Cps1 carbamoyl-phosphate synthetase 1 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Cps1provided by MGI
Official Full Name: carbamoyl-phosphate synthetase 1provided by MGI
Primary source: MGI:MGI:891996
See related: Ensembl:ENSMUSG00000025991 AllianceGenome:MGI:891996
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: CPS; D1Ucla3; 4732433M03Rik
Summary: This gene encodes a protein localized to the inner mitochondrial matrix. The encoded protein plays a role in the detoxification of ammonia by catalyzing the first step in the urea cycle in which carbomyl-phosphate is synthesized from ammonia and bicarbonate. Carbamoyl-phosphate is subsequently converted to urea that is excreted by the kidneys. Deficiency of the encoded enzyme leads to an accumulation of ammonia in the blood. High levels of ammonia are toxic to the central nervous system and result in neurological disorders. [provided by RefSeq, Oct 2013]
Expression: Biased expression in liver adult (RPKM 294.0), liver E18 (RPKM 157.3) and 1 other tissue See more
Orthologs: human all
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Genomic context

Location:: 1 C3; 1 33.75 cM

Exon count:: 40

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	1	NC_000067.7 (67151294..67270426)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	1	NC_000067.6 (67122426..67231267)

Chromosome 1 - NC_000067.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Hypoosmosis alters hepatocyte mitochondrial morphology and induces selective release of carbamoyl phosphate synthetase 1.
Title: Hypoosmosis alters hepatocyte mitochondrial morphology and induces selective release of carbamoyl phosphate synthetase 1.
O-GlcNAcylation enhances CPS1 catalytic efficiency for ammonia and promotes ureagenesis.
Title: O-GlcNAcylation enhances CPS1 catalytic efficiency for ammonia and promotes ureagenesis.
A constitutive knockout of murine carbamoyl phosphate synthetase 1 results in death with marked hyperglutaminemia and hyperammonemia.
Title: A constitutive knockout of murine carbamoyl phosphate synthetase 1 results in death with marked hyperglutaminemia and hyperammonemia.
To investigate the efficacy of gene therapy for CPS deficiency following knock-down of hepatic endogenous CPS1 expression, we injected these mice with a helper-dependent adenoviral vector (HDAd) expressing the large murine CPS1 cDNA under control of the phosphoenolpyruvate carboxykinase promoter
Title: Conditional disruption of hepatic carbamoyl phosphate synthetase 1 in mice results in hyperammonemia without orotic aciduria and can be corrected by liver-directed gene therapy.
these data suggest that AhR activation promotes CPS1 recruitment to DNA enhancer sites in the genome, resulting in a specific enzyme-independent post-translational modification of the linker histone H1 protein (H1K34hcit), pivotal in altering local chromatin structure and transcriptional activation.
Title: Homocitrullination Is a Novel Histone H1 Epigenetic Mark Dependent on Aryl Hydrocarbon Receptor Recruitment of Carbamoyl Phosphate Synthase 1.
The results suggest that elevated isoaspartate and CPS-1, and reduced CA-III levels could serve as biomarkers of hepatocellular injury.
Title: Isoaspartate, carbamoyl phosphate synthase-1, and carbonic anhydrase-III as biomarkers of liver injury.
CPS1 becomes readily detectable upon hepatocyte apoptotic and necrotic death. Its abundance and short serum half-life suggest that it may be a useful prognostic biomarker in acute liver injury.
Title: Carbamoyl phosphate synthetase-1 is a rapid turnover biomarker in mouse and human acute liver injury.
Taken together with previous findings regarding CPS1 structure and function, homology modeling of mouse CPS1 suggested that nitration at Y1450 in an alpha-helix of allosteric domain prevents activation of CPS1 by its activator, N-acetyl-l-glutamate.
Title: Protein tyrosine nitration of mitochondrial carbamoyl phosphate synthetase 1 and its functional consequences.
Because ammonia generated during fasting is toxic, SIRT5 protein might play a protective role by converting ammonia to non-toxic urea through deacetylation and activation of CPS1.
Title: Overexpression of SIRT5 confirms its involvement in deacetylation and activation of carbamoyl phosphate synthetase 1.
SIRT5 deacetylates CPS1 and upregulates its activity
Title: SIRT5 Deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle.

Submit: New GeneRIF Correction See all GeneRIFs (11)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (1) 1 citation
Endonuclease-mediated (7)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Cps1 (e-PCR), detects polymorphism
- UniSTS:545921

Cps1 (e-PCR), detects polymorphism
- UniSTS:546708

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables ATP binding	ISO Inferred from Sequence Orthology more info
enables calcium ion binding	ISO Inferred from Sequence Orthology more info
enables carbamoyl-phosphate synthase (ammonia) activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables carbamoyl-phosphate synthase (ammonia) activity	ISO Inferred from Sequence Orthology more info
contributes_to carbamoyl-phosphate synthase (glutamine-hydrolyzing) activity	IBA Inferred from Biological aspect of Ancestor more info
enables catalytic activity	IEA Inferred from Electronic Annotation more info
enables endopeptidase activity	ISO Inferred from Sequence Orthology more info
enables glutamate binding	ISO Inferred from Sequence Orthology more info
enables ligase activity	IEA Inferred from Electronic Annotation more info
enables metal ion binding	ISO Inferred from Sequence Orthology more info
enables modified amino acid binding	ISO Inferred from Sequence Orthology more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables phospholipid binding	ISO Inferred from Sequence Orthology more info
enables potassium ion binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	ISO Inferred from Sequence Orthology more info
enables small molecule binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
involved_in 'de novo' pyrimidine nucleobase biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in carbamoyl phosphate biosynthetic process	ISO Inferred from Sequence Orthology more info
involved_in cellular response to ammonium ion	ISO Inferred from Sequence Orthology more info
involved_in glutamine metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in homocysteine metabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within metabolic process	IEA Inferred from Electronic Annotation more info
involved_in monoatomic anion homeostasis	ISO Inferred from Sequence Orthology more info
involved_in nitric oxide metabolic process	ISO Inferred from Sequence Orthology more info
involved_in nitrogen compound metabolic process	IEA Inferred from Electronic Annotation more info
involved_in response to lipopolysaccharide	ISO Inferred from Sequence Orthology more info
involved_in triglyceride catabolic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within urea cycle	IC Inferred by Curator more info	PubMed
involved_in urea cycle	ISO Inferred from Sequence Orthology more info
involved_in vasodilation	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in membrane	IEA Inferred from Electronic Annotation more info
located_in mitochondrial inner membrane	ISO Inferred from Sequence Orthology more info
located_in mitochondrial nucleoid	ISO Inferred from Sequence Orthology more info
located_in mitochondrion	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrion	ISO Inferred from Sequence Orthology more info
located_in nucleolus	ISO Inferred from Sequence Orthology more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
part_of protein-containing complex	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: carbamoyl-phosphate synthase [ammonia], mitochondrial

Names: CPSase I; carbamoyl-phosphate synthetase I; carbamoylphosphate synthetase I

NP_001074278.1

EC 6.3.4.16

XP_011236802.1

EC 6.3.4.16

XP_036020343.1

EC 6.3.4.16

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001080809.2 → NP_001074278.1 carbamoyl-phosphate synthase [ammonia], mitochondrial precursor

See identical proteins and their annotated locations for NP_001074278.1

Status: REVIEWED

Source sequence(s)

AI046442, AK028683, BC126969, BY790286

Consensus CDS

CCDS35605.1

UniProtKB/Swiss-Prot

A0JNU4, Q6NX75, Q8C196

Related

ENSMUSP00000027144.8, ENSMUST00000027144.8

Conserved Domains (2) summary

TIGR01368
Location:46 → 400

CPSaseIIsmall; carbamoyl-phosphate synthase, small subunit

TIGR01369
Location:419 → 1477

CPSaseII_lrg; carbamoyl-phosphate synthase, large subunit

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000067.7 Reference GRCm39 C57BL/6J

Range

67151294..67270426

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_036164450.1 → XP_036020343.1 carbamoyl-phosphate synthase [ammonia], mitochondrial isoform X1

UniProtKB/Swiss-Prot

A0JNU4, Q6NX75, Q8C196

Conserved Domains (2) summary

TIGR01368
Location:46 → 400

CPSaseIIsmall; carbamoyl-phosphate synthase, small subunit

TIGR01369
Location:419 → 1477

CPSaseII_lrg; carbamoyl-phosphate synthase, large subunit
XM_011238500.1 → XP_011236802.1 carbamoyl-phosphate synthase [ammonia], mitochondrial isoform X1

See identical proteins and their annotated locations for XP_011236802.1

UniProtKB/Swiss-Prot

A0JNU4, Q6NX75, Q8C196

Conserved Domains (2) summary

TIGR01368
Location:46 → 400

CPSaseIIsmall; carbamoyl-phosphate synthase, small subunit

TIGR01369
Location:419 → 1477

CPSaseII_lrg; carbamoyl-phosphate synthase, large subunit