| Property | Summary |
|---|---|
| Gene name | **ASS1**; synonym: **ASS** (human argininosuccinate synthase 1) (pqac-00000001, pqac-00000009) |
| Protein name | **Argininosuccinate synthase 1**; catalyzes argininosuccinate formation in arginine biosynthesis/urea cycle (pqac-00000001, pqac-00000017) |
| UniProt ID | **P00966** |
| EC number | **EC 6.3.4.5** (argininosuccinate synthase) (pqac-00000001) |
| Organism | **Homo sapiens (Human)** |
| Molecular weight | Monomer is approximately **46 kDa** (pqac-00000009) |
| Oligomeric state | **Homotetramer**; tetrameric state is conserved and required for activity (pqac-00000009, pqac-00000010) |
| Subcellular localization | Primarily **cytosolic**; in liver associated with periportal hepatocyte urea-cycle function; can accumulate in the **nucleus** during DNA damage responses; reported association with **caveolae** in endothelial cells (pqac-00000008, pqac-00000021, pqac-00000025) |
| Primary substrates | **Citrulline**, **L-aspartate**, and **ATP** (pqac-00000001, pqac-00000005) |
| Primary products | **Argininosuccinate**, **AMP**, and **pyrophosphate (PPi)** (pqac-00000001) |
| Catalyzed reaction | ATP-dependent condensation of citrulline with aspartate to form argininosuccinate; rate-limiting step of de novo arginine synthesis and a key urea-cycle step (pqac-00000001, pqac-00000018) |
| Key active-site residues | Residues implicated in substrate binding/catalysis include **Glu270, Tyr282, Arg127, Asn123, Tyr87, Ser189, Thr119, Gln40**; Arg127 and Asn123 help bind substrates, and domain movement helps position citrulline for attack on ATP (pqac-00000005, pqac-00000011, pqac-00000012) |
| Domain architecture | Three-part architecture: **nucleotide-binding domain**, **synthetase domain**, and **C-terminal oligomerization helix** (pqac-00000009, pqac-00000010) |
| Key regulatory modifications | **CLOCK-mediated acetylation** at **K165/K176** rhythmically inhibits ASS1 activity and drives circadian ureagenesis; **Cys132 nitrosylation** has been reported as an inactivating mammalian regulatory modification (pqac-00000042, pqac-00000044, pqac-00000046, pqac-00000011) |
| Major pathway roles | Functions in the **urea cycle**, **de novo arginine biosynthesis**, and **citrulline–NO cycle**; also influences nucleotide synthesis by competing for aspartate and can link ureagenesis to hepatic **AMPK/lipid metabolism** (pqac-00000017, pqac-00000018, pqac-00000019, pqac-00000023) |
| Recent non-canonical functions | In 2024, ASS1 was shown to have a **nuclear DNA-damage-response role**: after DNA damage it accumulates in the nucleus, generates fumarate with ASL, promotes **SMARCC1 succination**, and modulates p53-regulated chromatin accessibility/transcription (pqac-00000025, pqac-00000026, pqac-00000050) |
| Associated diseases/contexts | **Citrullinemia type I (CTLN1)** from biallelic ASS1 deficiency causes hyperammonemia and elevated citrulline; in cancer, **ASS1 silencing** creates **arginine auxotrophy** and therapeutic vulnerability to arginine deprivation (pqac-00000039, pqac-00000040, pqac-00000041, pqac-00000033, pqac-00000034) |
| PDB structure ID | **2NZ2** (human ASS1 crystal structure) (pqac-00000014) |
| Protein family | **Argininosuccinate synthase family**, type 1 subfamily; structurally conserved tetrameric enzyme family (pqac-00000009, pqac-00000010) |


*Table: This table summarizes the core biochemical, structural, localization, regulatory, and disease-associated properties of human ASS1. It is useful as a compact reference for functional annotation and interpretation of recent ASS1 literature.*