ManY is the EIIC component of the mannose-specific phosphotransferase system (Man-PTS) in E. coli K12. It is an integral inner membrane protein with multiple transmembrane helices that, together with ManZ (EIID), forms the transmembrane translocation channel of the mannose permease. The ManY/ManZ heterodimer assembles into a homotrimer of protomers (PMID:31209249). ManY contains the specific substrate-binding site within its PTS EIIC type-4 domain (UniProt). The ManXYZ complex transports mannose, glucose, fructose, and N-acetylglucosamine via PEP-dependent phosphorylation (PMID:2951378). The Man-PTS also serves as a receptor for bacteriophage lambda DNA injection (ManY was originally identified as the "pel" gene; PMID:353494) and as a chemoreceptor for sugars (PMID:4604906). ManY and ManZ alone are sufficient for lambda DNA penetration, while all three subunits (ManX, ManY, ManZ) are required for sugar transport and phosphorylation (PMID:2951378).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: ManY is an integral inner membrane protein confirmed by multiple experimental approaches including topology mapping (PMID:8774730, PMID:15919996), cryo-EM structure (PMID:31209249), and biochemical fractionation (PMID:2951378). In E. coli, "plasma membrane" corresponds to the inner (cytoplasmic) membrane. The IBA annotation is phylogenetically well-supported and matches all available evidence. Reason: ManY is unambiguously an inner membrane protein. The IBA annotation is consistent with extensive experimental evidence from topology studies, structural data, and biochemical characterization. The term "plasma membrane" (GO:0005886) is the standard GO term for the bacterial inner membrane. Supporting Evidence: PMID:2951378 II-PMan (28 kDa) is very hydrophobic...Both are integral membrane proteins and most likely form the transmembrane channel PMID:15919996 Using C-terminal tagging with the alkaline phosphatase and green fluorescent protein, we established the periplasmic or cytoplasmic locations of the C termini for 601 inner membrane proteins file:ECOLI/manY/manY-deep-research-falcon.md forms the **membrane channel and substrate-binding/translocation machinery** responsible for selectively transporting sugars across the inner membrane during PTS-mediated uptake |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation from UniProt subcellular location mapping. Redundant with IBA and IDA annotations for the same term. Correct but adds no additional information. Reason: This IEA annotation is consistent with the experimentally supported plasma membrane localization. It is redundant with the IBA (GO_REF:0000033) and IDA (PMID:15919996, PMID:2951378) annotations for the same term, but is not incorrect. |
| GO:0005886 plasma membrane | IDA PMID:15919996 Global topology analysis of the Escherichia coli inner membr... | ACCEPT | Summary: Daley et al. (2005) performed a global topology analysis of the E. coli inner membrane proteome using C-terminal GFP and PhoA fusions for 601 inner membrane proteins. ManY was included in this study and its inner membrane localization was confirmed experimentally. Reason: Direct experimental evidence from a large-scale but rigorous topology study confirming ManY as an inner membrane protein. This is valid IDA evidence. Supporting Evidence: PMID:15919996 Using C-terminal tagging with the alkaline phosphatase and green fluorescent protein, we established the periplasmic or cytoplasmic locations of the C termini for 601 inner membrane proteins |
| GO:0005886 plasma membrane | IDA PMID:2951378 The mannose permease of Escherichia coli consists of three d... | ACCEPT | Summary: Erni et al. (1987) characterized ManY (II-PMan) as a very hydrophobic integral membrane protein that forms the transmembrane channel. This characterization established the membrane localization of ManY. Reason: The original characterization paper by Erni et al. directly identified ManY as an integral membrane protein through biochemical analysis. Valid IDA evidence. Supporting Evidence: PMID:2951378 II-PMan (28 kDa) is very hydrophobic...Both are integral membrane proteins and most likely form the transmembrane channel |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation from InterPro domain mapping (IPR004700, PTS_IIC_man). This is a very general term. ManY is indeed a membrane protein, but the more specific term GO:0005886 (plasma membrane) is already annotated with stronger evidence. Reason: While this is a less specific term than GO:0005886, it is technically correct and IEA annotations at a broader level than experimentally supported ones are acceptable. The InterPro mapping from PTS_IIC_man domain is appropriate. |
| GO:0016020 membrane | HDA PMID:16858726 A complexomic study of Escherichia coli using two-dimensiona... | ACCEPT | Summary: Lasserre et al. (2006) identified ManY in membrane protein complexes using 2D BN/SDS-PAGE and LC-MS/MS in a global complexomic study. This provides high-throughput experimental evidence for membrane localization. Reason: High-throughput direct assay evidence for membrane localization. While the term GO:0016020 (membrane) is less specific than GO:0005886 (plasma membrane), this annotation reflects the evidence available from the complexomic study, which identified ManY in the membrane fraction. Correct and acceptable. Supporting Evidence: PMID:16858726 the cytosolic and membrane protein complexes of Escherichia coli were separated...the different partners of each protein complex were identified by LC-MS/MS |
| GO:0009401 phosphoenolpyruvate-dependent sugar phosphotransferase system | IBA GO_REF:0000033 | ACCEPT | Summary: ManY is a core component of the mannose-specific PEP-dependent sugar PTS. The IBA annotation is phylogenetically sound and reflects the primary biological process in which ManY participates. The ManXYZ complex catalyzes PEP-dependent phosphorylation concomitant with sugar translocation (PMID:2951378). Reason: This is the central biological process for ManY. The IBA annotation accurately captures the core function of ManY as a component of the PTS. Well supported by extensive experimental literature. Supporting Evidence: PMID:2951378 The mannose permease of the bacterial phosphotransferase system mediates sugar transport across the cytoplasmic membrane concomitant with sugar phosphorylation file:ECOLI/manY/manY-deep-research-falcon.md so that **transport and phosphorylation occur in a coupled process** |
| GO:0009401 phosphoenolpyruvate-dependent sugar phosphotransferase system | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation from InterPro domain mapping (IPR004700, PTS_IIC_man). Redundant with IBA and IDA annotations for the same term but correct. Reason: Correct IEA annotation that is consistent with and redundant to the experimentally supported and phylogenetically inferred annotations. |
| GO:0009401 phosphoenolpyruvate-dependent sugar phosphotransferase system | IDA PMID:2951378 The mannose permease of Escherichia coli consists of three d... | ACCEPT | Summary: Erni et al. (1987) directly demonstrated that ManY is part of the mannose PTS permease, which mediates sugar transport with concomitant phosphorylation. All three subunits are required for sugar transport and phosphorylation. This annotation was made by ComplexPortal based on PMID:2951378. Reason: Strong experimental evidence directly establishing ManY as a component of the PTS. This is a core function annotation. Supporting Evidence: PMID:2951378 The mannose permease of the bacterial phosphotransferase system mediates sugar transport across the cytoplasmic membrane concomitant with sugar phosphorylation...All three subunits are required for sugar transport and phosphorylation |
| GO:0015761 mannose transmembrane transport | NAS PMID:2951378 The mannose permease of Escherichia coli consists of three d... | ACCEPT | Summary: Erni et al. (1987) described the mannose permease and its role in mannose transport. The NAS evidence code indicates non-traceable author statement. The annotation is correct as mannose is the primary substrate of the Man-PTS. Reason: Mannose transport is the canonical and primary function of the Man-PTS system. ManY forms the translocation channel with ManZ through which mannose is transported. This is a core biological process for ManY. Supporting Evidence: PMID:2951378 The mannose permease of the bacterial phosphotransferase system mediates sugar transport across the cytoplasmic membrane concomitant with sugar phosphorylation |
| GO:0015761 mannose transmembrane transport | IDA PMID:5545083 Sugar transport. II. Characterization of constitutive membra... | ACCEPT | Summary: Kundig & Roseman (1971) characterized the constitutive membrane-bound enzyme II of the PTS system, including its mannose transport activity. This early work established the biochemical basis for mannose transport by the PTS. Note that the GOA qualifier is "acts_upstream_of_or_within" rather than "involved_in", which is appropriate given the early nature of this work. Reason: Early foundational work establishing mannose transport activity of the PTS enzyme II. Mannose is the primary substrate, making this a core function. |
| GO:0015764 N-acetylglucosamine transport | EXP PMID:6252281 Amino-sugar transport systems of Escherichia coli K12. | KEEP AS NON CORE | Summary: Jones-Mortimer & Kornberg (1980) demonstrated that N-acetylglucosamine enters E. coli via the PtsM (Man-PTS) system as one of two distinct PTS pathways for this sugar. ManY, as the EIIC channel component, is directly involved in this transport. GlcNAc is a well-established secondary substrate of the Man-PTS. Reason: N-acetylglucosamine transport via the Man-PTS is experimentally demonstrated but represents a secondary substrate rather than the primary (mannose) substrate. This is a legitimate function but not the core evolved function of ManY. Supporting Evidence: PMID:6252281 N-Acetylglucosamine enters E. coli by two distinct phosphotransferase systems...One of these is the PtsM system file:ECOLI/manY/manY-deep-research-falcon.md ManXYZ/ManY is described as mediating PTS uptake/phosphorylation of **mannose** and several other sugars/analogs including **glucose**, **mannosamine**, and **N-acetylglucosamine**, and it can accommodate certain substitutions (e.g., transport/phosphorylation of **2-deoxyglucose**; poor tolerance of substitutions at C-4 and C-6). |
| GO:0098708 D-glucose import across plasma membrane | IDA PMID:5545083 Sugar transport. II. Characterization of constitutive membra... | KEEP AS NON CORE | Summary: Kundig & Roseman (1971) characterized the PTS enzyme II activities including glucose transport. Glucose is a known substrate of the Man-PTS, though glucose is primarily transported by the glucose-specific PTS (PtsG/Crr). The Man-PTS serves as a secondary glucose uptake system. ManY contributes to this function as the channel-forming EIIC subunit. Reason: Glucose transport via the Man-PTS is experimentally supported but is a secondary function. Glucose is primarily transported by the dedicated PtsG system. The Man-PTS provides a backup glucose transport route. This is a legitimate but non-core function of ManY. Supporting Evidence: file:ECOLI/manY/manY-deep-research-falcon.md ManXYZ/ManY is described as mediating PTS uptake/phosphorylation of **mannose** and several other sugars/analogs including **glucose**, **mannosamine**, and **N-acetylglucosamine**, and it can accommodate certain substitutions (e.g., transport/phosphorylation of **2-deoxyglucose**; poor tolerance of substitutions at C-4 and C-6). |
| GO:1990539 fructose import across plasma membrane | EXP PMID:4153999 The role of phosphotransferase-mediated syntheses of fructos... | KEEP AS NON CORE | Summary: Ferenci & Kornberg (1974) studied the role of PTS-mediated fructose phosphorylation in E. coli growth on fructose, demonstrating that the mannose PTS (ptsM) can transport fructose producing fructose 6-phosphate. Fructose is a secondary substrate of the Man-PTS, with fructose being primarily transported by the fructose-specific PTS (FruAB). Reason: Fructose transport via the Man-PTS is experimentally documented but represents a secondary transport pathway. The primary fructose PTS is FruAB. This is a legitimate but non-core function. |
| GO:1990539 fructose import across plasma membrane | EXP PMID:4154035 Genetical analysis of fructose utilization by Escherichia co... | KEEP AS NON CORE | Summary: Jones-Mortimer & Kornberg (1974) performed genetic analysis of fructose utilization in E. coli, providing genetic evidence for the involvement of ptsM (Man-PTS) in fructose uptake. This is a duplicate annotation for the same GO term from a companion paper to PMID:4153999. Reason: Additional genetic evidence for fructose transport via the Man-PTS. Same rationale as the companion annotation from PMID:4153999 -- fructose is a secondary substrate of the Man-PTS. |
| GO:0022870 protein-N(PI)-phosphohistidine-mannose phosphotransferase system transporter activity | IDA PMID:2951378 The mannose permease of Escherichia coli consists of three d... | ACCEPT | Summary: Erni et al. (1987) directly characterized the mannose permease as mediating PEP-dependent mannose transport with concomitant phosphorylation. GO:0022870 is the specific molecular function term for the mannose PTS transporter activity. ManY (EIIC) contains the specific substrate-binding site and forms the translocation channel with ManZ (EIID). While the full transporter activity requires all three subunits (ManXYZ), ManY is the channel-forming component that directly enables this activity. Reason: This is the most specific and accurate molecular function term for ManY. The mannose PTS transporter activity is the core molecular function of the ManXYZ complex, and ManY is the EIIC component that contains the substrate binding site and forms the channel. Strongly supported by experimental evidence. Supporting Evidence: PMID:2951378 The mannose permease of the bacterial phosphotransferase system mediates sugar transport across the cytoplasmic membrane concomitant with sugar phosphorylation...All three subunits are required for sugar transport and phosphorylation file:ECOLI/manY/manY-deep-research-falcon.md forms the **membrane channel and substrate-binding/translocation machinery** responsible for selectively transporting sugars across the inner membrane during PTS-mediated uptake |
| GO:1902495 transmembrane transporter complex | IPI PMID:31209249 Structure of the mannose transporter of the bacterial phosph... | NEW | Summary: The UniProt record lists GO:1902495 (transmembrane transporter complex, IPI, ComplexPortal) based on the cryo-EM structure showing ManY-ManZ heterodimer forming a homotrimer (PMID:31209249). This annotation was not present in the GOA TSV but is in the UniProt GO cross-references. ManY is part of the D-mannose-specific enzyme II complex (ComplexPortal CPX-5968). Reason: This CC annotation accurately describes ManY as part of a transmembrane transporter complex. The cryo-EM structure (PMID:31209249) directly demonstrates that ManY and ManZ form a heterodimeric complex that assembles into a homotrimer. ComplexPortal entry CPX-5968 documents this complex. Supporting Evidence: PMID:2951378 II-PMan (28 kDa) is very hydrophobic...Both are integral membrane proteins and most likely form the transmembrane channel file:ECOLI/manY/manY-deep-research-falcon.md The complex assembles with **threefold symmetry** and a **3:3 stoichiometry** (3 MccE492 : 3 ManYZ), with **mannose localized mid-membrane** in the complex. |
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Download this section (compressed HTML)Q: What is the precise substrate specificity profile of ManY compared to other EIIC components? Are there additional substrates beyond mannose, glucose, fructose, and GlcNAc?
Q: Is there a more specific GO CC term than "transmembrane transporter complex" (GO:1902495) that could capture the specific Man-PTS complex architecture?
Q: Should the phage lambda DNA receptor function and chemoreceptor function of ManY be annotated with GO terms? These are well-documented non-transport functions.
Suggested experts: Erni B
Q: What is the relative contribution of the Man-PTS versus PtsG for glucose uptake under physiological conditions?
Experiment: Systematic substrate specificity profiling of the ManYZ channel using purified reconstituted proteoliposomes to determine the full range of transported sugars.
Hypothesis: The Man-PTS may transport additional sugar substrates beyond mannose, glucose, fructose, and N-acetylglucosamine.
Experiment: Higher resolution cryo-EM structures of ManYZ in different conformational states (with and without substrate) to understand the transport mechanism and substrate binding in ManY.
Hypothesis: ManY undergoes conformational changes during substrate translocation that can be captured by structural studies.
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