmodified CPS1, O-GlcNAcase pharmacological inhibition in two mouse disease models, biochemical ammonia measurements | Nature communications | High | 36064721 |
| 2022 | CPS1 O-GlcNAcylation is increased by high glucose and in aged liver, and inhibits CPS1 enzymatic activity. Liver-specific deletion of OGT (O-GlcNAc transferase) potentiates CPS1 activity and renders it irresponsive to stimulation by prolonged fasting. Calorie restriction reverses CPS1 O-GlcNAcylation. This identifies CPS1 O-GlcNAcylation as a nutrient-sensing regulatory step in the urea cycle during aging. | Liver-specific OGT knockout mice, O-GlcNAc mass spectrometry of aged liver, glucose stimulation assays, calorie restriction experiments, CPS1 activity measurements | Journal of molecular cell biology | High | 35285892 |
| 2013 | Human recombinant CPS1 expressed in baculovirus/insect cells has the same kinetic and molecular properties as natural human CPS1. Glycerol partially substitutes for the essential allosteric activator N-acetyl-L-glutamate (NAG). NAG and its analogue N-carbamoyl-L-glutamate (NCG), together with MgATP, protect CPS1 against proteolytic and thermal inactivation, suggesting a stabilizing/chaperone effect. Site-limited proteolysis confirmed the multidomain architecture of CPS1. | Recombinant protein expression and purification, enzymatic kinetics, thermal stability assays, site-limited proteolysis | Human mutation | High | 23649895 |
| 2010 | Using recombinant CPS1 expressed in baculovirus/insect cells, nine clinical CPS1 mutations were shown to affect enzyme solubility, stability, and/or kinetic parameters including NAG affinity; the C-terminal domain mutations were rationalized using the crystal structure of that domain which includes the NAG binding site. This established the functional importance of specific residues, including those at the NAG allosteric site. | Baculovirus/insect cell expression, enzyme purification, kinetic analysis, thermal stability, site-directed mutagenesis, structure-function analysis using C-terminal domain crystal structure | Human mutation | High | 20578160 |
| 2014 | Missense mutations concentrated in the 'unknown function subdomain' (UFSD) of CPS1, here renamed the 'Integrating Domain', primarily cause disease by decreasing CPS1 solubility (misfolding) and reducing specific activity (decreased Vmax). Structural modelling shows the Integrating Domain occupies the middle of the 1462-residue multidomain protein and creates key interdomain contacts; most mutations disrupt these contacts, causing misfolding. | Baculovirus/insect cell recombinant expression of 18 mutants, CPS1 yield/solubility measurements, enzymatic activity assays, Km/Vmax determination, thermal stability, structural modelling | Molecular genetics and metabolism | High | 24813853 |
| 2014 | The recurrent Turkish founder mutation p.Val1013del in CPS1 abolishes all catalytic activities (global CPS1 reaction, ATPase partial reaction reflecting bicarbonate phosphorylation, and ATP synthesis partial reaction reflecting carbamate phosphorylation) without causing gross protein instability or insolubility. V1013 maps to a hydrophobic β-strand near the predicted carbamate tunnel linking both phosphorylation sites. | Baculovirus/insect cell recombinant expression, enzymatic activity assays for global reaction and partial reactions, protein yield/solubility analysis, structural modelling, haplotype analysis | Molecular genetics and metabolism | High | 25410056 |
| 2016 | N-carbamyl-L-glutamate (NCG) activates CPS1 sub-optimally compared to NAG and competes with NAG binding. For the E1034G mutation (located outside the NAG site), NCG activates CPS1 molecules not already bound to NAG, enhancing ureagenesis. For the M792I mutation (which reduces the amount of functional enzyme), NCG competition with the scarce NAG further decreases residual ureagenesis. NCG in combination with MgATP stabilizes wild-type CPS1. | Purified recombinant wild-type and mutant mouse CPS1, enzymatic activity assays, competition kinetics, thermal stability assays | Molecular genetics and metabolism | High | 28007335 |
| 2024 | During APAP-induced liver injury, GSDME activation leads to loss of ISG15 (interferon-stimulated gene 15), causing deISGylation of CPS1. DeISGylated CPS1 is then degraded via K48-linked ubiquitination, resulting in ammonia clearance dysfunction. GSDME deletion prevents CPS1 deISGylation and degradation, preserving urea cycle function. | GSDME knockout and hepatocyte-specific rescue mice, ISG15 loss-of-function, K48-ubiquitination pulldown/MS, CPS1 protein stability assays, APAP liver injury model | Advanced science | High | 38417117 |
| 2025 | CPS1 regulates glucagon-induced hepatic gluconeogenesis through the CaMKII/FOXO1 pathway: CPS1 induces calcium release from the endoplasmic reticulum, triggering CaMKII phosphorylation, which facilitates dephosphorylation and nuclear translocation of FOXO1 to enhance gluconeogenic gene expression. CPS1 knockdown reduced glucagon response in vivo and in vitro; overexpression produced the opposite effect. | CPS1 knockdown and overexpression in hepatocytes (in vitro) and mice (in vivo), CaMKII/FOXO1 phosphorylation and nuclear translocation assays, calcium release measurements, gluconeogenesis assays | Frontiers in pharmacology | Medium | 39193349 |
| 2025 | CPS1 overexpression in metastatic lung cancer cells produces excessive fumarate (a urea cycle intermediate). Fumarate accumulation inhibits TET2 activity, altering miR-200a gene methylation and driving epithelial-to-mesenchymal transition (EMT) to enhance cell migration and invasion. CPS1 inhibition reduces fumarate accumulation, enhances TET2 activity, and epigenetically upregulates PD-L1, leading to immune evasion; combining a CPS1 inhibitor with anti-PD-1 therapy had synergistic anti-tumor effects. | CPS1 genetic knockdown and pharmacological inhibition, quantitative proteomics, RNA-seq, untargeted and targeted metabolomics (urea cycle), TET2 activity assay, miR-200a methylation analysis, Transwell/wound healing assay, spontaneous and induced lung cancer metastasis mouse models, combination immunotherapy | Theranostics | Medium | 41356199 |
| 2019 | CPS1 recombinant p.(Pro1211Arg) mutant showed decreased solubility/yield (consistent with misfolding tendency), reduced thermal stability, ~2-fold lower Vmax, and ~5-fold reduced apparent affinity for ATP. NCG stabilizes CPS1 and could minimize the decrease in effective affinity for ATP by increasing NAG-site saturation, explaining the clinical NCG response in this patient. | Baculovirus/insect cell recombinant expression of mutant CPS1, enzymatic kinetics, thermal stability assay, protein yield/solubility measurement | JIMD reports | Medium | 31392111 |
| 2015 | Nobiletin (NOB), a dietary flavonoid, induces CPS1 expression through transcription factors C/EBPα and C/EBPβ via CCAAT consensus elements on the Cps1 gene promoter; a functional circadian clock (CLOCK) is required for this induction under high-fat diet conditions. This establishes a C/EBP- and clock-dependent transcriptional regulatory mechanism for CPS1. | Mouse dietary/NOB treatment experiments, CPS1 mRNA/protein quantification over circadian cycle, luciferase reporter assay with Cps1 promoter CCAAT elements, Clock mutant mice, C/EBP factor expression analysis | Nutrition & metabolism | Medium | 26075008 |
| 2024 | The histone demethylase JMJD1C represses CPS1 expression in PNH clones by reducing H3K36me3 at the CPS1 locus. Chromatin immunoprecipitation confirmed H3K36me3 occupancy at CPS1. Knockdown of JMJD1C in PIG-A knockout K562 cells upregulated CPS1 and H3K36me3 expression, decreased proliferation, and increased apoptosis. | ChIP for H3K36me3 at CPS1 locus, JMJD1C knockdown, CPS1 expression and H3K36me3 quantification, proliferation and apoptosis assays, PNH mouse model | British journal of haematology | Medium | 38650379 |
| 2018 | Wood frog CPS1 purified from frozen animals shows increased affinity for ammonium (1.26-fold) compared to control, and with glucose addition, higher affinity for ATP and NAG. The frozen enzyme has lower thermal stability and lower levels of glutarylated lysine residues compared to control. This post-translational difference (glutarylation) correlates with altered kinetics in the freeze-tolerant state. | Three-step chromatographic purification, Michaelis-Menten kinetics for three substrates, thermal denaturation, mass spectrometry quantification of glutarylation | Molecular and cellular biochemistry | Medium | 30421312 |
| 2026 | Acetylation at lysine 1168 (K1168) of CPS1 is induced by PFOA/PFO4DA exposure. Mutation of K1168 to arginine (mimicking unacetylated state) restored CPS1 enzymatic activity under PFOA/PFO4DA exposure, while mutation to acetyl-lysine mimic reduced ATP binding capacity, suggesting K1168 acetylation impairs ATP binding and CPS1 activity. | Quantitative acetylomics (mass spectrometry), site-directed mutagenesis (K1168R and K1168Kac mimics), in vitro ATP-binding and enzymatic activity assays, in silico docking | Environmental pollution | Medium | 41720236 |
| 2025 | circSETD2 directly binds to CPS1 protein (identified by RNA pulldown with LC-MS/MS, validated by RNA immunoprecipitation and FISH), reducing CPS1 enzymatic activity and exacerbating lipid metabolic disturbances in MAFLD. Pharmacological modulation of CPS1 enzymatic activity in circSETD2-silenced cells confirmed CPS1 as the mediator of circSETD2's effects on lipid homeostasis. | RNA pulldown + LC-MS/MS, RNA immunoprecipitation, FISH co-localization, CPS1 enzymatic activity assay, CPS1 pharmacological modulation rescue experiment, in vivo HFD mouse model | International journal of biological macromolecules | Medium | 41224057 |
| 2025 | LOC401312 lncRNA transcriptionally upregulates CPS1 in NSCLC; CPS1 overexpression recapitulates the radiosensitization phenotype of LOC401312. Mechanistically, CPS1 suppresses phosphorylation of ATM kinase (Ser1981), a key mediator of DNA damage checkpoint activation, thereby impairing DNA repair. | Genome-wide CRISPRa screening, stable LOC401312 overexpression, RNA-seq, CPS1 overexpression/KD, ATM Ser1981 phosphorylation assay, irradiation cell survival assays | International journal of molecular sciences | Low | 40565327 |
| 2026 | CPS1 activation (via NCG) in ovarian granulosa-like cells elevates intracellular arginine levels, which reduces CASTOR1 binding to its inhibitor GATOR2, thereby facilitating S6K phosphorylation and mTORC1 pathway activation. siRNA knockdown of CPS1 eliminated NCG's effect on arginine levels and S6K phosphorylation. This pathway promotes primordial follicle activation in mouse and human ovarian tissue. | NCG treatment of murine ovaries and human ovarian cortical tissue, KGN granulosa cell siRNA-KD of CPS1, arginine measurement, pS6K/S6K ratio, CASTOR1-GATOR2 interaction assay, mTORC1 pathway readouts, primordial follicle counting | Frontiers in cell and developmental biology | Medium | 42111264 |
| 2025 | In torpid bats, CPS1 protein abundance is significantly increased and co-localizes and co-immunoprecipitates with agmatinase (AGMAT) in liver mitochondria. FRET analysis supports an indirect CPS1-AGMAT interaction. This association is conserved in two phylogenetically distant bat species (Myotis ricketti and Rhinolophus ferrumequinum), suggesting a functional role in coordinating urea cycle nitrogen metabolism during torpor. | Proteomics, confocal co-localization, co-immunoprecipitation, FRET, metabolic profiling | bioRxivpreprint | Low | |
| 2021 | AFF1 occupies the NTS (neurotensin) enhancer in lung adenocarcinoma cells and suppresses NTS transcription; NTS expression is highly correlated with CPS1 expression. The IL6 pathway antagonizes NTS in regulating CPS1, establishing a NTS-AFF1-IL6-CPS1 regulatory axis in lung adenocarcinoma cells. | ChIP-seq for AFF1 at NTS enhancer, gene expression correlation analysis, NTS and IL6 pathway perturbation experiments, CPS1 expression readout | The Journal of biological chemistry | Low | 33493519 |
| 2016 | In HCC cells treated with aflatoxin B1, CPS1 was shown by Co-IP to interact with KRT1 (type II cytoskeletal keratin 1), albumin (ALB), and ubiquitin C (UBC). CPS1 co-localizes with KRT1 and ALB, and aflatoxin B1 changes the intensity correlation between these proteins. | Co-immunoprecipitation, mass spectrometry, immunofluorescence co-localization, siRNA knockdown | Gene | Low | 27425868 |
| 1995 | The human CPS1 gene was physically mapped by FISH to chromosome 2q34→q35, correcting an earlier assignment to 2p. | FISH physical mapping, CEPH family linkage analysis | Cytogenetics and cell genetics | Medium | 7587391 |
| Year | Title | Journal | Citations | PMID |
|---|---|---|---|---|
| 2017 | CPS1 maintains pyrimidine pools and DNA synthesis in KRAS/LKB1-mutant lung cancer cells. | Nature | 276 | 28538732 |
| 1999 | Analysis of the cps1 gene provides evidence for a septation checkpoint in Schizosaccharomyces pombe. | Molecular & general genetics : MGG | 112 | 10503548 |
| 1997 | cps1+, a Schizosaccharomyces pombe gene homolog of Saccharomyces cerevisiae FKS genes whose mutation confers hypersensitivity to cyclosporin A and papulacandin B. | Journal of bacteriology | 112 | 9401022 |
| 2016 | Genome-wide association study and targeted metabolomics identifies sex-specific association of CPS1 with coronary artery disease. | Nature communications | 103 | 26822151 |
| 2011 | DNA methylation suppresses expression of the urea cycle enzyme carbamoyl phosphate synthetase 1 (CPS1) in human hepatocellular carcinoma. | The American journal of pathology | 103 | 21281797 |
| 2017 | LncRNA CPS1-IT1 suppresses EMT and metastasis of colorectal cancer by inhibiting hypoxia-induced autophagy through inactivation of HIF-1α. | Biochimie | 90 | 29017924 |
| 2007 | Identification and characterization of CPS1 as a hyaluronic acid synthase contributing to the pathogenesis of Cryptococcus neoformans infection. | Eukaryotic cell | 89 | 17545316 |
| 2016 | Long noncoding RNA CPS1-IT1 suppresses the metastasis of hepatocellular carcinoma by regulating HIF-1α activity and inhibiting epithelial-mesenchymal transition. | Oncotarget | 64 | 27248828 |
| 2010 | Genome-wide association study of homocysteine levels in Filipinos provides evidence for CPS1 in women and a stronger MTHFR effect in young adults. | Human molecular genetics | 62 | 20154341 |
| 2017 | LncRna CPS1-IT1 Suppresses Cell Proliferation, Invasion and Metastasis in Colorectal Cancer. | Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology | 59 | 29145177 |
| 2006 | CPS1, a homolog of the Streptococcus pneumoniae type 3 polysaccharide synthase gene, is important for the pathobiology of Cryptococcus neoformans. | Infection and immunity | 58 | 16790766 |
| 2016 | A Coccidioides posadasii CPS1 Deletion Mutant Is Avirulent and Protects Mice from Lethal Infection. | Infection and immunity | 56 | 27481239 |
| 2017 | Targeting CPS1 in the treatment of Carbamoyl phosphate synthetase 1 (CPS1) deficiency, a urea cycle disorder. | Expert opinion on therapeutic targets | 47 | 28281899 |
| 2007 | Molecular and clinical analyses of Japanese patients with carbamoylphosphate synthetase 1 (CPS1) deficiency. | Journal of human genetics | 40 | 17310273 |
| 2017 | Melatonin suppresses hepatocellular carcinoma progression via lncRNA-CPS1-IT-mediated HIF-1α inactivation. | Oncotarget | 39 | 29137263 |
| 2020 | Small Molecule Inhibition of CPS1 Activity through an Allosteric Pocket. | Cell chemical biology | 36 | 32017919 |
| 2019 | Constitutive release of CPS1 in bile and its role as a protective cytokine during acute liver injury. | Proceedings of the National Academy of Sciences of the United States of America | 35 | 30979808 |
| 2013 | Molecular characterization of carbamoyl-phosphate synthetase (CPS1) deficiency using human recombinant CPS1 as a key tool. | Human mutation | 35 | 23649895 |
| 2010 | Understanding carbamoyl-phosphate synthetase I (CPS1) deficiency by using expression studies and structure-based analysis. | Human mutation | 35 | 20578160 |
| 2019 | Overexpressed long noncoding RNA CPS1-IT alleviates pulmonary arterial hypertension in obstructive sleep apnea by reducing interleukin-1β expression via HIF1 transcriptional activity. | Journal of cellular physiology | 33 | 30982984 |
| 2016 | Long Noncoding RNA CPS1-IT1 Suppresses Cell Proliferation and Metastasis in Human Lung Cancer. | Oncology research | 31 | 27662619 |
| 2020 | CPS1: Looking at an ancient enzyme in a modern light. | Molecular genetics and metabolism | 30 | 33317798 |
| 2014 | Understanding carbamoyl phosphate synthetase (CPS1) deficiency by using the recombinantly purified human enzyme: effects of CPS1 mutations that concentrate in a central domain of unknown function. | Molecular genetics and metabolism | 30 | 24813853 |
| 1998 | Prenatal diagnosis of carbamoyl phosphate synthetase I deficiency by identification of a missense mutation in CPS1. | Human mutation | 30 | 9711878 |
| 2015 | Ammonia-lowering activities and carbamoyl phosphate synthetase 1 (Cps1) induction mechanism of a natural flavonoid. | Nutrition & metabolism | 29 | 26075008 |
| 1995 | Physical and linkage mapping of human carbamyl phosphate synthetase I (CPS1) and reassignment from 2p to 2q35. | Cytogenetics and cell genetics | 29 | 7587391 |
| 1994 | P1 and cosmid clones define the organization of 280 kb of the mouse H-2 complex containing the Cps-1 and Hsp70 loci. | Immunogenetics | 27 | 7993390 |
| 2019 | Long noncoding RNA CPS1-IT1 suppresses melanoma cell metastasis through inhibiting Cyr61 via competitively binding to BRG1. | Journal of cellular physiology | 26 | 31111478 |
| 2019 | Expression and clinical significance of CPS1 in glioblastoma multiforme. | Current research in translational medicine | 24 | 31492588 |
| 2019 | Capsular Polysaccharide Is a Receptor of a Clostridium perfringens Bacteriophage CPS1. | Viruses | 22 | 31683584 |
| 2003 | Structural organization of the human carbamyl phosphate synthetase I gene (CPS1) and identification of two novel genetic lesions. | Human mutation | 22 | 12955727 |
| 2024 | Gasdermin-E-Dependent Non-Canonical Pyroptosis Promotes Drug-Induced Liver Failure by Promoting CPS1 deISGylation and Degradation. | Advanced science (Weinheim, Baden-Wurttemberg, Germany) | 21 | 38417117 |
| 2018 | In Silico Preliminary Association of Ammonia Metabolism Genes GLS, CPS1, and GLUL with Risk of Alzheimer's Disease, Major Depressive Disorder, and Type 2 Diabetes. | Journal of molecular neuroscience : MN | 21 | 29441491 |
| 1986 | A processed chicken pseudogene (CPS1) related to the ras oncogene superfamily. | Nucleic acids research | 20 | 3083400 |
| 2022 | O-GlcNAcylation enhances CPS1 catalytic efficiency for ammonia and promotes ureagenesis. | Nature communications | 19 | 36064721 |
| 2015 | Carbamoylphosphate synthetase 1 (CPS1) deficiency: clinical, biochemical, and molecular characterization in Malaysian patients. | European journal of pediatrics | 16 | 26440671 |
| 2023 | NAGS, CPS1, and SLC25A13 (Citrin) at the Crossroads of Arginine and Pyrimidines Metabolism in Tumor Cells. | International journal of molecular sciences | 15 | 37047726 |
| 2014 | The Neurospora crassa CPS-1 polysaccharide synthase functions in cell wall biosynthesis. | Fungal genetics and biology : FG & B | 15 | 24953997 |
| 2020 | Exploring Metabolic Consequences of CPS1 and CAD Dysregulation in Hepatocellular Carcinoma by Network Reconstruction. | Journal of hepatocellular carcinoma | 14 | 32021853 |
| 2015 | Biochemical Characterization of CPS-1, a Subclass B3 Metallo-β-Lactamase from a Chryseobacterium piscium Soil Isolate. | Antimicrobial agents and chemotherapy | 14 | 26666948 |
| 2019 | N-carbamoylglutamate-responsive carbamoyl phosphate synthetase 1 (CPS1) deficiency: A patient with a novel CPS1 mutation and an experimental study on the mutation's effects. | JIMD reports | 13 | 31392111 |
| 2015 | Fatal hyperammonemia and carbamoyl phosphate synthetase 1 (CPS1) deficiency following high-dose chemotherapy and autologous hematopoietic stem cell transplantation. | Molecular genetics and metabolism | 13 | 25639153 |
| 2022 | Regulation of the urea cycle by CPS1 O-GlcNAcylation in response to dietary restriction and aging. | Journal of molecular cell biology | 12 | 35285892 |
| 2021 | The Role of TRIP6, ABCC3 and CPS1 Expression in Resistance of Ovarian Cancer to Taxanes. | International journal of molecular sciences | 12 | 35008510 |
| 2020 | A Promising CPS1 Inhibitor Keeping Ammonia from Fueling Cancer. | Cell chemical biology | 12 | 32200911 |
| 2016 | Precision medicine in rare disease: Mechanisms of disparate effects of N-carbamyl-l-glutamate on mutant CPS1 enzymes. | Molecular genetics and metabolism | 12 | 28007335 |
| 2022 | Evidencing New Roles for the Glycosyl-Transferase Cps1 in the Phytopathogenic Fungus Botrytis cinerea. | Journal of fungi (Basel, Switzerland) | 11 | 36135623 |
| 2020 | Therapeutic effect of N-carbamylglutamate in CPS1 deficiency. | Molecular genetics and metabolism reports | 11 | 32670798 |
| 2022 | Unraveling the therapeutic potential of carbamoyl phosphate synthetase 1 (CPS1) in human diseases. | Bioorganic chemistry | 10 | 36356370 |
| 2017 | Novel Pathogenic Variant (c.580C>T) in the CPS1 Gene in a Newborn With Carbamoyl Phosphate Synthetase 1 Deficiency Identified by Whole Exome Sequencing. | Annals of laboratory medicine | 10 | 27834067 |
| 2014 | Recurrence of carbamoyl phosphate synthetase 1 (CPS1) deficiency in Turkish patients: characterization of a founder mutation by use of recombinant CPS1 from insect cells expression. | Molecular genetics and metabolism | 10 | 25410056 |
| 2010 | Molecular characterization of CPS1 deletions by array CGH. | Molecular genetics and metabolism | 10 | 20855223 |
| 2021 | CRISPR-Mediated Genomic Addition to CPS1 Deficient iPSCs is Insufficient to Restore Nitrogen Homeostasis. | The Yale journal of biology and medicine | 9 | 34970092 |
| 2021 | Suppression of the NTS-CPS1 regulatory axis by AFF1 in lung adenocarcinoma cells. | The Journal of biological chemistry | 8 | 33493519 |
| 2021 | Whole-genome sequencing, genome mining, metabolic reconstruction and evolution of pentachlorophenol and other xenobiotic degradation pathways in Bacillus tropicus strain AOA-CPS1. | Functional & integrative genomics | 8 | 33547987 |
| 2019 | LncRNA CPS1-IT1 serves as anti-oncogenic role in glioma. | Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie | 8 | 31545272 |
| 2016 | Studies on the biological functions of CPS1 in AFB1 induced hepatocarcinogenesis. | Gene | 8 | 27425868 |
| 2020 | Biotransformation of pentachlorophenol by an indigenous Bacillus cereus AOA-CPS1 isolated from wastewater effluent in Durban, South Africa. | Biodegradation | 7 | 33011889 |
| 2019 | CPS1 T1405N polymorphism, HDL cholesterol, homocysteine and renal function are risk factors of VPA induced hyperammonemia among epilepsy patients. | Epilepsy research | 7 | 31151073 |
| 2018 | Two novel CPS1 mutations in a case of carbamoyl phosphate synthetase 1 deficiency causing hyperammonemia and leukodystrophy. | Journal of clinical laboratory analysis | 7 | 29314318 |
| 2018 | Purification of carbamoyl phosphate synthetase 1 (CPS1) from wood frog (Rana sylvatica) liver and its regulation in response to ice-nucleation and subsequent whole-body freezing. | Molecular and cellular biochemistry | 7 | 30421312 |
| 2020 | Improvement of diagnostic yield in carbamoylphosphate synthetase 1 (CPS1) molecular genetic investigation by RNA sequencing. | JIMD reports | 6 | 32154057 |
| 2020 | Discovery of 2,6-Dimethylpiperazines as Allosteric Inhibitors of CPS1. | ACS medicinal chemistry letters | 6 | 32551016 |
| 2018 | Is there any relationship between mutation in CPS1 Gene and pregnancy loss? | International journal of reproductive biomedicine | 6 | 31435610 |
| 2024 | CPS1 augments hepatic glucagon response through CaMKII/FOXO1 pathway. | Frontiers in pharmacology | 5 | 39193349 |
| 2022 | Novel compound heterozygote variants: c.4193_4206delinsG (p.Leu1398Argfs*25), c.793C > A (p.Pro265Thr), in the CPS1 gene (NM_001875.4) causing late onset carbamoyl phosphate synthetase 1 deficiency-Lessons learned. | Molecular genetics and metabolism reports | 5 | 36466970 |
| 2019 | Author Correction: CPS1 maintains pyrimidine pools and DNA synthesis in KRAS/LKB1-mutant lung cancer cells. | Nature | 5 | 31043737 |
| 1995 | Cis and trans-acting regulatory elements required for regulation of the CPS1 gene in Saccharomyces cerevisiae. | Molecular & general genetics : MGG | 5 | 7700231 |
| 2024 | Urea cycle promotion via ammonia-upregulated CPS1 is involved in arsenite-induced pulmonary fibrosis through enhancing collagen synthesis. | Chemico-biological interactions | 4 | 38703806 |
| 2023 | Clinical and genetic analysis of a case of late onset carbamoyl phosphate synthase I deficiency caused by CPS1 mutation and literature review. | BMC medical genomics | 4 | 37365635 |
| 2023 | Variant in the allosteric domain of CPS1 protein associated with effectiveness of N-carbamoyl glutamate therapy in neonatal onset CPS1 deficiency. | Journal of pediatric endocrinology & metabolism : JPEM | 3 | 37427576 |
| 2020 | Role of tetrachloro-1,4-benzoquinone reductase in phenylalanine hydroxylation system and pentachlorophenol degradation in Bacillus cereus AOA-CPS1. | International journal of biological macromolecules | 3 | 32535205 |
| 2018 | Association of CPS1 rs1047891 SNP and serum lipid levels in two Chinese ethnic groups. | International journal of clinical and experimental pathology | 3 | 31938413 |
| 2025 | Use of an oversized AAV8 vector for CPS1 deficiency results in long-term survival and ammonia control. | Molecular therapy. Nucleic acids | 2 | 40083646 |
| 2024 | The histone demethylase JMJD1C regulates CPS1 expression and promotes the proliferation of paroxysmal nocturnal haemoglobinuria clones through cell metabolic reprogramming. | British journal of haematology | 2 | 38650379 |
| 2024 | Clinical features and CPS1 variants in Chinese patients with carbamoyl phosphate synthetase 1 deficiency. | BMC pediatrics | 2 | 39174957 |
| 2000 | Comparison of total body urea production potential with total body carbamoyl phosphate synthetase (CPS-1) activity in newborn piglets infused with alanine at 50% of resting energy expenditure for 36 hours. | The Journal of nutrition | 2 | 10917911 |
| 2026 | Targeting CPS1 attenuates lung cancer metastasis by regulating EMT through an epigenetic mechanism. | Theranostics | 1 | 41356199 |
| 2026 | Pulmonary Solid and Granular Adenocarcinomas Expressing HepPar1/CPS1: Highly Aggressive Tumors Exhibiting Mitochondrial Adaptation to STK11 Mutations Rather Than Hepatoid Differentiation. | Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc | 1 | 41580239 |
| 2026 | Quantitative acetylomic analysis reveals a key role of acetylation site 1168K in carbamoyl-phosphate synthase 1 (CPS1) following exposure to PFOA and PFO4DA in mouse liver. | Environmental pollution (Barking, Essex : 1987) | 1 | 41720236 |
| 2025 | Long Non-Coding RNA LOC401312 Induces Radiosensitivity Through Upregulation of CPS1 in Non-Small Cell Lung Cancer. | International journal of molecular sciences | 1 | 40565327 |
| 2025 | CPS1-promoted the progression of lung adenocarcinoma via suppressing ammonia induced the activation of ROS/AMPK/P53/LKB1 signaling pathway. | Scientific reports | 1 | 40796927 |
| 2025 | Single-cell multi-omics uncovers CPS1 as a breast cancer immune evasion therapeutic target. | Scientific reports | 1 | 41102194 |
| 2024 | Carbamoly-phosphate synthetase 1 (CPS1) deficiency: A tertiary center retrospective cohort study and literature review. | Molecular genetics and metabolism reports | 1 | 39469307 |
| 2021 | Classic Pentachlorophenol Hydroxylating Phenylalanine 4-Monooxygenase from Indigenous Bacillus tropicus Strain AOA-CPS1: Cloning, Overexpression, Purification, Characterization and Structural Homology Modelling. | Applied biochemistry and biotechnology | 1 | 34417677 |
| 2026 | CPS1: a multipurpose mitochondrial enzyme, bile protein, acute liver injury biomarker, and cytokine. | Gut | 0 | 41629147 |
| 2026 | Activation of mitochondrial CPS1 promotes dormant ovarian follicle activation via arginine elevation and the mTORC1 pathway. | Frontiers in cell and developmental biology | 0 | 42111264 |
| 2026 | Metabolic checkpoint CPS1 sustains TCA anaplerosis via urea cycle in IDH-mutant gliomas. | Cancer letters | 0 | 42173273 |
| 2025 | Identification of novel variants in carbamoyl phosphate synthetase 1 gene and comparative pathogenicity assessments of CPS1 missense variants following ACMG/AMP-ClinGen recommendation for computational tools. | Molecular genetics and metabolism reports | 0 | 40212732 |
| 2025 | A hypomorphic model of CPS1 deficiency for investigating the effects of hyperammonemia on the developing nervous system. | Disease models & mechanisms | 0 | 40421838 |
| 2025 | CircSETD2 impairs hepatic lipid homeostasis in metabolic dysfunction-associated fatty liver disease by binding CPS1. | International journal of biological macromolecules | 0 | 41224057 |
| 2024 | Establishment of iPS cell line (SDQLCHi061-A) from a patient with carbamoylphosphate synthetase I deficiency due to CPS1 mutation. | Stem cell research | 0 | 38394969 |
| 2018 | [Detection of CPS1 gene mutation in a neonate with carbamoyl phosphate synthetase I deficiency]. | Zhonghua yi xue yi chuan xue za zhi = Zhonghua yixue yichuanxue zazhi = Chinese journal of medical genetics | 0 | 30512161 |
| 2008 | [Preparation, characterization and application of monoclonal antibody against CPS1]. | Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | 0 | 18466707 |
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