Cpx envelope-stress periplasmic quality control

A periplasmic envelope-stress quality-control module covering two Cpx-regulated effector branches. CpxP inhibits the CpxA sensor kinase in the unstressed state and can act as a DegP adaptor for a subset of misfolded periplasmic substrates, while Spy binds non-native periplasmic clients in situ to prevent aggregation and assist refolding. Transcriptional control by CpxR/BaeR and DegP proteolysis itself are outside this CpxP/Spy-focused module.

MODULE:cpx_envelope_stress_quality_controlDRAFTCONCRETEBiological Processmodules/cpx_envelope_stress_quality_control.yaml

negative regulation of phosphorelay signal transduction systemGO:0070298 protein stabilizationGO:0050821

GO:0030547

signaling receptor inhibitor activity

Defines CpxP inhibition of the CpxA sensor kinase.

GO:0140767

enzyme-substrate adaptor activity

Defines CpxP adaptor activity for DegP-mediated proteolysis.

GO:0044183

protein folding chaperone

Defines Spy's periplasmic refolding-chaperone function.

file:genes/ECOLI/CpxP/CpxP-ai-review.yaml

ECOLI CpxP gene review

The completed E. coli CpxP review grounds CpxP as a CpxA inhibitor and DegP adaptor.

file:genes/ECOLI/Spy/Spy-ai-review.yaml

ECOLI Spy gene review

The completed E. coli Spy review grounds Spy as a periplasmic in-situ holdase and refolding chaperone.

PMID:16303867

The extracytoplasmic adaptor protein CpxP is degraded with substrate by DegP.

Establishes CpxP adaptor function in DegP-mediated proteolysis.

PMID:17259177

Purification, reconstitution, and characterization of the CpxRAP envelope stress system of Escherichia coli.

Establishes CpxP inhibition of CpxA autophosphorylation.

PMID:25207645

Dynamic interaction between the CpxA sensor kinase and the periplasmic accessory protein CpxP mediates signal recognition in E. coli.

Demonstrates dynamic CpxP-CpxA interaction during envelope-stress sensing.

PMID:21317898

Genetic selection designed to stabilize proteins uncovers a chaperone called Spy.

Establishes Spy as an ATP-independent aggregation-suppressing chaperone.

PMID:26619265

Substrate protein folds while it is bound to the ATP-independent chaperone Spy.

Shows that a Spy-associated client can fold while bound to Spy.

CpxP's weak in vitro chaperone activity is deliberately not represented as a core holdase activity. The reviewed biology supports CpxA inhibition and substrate delivery to DegP as CpxP's primary activities. CpxP and Spy are grouped here as periplasmic quality-control effectors in the Cpx regulon, not as direct binding partners or sequential handoff components.

4Nodes

3Parts

0Variant Sets

0Variants

4Annotons

0Connections

Derived QC

Recommended-field compliance

100.0% recommended fields populated

All recommended fields populated.

Module deep research

✗ none found

No MODULE:cpx_envelope_stress_quality_control deep-research report alongside the module YAML.

Leaf nodes lacking representative members

✓ every leaf node grounds to a representative protein.

Template conformance

✓ every declared conforms_to bundle matches its template motif.

Function consistency and core coverage

3 gene-function check(s) reflected in core functions · 0 conflict(s) · 1 evidence or coverage gap(s) (4 comparison(s))

Retained noncore functions are reported separately; they do not require promotion to core functions. Support from representative genes does not establish conservation across the whole family. Missing reviews or identifiers leave a claim unverified.

Annoton	Participant	Function	Assessment
cpxp_cpxa_inhibitor	E. coli CpxP UniProtKB:P0AE85 Gene	signaling receptor inhibitor activity GO:0030547	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
cpxp_enzyme_substrate_adaptor	E. coli CpxP UniProtKB:P0AE85 Gene	enzyme-substrate adaptor activity GO:0140767	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).
spy_holdase	E. coli Spy UniProtKB:P77754 Gene	holdase chaperone activity No function ID	No Function Id A gene review exists, but this function lacks a GO identifier. Free-text chemistry is not automatically compared.
spy_refolding_chaperone	E. coli Spy UniProtKB:P77754 Gene	protein folding chaperone GO:0044183	Core Supported The GO molecular function is reflected in core_functions (exact term or a reviewed subclass).

Gene-review completeness (2/2 grounded genes reviewed)

2 complete review(s) · 2 with deep research · 0 missing review · 0 reviewed but lacking deep research

Gene	Review	Complete	Deep research
CpxP P0AE85	✓	✓	✓
Spy P77754	✓	✓	✓

Tree

Cpx envelope-stress periplasmic quality controlBiological Processcpx_envelope_stress_quality_control

Parts
1. 1. CpxA inhibition by CpxP
2. CpxP inhibition of CpxA signalingBiological Processcpxp_cpxa_inhibition
  
  Annotons
  - CpxP CpxA inhibitor Gene Product: E. coli CpxP
3. 2. CpxP adaptor-mediated substrate proteolysis
4. CpxP adaptor delivery to DegPBiological Processcpxp_degp_adaptor
  
  Annotons
  - CpxP DegP adaptor Gene Product: E. coli CpxP
5. 3. Spy in-situ holdase and refolding activity
6. Spy periplasmic chaperone activityBiological Processspy_periplasmic_chaperone
  
  Annotons
  - Spy in-situ holdase Gene Product: E. coli Spy
  - Spy refolding chaperone Gene Product: E. coli Spy

Details

Context

Escherichia coliNCBITaxon:83333

Cpx envelope-stress periplasmic quality controlBiological Processcpx_envelope_stress_quality_control

negative regulation of phosphorelay signal transduction systemGO:0070298 protein stabilizationGO:0050821

Context

Escherichia coliNCBITaxon:83333

Part 1: CpxA inhibition by CpxP

CpxP inhibition of CpxA signalingBiological Processcpxp_cpxa_inhibition

Annotons

CpxP CpxA inhibitor

cpxp_cpxa_inhibitor

Participant: Gene Product: E. coli CpxP

Gene Product:

E. coli CpxPUniProtKB:P0AE85

Function

signaling receptor inhibitor activityGO:0030547

Targets: CpxA sensor kinase

Processes

negative regulation of phosphorelay signal transduction systemGO:0070298

Locations

outer membrane-bounded periplasmic spaceGO:0030288

Auxiliary periplasmic inhibitor that binds the CpxA sensor domain and reduces CpxA autophosphorylation in the unstressed state.

Part 2: CpxP adaptor-mediated substrate proteolysis

CpxP adaptor delivery to DegPBiological Processcpxp_degp_adaptor

Annotons

CpxP DegP adaptor

cpxp_enzyme_substrate_adaptor

Participant: Gene Product: E. coli CpxP

Gene Product:

E. coli CpxPUniProtKB:P0AE85

Function

enzyme-substrate adaptor activityGO:0140767

Substrates: misfolded periplasmic protein

Targets: DegP protease

Processes

positive regulation of proteolysisGO:0045862

Locations

outer membrane-bounded periplasmic spaceGO:0030288

Periplasmic adaptor that promotes DegP-mediated degradation of a subset of misfolded substrates and is degraded during the process.

Part 3: Spy in-situ holdase and refolding activity

Spy periplasmic chaperone activityBiological Processspy_periplasmic_chaperone

Annotons

Spy in-situ holdase

spy_holdase

Participant: Gene Product: E. coli Spy

Gene Product:

E. coli SpyUniProtKB:P77754

Function

holdase chaperone activity

Substrates: non-native periplasmic client protein

Products: soluble Spy-bound periplasmic client protein

Processes

protein stabilizationGO:0050821

Locations

outer membrane-bounded periplasmic spaceGO:0030288

Stress-induced in-situ holdase that binds non-native periplasmic clients and suppresses aggregation.

Spy refolding chaperone

spy_refolding_chaperone

Participant: Gene Product: E. coli Spy

Gene Product:

E. coli SpyUniProtKB:P77754

Function

protein folding chaperoneGO:0044183

Processes

protein refoldingGO:0042026

Locations

outer membrane-bounded periplasmic spaceGO:0030288

Flexible periplasmic dimer that can allow client folding while the client remains associated with Spy.