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MT000145

UniProt Annotations

Entry Information

Gene Name	carbamoyl-phosphate synthase 1, mitochondrial
Protein Entry	CPSM_HUMAN
UniProt ID	P31327
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=3; Name=1; IsoId=P31327-1; Sequence=Displayed; Name=2; IsoId=P31327-2; Sequence=VSP_009332; Name=3; IsoId=P31327-3; Sequence=VSP_046685; Note=Ref.11 (BAD92037) sequence is in conflict in position: 5:I->IF. {ECO:0000305};
Catalytic Activity	2 ATP + NH(3) + CO(2) + H(2)O = 2 ADP + phosphate + carbamoyl phosphate.
Disease	Carbamoyl phosphate synthetase 1 deficiency (CPS1D) [MIM:237300]: An autosomal recessive disorder of the urea cycle causing hyperammonemia. It can present as a devastating metabolic disease dominated by severe hyperammonemia in neonates or as a more insidious late-onset condition, generally manifesting as life-threatening hyperammonemic crises under catabolic situations. Clinical features include protein intolerance, intermittent ataxia, seizures, lethargy, developmental delay and mental retardation. {ECO:0000269\|PubMed:11388595, ECO:0000269\|PubMed:11474210, ECO:0000269\|PubMed:12655559, ECO:0000269\|PubMed:12955727, ECO:0000269\|PubMed:15164414, ECO:0000269\|PubMed:15617192, ECO:0000269\|PubMed:16737834, ECO:0000269\|PubMed:17310273, ECO:0000269\|PubMed:20578160, ECO:0000269\|PubMed:21120950, ECO:0000269\|PubMed:9711878}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Pulmonary hypertension, neonatal (PHN) [MIM:615371]: A disease characterized by elevated pulmonary artery pressure. Pulmonary hypertension in the neonate is associated with multiple underlying problems such as respiratory distress syndrome, meconium aspiration syndrome, congenital diaphragmatic hernia, bronchopulmonary dysplasia, sepsis, or congenital heart disease. {ECO:0000269\|PubMed:11407344}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. CPS1 variants influence the availability of precursors for nitric oxide (NO) synthesis and play a role in clinical situations where endogenous NO production is critically important, such as neonatal pulmonary hypertension, increased pulmonary artery pressure following surgical repair of congenital heart defects or hepatovenocclusive disease following bone marrow transplantation. Infants with neonatal pulmonary hypertension homozygous for Thr- 1406 have lower L-arginine concentrations than neonates homozygous for Asn-1406 (PubMed:11407344). {ECO:0000269\|PubMed:11407344}.
Domain	The type-1 glutamine amidotransferase domain is defective.
Enzyme Regulation	Requires N-acetyl-L-glutamate (NAG) as an allosteric activator.
Function	Involved in the urea cycle of ureotelic animals where the enzyme plays an important role in removing excess ammonia from the cell.
Interaction	P10398:ARAF; NbExp=3; IntAct=EBI-536811, EBI-365961; P04049:RAF1; NbExp=4; IntAct=EBI-536811, EBI-365996; P63104:YWHAZ; NbExp=2; IntAct=EBI-536811, EBI-347088;
Ptm	Succinylated at Lys-287 and Lys-1291. Desuccinylated at Lys- 1291 by SIRT5, leading to activation (By similarity). {ECO:0000250}.
Sequence Caution	Sequence=BAD92037.1; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};
Similarity	Contains 1 glutamine amidotransferase type-1 domain. {ECO:0000305}.
Similarity	Contains 2 ATP-grasp domains. {ECO:0000305}.
Subcellular Location	Mitochondrion {ECO:0000269\|PubMed:22002106}. Nucleus, nucleolus {ECO:0000269\|PubMed:22002106}.
Tissue Specificity	Primarily in the liver and small intestine.
Web Resource	Name=LOVD-Leiden Open Variation Database; Note=Carbamoyl-Phosphate Synthetase 1 (CPS1); URL="http://chromium.liacs.nl/lovd2/home.php?select_db=CPS1";