id: P69801
gene_symbol: manY
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:83333
  label: Escherichia coli (strain K12)
description: >-
  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).
references:
- id: PMID:2951378
  title: The mannose permease of Escherichia coli consists of three different proteins.
    Amino acid sequence and function in sugar transport, sugar phosphorylation, and
    penetration of phage lambda DNA.
  findings:
  - statement: The mannose permease consists of three subunits (IIIMan/ManX, II-PMan/ManY,
      II-MMan/ManZ) that are all required for sugar transport and phosphorylation.
    supporting_text: The permease consists of three different subunits, IIIMan, II-PMan,
      and II-MMan, which are encoded in a single transcriptional unit ptsLPM
  - statement: ManY (II-PMan) is very hydrophobic and is an integral membrane protein
      that forms the transmembrane channel together with ManZ (II-MMan).
    supporting_text: II-PMan (28 kDa) is very hydrophobic...Both are integral membrane
      proteins and most likely form the transmembrane channel
  - statement: ManY and ManZ alone are sufficient for lambda DNA penetration.
    supporting_text: II-PMan and II-MMan alone are sufficient for penetration of lambda
      DNA
  - statement: The Man-PTS mediates sugar transport concomitant with phosphorylation
      and also functions as a chemoreceptor and phage lambda pore.
    supporting_text: The mannose permease of the bacterial phosphotransferase system
      mediates sugar transport across the cytoplasmic membrane concomitant with sugar
      phosphorylation. It also functions as a receptor for bacterial chemotaxis and
      is required for infection of the cell by bacteriophage lambda where it most
      likely functions as a pore for penetration of lambda DNA
- id: PMID:5545083
  title: Sugar transport. II. Characterization of constitutive membrane-bound enzymes
    II of the Escherichia coli phosphotransferase system.
  findings:
  - statement: Characterization of PTS enzyme II activities for mannose and glucose
      transport in E. coli membranes.
- id: PMID:6252281
  title: Amino-sugar transport systems of Escherichia coli K12.
  findings:
  - statement: N-acetylglucosamine enters E. coli by two distinct PTS systems; one
      of these is the PtsM (Man-PTS) system.
    supporting_text: N-Acetylglucosamine enters E. coli by two distinct phosphotransferase
      systems...One of these is the PtsM system
- id: PMID:4153999
  title: The role of phosphotransferase-mediated syntheses of fructose 1-phosphate
    and fructose 6-phosphate in the growth of Escherichia coli on fructose.
  findings:
  - statement: Fructose can be transported via the mannose PTS (ptsM) producing fructose
      6-phosphate.
- id: PMID:4154035
  title: Genetical analysis of fructose utilization by Escherichia coli.
  findings:
  - statement: Genetic analysis of fructose utilization pathways in E. coli, including
      the role of ptsM.
- id: PMID:15919996
  title: Global topology analysis of the Escherichia coli inner membrane proteome.
  findings:
  - statement: Global topology analysis confirmed ManY as an inner membrane protein
      with cytoplasmic C-terminus using C-terminal GFP/PhoA fusions.
    supporting_text: 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
- id: PMID:16858726
  title: A complexomic study of Escherichia coli using two-dimensional blue native/SDS
    polyacrylamide gel electrophoresis.
  findings:
  - statement: ManY was identified in membrane protein complexes by 2D BN/SDS-PAGE
      and LC-MS/MS, confirming its membrane localization.
    supporting_text: the cytosolic and membrane protein complexes of Escherichia coli
      were separated...the different partners of each protein complex were identified
      by LC-MS/MS
- id: PMID:353494
  title: E. coli K-12 pel mutants, which block phage lambda DNA injection, coincide
    with ptsM, which determines a component of a sugar transport system.
  findings:
  - statement: pel mutations that block phage lambda DNA injection map to ptsM (manY),
      establishing the mannose permease as the receptor for phage lambda DNA injection.
- id: PMID:4604906
  title: Phosphotransferase-system enzymes as chemoreceptors for certain sugars in
    Escherichia coli chemotaxis.
  findings:
  - statement: PTS enzymes serve as chemoreceptors for sugars in E. coli chemotaxis,
      with the mannose PTS functioning as a chemoreceptor.
- id: PMID:31209249
  title: Structure of the mannose transporter of the bacterial phosphotransferase
    system.
  findings:
  - statement: Cryo-EM structure of ManYZ shows the complex forms a homotrimer of
      ManY-ManZ heterodimers.
- id: PMID:8774730
  title: Membrane topology of the mannose transporter of Escherichia coli K12.
  findings:
  - statement: Membrane topology study establishing ManY as a multi-pass inner membrane
      protein.
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
- id: file:ECOLI/manY/manY-deep-research-falcon.md
  title: 'Falcon (Edison Scientific) deep research report: manY (UniProt P69801),
    PTS system mannose-specific EIIC component in E. coli K-12'
  findings:
  - statement: Seip et al. (1994) explicitly map the E. coli mannose-PTS genes to subunits,
      confirming manY encodes the IIC_Man membrane permease subunit.
    supporting_text: |-
      manX, manY, and manZ, genes encoding IIAB\_Man, IIC\_Man, and IID\_Man, respectively.
    reference_section_type: OTHER
  - statement: ManY (IIC_Man) together with ManZ (IID_Man) forms the membrane channel
      and substrate-binding/translocation machinery; both IIC and IID subunits are
      required for functional membrane transport and certain receptor functions.
    supporting_text: |-
      forms the **membrane channel and substrate-binding/translocation machinery** responsible for selectively transporting sugars across the inner membrane during PTS-mediated uptake
    reference_section_type: OTHER
  - statement: The mannose-family PTS couples transport to phosphorylation in a single
      group-translocation step, with phosphate relayed from PEP through EI->HPr->EIIA->EIIB
      to the incoming sugar.
    supporting_text: |-
      so that **transport and phosphorylation occur in a coupled process**
    reference_section_type: OTHER
  - statement: The ManXYZ/ManY transporter has broad substrate specificity beyond mannose,
      including glucose, mannosamine, N-acetylglucosamine and 2-deoxyglucose, with poor
      tolerance for substitutions at C-4 and C-6.
    supporting_text: |-
      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).
    reference_section_type: OTHER
  - statement: ManY requires ManZ for stable, functional membrane complex formation;
      ManY is thought to be unstable in the absence of ManZ, and manY-alone overexpression
      gives only modest uptake effects.
    supporting_text: |-
      authors note **ManY is thought to be unstable in the absence of ManZ**
    reference_section_type: OTHER
  - statement: The cryo-EM ManYZ-microcin E492 structure shows a threefold-symmetric
      3:3 assembly with mannose localized mid-membrane, supporting ManY as a core
      inner-membrane structural component of the transporter complex.
    supporting_text: |-
      The complex assembles with **threefold symmetry** and a **3:3 stoichiometry** (3 MccE492 : 3 ManYZ), with **mannose localized mid-membrane** in the complex.
    reference_section_type: OTHER
  - statement: The ManYZ (IIC/IID) membrane complex serves as an inner-membrane receptor/gateway,
      being used by the pore-forming bacteriocin microcin E492 in a Trojan-horse entry
      mechanism.
    supporting_text: |-
      Microcin E492** inserts into the cytoplasmic membrane and associates with ManYZ, using ManYZ as a receptor in a Trojan-horse entry mechanism
    reference_section_type: OTHER
  - statement: The ManYZ complex is implicated as the inner-membrane receptor for
      bacteriophage lambda entry.
    supporting_text: |-
      The ManYZ complex is implicated as an inner-membrane receptor involved in **bacteriophage λ** entry
    reference_section_type: OTHER
existing_annotations:
# ==========================================
# CELLULAR COMPONENT ANNOTATIONS
# ==========================================

# --- plasma membrane (IBA) ---
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:2951378
      supporting_text: II-PMan (28 kDa) is very hydrophobic...Both are integral membrane
        proteins and most likely form the transmembrane channel
    - reference_id: PMID:15919996
      supporting_text: 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
    - reference_id: file:ECOLI/manY/manY-deep-research-falcon.md
      supporting_text: |-
        forms the **membrane channel and substrate-binding/translocation machinery** responsible for selectively transporting sugars across the inner membrane during PTS-mediated uptake

# --- plasma membrane (IEA from UniProt SubCell) ---
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: IEA annotation from UniProt subcellular location mapping. Redundant with
      IBA and IDA annotations for the same term. Correct but adds no additional information.
    action: ACCEPT
    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.

# --- plasma membrane (IDA from Daley 2005) ---
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:15919996
  review:
    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.
    action: ACCEPT
    reason: Direct experimental evidence from a large-scale but rigorous topology study
      confirming ManY as an inner membrane protein. This is valid IDA evidence.
    supported_by:
    - reference_id: PMID:15919996
      supporting_text: 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

# --- plasma membrane (IDA from Erni 1987) ---
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:2951378
  review:
    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.
    action: ACCEPT
    reason: The original characterization paper by Erni et al. directly identified
      ManY as an integral membrane protein through biochemical analysis. Valid IDA
      evidence.
    supported_by:
    - reference_id: PMID:2951378
      supporting_text: II-PMan (28 kDa) is very hydrophobic...Both are integral membrane
        proteins and most likely form the transmembrane channel

# --- membrane (IEA from InterPro) ---
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    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.
    action: ACCEPT
    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.

# --- membrane (HDA from complexomic study) ---
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:16858726
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:16858726
      supporting_text: the cytosolic and membrane protein complexes of Escherichia
        coli were separated...the different partners of each protein complex were
        identified by LC-MS/MS

# ==========================================
# BIOLOGICAL PROCESS ANNOTATIONS
# ==========================================

# --- PEP-dependent sugar PTS (IBA) ---
- term:
    id: GO:0009401
    label: phosphoenolpyruvate-dependent sugar phosphotransferase system
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    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).
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:2951378
      supporting_text: The mannose permease of the bacterial phosphotransferase system
        mediates sugar transport across the cytoplasmic membrane concomitant with
        sugar phosphorylation
    - reference_id: file:ECOLI/manY/manY-deep-research-falcon.md
      supporting_text: |-
        so that **transport and phosphorylation occur in a coupled process**

# --- PEP-dependent sugar PTS (IEA from InterPro) ---
- term:
    id: GO:0009401
    label: phosphoenolpyruvate-dependent sugar phosphotransferase system
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: IEA annotation from InterPro domain mapping (IPR004700, PTS_IIC_man).
      Redundant with IBA and IDA annotations for the same term but correct.
    action: ACCEPT
    reason: Correct IEA annotation that is consistent with and redundant to the
      experimentally supported and phylogenetically inferred annotations.

# --- PEP-dependent sugar PTS (IDA from Erni 1987, ComplexPortal) ---
- term:
    id: GO:0009401
    label: phosphoenolpyruvate-dependent sugar phosphotransferase system
  evidence_type: IDA
  original_reference_id: PMID:2951378
  review:
    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.
    action: ACCEPT
    reason: Strong experimental evidence directly establishing ManY as a component
      of the PTS. This is a core function annotation.
    supported_by:
    - reference_id: PMID:2951378
      supporting_text: 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

# --- mannose transmembrane transport (NAS from Erni 1987) ---
- term:
    id: GO:0015761
    label: mannose transmembrane transport
  evidence_type: NAS
  original_reference_id: PMID:2951378
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:2951378
      supporting_text: The mannose permease of the bacterial phosphotransferase system
        mediates sugar transport across the cytoplasmic membrane concomitant with
        sugar phosphorylation

# --- mannose transmembrane transport (IDA from Kundig 1971) ---
- term:
    id: GO:0015761
    label: mannose transmembrane transport
  evidence_type: IDA
  original_reference_id: PMID:5545083
  review:
    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.
    action: ACCEPT
    reason: Early foundational work establishing mannose transport activity of the
      PTS enzyme II. Mannose is the primary substrate, making this a core function.

# --- N-acetylglucosamine transport (EXP) ---
- term:
    id: GO:0015764
    label: N-acetylglucosamine transport
  evidence_type: EXP
  original_reference_id: PMID:6252281
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: PMID:6252281
      supporting_text: N-Acetylglucosamine enters E. coli by two distinct phosphotransferase
        systems...One of these is the PtsM system
    - reference_id: file:ECOLI/manY/manY-deep-research-falcon.md
      supporting_text: |-
        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).

# --- D-glucose import across plasma membrane (IDA) ---
- term:
    id: GO:0098708
    label: D-glucose import across plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:5545083
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.
    supported_by:
    - reference_id: file:ECOLI/manY/manY-deep-research-falcon.md
      supporting_text: |-
        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).

# --- fructose import across plasma membrane (EXP, PMID:4153999) ---
- term:
    id: GO:1990539
    label: fructose import across plasma membrane
  evidence_type: EXP
  original_reference_id: PMID:4153999
  review:
    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).
    action: KEEP_AS_NON_CORE
    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.

# --- fructose import across plasma membrane (EXP, PMID:4154035) ---
- term:
    id: GO:1990539
    label: fructose import across plasma membrane
  evidence_type: EXP
  original_reference_id: PMID:4154035
  review:
    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.
    action: KEEP_AS_NON_CORE
    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.

# ==========================================
# MOLECULAR FUNCTION ANNOTATIONS
# ==========================================

# --- protein-N(PI)-phosphohistidine-mannose PTS transporter activity (IDA) ---
- term:
    id: GO:0022870
    label: protein-N(PI)-phosphohistidine-mannose phosphotransferase system transporter
      activity
  evidence_type: IDA
  original_reference_id: PMID:2951378
  review:
    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.
    action: ACCEPT
    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.
    supported_by:
    - reference_id: PMID:2951378
      supporting_text: 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
    - reference_id: file:ECOLI/manY/manY-deep-research-falcon.md
      supporting_text: |-
        forms the **membrane channel and substrate-binding/translocation machinery** responsible for selectively transporting sugars across the inner membrane during PTS-mediated uptake

# ==========================================
# NEW ANNOTATIONS (not in GOA)
# ==========================================

# --- transmembrane transporter complex (IPI, from ComplexPortal via UniProt) ---
- term:
    id: GO:1902495
    label: transmembrane transporter complex
  evidence_type: IPI
  original_reference_id: PMID:31209249
  review:
    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).
    action: NEW
    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.
    supported_by:
    - reference_id: PMID:2951378
      supporting_text: II-PMan (28 kDa) is very hydrophobic...Both are integral membrane
        proteins and most likely form the transmembrane channel
    - reference_id: file:ECOLI/manY/manY-deep-research-falcon.md
      supporting_text: |-
        The complex assembles with **threefold symmetry** and a **3:3 stoichiometry** (3 MccE492 : 3 ManYZ), with **mannose localized mid-membrane** in the complex.

core_functions:
- description: ManY is the EIIC component of the mannose-specific phosphotransferase
    system (Man-PTS), forming the transmembrane translocation channel together with
    ManZ (EIID) for PEP-dependent sugar transport with concomitant phosphorylation.
    ManY contains the specific substrate-binding site. The full transporter activity
    requires all three subunits ManX, ManY, and ManZ.
  molecular_function:
    id: GO:0022870
    label: protein-N(PI)-phosphohistidine-mannose phosphotransferase system transporter
      activity
  directly_involved_in:
  - id: GO:0009401
    label: phosphoenolpyruvate-dependent sugar phosphotransferase system
  - id: GO:0015761
    label: mannose transmembrane transport
  locations:
  - id: GO:0005886
    label: plasma membrane
  in_complex:
    id: GO:1902495
    label: transmembrane transporter complex
  supported_by:
  - reference_id: PMID:2951378
    supporting_text: 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
  - reference_id: file:ECOLI/manY/manY-deep-research-falcon.md
    supporting_text: |-
      manX, manY, and manZ, genes encoding IIAB\_Man, IIC\_Man, and IID\_Man, respectively.

suggested_questions:
- question: What is the precise substrate specificity profile of ManY compared to
    other EIIC components? Are there additional substrates beyond mannose, glucose,
    fructose, and GlcNAc?
- question: Is there a more specific GO CC term than "transmembrane transporter
    complex" (GO:1902495) that could capture the specific Man-PTS complex architecture?
- question: Should the phage lambda DNA receptor function and chemoreceptor function
    of ManY be annotated with GO terms? These are well-documented non-transport
    functions.
  experts:
  - Erni B
- question: What is the relative contribution of the Man-PTS versus PtsG for glucose
    uptake under physiological conditions?

suggested_experiments:
- description: 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.
- description: 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.