| Property | Summary |
|---|---|
| Gene name | **CPS1** (carbamoyl-phosphate synthase 1) (pqac-00000000, pqac-00000007) |
| Protein name | **Carbamoyl-phosphate synthase [ammonia], mitochondrial**; carbamoyl-phosphate synthetase I; CPSase I (pqac-00000000, pqac-00000007) |
| EC number | **EC 6.3.4.16** (pqac-00000000, pqac-00000004) |
| UniProt ID | **P31327** (pqac-00000000) |
| Organism | **Homo sapiens (Human)** (pqac-00000000) |
| Molecular weight | ~**160 kDa** mature mitochondrial enzyme (pqac-00000004, pqac-00000010) |
| Precursor length | **1500 aa precursor** with N-terminal mitochondrial targeting sequence (pqac-00000007) |
| Mature length | **1462 aa** after cleavage of ~38 aa transit peptide upon mitochondrial import (pqac-00000008, pqac-00000009) |
| Subcellular localization | **Mitochondrial matrix**; a substantial fraction also associates in clusters near the **inner mitochondrial membrane** with NAGS and OTC (pqac-00000010, pqac-00000038, pqac-00000039) |
| Tissue expression | Expressed predominantly in **hepatocytes** and **enterocytes** (liver and small intestine) (pqac-00000007, pqac-00000008) |
| Substrates | **2 ATP + NH3 + HCO3-**; CPS1 uses **free ammonia** rather than glutamine (pqac-00000001, pqac-00000004, pqac-00000006) |
| Products | **Carbamoyl phosphate + 2 ADP + Pi** (pqac-00000001, pqac-00000004) |
| Primary biochemical function | Catalyzes the **first and rate-limiting step of the urea cycle**, producing carbamoyl phosphate for conversion with ornithine to citrulline by OTC (pqac-00000022, pqac-00000026) |
| Catalytic mechanism | Three-step mechanism with **carboxyphosphate** and **carbamate** intermediates; two distinct phosphorylation sites for bicarbonate and carbamate phosphorylation (pqac-00000001, pqac-00000003) |
| Allosteric activator | **N-acetyl-L-glutamate (NAG)** is an essential allosteric activator; CPS1 is inactive without it (pqac-00000003, pqac-00000015, pqac-00000034) |
| Key regulatory modification: SIRT5 deacetylation | **SIRT5 deacetylates and activates CPS1** in the mitochondrial matrix, especially during fasting/calorie restriction, promoting ammonia detoxification (pqac-00000015, pqac-00000018, pqac-00000061) |
| Key regulatory modification: O-GlcNAcylation | **O-GlcNAcylation regulates CPS1 activity** in a nutrient-sensitive manner; reported sites include **Thr109, Thr110, Thr1078** that enhance catalytic efficiency for ammonia, while aging/dietary studies also identify nutrient-responsive O-GlcNAc regulation affecting ureagenesis (pqac-00000014, pqac-00000016, pqac-00000054, pqac-00000056) |
| Structural/domain features | Multidomain enzyme with bicarbonate-phosphorylation and carbamate-phosphorylation domains plus a **C-terminal allosteric NAG-binding domain** and integrating/unknown-function subdomain (pqac-00000008, pqac-00000013) |
| Disease association: inherited disorder | **CPS1 deficiency (OMIM 237300)**, an autosomal recessive urea-cycle disorder causing severe **hyperammonemia**; neonatal and late-onset forms are reported (pqac-00000031, pqac-00000034) |
| Clinical features/statistics in recent cohorts | In a 2024 Chinese series of **7 patients**, peak ammonia ranged **160-1000 umol/L**; **4 died** and **3 survived** with treatment; **10 of 12 variants** identified were novel (pqac-00000030) |
| Typical treatment/management | Ammonia scavengers (**sodium phenylbutyrate**, **sodium benzoate**), **arginine**, low-protein diet, hemodialysis in crises, and sometimes **liver transplantation** (pqac-00000030, pqac-00000032) |
| Disease association: cancer | CPS1 can be **downregulated in hepatocellular carcinoma** via promoter DNA methylation, but is **upregulated in several other cancers** where it supports **pyrimidine synthesis** and tumor growth (pqac-00000035, pqac-00000036) |
| Real-world/therapeutic relevance | CPS1 is a candidate target in hyperammonemia and oncology; small-molecule inhibition in primary human hepatocytes reduces urea production and affects pyrimidine metabolism (pqac-00000049, pqac-00000053) |
| PDB structure codes | **5DOT** (apo human CPS1 used as structural reference), **5DOU** (human CPS1 structure), **6UEL** (CPS1 in complex with allosteric inhibitor H3B-193 at 1.90 A resolution) (pqac-00000039, pqac-00000050) |


*Table: This table summarizes the verified identity, biochemical function, regulation, localization, disease relevance, and structural resources for human CPS1 (UniProt P31327). It is useful as a compact reference for the main facts needed in a functional-annotation report.*