ManZ is the EIID component of the mannose-specific phosphoenolpyruvate-dependent sugar phosphotransferase system (Man-PTS) in E. coli K12. It is an integral inner membrane protein with multiple transmembrane helices that, together with ManY (EIIC), forms the transmembrane translocation channel of the mannose permease. The ManY/ManZ heterodimer assembles as a homotrimer of protomers (PMID:31209249). ManZ contains part of the substrate-binding site. The ManXYZ complex transports mannose, glucose, fructose, and N-acetylglucosamine via PEP-dependent phosphorylation (PMID:2951378, PMID:2999119). The Man-PTS also serves as a receptor for bacteriophage lambda DNA injection (PMID:353494, PMID:2951378) and as a chemoreceptor for sugars (PMID:4604906). ManZ (II-MMan) together with ManY (II-PMan) alone are sufficient for penetration of lambda DNA, 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: ManZ is an integral inner membrane protein of E. coli, experimentally demonstrated by topology analysis (PMID:15919996, PMID:8774730), membrane proteomics (PMID:17309111), and cryo-EM structure (PMID:31209249). The IBA annotation from phylogenetic inference is fully consistent with the experimental data. Reason: Plasma membrane (inner membrane in E. coli) localization is a core aspect of ManZ function. This is supported by extensive experimental evidence from topology studies and structural determination. The IBA annotation is appropriate. Supporting Evidence: PMID:2999119 IIMan, a 27-kDa protein, is the transmembrane component of the complex. PMID:15919996 we established the periplasmic or cytoplasmic locations of the C termini for 601 inner membrane proteins file:ECOLI/manZ/manZ-deep-research-falcon.md ManZ is an **inner (cytoplasmic) membrane** protein in the ManXYZ complex. |
| GO:0009401 phosphoenolpyruvate-dependent sugar phosphotransferase system | IBA GO_REF:0000033 | ACCEPT | Summary: ManZ is the EIID component of the mannose PTS. The IBA annotation from phylogenetic inference is consistent with experimental demonstration that ManZ is part of the mannose permease of the PEP-dependent PTS (PMID:2951378, PMID:2999119). Reason: Involvement in the PEP-dependent sugar PTS is the core biological process for ManZ. This is supported by direct experimental evidence from multiple publications. Supporting Evidence: PMID:2951378 The mannose permease of the bacterial phosphotransferase system mediates sugar transport across the cytoplasmic membrane concomitant with sugar phosphorylation. PMID:2999119 The mannose-permease complex of the phosphoenolpyruvate-dependent phosphotranferase system exhibits two apparently unrelated activities. file:ECOLI/manZ/manZ-deep-research-falcon.md ManZ is the **EIID** subunit that partners with ManY (EIIC) to form the membrane translocation module. Foundational work describes the PTS chemical steps (phosphate transfer through ManX domains to the sugar at the membrane-embedded IIC module), while positioning ManZ as a critical membrane component that is not a classic phosphoryl-transfer domain but is required for transport and forms part of the **pore/translocation** apparatus. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: IEA annotation based on UniProt subcellular location mapping. Duplicates the experimentally supported and IBA annotations for the same term. Reason: This IEA annotation is redundant with the IBA and multiple IDA annotations for GO:0005886, but it is not incorrect. Plasma membrane localization is well established. |
| GO:0009401 phosphoenolpyruvate-dependent sugar phosphotransferase system | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation inferred from InterPro domain IPR004704 (PTS_IID_man). Duplicates the IBA and IDA annotations for the same term. Reason: This IEA annotation from InterPro domain mapping is redundant with experimental annotations but is not incorrect. The InterPro domain PTS_IID_man correctly maps to PTS involvement. |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation from InterPro mapping. GO:0016020 (membrane) is a parent of GO:0005886 (plasma membrane), which is already annotated with experimental evidence. Reason: While this is less specific than the plasma membrane annotation, it is not incorrect. IEA annotations at broader levels are acceptable when more specific experimental annotations also exist. |
| 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 determined the complete amino acid sequence of the mannose permease subunits and demonstrated that all three subunits (IIIMan/ManX, II-PMan/ManY, II-MMan/ManZ) are required for sugar transport and phosphorylation via the PTS (PMID:2951378). This is direct experimental evidence for ManZ involvement in the PTS. Reason: Strong direct experimental evidence from the foundational study characterizing the mannose permease components. 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: NAS annotation based on PMID:2951378, which describes the mannose permease and its role in mannose transport. The abstract states the permease "mediates sugar transport across the cytoplasmic membrane" and the system is named the mannose permease. Reason: Mannose transmembrane transport is a core function of the ManXYZ complex, of which ManZ is the EIID subunit. While the NAS evidence code is weaker, the annotation is well supported by the literature. Supporting Evidence: PMID:2951378 The mannose permease of the bacterial phosphotransferase system mediates sugar transport across the cytoplasmic membrane concomitant with sugar phosphorylation. PMID:2999119 It mediates active transport concomitant with phosphorylation of mannose, 2-deoxyglucose, and a number of other hexoses file:ECOLI/manZ/manZ-deep-research-falcon.md It transports mannose as its principal substrate, but multiple sources emphasize it can also transport and/or phosphorylate additional hexoses and amino-sugars. |
| GO:0015761 mannose transmembrane transport | IDA PMID:5545083 Sugar transport. II. Characterization of constitutive membra... | ACCEPT | Summary: Kundig and Roseman 1971 characterized constitutive membrane-bound enzymes II of the E. coli PTS, including characterization of mannose transport. Only the abstract is available for this early publication. Reason: Mannose transport is a core function of the Man-PTS. This early characterization study provided foundational evidence. The qualifier in GOA is "acts_upstream_of_or_within" which is appropriate for the older literature where the specific gene product contribution was less precisely defined. Supporting Evidence: PMID:5545083 Sugar transport. II. Characterization of constitutive membrane-bound enzymes II of the Escherichia coli phosphotransferase system. |
| GO:0015764 N-acetylglucosamine transport | EXP PMID:6252281 Amino-sugar transport systems of Escherichia coli K12. | KEEP AS NON CORE | Summary: Jones-Mortimer and Kornberg 1980 demonstrated that N-acetylglucosamine enters E. coli by two distinct PTS systems, one of which is the PtsM (manZ) system (PMID:6252281). This is a secondary transport substrate of the mannose PTS. Reason: N-acetylglucosamine transport is a genuine but non-core function of the Man-PTS. The primary substrates are mannose and glucose. The ptsM system is one of two PTS systems that can transport N-acetylglucosamine. Supporting Evidence: PMID:6252281 N-Acetylglucosamine enters E. coli by two distinct phosphotransferase systems ...One of these is the PtsM system file:ECOLI/manZ/manZ-deep-research-falcon.md EcoSal Plus summarizes that ManXYZ transports **mannose** and is “relatively promiscuous,” transporting **glucose**, **2-deoxyglucose**, **N-acetylglucosamine**, **N-acetylmannosamine**, and **galactosamine**. |
| GO:0098708 D-glucose import across plasma membrane | IDA PMID:5545083 Sugar transport. II. Characterization of constitutive membra... | KEEP AS NON CORE | Summary: Kundig and Roseman 1971 characterized membrane-bound enzymes II of the PTS. The mannose PTS is known to transport glucose (as 2-deoxyglucose) in addition to mannose (PMID:2999119). Glucose import is a secondary but well-established substrate of the Man-PTS. Reason: Glucose transport via the Man-PTS is well established but is not the primary evolved function of the mannose permease. E. coli has a dedicated glucose PTS (PtsG). The Man-PTS can transport glucose but it is a secondary substrate. Supporting Evidence: PMID:2999119 It mediates active transport concomitant with phosphorylation of mannose, 2-deoxyglucose, and a number of other hexoses |
| GO:1990539 fructose import across plasma membrane | EXP PMID:4153999 The role of phosphotransferase-mediated syntheses of fructos... | KEEP AS NON CORE | Summary: Ferenci and Kornberg 1974 studied the role of PTS-mediated fructose phosphorylation in E. coli growth on fructose. The mannose PTS can transport fructose, but fructose is a secondary substrate and E. coli has a dedicated fructose PTS. Note: the primary citation (PMID:4153999) is only partially cached (title/metadata only; no full text or abstract body), so the substrate confirmation supporting this annotation is drawn from secondary sources (the falcon deep research quoting later functional/regulatory studies). The companion genetic study PMID:4154035 provides independent support for mannose-PTS involvement in fructose utilization. Reason: Fructose import is a genuine but non-core function of the Man-PTS. E. coli has a dedicated fructose-specific PTS. The Man-PTS can phosphorylate fructose to fructose 6-phosphate as a secondary activity. Supporting Evidence: file:ECOLI/manZ/manZ-deep-research-falcon.md A detailed regulatory/functional study likewise states manXYZ can transport many sugars, including **glucose**, **mannose**, and the amino sugars **glucosamine** and **N-acetylglucosamine**, and also reports transport of **2-deoxyglucose**, **fructose**, and more. |
| 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 and Kornberg 1974 performed genetical analysis of fructose utilization in E. coli. This provides genetic evidence for the involvement of the mannose PTS in fructose uptake as a secondary activity. Reason: Duplicate annotation for fructose import with a different reference. Fructose transport is a genuine secondary function of the Man-PTS, not a core function. |
| GO:0005886 plasma membrane | IDA PMID:15919996 Global topology analysis of the Escherichia coli inner membr... | ACCEPT | Summary: Daley et al. 2005 performed global topology analysis of the E. coli inner membrane proteome using C-terminal GFP/PhoA fusions, establishing the topology and inner membrane localization of 601 proteins including ManZ (PMID:15919996). Reason: Direct experimental evidence for inner membrane (plasma membrane) localization from a large-scale topology study. This is strong IDA evidence. Supporting Evidence: PMID:15919996 we established the periplasmic or cytoplasmic locations of the C termini for 601 inner membrane proteins |
| GO:0005886 plasma membrane | IDA PMID:17309111 Comparison of SDS- and methanol-assisted protein solubilizat... | ACCEPT | Summary: Zhang et al. 2007 identified ManZ as an integral membrane protein in the inner membrane fraction of E. coli by 2-D LC-MS/MS membrane proteome analysis (PMID:17309111). Reason: Direct identification of ManZ in the inner membrane proteome fraction. While this is a proteomic detection study rather than a targeted experiment, it provides valid IDA evidence for membrane localization. Supporting Evidence: PMID:17309111 Both organic solvent and surfactant have been used for dissolving membrane proteins for shotgun proteomics. ...to dissolve and analyze the inner membrane fraction of an Escherichia coli K12 cell lysate |
| GO:0005886 plasma membrane | IDA PMID:2999119 The mannose-permease of the bacterial phosphotransferase sys... | ACCEPT | Summary: Erni and Zanolari 1985 purified the IIMan/IIIMan complex and demonstrated that IIMan (ManZ) is the transmembrane component (PMID:2999119). Reason: Foundational experimental evidence from the original characterization study that ManZ is a transmembrane component localized to the cytoplasmic membrane. Supporting Evidence: PMID:2999119 IIMan, a 27-kDa protein, is the transmembrane component of the complex. |
| GO:0009401 phosphoenolpyruvate-dependent sugar phosphotransferase system | IDA PMID:2999119 The mannose-permease of the bacterial phosphotransferase sys... | ACCEPT | Summary: Erni and Zanolari 1985 cloned the genes and purified the mannose permease complex, demonstrating its function in the PEP-dependent PTS (PMID:2999119). Reason: Direct experimental evidence from gene cloning and protein purification study demonstrating ManZ role in the PEP-dependent PTS. Supporting Evidence: PMID:2999119 The mannose-permease complex of the phosphoenolpyruvate-dependent phosphotranferase system exhibits two apparently unrelated activities. It mediates active transport concomitant with phosphorylation of mannose, 2-deoxyglucose, and a number of other hexoses |
| GO:0022870 protein-N(PI)-phosphohistidine-mannose phosphotransferase system transporter activity | IDA PMID:2999119 The mannose-permease of the bacterial phosphotransferase sys... | ACCEPT | Summary: GO:0022870 describes the mannose PTS transporter activity, defined as catalysis of PEP-dependent phosphoryl transfer-driven transport of mannose across a membrane. Erni and Zanolari 1985 demonstrated that the purified IIMan/IIIMan complex mediates PEP-dependent mannose transport and phosphorylation (PMID:2999119). Both IIMan and IIIMan are required for phosphorylation of 2-deoxyglucose in vitro. Reason: This is the most specific and informative molecular function annotation for ManZ. It correctly captures the mannose PTS transporter activity as the core molecular function. Note that this activity is a property of the ManXYZ complex rather than ManZ alone, but ManZ (EIID) is an essential component of the translocation channel. Supporting Evidence: PMID:2999119 It mediates active transport concomitant with phosphorylation of mannose, 2-deoxyglucose, and a number of other hexoses ...IIMan and IIIMan are both required for phosphorylation of 2-deoxyglucose in vitro |
| GO:0016020 membrane | HDA PMID:16858726 A complexomic study of Escherichia coli using two-dimensiona... | ACCEPT | Summary: Lasserre et al. 2006 identified ManZ as part of membrane protein complexes in E. coli using 2-D BN/SDS-PAGE complexomics (PMID:16858726). GO:0016020 (membrane) is less specific than GO:0005886 (plasma membrane). Reason: This is a valid HDA annotation from a complexomics study. While less specific than the plasma membrane annotations, it is not incorrect and provides independent high-throughput evidence for membrane association. Supporting Evidence: PMID:16858726 the cytosolic and membrane protein complexes of Escherichia coli were separated. Then, the different partners of each protein complex were identified by LC-MS/MS. |
| 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) with IPI evidence from ComplexPortal, but this annotation is absent from the GOA file. The cryo-EM structure (PMID:31209249) shows ManZ forms a homotrimer of ManY/ManZ heterodimers, constituting a transmembrane transporter complex. Reason: ManZ is part of the ManYZ transmembrane transporter complex (CPX-5968 in ComplexPortal). The cryo-EM structure definitively demonstrates this complex architecture. This is a core cellular component annotation that should be present. Supporting Evidence: PMID:31209249 we have solved the cryo-EM structure of ManYZ at the inward-facing conformational state. Man-PTS transporters use an elevator mechanism for substrate transportation, in which the substrate-binding Core domain can undergo a rigid-body rotation across the cell membrane. PMID:31209249 Cartoon representation of the ManYZ structure is shown in two perpendicular views. ... VmotifY and VmotifZ interlocked to form Vmotif domain, whereas CoreY and CoreZ give rise to Core domain. |
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Download this section (compressed HTML)Q: Should ManZ have a dedicated GO annotation for its role as a receptor for bacteriophage lambda DNA injection? This is a well-characterized secondary function (PMID:353494, PMID:2951378) but there may not be an appropriate GO term for "phage DNA translocation channel" or similar.
Q: Should ManZ have a chemotaxis-related annotation based on PMID:4604906 showing PTS enzymes function as chemoreceptors? This may be an indirect effect mediated through the PTS signaling cascade rather than a direct molecular function of ManZ.
Q: The GOA qualifier for several transport annotations is "acts_upstream_of_or_within" rather than "involved_in". Given that ManZ is a direct structural component of the translocation channel, should these be upgraded to "involved_in"?
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