| Property | Summary |
|---|---|
| Gene name | **PCCA**; encodes the mitochondrial **propionyl-CoA carboxylase alpha chain** in human, matching UniProt accession **P05165** (pqac-00000001, pqac-00000023) |
| UniProt accession | **P05165** (user-provided target context) |
| Chromosomal location | **Chromosome 13** in human (pqac-00000001) |
| Protein size | **~70 kDa** alpha subunit of PCC (pqac-00000001) |
| Enzyme classification | **EC 6.4.1.3**, propionyl-CoA carboxylase (pqac-00000000, pqac-00000001) |
| Cofactor | **Biotin**; PCC is a **biotin-dependent carboxylase** (pqac-00000000, pqac-00000020) |
| Reaction catalyzed | **Propionyl-CoA + HCO3− + ATP → D-methylmalonyl-CoA + ADP + Pi**; ATP-dependent biotin-mediated carboxylation (pqac-00000000, pqac-00000001, pqac-00000031) |
| Subcellular localization | **Mitochondrial matrix** (pqac-00000001, pqac-00000023) |
| Mitochondrial targeting | Synthesized as a precursor with an **N-terminal mitochondrial leader/presequence**; mature alpha subunit begins at about **residue 26**, implying a ~25 aa targeting peptide (pqac-00000022, pqac-00000023) |
| Holoenzyme assembly | **α6β6 dodecamer**; four-layer architecture with six β subunits forming the core and α subunits arranged on top and bottom (pqac-00000001, pqac-00000016, pqac-00000017) |
| Key domains | **Alpha/PCCA:** **BC** (biotin carboxylase), **BT** linker/hub domain, **BCCP** (biotin carboxyl carrier protein); **Beta/PCCB:** **CT** (carboxyltransferase) domain with CT-N and CT-C subdomains (pqac-00000016, pqac-00000017, pqac-00000020) |
| Primary metabolic pathway | **Propionate metabolism**: propionyl-CoA → D-methylmalonyl-CoA → L-methylmalonyl-CoA → **succinyl-CoA**, which enters the **TCA cycle** and supports gluconeogenesis (pqac-00000002, pqac-00000005) |
| Metabolic inputs to pathway | Propionyl-CoA arises from catabolism of **isoleucine, valine, threonine, methionine**, **odd-chain fatty acids**, and **cholesterol side chains** (pqac-00000001, pqac-00000002, pqac-00000005) |
| Disease association | Biallelic loss-of-function variants in **PCCA** cause **propionic acidemia**, a severe autosomal recessive organic acidemia with metabolic decompensation, neurologic disease, and cardiomyopathy risk (pqac-00000008, pqac-00000010) |
| Substrate specificity | **Primary substrate:** propionyl-CoA. Human PCC can also carboxylate **acetyl-CoA** at a much lower rate, about **1.5%** of the propionyl-CoA rate; recent structural work found acetyl-CoA and propionyl-CoA bind in highly similar modes (pqac-00000028, pqac-00000030) |
| Representative recent structural data | High-resolution human PCC cryo-EM structures reported in 2024: **apo 3.02 Å**, **propionyl-CoA-bound 2.80 Å**, with overall structures reported in the **2.29–3.38 Å** range; PDB entries include **8XL3, 8XL4, 8XL5** (pqac-00000016, pqac-00000018, pqac-00000021) |


*Table: This table summarizes the core molecular, biochemical, structural, and disease-related properties of human PCCA/propionyl-CoA carboxylase alpha chain. It is useful as a compact reference for functional annotation and for linking enzyme function to propionic acidemia.*