ManZ (EIID-Man) - Research Notes

Summary

ManZ (P69805) is the EIID component of the mannose-specific PTS in E. coli K12. It is encoded by the manXYZ operon (b1819).

Key findings

Membrane topology and structure

• Integral inner membrane protein with multiple transmembrane helices [PMID:8774730, PMID:15919996]
• UniProt P69805 lists 5 TRANSMEM helices (residues 101-140, 145-173, 184-209, 242-255, 262-280), derived from the cryo-EM structure
• Cryo-EM (PMID:31209249) shows ManZ has CoreZ, VmotifZ, and ArmZ structural domains — a complex multi-domain, multi-pass architecture
• Forms the translocation channel together with ManY (EIIC) PMID:2951378
• ManY/ManZ heterodimer assembles as homotrimer of protomers PMID:31209249
• Cryo-EM structures available: 3.52 A (PDB: 6K1H) and 2.28 A (PDB: 7DYR)
• ManZ is moderately hydrophobic (31 kDa) PMID:2951378

CURATOR CAUTION — falcon deep research topology is outdated. The manZ-deep-research-falcon.md
file (sections 4 and 9) states ManZ/IID is "anchored by a single C-terminal transmembrane helix"
with ~250 residues projecting into the cytoplasm, based on the Huber & Erni 1996 PhoA/LacZ-fusion
topology study (PMID:8774730). This single-TM-anchor claim is superseded by the 2019 cryo-EM
structure (PMID:31209249) and the current UniProt P69805 record, which show 5 transmembrane
helices and a multi-domain (CoreZ/VmotifZ/ArmZ) fold. The review YAML deliberately does NOT cite
or propagate the single-TM statement; the description and all annotations use "multiple
transmembrane helices". Future curators should disregard the falcon topology section for this gene.

Function

• EIID domain contains part of the substrate-binding site [UniProt, PROSITE PRU00431]
• Together with ManY, forms the PTS translocation channel
• All three subunits (ManX, ManY, ManZ) required for sugar transport and phosphorylation PMID:2951378
• ManY and ManZ alone sufficient for phage lambda DNA penetration PMID:2951378

Substrate specificity

• Primary: mannose
• Secondary: glucose (2-deoxyglucose), fructose, N-acetylglucosamine [PMID:2999119, PMID:6252281]

Regulation

• Same operon regulation as ManX and ManY (cAMP-CRP positive, Mlc negative, NagC weak negative)

Review decisions

• All plasma membrane annotations ACCEPTED (multiple IDA evidence)
• PTS and mannose transport annotations ACCEPTED as core
• Secondary substrates (glucose, fructose, GlcNAc) kept as non-core
• Added NEW annotation: GO:1902495 (transmembrane transporter complex) from ComplexPortal
• Core MF: GO:0022870 (mannose PTS transporter activity)