| Aspect | Key evidence/notes | Key sources |
|---|---|---|
| identity/domains | **Candida albicans** **CSH3** encodes **Csh3p**, a functional and structural homolog of **Saccharomyces cerevisiae Shr3p**. The reported protein has **four transmembrane segments**, ~**36% identity / 48% similarity** to S. cerevisiae Shr3p, matching the UniProt-assigned **Shr3/Psh3 family** context rather than an unrelated CSH3 symbol from another organism. (pqac-00000004, pqac-00000022) | Martínez & Ljungdahl 2004, DOI: https://doi.org/10.1046/j.1365-2958.2003.03845.x; Ljungdahl et al. 1992, DOI: https://doi.org/10.1016/0092-8674(92)90515-e |
| localization | Functional **Csh3p-GFP** localizes to the **perinuclear rim** and a filamentous cytoplasmic network, consistent with the **endoplasmic reticulum (ER)**. Reviews and comparative studies consistently describe Csh3/Shr3 proteins as **ER-membrane-localized** chaperones. (pqac-00000003, pqac-00000005, pqac-00000017) | Martínez & Ljungdahl 2004, DOI: https://doi.org/10.1046/j.1365-2958.2003.03845.x; Silao & Ljungdahl 2021, DOI: https://doi.org/10.3390/pathogens11010005 |
| molecular function | Csh3p is **not an enzyme or transporter**; it is a **specialized ER packaging/folding chaperone** required for the productive biogenesis of **amino acid permeases (AAPs)**. By analogy with Shr3-family mechanistic work, it assists early folding/assembly of multipass transporters, promotes their **COPII-dependent ER exit**, and helps prevent aggregation and premature **ERAD**. (pqac-00000002, pqac-00000007, pqac-00000008, pqac-00000009) | Martínez & Ljungdahl 2004, DOI: https://doi.org/10.1046/j.1365-2958.2003.03845.x; Kota et al. 2007, DOI: https://doi.org/10.1083/jcb.200612100; Diallinas & Martzoukou 2019, DOI: https://doi.org/10.1111/febs.15078 |
| client proteins | The best-supported clients are the **AAP family** in C. albicans; the genome was noted to encode ~**22 AAP-related ORFs**. The literature also predicts dependence of the **Ssy1** amino-acid sensor/permease-like component on Csh3 for proper plasma-membrane localization, consistent with Shr3-family substrate specificity for related multipass membrane proteins. (pqac-00000002, pqac-00000021, pqac-00000023) | Martínez & Ljungdahl 2004, DOI: https://doi.org/10.1046/j.1365-2958.2003.03845.x; Garbe 2023 (review context summarized in available text) |
| pathway context | Csh3p functions upstream of **amino acid uptake** and intersects the **SPS amino-acid sensing pathway** because proper localization of AAPs, and likely **Ssy1**, is required for extracellular amino-acid responses. In the broader model, extracellular amino acids activate **Ssy1-Ptr3-Ssy5**, causing **Stp1/Stp2** processing and induction of AAP genes; Csh3 is needed so these induced permeases become functional at the plasma membrane. (pqac-00000021, pqac-00000023, pqac-00000005) | Martínez & Ljungdahl 2004, DOI: https://doi.org/10.1046/j.1365-2958.2003.03845.x; Silao & Ljungdahl 2021, DOI: https://doi.org/10.3390/pathogens11010005 |
| phenotypes | **csh3Δ/csh3Δ** mutants show broad defects in amino-acid utilization and uptake, including inability to efficiently use several amino acids as nitrogen sources and failure to undergo **amino-acid-induced filamentation**. **CSH3/csh3Δ** heterozygotes are **haploinsufficient** for high-capacity uptake, showing intermediate uptake defects while often retaining amino-acid-induced morphogenetic signaling. (pqac-00000001, pqac-00000003, pqac-00000015) | Martínez & Ljungdahl 2004, DOI: https://doi.org/10.1046/j.1365-2958.2003.03845.x |
| virulence data | In a mouse intravenous infection model using **1 × 10^6 cells** per inoculum, wild-type **CSH3/CSH3** strains killed all mice rapidly, whereas both **heterozygous** and **homozygous csh3 mutants** were markedly attenuated. Reported summary outcomes include wild type killing all mice within **9 days** (one wild-type comparator by **day 5**), while mutant groups showed prolonged survival, with **50% alive at day 16** and some animals surviving to **day 30**. (pqac-00000000, pqac-00000016, pqac-00000021) | Martínez & Ljungdahl 2004, DOI: https://doi.org/10.1046/j.1365-2958.2003.03845.x |
| quantitative measures | Uptake assays measured initial rates with **14C-labeled amino acids** at **50 mM** substrate and reported activity in **nmol min^-1**. Quantitatively, the null mutant had **undetectable lysine and phenylalanine uptake**, **greatly diminished histidine and proline uptake**, and even **increased adenine uptake**; figure-based evidence also shows gene-dosage effects in heterozygotes and a **5 h** proline-uptake induction time course. (pqac-00000003, pqac-00000006, pqac-00000017) | Martínez & Ljungdahl 2004, DOI: https://doi.org/10.1046/j.1365-2958.2003.03845.x |


*Table: This table summarizes the experimentally supported functional annotation of Candida albicans Csh3p (CSH3; UniProt A0A1D8PLU5), including identity, localization, mechanism, pathway placement, and phenotype/virulence evidence. It is useful as a concise evidence map for interpreting this Shr3-family ER membrane chaperone.*