id: P0ABZ6
gene_symbol: surA
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:83333
  label: Escherichia coli (strain K12)
description: >-
  SurA is a periplasmic chaperone that functions as the primary pathway for delivery
  of unfolded outer membrane proteins (OMPs) to the BAM complex for insertion into
  the outer membrane. It also possesses peptidyl-prolyl cis-trans isomerase (PPIase)
  activity via its second parvulin domain, but this enzymatic activity is dispensable
  for its in vivo chaperone function. The N-terminal domain and C-terminal tail are
  necessary and sufficient for chaperone activity and OMP substrate recognition.
  SurA binds preferentially to unfolded OMPs, recognizing aromatic-rich peptide motifs
  characteristic of integral outer membrane beta-barrel proteins. It functions as a
  holdase, stabilizing unfolded OMPs in a dynamic state to prevent aggregation while
  enabling stepwise membrane insertion of beta-hairpins. SurA is required for the
  efficient folding of OmpA, OmpF, LamB, and FimD, and for overall outer membrane
  integrity. Loss of SurA leads to decreased outer membrane density and activates
  the sigmaE stress response.
existing_annotations:
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      SurA participates in the maturation of outer membrane porins, which involves
      conversion of unfolded monomers into folded monomers and subsequent trimerization
      (PMID:8985185). SurA mutants show defective folding of OmpA, OmpF, and LamB
      (PMID:8626309). The IBA annotation to protein folding is phylogenetically
      supported and consistent with experimental evidence.
    action: ACCEPT
    reason: >-
      SurA is directly involved in protein folding as demonstrated by multiple
      experimental studies. Loss of SurA blocks the LamB assembly pathway at a
      step prior to folded monomer formation (PMID:8985185), and surA mutants
      show defective folding of three outer membrane proteins (PMID:8626309).
      This IBA annotation is well supported.
    supported_by:
      - reference_id: PMID:8985185
        supporting_text: "We demonstrate that SurA is involved in the conversion of unfolded monomers into a newly identified intermediate in LamB assembly, which behaves as a folded monomer."
      - reference_id: PMID:8626309
        supporting_text: "We determined that the efficient folding of three outer membrane proteins (OmpA, OmpF, and LamB) requires SurA in vivo"
- term:
    id: GO:0003755
    label: peptidyl-prolyl cis-trans isomerase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      SurA has confirmed PPIase activity (EC 5.2.1.8) residing in its second parvulin
      domain (PMID:8985185, PMID:11226178). However, this enzymatic activity is dispensable
      for SurA's primary chaperone function in vivo, as a SurA variant lacking both
      parvulin domains is almost completely functional (PMID:11226178). The IBA annotation
      is phylogenetically supported and experimentally validated.
    action: ACCEPT
    reason: >-
      PPIase activity is experimentally confirmed for SurA (PMID:8985185) and is
      a real enzymatic activity of this protein, even though it is not essential
      for SurA's primary in vivo function. The IBA annotation is appropriate.
    supported_by:
      - reference_id: PMID:8985185
        supporting_text: "SurA, a periplasmic protein with peptidyl-prolyl isomerase activity, participates in the assembly of outer membrane porins."
      - reference_id: PMID:11226178
        supporting_text: "a variant of SurA lacking both parvulin-like domains exhibits a PPIase-independent chaperone-like activity in vitro and almost completely complements the in vivo function of intact SurA"
- term:
    id: GO:0030288
    label: outer membrane-bounded periplasmic space
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      SurA is a periplasmic protein with a cleavable signal peptide (residues 1-20).
      Multiple proteomics studies have confirmed its periplasmic localization
      (PMID:15911532, PMID:24140104, PMID:8985185). UniProt annotates it as
      periplasmic with the note that it can associate with the outer membrane.
    action: ACCEPT
    reason: >-
      Periplasmic localization is firmly established by direct experimental evidence
      (IDA from multiple studies) and is consistent with the IBA annotation.
    supported_by:
      - reference_id: PMID:8985185
        supporting_text: "SurA, a periplasmic protein with peptidyl-prolyl isomerase activity"
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      SurA directly binds unfolded outer membrane proteins in the periplasm. Behrens
      et al. (PMID:11226178) demonstrated that SurA interacts preferentially (>50-fold)
      with in vitro synthesized porins over other similarly sized proteins, and this
      chaperone activity resides in the N-terminal and C-terminal domains independent
      of PPIase activity. Thoma et al. (PMID:26344570) characterized SurA as a holdase
      that stabilizes a dynamic unfolded state, preventing misfolding and allowing
      stepwise beta-hairpin insertion into the membrane. Per the UPB project decision
      rules, SurA functions as a holdase-type chaperone that prevents aggregation of
      unfolded OMPs in transit to the BAM complex. It does not actively refold substrates
      via ATPase cycles. However, because it escorts unfolded OMPs from the Sec translocon
      to the BAM complex (between two cellular locations), GO:0140309 (unfolded protein
      carrier activity) could potentially apply. Since the primary mode of action
      described in the literature is holdase/carrier, not foldase, the most appropriate
      replacement depends on whether SurA's escort function qualifies for GO:0140309
      or whether a general holdase NTR is needed.
    action: MODIFY
    reason: >-
      GO:0051082 is proposed for obsoletion. SurA is described as a holdase chaperone
      by Thoma et al. (PMID:26344570), who explicitly titled their paper "Impact of
      holdase chaperones Skp and SurA on the folding of beta-barrel outer-membrane
      proteins." SurA stabilizes unfolded OMPs in a dynamic state without actively
      refolding them via ATPase cycles, instead allowing stepwise membrane insertion.
      SurA also escorts OMPs from the Sec translocon across the periplasm to the BAM
      complex, which constitutes transport between two cellular components.
      GO:0044183 (protein folding chaperone) could apply if SurA is considered to
      actively assist folding, but the evidence from PMID:26344570 characterizes it
      more as a holdase. Given the escort/carrier function, GO:0140309 may be
      appropriate, but if the carrier semantics do not fit (since SurA acts in a
      single compartment, the periplasm), then the holdase NTR is needed. As an
      interim, retain GO:0051082 until the holdase NTR is created.
    proposed_replacement_terms:
      - id: GO:0044183
        label: protein folding chaperone
    additional_reference_ids:
      - PMID:26344570
      - PMID:11226178
    supported_by:
      - reference_id: PMID:26344570
        supporting_text: "Either chaperone prevents FhuA from misfolding by stabilizing a dynamic, unfolded state, thus allowing the substrate to search for structural intermediates."
      - reference_id: PMID:11226178
        supporting_text: "SurA interacts preferentially (>50-fold) with in vitro synthesized porins over other similarly sized proteins, leading us to suggest that the chaperone-like function of SurA preferentially facilitates maturation of outer membrane proteins."
      - reference_id: PMID:17908933
        supporting_text: "SurA is the primary chaperone responsible for the periplasmic transit of the bulk mass of OMPs to the YaeT complex."
- term:
    id: GO:0003755
    label: peptidyl-prolyl cis-trans isomerase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      IEA annotation from InterPro/UniRule based on SurA's parvulin PPIase domains
      (IPR000297, IPR023034) and EC:5.2.1.8. This is consistent with experimental
      evidence (PMID:8985185) confirming PPIase activity.
    action: ACCEPT
    reason: >-
      The IEA annotation correctly reflects SurA's PPIase activity, which is
      experimentally confirmed. The annotation is broader than necessary (the PPIase
      activity resides only in the second parvulin domain) but the term itself is
      appropriate.
    supported_by:
      - reference_id: PMID:8985185
        supporting_text: "SurA, a periplasmic protein with peptidyl-prolyl isomerase activity"
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      IEA annotation from InterPro/UniRule. SurA's involvement in protein folding
      is well established experimentally (PMID:8985185, PMID:8626309).
    action: ACCEPT
    reason: >-
      Consistent with experimental evidence and IBA annotation. The IEA mapping
      correctly identifies SurA's role in protein folding.
    supported_by:
      - reference_id: PMID:8626309
        supporting_text: "SurA assists the folding of Escherichia coli outer membrane proteins."
- term:
    id: GO:0016853
    label: isomerase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      IEA annotation from UniProtKB-KW (KW-0413 Isomerase). SurA is classified
      as an isomerase based on its PPIase activity (EC 5.2.1.8). This is a parent
      term of GO:0003755 (peptidyl-prolyl cis-trans isomerase activity), which is
      the more specific and informative term.
    action: ACCEPT
    reason: >-
      While this is a very broad parent term, it is not incorrect. The more specific
      GO:0003755 is annotated separately. IEA from keyword mapping is acceptable
      here as it simply reflects the isomerase classification.
    supported_by:
      - reference_id: PMID:8985185
        supporting_text: "SurA, a periplasmic protein with peptidyl-prolyl isomerase activity"
- term:
    id: GO:0030288
    label: outer membrane-bounded periplasmic space
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      IEA annotation from InterPro (IPR023034). Consistent with experimentally
      confirmed periplasmic localization (PMID:8985185, PMID:15911532, PMID:24140104).
    action: ACCEPT
    reason: >-
      The InterPro-derived localization is correct and supported by multiple
      experimental studies. Redundant with IDA and IBA annotations but acceptable.
    supported_by:
      - reference_id: PMID:8985185
        supporting_text: "SurA, a periplasmic protein with peptidyl-prolyl isomerase activity"
- term:
    id: GO:0042277
    label: peptide binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      IEA annotation from InterPro (IPR023034). SurA does bind peptide motifs
      characteristic of OMPs, specifically recognizing aromatic-rich patterns. Bitto
      and McKay (PMID:14506253) showed that SurA binds peptide motifs found in integral
      outer membrane proteins. Hennecke et al. (PMID:15840585) demonstrated selective
      substrate recognition through features characteristic of OMPs.
    action: ACCEPT
    reason: >-
      SurA does bind peptide motifs as part of its substrate recognition mechanism.
      While more specific terms might be preferable, this general IEA annotation
      is not incorrect. SurA's N-terminal domain and C-terminal tail form the
      peptide binding site for OMP recognition.
    supported_by:
      - reference_id: PMID:11226178
        supporting_text: "SurA interacts preferentially (>50-fold) with in vitro synthesized porins over other similarly sized proteins"
- term:
    id: GO:0042597
    label: periplasmic space
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      IEA annotation from UniProtKB-SubCell (SL-0200). SurA is located in the
      periplasmic space. This is a broader parent of GO:0030288 (outer membrane-bounded
      periplasmic space), which is also annotated. Both are correct.
    action: ACCEPT
    reason: >-
      Correct localization. This is a broader parent of the more specific GO:0030288
      which is annotated with experimental evidence. The IEA annotation is acceptable
      as a general localization.
    supported_by:
      - reference_id: PMID:8985185
        supporting_text: "SurA, a periplasmic protein with peptidyl-prolyl isomerase activity"
- term:
    id: GO:0043165
    label: Gram-negative-bacterium-type cell outer membrane assembly
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      IEA annotation from InterPro (IPR023034). SurA is critically involved in
      outer membrane assembly as the primary chaperone for OMP biogenesis
      (PMID:17908933, PMID:8985185).
    action: ACCEPT
    reason: >-
      Consistent with experimental evidence. SurA depletion causes marked decrease
      in outer membrane density (PMID:17908933), confirming its essential role in
      outer membrane assembly.
    supported_by:
      - reference_id: PMID:17908933
        supporting_text: "Depletion of SurA alone results in a marked decrease in outer membrane density"
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      IEA annotation from InterPro (IPR023034). SurA stabilizes unfolded OMPs
      in the periplasm, preventing their aggregation and degradation (PMID:8626309,
      PMID:26344570).
    action: ACCEPT
    reason: >-
      Consistent with experimental evidence showing SurA prevents OMP degradation
      and misfolding. Redundant with IMP annotations but acceptable as an IEA.
    supported_by:
      - reference_id: PMID:26344570
        supporting_text: "Either chaperone prevents FhuA from misfolding by stabilizing a dynamic, unfolded state"
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      IEA annotation from InterPro/UniRule. SurA binds unfolded OMPs as demonstrated
      experimentally (PMID:11226178). This term is proposed for obsoletion per the
      UPB project; see review of the IBA annotation for this term above.
    action: MODIFY
    reason: >-
      Same rationale as the IBA GO:0051082 annotation above. SurA functions as a
      holdase chaperone for unfolded OMPs. GO:0051082 is proposed for obsoletion.
      Replace with GO:0044183 (protein folding chaperone) as the most appropriate
      existing replacement term, pending creation of holdase NTR.
    proposed_replacement_terms:
      - id: GO:0044183
        label: protein folding chaperone
    supported_by:
      - reference_id: PMID:11226178
        supporting_text: "SurA interacts preferentially (>50-fold) with in vitro synthesized porins over other similarly sized proteins"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18165306
  review:
    summary: >-
      IntAct-derived annotation showing SurA interacts with BamB (YfgL, P77774).
      Vuong et al. (PMID:18165306) used genetic and biochemical approaches to show
      that SurA binds to BamA/YaeT or another BAM complex member without going through
      BamB/YfgL. The interaction with BamB itself is detected by IntAct but the paper
      primarily discusses YfgL-YaeT interactions and shows SurA-YaeT binding is
      independent of YfgL.
    action: REMOVE
    reason: >-
      The generic "protein binding" term is uninformative. SurA's interaction with
      BAM complex components is better captured by its biological process annotations
      (GO:0043165, outer membrane assembly). The specific interaction should be
      annotated with a more specific molecular function term if available, not the
      generic protein binding. Per curation guidelines, GO:0005515 should be avoided.
    supported_by:
      - reference_id: PMID:18165306
        supporting_text: "SurA binds to YaeT (or another complex member) without going through YfgL."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:22544271
  review:
    summary: >-
      IntAct-derived annotation showing SurA interacts with BamB (P77774). Workman
      et al. (PMID:22544271) studied BamA POTRA domain mutations and showed that
      BamA-SurA interactions correlated with improved OMP biogenesis. The SurA-BamB
      interaction is detected but the paper focuses on BamA structure-function.
    action: REMOVE
    reason: >-
      Generic protein binding is uninformative. SurA's interaction with BAM complex
      components reflects its chaperone function in OMP biogenesis, which is captured
      by more informative annotations. Per curation guidelines, GO:0005515 should
      be avoided.
    supported_by:
      - reference_id: PMID:22544271
        supporting_text: "OMP biogenesis improved dramatically, and this correlated with improved BamA folding, BamA-SurA interactions, and LptD (lipopolysaccharide transporter) biogenesis."
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IMP
  original_reference_id: PMID:8626309
  review:
    summary: >-
      Lazar and Kolter (PMID:8626309) used trypsin sensitivity as a folding assay
      and demonstrated that the efficient folding of three outer membrane proteins
      (OmpA, OmpF, and LamB) requires SurA in vivo, while folding of four periplasmic
      proteins was independent of SurA.
    action: ACCEPT
    reason: >-
      Strong experimental evidence (IMP) directly demonstrating SurA's role in
      protein folding. The trypsin sensitivity assay is a validated approach for
      assessing protein conformation, and the specificity for OMPs over periplasmic
      proteins is informative.
    supported_by:
      - reference_id: PMID:8626309
        supporting_text: "We determined that the efficient folding of three outer membrane proteins (OmpA, OmpF, and LamB) requires SurA in vivo, while the folding of four periplasmic proteins was independent of SurA."
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IMP
  original_reference_id: PMID:8985185
  review:
    summary: >-
      Rouviere and Gross (PMID:8985185) demonstrated that SurA is involved in the
      conversion of unfolded LamB monomers into folded monomers. Absence of SurA
      blocks the assembly pathway and leads to accumulation of species prior to the
      folded monomer stage.
    action: ACCEPT
    reason: >-
      Strong experimental evidence (IMP) showing SurA is required for protein
      folding of LamB. The identification of a specific folding intermediate
      (folded monomer) that requires SurA provides direct evidence for involvement
      in protein folding.
    supported_by:
      - reference_id: PMID:8985185
        supporting_text: "We demonstrate that SurA is involved in the conversion of unfolded monomers into a newly identified intermediate in LamB assembly, which behaves as a folded monomer."
- term:
    id: GO:0036506
    label: maintenance of unfolded protein
  evidence_type: IDA
  original_reference_id: PMID:26344570
  review:
    summary: >-
      Thoma et al. (PMID:26344570) used single-molecule force spectroscopy and NMR
      to demonstrate that SurA (and Skp) function as holdase chaperones that stabilize
      a dynamic unfolded state of the OMP FhuA. SurA prevents misfolding by maintaining
      the polypeptide in an unfolded, folding-competent state that allows stepwise
      beta-hairpin insertion.
    action: ACCEPT
    reason: >-
      This is a core function of SurA. The term "maintenance of unfolded protein"
      (GO:0036506) accurately describes SurA's holdase mechanism of keeping OMPs in
      a dynamic unfolded state until they can insert into the membrane. This is
      direct experimental evidence from single-molecule studies.
    supported_by:
      - reference_id: PMID:26344570
        supporting_text: "Either chaperone prevents FhuA from misfolding by stabilizing a dynamic, unfolded state, thus allowing the substrate to search for structural intermediates."
      - reference_id: PMID:26344570
        supporting_text: "the SurA-chaperoned FhuA polypeptide inserts beta-hairpins into the membrane in a stepwise manner until the beta-barrel is folded"
- term:
    id: GO:0043165
    label: Gram-negative-bacterium-type cell outer membrane assembly
  evidence_type: IGI
  original_reference_id: PMID:17908933
  review:
    summary: >-
      Sklar et al. (PMID:17908933) used depletion analysis and genetic interactions
      to establish that SurA is the primary chaperone for periplasmic transit of OMPs
      to the YaeT/BamA complex. SurA and YaeT interact directly in vivo. Depletion
      of SurA alone results in a marked decrease in outer membrane density. The IGI
      evidence reflects the genetic interaction analysis with Skp/DegP.
    action: ACCEPT
    reason: >-
      Strong genetic evidence demonstrating SurA's essential role in outer membrane
      assembly. The study establishes the SurA pathway as the primary route for OMP
      biogenesis, with Skp/DegP serving as a rescue pathway.
    supported_by:
      - reference_id: PMID:17908933
        supporting_text: "SurA is the primary chaperone responsible for the periplasmic transit of the bulk mass of OMPs to the YaeT complex."
      - reference_id: PMID:17908933
        supporting_text: "Depletion of SurA alone results in a marked decrease in outer membrane density"
- term:
    id: GO:0043165
    label: Gram-negative-bacterium-type cell outer membrane assembly
  evidence_type: IMP
  original_reference_id: PMID:8985185
  review:
    summary: >-
      Rouviere and Gross (PMID:8985185) demonstrated that SurA participates in
      the assembly of outer membrane porins. Loss of SurA blocks the LamB assembly
      pathway and leads to accumulation of unfolded intermediates.
    action: ACCEPT
    reason: >-
      Direct experimental evidence showing SurA is required for outer membrane
      protein assembly. This is a core function of SurA.
    supported_by:
      - reference_id: PMID:8985185
        supporting_text: "SurA, a periplasmic protein with peptidyl-prolyl isomerase activity, participates in the assembly of outer membrane porins."
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: IMP
  original_reference_id: PMID:8626309
  review:
    summary: >-
      Lazar and Kolter (PMID:8626309) showed that SurA is required for maintaining
      the stability/conformation of outer membrane proteins. In surA mutants, OMPs
      become trypsin-sensitive, indicating loss of stable folded conformation.
    action: ACCEPT
    reason: >-
      The trypsin sensitivity assay demonstrates that SurA contributes to
      protein stabilization of OMPs. Loss of SurA leads to unstable OMP
      conformations. This is consistent with SurA's chaperone function.
    supported_by:
      - reference_id: PMID:8626309
        supporting_text: "We tested whether SurA was involved in folding periplasmic and outer membrane proteins by using trypsin sensitivity as an assay for protein conformation."
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:11226178
  review:
    summary: >-
      Behrens et al. (PMID:11226178) demonstrated that SurA interacts preferentially
      with in vitro synthesized porins (including OmpF, P02932) over other similarly
      sized proteins. This interaction reflects SurA's chaperone substrate specificity.
    action: REMOVE
    reason: >-
      Generic protein binding is uninformative. This interaction represents SurA's
      chaperone-substrate interaction with OmpF, which is better captured by the
      unfolded protein binding / chaperone annotations (GO:0051082, GO:0036506,
      GO:0006457). Per curation guidelines, GO:0005515 should be avoided.
    supported_by:
      - reference_id: PMID:11226178
        supporting_text: "SurA interacts preferentially (>50-fold) with in vitro synthesized porins over other similarly sized proteins"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:17908933
  review:
    summary: >-
      Sklar et al. (PMID:17908933) demonstrated that SurA and YaeT (BamA, P0A940)
      interact directly in vivo. This interaction is functionally significant as
      SurA delivers OMPs to the YaeT/BAM complex for membrane insertion.
    action: REMOVE
    reason: >-
      Generic protein binding is uninformative. The SurA-BamA interaction is
      functionally important for OMP delivery but is better represented by the
      biological process annotation GO:0043165 (outer membrane assembly). Per
      curation guidelines, GO:0005515 should be avoided.
    supported_by:
      - reference_id: PMID:17908933
        supporting_text: "we demonstrate that SurA and YaeT interact directly in vivo"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18165306
  review:
    summary: >-
      Vuong et al. (PMID:18165306) from EcoCyc annotation showing SurA binds to
      BamA/YaeT (P0A940). The paper demonstrates that SurA binds to YaeT or another
      BAM complex member independently of YfgL/BamB.
    action: REMOVE
    reason: >-
      Generic protein binding is uninformative. This is a duplicate reference to the
      same SurA-BamA interaction captured by the previous PMID:17908933 entry and
      is better represented by GO:0043165. Per curation guidelines, GO:0005515 should
      be avoided.
    supported_by:
      - reference_id: PMID:18165306
        supporting_text: "SurA binds to YaeT (or another complex member) without going through YfgL."
- term:
    id: GO:0030288
    label: outer membrane-bounded periplasmic space
  evidence_type: IDA
  original_reference_id: PMID:15911532
  review:
    summary: >-
      Lopez-Campistrous et al. (PMID:15911532) identified SurA in the periplasmic
      fraction through proteomic analysis using biochemical fractionation followed
      by 2D gel electrophoresis and tandem mass spectrometry.
    action: ACCEPT
    reason: >-
      Direct experimental evidence (IDA) from proteomics confirming periplasmic
      localization. Consistent with signal peptide cleavage and all other evidence.
    supported_by:
      - reference_id: PMID:15911532
        supporting_text: "2,160 were annotated and assigned to the cytosol, periplasm, inner membrane, and outer membrane by biochemical fractionation followed by two-dimensional gel electrophoresis and tandem mass spectrometry"
- term:
    id: GO:0030288
    label: outer membrane-bounded periplasmic space
  evidence_type: IDA
  original_reference_id: PMID:24140104
  review:
    summary: >-
      Han et al. (PMID:24140104) identified SurA in the periplasmic proteome of
      E. coli K-12 using large-scale periplasmic fractionation and mass spectrometry.
    action: ACCEPT
    reason: >-
      Direct experimental evidence (IDA) from periplasmic proteomics confirming
      localization. Consistent with all other evidence for periplasmic localization.
    supported_by:
      - reference_id: PMID:24140104
        supporting_text: "high-resolution periplasmic proteome reference maps of the E. coli K-12 and B strains were constructed"
- term:
    id: GO:0050821
    label: protein stabilization
  evidence_type: IMP
  original_reference_id: PMID:21784935
  review:
    summary: >-
      Palomino et al. (PMID:21784935) demonstrated that FimD protein levels are
      dramatically reduced (~30-fold) in a surA null mutant. Using a conditional surA
      mutant, they showed FimD is depleted from bacteria in parallel to SurA depletion,
      demonstrating SurA's direct role in stabilizing FimD.
    action: ACCEPT
    reason: >-
      Strong experimental evidence (IMP) showing SurA is required for the stability
      of FimD usher protein. The conditional depletion experiment provides direct
      evidence for SurA-dependent protein stabilization.
    supported_by:
      - reference_id: PMID:21784935
        supporting_text: "The FimD level is dramatically reduced (∼30-fold) in a surA null mutant"
      - reference_id: PMID:21784935
        supporting_text: "FimD is depleted from bacteria in parallel to SurA without significant upregulation of DegP"
- term:
    id: GO:0030288
    label: outer membrane-bounded periplasmic space
  evidence_type: IDA
  original_reference_id: PMID:8985185
  review:
    summary: >-
      Rouviere and Gross (PMID:8985185) characterized SurA as a periplasmic protein
      in the original study identifying its role in OMP assembly.
    action: ACCEPT
    reason: >-
      Foundational experimental evidence for periplasmic localization from the key
      characterization study.
    supported_by:
      - reference_id: PMID:8985185
        supporting_text: "SurA, a periplasmic protein with peptidyl-prolyl isomerase activity"
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IPI
  original_reference_id: PMID:11226178
  review:
    summary: >-
      Behrens et al. (PMID:11226178) showed that SurA exhibits chaperone activity
      and interacts preferentially with in vitro synthesized porins (OmpA/P02931,
      OmpF/P02932, LamB/P02943) with >50-fold selectivity over other proteins. The
      interaction is mediated by the N-terminal and C-terminal domains, independent
      of PPIase activity. This is direct evidence for SurA binding unfolded OMPs.
    action: MODIFY
    reason: >-
      Same rationale as other GO:0051082 annotations. GO:0051082 is proposed for
      obsoletion. SurA's binding to unfolded porins represents its holdase/chaperone
      activity. Replace with GO:0044183 (protein folding chaperone) as interim,
      pending holdase NTR creation.
    proposed_replacement_terms:
      - id: GO:0044183
        label: protein folding chaperone
    supported_by:
      - reference_id: PMID:11226178
        supporting_text: "a variant of SurA lacking both parvulin-like domains exhibits a PPIase-independent chaperone-like activity in vitro and almost completely complements the in vivo function of intact SurA"
      - reference_id: PMID:11226178
        supporting_text: "SurA interacts preferentially (>50-fold) with in vitro synthesized porins over other similarly sized proteins"
- term:
    id: GO:0003755
    label: peptidyl-prolyl cis-trans isomerase activity
  evidence_type: IDA
  original_reference_id: PMID:8985185
  review:
    summary: >-
      Rouviere and Gross (PMID:8985185) demonstrated that SurA has peptidyl-prolyl
      isomerase activity. The PPIase activity was confirmed biochemically and the
      EC number 5.2.1.8 was assigned. However, later work showed this activity is
      dispensable for SurA's primary function (PMID:11226178).
    action: ACCEPT
    reason: >-
      Direct experimental evidence (IDA) for PPIase enzymatic activity. Although
      this activity is dispensable for SurA's primary chaperone function in vivo,
      it is a real, experimentally demonstrated enzymatic activity of this protein.
    supported_by:
      - reference_id: PMID:8985185
        supporting_text: "SurA, a periplasmic protein with peptidyl-prolyl isomerase activity, participates in the assembly of outer membrane porins."
- term:
    id: GO:0044183
    label: protein folding chaperone
  evidence_type: IDA
  original_reference_id: PMID:11226178
  review:
    summary: >-
      Behrens et al. (PMID:11226178) directly demonstrated that SurA has chaperone
      activity independent of its PPIase domains. A SurA variant lacking both parvulin
      domains exhibited PPIase-independent chaperone-like activity in vitro and almost
      completely complemented full-length SurA function in vivo. SurA preferentially
      binds in vitro synthesized porins (>50-fold selectivity) through its N-terminal
      and C-terminal domains. This is the core molecular function of SurA.
    action: NEW
    reason: >-
      GO:0044183 (protein folding chaperone) is not currently annotated for SurA
      but is the most appropriate MF term for its primary function. SurA acts as a
      chaperone that facilitates OMP folding and assembly, with direct in vitro
      evidence for chaperone activity. This annotation should be added to replace
      GO:0051082 which is proposed for obsoletion. Evidence supports both holdase
      and chaperone mechanisms - SurA prevents aggregation (holdase) and enables
      stepwise folding (facilitating folding). GO:0044183 is the best available
      existing term.
    supported_by:
      - reference_id: PMID:11226178
        supporting_text: "a variant of SurA lacking both parvulin-like domains exhibits a PPIase-independent chaperone-like activity in vitro and almost completely complements the in vivo function of intact SurA"
      - reference_id: PMID:26344570
        supporting_text: "the SurA-chaperoned FhuA polypeptide inserts beta-hairpins into the membrane in a stepwise manner until the beta-barrel is folded"
      - reference_id: PMID:17908933
        supporting_text: "SurA is the primary chaperone responsible for the periplasmic transit of the bulk mass of OMPs to the YaeT complex."
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:11226178
  title: >-
    The SurA periplasmic PPIase lacking its parvulin domains functions in vivo
    and has chaperone activity.
  findings:
    - statement: SurA has PPIase-independent chaperone activity mediated by N-terminal and C-terminal domains
    - statement: SurA preferentially binds porins with >50-fold selectivity
    - statement: PPIase domains are dispensable for in vivo function
- id: PMID:15911532
  title: >-
    Localization, annotation, and comparison of the Escherichia coli K-12 proteome
    under two states of growth.
  findings:
    - statement: Proteomic confirmation of SurA periplasmic localization
- id: PMID:17908933
  title: >-
    Defining the roles of the periplasmic chaperones SurA, Skp, and DegP in
    Escherichia coli.
  findings:
    - statement: SurA is the primary chaperone for periplasmic transit of OMPs to the BAM complex
    - statement: SurA interacts directly with BamA/YaeT in vivo
    - statement: SurA depletion causes marked decrease in outer membrane density
    - statement: Skp/DegP serve as a rescue pathway when SurA is absent
- id: PMID:18165306
  title: >-
    Analysis of YfgL and YaeT interactions through bioinformatics, mutagenesis,
    and biochemistry.
  findings:
    - statement: SurA binds to BamA/YaeT independently of BamB/YfgL
- id: PMID:21784935
  title: >-
    The fimbrial usher FimD follows the SurA-BamB pathway for its assembly in the
    outer membrane of Escherichia coli.
  findings:
    - statement: FimD levels dramatically reduced (~30-fold) in surA null mutant
    - statement: FimD has higher dependency on SurA than other OMPs
    - statement: SurA-BamB pathway is the primary route for FimD assembly
- id: PMID:22544271
  title: >-
    Genetic, biochemical, and molecular characterization of the polypeptide
    transport-associated domain of Escherichia coli BamA.
  findings:
    - statement: BamA-SurA interactions correlate with OMP biogenesis efficiency
- id: PMID:24140104
  title: >-
    Comparison of the large-scale periplasmic proteomes of the Escherichia coli
    K-12 and B strains.
  findings:
    - statement: Proteomic confirmation of SurA periplasmic localization
- id: PMID:26344570
  title: >-
    Impact of holdase chaperones Skp and SurA on the folding of β-barrel
    outer-membrane proteins.
  findings:
    - statement: SurA characterized as a holdase chaperone
    - statement: SurA stabilizes dynamic unfolded state of FhuA
    - statement: SurA-chaperoned FhuA inserts beta-hairpins stepwise into the membrane
    - statement: Membrane acts as free-energy sink for beta-hairpin insertion
- id: PMID:8626309
  title: SurA assists the folding of Escherichia coli outer membrane proteins.
  findings:
    - statement: SurA required for efficient folding of OmpA, OmpF, and LamB in vivo
    - statement: Folding of periplasmic proteins is independent of SurA
    - statement: Trypsin sensitivity used as folding assay
- id: PMID:8985185
  title: >-
    SurA, a periplasmic protein with peptidyl-prolyl isomerase activity,
    participates in the assembly of outer membrane porins.
  findings:
    - statement: SurA has PPIase activity and participates in LamB assembly
    - statement: SurA required for conversion of unfolded monomers to folded monomers
    - statement: Absence of SurA blocks assembly pathway
    - statement: Loss of SurA induces sigmaE stress response
- id: PMID:14506253
  title: >-
    The periplasmic molecular chaperone protein SurA binds a peptide motif that is
    characteristic of integral outer membrane proteins.
  findings:
    - statement: SurA recognizes aromatic-rich peptide motifs characteristic of OMPs
- id: PMID:15840585
  title: >-
    The periplasmic chaperone SurA exploits two features characteristic of integral
    outer membrane proteins for selective substrate recognition.
  findings:
    - statement: SurA uses aromatic residue patterns and side chain orientation for OMP recognition
core_functions:
- description: >-
    Chaperone activity -- SurA functions as the primary periplasmic chaperone for
    outer membrane protein biogenesis. It binds unfolded OMPs via its N-terminal
    and C-terminal domains (independent of PPIase activity) and escorts them to the
    BAM complex. SurA acts as a holdase, stabilizing OMPs in a dynamic unfolded
    state to prevent aggregation while enabling stepwise beta-hairpin membrane
    insertion.
  molecular_function:
    id: GO:0044183
    label: protein folding chaperone
  directly_involved_in:
    - id: GO:0043165
      label: Gram-negative-bacterium-type cell outer membrane assembly
    - id: GO:0006457
      label: protein folding
    - id: GO:0036506
      label: maintenance of unfolded protein
  locations:
    - id: GO:0030288
      label: outer membrane-bounded periplasmic space
  supported_by:
    - reference_id: PMID:11226178
      supporting_text: "a variant of SurA lacking both parvulin-like domains exhibits a PPIase-independent chaperone-like activity in vitro and almost completely complements the in vivo function of intact SurA"
    - reference_id: PMID:17908933
      supporting_text: "SurA is the primary chaperone responsible for the periplasmic transit of the bulk mass of OMPs to the YaeT complex."
    - reference_id: PMID:26344570
      supporting_text: "the SurA-chaperoned FhuA polypeptide inserts beta-hairpins into the membrane in a stepwise manner until the beta-barrel is folded"
- description: >-
    Peptidyl-prolyl cis-trans isomerase activity -- SurA has PPIase activity
    (EC 5.2.1.8) residing in its second parvulin domain. This is a real enzymatic
    activity but is dispensable for SurA's primary in vivo chaperone function.
  molecular_function:
    id: GO:0003755
    label: peptidyl-prolyl cis-trans isomerase activity
  locations:
    - id: GO:0030288
      label: outer membrane-bounded periplasmic space
  supported_by:
    - reference_id: PMID:8985185
      supporting_text: "SurA, a periplasmic protein with peptidyl-prolyl isomerase activity, participates in the assembly of outer membrane porins."
    - reference_id: PMID:11226178
      supporting_text: "a variant of SurA lacking both parvulin-like domains exhibits a PPIase-independent chaperone-like activity in vitro and almost completely complements the in vivo function of intact SurA"