Carbamoyl-phosphate synthase [ammonia], mitochondrial

Function

Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell.

Classification

Family (Pfam)

PF25596 CPSase_L_D1, PF02786 CPSase_L_D2, PF02787 CPSase_L_D3, PF00988 CPSase_sm_chain, PF00117 GATase, PF02142 MGS

InterPro

ATP-grasp, ATP_grasp_subdomain_1, CarbamoylP_synth_lsu_oligo_sf, CarbamoylP_synth_ssu, CarbamoylP_synth_ssu_N, CarbP_synth_ssu_N_sf, Class_I_gatase-like, CPAse_ATP-bd, CPSase_dom, CPSase_GATase1, CPSase_lsu, CPSase_lsu_oligo, CPSase_preATP-grasp, GATASE, MGS-like_dom, MGS-like_dom_sf, PreATP-grasp_dom_sf

Functional cluster

Amino Acid & Cofactor Biosynthesis Enzymes

Experimental structures · PDB · 14

• 2YVQ X-ray 1.98A
• 4UTR X-ray 2.90A
• 4UTV X-ray 2.40A
• 4UTX X-ray 3.10A
• 4UTZ X-ray 3.30A
• 4UU7 X-ray 3.00A
• 4UU8 X-ray 2.90A
• 4UUA X-ray 2.80A
• 4UUB X-ray 2.90A
• 5DOT X-ray 2.40A
• 5DOU X-ray 2.60A
• 5OJO X-ray 3.10A
• … and 2 more

A predicted model is available from AlphaFold.

Gene Ontology · 49

• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0005743 mitochondrial inner membrane
• GO:0005759 mitochondrial matrix
• GO:0042645 mitochondrial nucleoid
• GO:0005739 mitochondrion
• GO:0005730 nucleolus
• GO:0005886 plasma membrane
• GO:0032991 protein-containing complex
• GO:0005524 ATP binding
• GO:0005509 calcium ion binding
• GO:0004087 carbamoyl-phosphate synthase (ammonia) activity
• GO:0004088 carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity
• GO:0004175 endopeptidase activity
• GO:0016595 glutamate binding
• GO:0046872 metal ion binding
• GO:0072341 modified amino acid binding
• GO:0005543 phospholipid binding
• GO:0030955 potassium ion binding
• GO:0044877 protein-containing complex binding
• GO:0036094 small molecule binding
• GO:0006207 'de novo' pyrimidine nucleobase biosynthetic process
• GO:0070409 carbamoyl phosphate biosynthetic process
• GO:0071242 cellular response to ammonium ion
• GO:0071320 cellular response to cAMP
• GO:0044344 cellular response to fibroblast growth factor stimulus
• GO:0071377 cellular response to glucagon stimulus
• GO:0071400 cellular response to oleic acid
• GO:0019240 citrulline biosynthetic process
• GO:0006541 glutamine metabolic process
• GO:0070365 hepatocyte differentiation
• GO:0050667 homocysteine metabolic process
• GO:0007494 midgut development
• GO:0055081 monoatomic anion homeostasis
• GO:0046209 nitric oxide metabolic process
• GO:0097305 response to alcohol
• GO:0014075 response to amine
• GO:0043200 response to amino acid
• GO:0071548 response to dexamethasone
• GO:0032094 response to food
• GO:0060416 response to growth hormone
• GO:0032496 response to lipopolysaccharide
• GO:0042594 response to starvation
• GO:0009636 response to toxic substance
• GO:0009410 response to xenobiotic stimulus
• GO:0010043 response to zinc ion
• GO:0019433 triglyceride catabolic process
• GO:0000050 urea cycle
• GO:0042311 vasodilation

Disease associations

• carbamoyl phosphate synthetase I deficiency disease MONDO:0009376

Drugs targeting this protein · 1

• CARGLUMIC ACID positive allosteric modulator

Related proteins · sequence + function similarity

• Carbamoyl-phosphate synthase [ammonia], mitochondrial 0.99
• Carbamoyl-phosphate synthase [ammonia], mitochondrial 0.99
• Carbamoyl-phosphate synthase [ammonia], mitochondrial 0.97
• Multifunctional protein pyr-3 0.88
• Multifunctional protein URA2 0.87
• Multifunctional protein ura1 0.85
• Multifunctional protein pyrABCN 0.84
• Carbamoyl phosphate synthase arginine-specific large chain, mitochondrial 0.81
• Multifunctional protein CAD 0.80
• Carbamoyl phosphate synthase arginine-specific large chain 0.78
• Carbamoyl phosphate synthase arginine-specific large chain, mitochondrial 0.78
• Multifunctional protein pyr-1 0.77

Co-cited proteins · studied together in the literature

• Carbamoyl-phosphate synthase [ammonia], mitochondrial 2 shared papers
• Protein HTATIP2 1 shared papers
• Glutaryl-CoA dehydrogenase, mitochondrial 1 shared papers
• Carbamoyl-phosphate synthase [ammonia], mitochondrial 1 shared papers
• NAD-dependent protein deacylase sirtuin-5, mitochondrial 1 shared papers
• NAD-dependent protein deacylase sirtuin-5, mitochondrial 1 shared papers
• NudC domain-containing protein 1 1 shared papers
• WD repeat-containing protein 36 1 shared papers
• U3 small nucleolar RNA-associated protein 25 homolog 1 shared papers
• Midasin 1 shared papers
• Prolyl 3-hydroxylase OGFOD1 1 shared papers
• Fumarylacetoacetase 1 shared papers

Literature · 32 cited papers

• Analysis of protein-coding genetic variation in 60,706 humans. Nature · 2016
• Carbamoylphosphate synthetase 1 (CPS1) deficiency: clinical, biochemical, and molecular characterization in Malaysian patients. Eur. J. Pediatr. · 2016
• 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. Mol. Genet. Metab. · 2014
• Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. Cell Metab. · 2014
• An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
• Large-scale quantification of single amino-acid variations by a variation-associated database search strategy. J. Proteome Res. · 2014
• Molecular characterization of carbamoyl-phosphate synthetase (CPS1) deficiency using human recombinant CPS1 as a key tool. Hum. Mutat. · 2013
• Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
• Carbamoyl phosphate synthetase 1 deficiency in Italy: clinical and genetic findings in a heterogeneous cohort. Gene · 2012
• Systematic analysis of protein pools, isoforms, and modifications affecting turnover and subcellular localization. Mol. Cell. Proteomics · 2012
• Personalized genomic medicine: lessons from the exome. Mol. Genet. Metab. · 2011
• Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
• … and 20 more in the literature graph