InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CPS1

Summary

InnateDB Protein

IDBP-388716.4

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

CPS1

Protein Name

carbamoyl-phosphate synthase 1, mitochondrial

Synonyms

CPSASE1; PHN;

Species

Homo sapiens

Ensembl Protein

ENSP00000406136

InnateDB Gene

IDBG-79973 (CPS1)

Protein Structure

UniProt Annotation

Function

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

Subcellular Localization

Mitochondrion {ECO:0000269PubMed:22002106}. Nucleus, nucleolus {ECO:0000269PubMed:22002106}.

Disease Associations

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:0000269PubMed:11388595, ECO:0000269PubMed:11474210, ECO:0000269PubMed:12655559, ECO:0000269PubMed:12955727, ECO:0000269PubMed:15164414, ECO:0000269PubMed:15617192, ECO:0000269PubMed:16737834, ECO:0000269PubMed:17310273, ECO:0000269PubMed:20578160, ECO:0000269PubMed:21120950, ECO:0000269PubMed:9711878}. Note=The disease is caused by mutations affecting the gene represented in this entry.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:0000269PubMed: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:0000269PubMed:11407344}.

Tissue Specificity

Primarily in the liver and small intestine.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 29 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	29 [view]
Protein-Protein	27 [view]
Protein-DNA	0
Protein-RNA	1 [view]
DNA-DNA	1 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003824	catalytic activity
GO:0004087	carbamoyl-phosphate synthase (ammonia) activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008716	D-alanine-D-alanine ligase activity
GO:0046872	metal ion binding
GO:0072341	modified amino acid binding

Biological Process

GO:0000050	urea cycle
GO:0005980	glycogen catabolic process
GO:0006543	glutamine catabolic process
GO:0006807	nitrogen compound metabolic process
GO:0008152	metabolic process
GO:0019240	citrulline biosynthetic process
GO:0019433	triglyceride catabolic process
GO:0032496	response to lipopolysaccharide
GO:0034641	cellular nitrogen compound metabolic process
GO:0044281	small molecule metabolic process
GO:0045909	positive regulation of vasodilation
GO:0046209	nitric oxide metabolic process
GO:0050667	homocysteine metabolic process
GO:0070409	carbamoyl phosphate biosynthetic process

Cellular Component

GO:0005730	nucleolus
GO:0005759	mitochondrial matrix
GO:0042645	mitochondrial nucleoid

Protein Structure and Domains

PDB ID

InterPro

IPR003135 ATP-grasp fold, ATP-dependent carboxylate-amine ligase-type
IPR005479 Carbamoyl-phosphate synthetase large subunit-like, ATP-binding domain
IPR005480 Carbamoyl-phosphate synthetase, large subunit oligomerisation domain
IPR005481 Carbamoyl-phosphate synthase, large subunit, N-terminal
IPR005483 Carbamoyl-phosphate synthase large subunit, CPSase domain
IPR006275 Carbamoyl-phosphate synthase, large subunit
IPR011095 D-alanine--D-alanine ligase, C-terminal
IPR011607 Methylglyoxal synthase-like domain
IPR011761 ATP-grasp fold
IPR016185 Pre-ATP-grasp domain

PFAM

PF02222
PF02786
PF02787
PF00289
PF07478
PF02142

PRINTS

PR00098

PIRSF

SMART

SM01096
SM00851

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt