| Component / gene | Protein name / subunit | Cellular localization / topology notes | Molecular function & substrates | Key quantitative data | Key references (year, DOI URL) |
|---|---|---|---|---|---|
| **manX** | **IIABMan** (cytosolic Enzyme IIAB component of mannose-family PTS) | Peripheral/cytosolic phosphotransfer protein; IIA is a homodimeric soluble domain and IIB carries the phospho-accepting histidine/cysteine chemistry typical of the mannose-family pathway; associates with membrane ManY/ManZ complex in the full transporter (pqac-00000019, pqac-00000018) | Receives phosphate from HPr and passes it toward the sugar during group translocation by ManXYZ; part of the transporter used for uptake/phosphorylation of **mannose**, and also contributes to transport of **glucose, 2-deoxyglucose, glucosamine / N-acetylglucosamine** in E. coli mannose-family PTS context (pqac-00000019, pqac-00000000, pqac-00000003) | Stable transport complex described as **IIABman2:(IICmanIIDman)2**; overall PEP→sugar phosphotransfer is strongly favorable (**ΔG° ≈ −48 kJ·mol−1**) for the PTS pathway (pqac-00000018, pqac-00000000) | Seip et al. **1994**, Biochemistry, DOI: https://doi.org/10.1021/bi00189a021 (pqac-00000019); Jeckelmann & Erni **2019**, DOI: https://doi.org/10.1007/978-3-030-18768-2_8 (pqac-00000000, pqac-00000018) |
| **manY** (**UniProt P69801; b1818/JW1807 in UniProt context**) | **IICMan / EIIC-Man**; mannose permease IIC component | **Integral inner-membrane** subunit of ManXYZ. **Seip 1994 explicitly maps manY → IICMan**. Experimental/speculative topology literature supports **~6 TM segments** (possibly **6–8 TM** in consensus models) with **cytoplasmic N- and C-termini**; forms a tight membrane complex with ManZ and contributes Core/Arm/Vmotif architecture in cryo-EM ManYZ structures (pqac-00000019, pqac-00000018, pqac-00000015, pqac-00000021) | Primary permease subunit for **PTS-mediated uptake coupled to phosphorylation** of **mannose**; broader specificity includes **glucose, mannosamine, 2-deoxyglucose, glucosamine/N-acetylglucosamine**, with poor tolerance for C-4/C-6 sugar substitutions. Physiologically part of the **sole mannose uptake system** in E. coli and involved in scavenging cell-wall-derived amino sugars (pqac-00000000, pqac-00000003) | Reconstituted mannose-family **IICIID** complexes: **vectorial phosphorylation Km ≈ 30 μM, kcat ≈ 1.2 s−1**; **non-vectorial phosphorylation Km ≈ 0.1 mM, kcat ≈ 3 s−1**. **manY alone** overexpression caused only modest uptake changes (e.g., ~**1.6-fold** for αMG, ~**1.1-fold** for GlcNAc), whereas **manYZ** co-overexpression strongly stimulated uptake (**αMG ~14.0-fold**, **2DG ~10.8-fold**, **mannitol ~2.1-fold**) (pqac-00000000, pqac-00000003, pqac-00000004, pqac-00000001) | Seip et al. **1994**, DOI: https://doi.org/10.1021/bi00189a021 (**explicit manY→IICMan**) (pqac-00000019); Jeckelmann & Erni **2019**, DOI: https://doi.org/10.1007/978-3-030-18768-2_8 (pqac-00000000, pqac-00000018); Aboulwafa et al. **2020**, DOI: https://doi.org/10.1159/000510257 (pqac-00000001, pqac-00000003, pqac-00000004); Huang et al. **2021**, DOI: https://doi.org/10.1038/s41421-021-00253-6 (pqac-00000015) |
| **manZ** | **IIDMan / EIID-Man** | Integral inner-membrane partner of ManY; tightly associated and apparently required for stable ManY function/expression. Topology models suggest a **large N-terminal cytoplasmic domain** plus multiple C-terminal TM segments; in cryo-EM ManYZ each protomer contributes **Core/Arm/Vmotif** elements, and ManY/ManZ assemble as a membrane complex (pqac-00000018, pqac-00000015, pqac-00000014) | Partner permease subunit that works with ManY to form the membrane translocation/phosphorylation apparatus for mannose-family substrates; required for full transport activity and receptor functions for certain toxins/phages (pqac-00000018, pqac-00000016) | **manYZ**, but not manY alone, strongly increased uptake of heterologous PTS substrates in overexpression assays; authors note **ManY is thought to be unstable in the absence of ManZ** (pqac-00000004, pqac-00000005) | Jeckelmann & Erni **2019**, DOI: https://doi.org/10.1007/978-3-030-18768-2_8 (pqac-00000016, pqac-00000018); Huang et al. **2021**, DOI: https://doi.org/10.1038/s41421-021-00253-6 (pqac-00000014, pqac-00000015); Aboulwafa et al. **2020**, DOI: https://doi.org/10.1159/000510257 (pqac-00000004, pqac-00000005) |
| **ManXYZ system-level finding** | Mannose-family PTS transporter (IIAB/IIC/IID) | Inner membrane transporter with cytosolic phosphotransfer components; historic biochemical models described a dimer of IICIID protomers, while cryo-EM of the **MccE492–ManYZ** complex resolved a **3:3 assembly** with mannose located mid-membrane and domain organization into **Core, Arm, Vmotif** (pqac-00000018, pqac-00000015, pqac-00000021) | Main physiological role is **group translocation**: transport plus phosphorylation of mannose-family sugars. Also acts as an inner-membrane receptor exploited by **bacteriophage λ** and **microcin E492**; microcin binding occurs without blocking λ receptor interface (pqac-00000016, pqac-00000014) | Cryo-EM reconstruction of MccE492–ManYZ reached **2.28 Å** from **92,052 particles**; conformational change to occluded state involved ~**47°** Core rotation and ~**11 Å** translation (pqac-00000015, pqac-00000014) | Huang et al. **2021**, DOI: https://doi.org/10.1038/s41421-021-00253-6 (pqac-00000014, pqac-00000015, pqac-00000021); Jeckelmann & Erni **2019**, DOI: https://doi.org/10.1007/978-3-030-18768-2_8 (pqac-00000016, pqac-00000018) |
| **Recent 2024 development relevant to manY/manXYZ** | Promoter-engineered mannose PTS / mannose catabolism strain | Chromosomal promoter driving **manXYZ** replaced with strong heterologous promoter (**PptsG** or **Ptet**), combined with **Δmlc** and stronger **manA** expression to rewire mannose utilization (pqac-00000012, pqac-00000013) | Demonstrated that slow E. coli growth on mannose is not an intrinsic limitation of ManXYZ chemistry alone; instead, **regulatory/proteome allocation** limits mannose performance. Strengthening **manXYZ** and downstream mannose catabolic expression can make mannose behave like a high-quality substrate (pqac-00000010, pqac-00000011) | Engineered strain **YCE119** grew on **mannose minimal medium at the same rate as wild-type on glucose**; statistics reported **WT glucose vs WT mannose P < 0.0001**, **WT mannose vs YCE119 mannose P < 0.0001**, while **WT glucose vs YCE119 mannose was not significant** (pqac-00000010, pqac-00000011) | Mukherjee et al. **2024**, PLOS Comput Biol, DOI: https://doi.org/10.1371/journal.pcbi.1011735 (pqac-00000010, pqac-00000011, pqac-00000012, pqac-00000013) |


*Table: This table summarizes the E. coli K-12 mannose-family PTS with emphasis on manY (UniProt P69801), including subunit assignments, membrane topology/function, quantitative transport data, and recent 2024 regulatory-engineering findings. It is useful for quickly verifying that manY is the EIIC permease subunit and for linking classic biochemical understanding to current physiological and structural studies.*