Hsp27

id: P02518
gene_symbol: Hsp27
product_type: PROTEIN
status: DRAFT
taxon:
  id: NCBITaxon:7227
  label: Drosophila melanogaster
description: >-
  Hsp27 is a small heat shock protein (sHSP) of Drosophila melanogaster belonging to the
  HSP20/alpha-crystallin family. It is one of four classical Drosophila sHSPs (Hsp22, Hsp23,
  Hsp26, Hsp27) that share a conserved alpha-crystallin domain and possess ATP-independent
  chaperone-like (holdase) activity. Hsp27 prevents heat-induced protein aggregation and
  maintains substrates in a refoldable state, with high efficiency at a 1:1 molar ratio to
  substrate (PMID:16572729). Approximately 40% of luciferase activity is recovered in in
  vitro refolding assays with Hsp27 (PMID:16572729), and its refolding capacity is partially
  dependent on the HSP70 machine (PMID:26705243). Hsp27 localizes primarily to the cytoplasm
  and is strongly heat-inducible. Overexpression of Hsp27 extends mean lifespan by 30% and
  increases stress resistance (PMID:15308776). Although not essential for development, Hsp27
  is associated with starvation resistance (PMID:18229455). Hsp27 interacts with the SUMO-
  conjugating enzyme DmUbc9 (PMID:9514881) and with the ER chaperone XPORT in the secretory
  pathway (PMID:22099462).
existing_annotations:
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'Manual review: cytoplasm is consistent with known biology of Hsp27.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'Manual review: nucleus may be context-dependent or peripheral for Hsp27.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
- term:
    id: GO:0009408
    label: response to heat
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'Manual review: response to heat is consistent with known biology of Hsp27.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0042026
    label: protein refolding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: 'Manual review: protein refolding is consistent with known biology of Hsp27.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      GO:0051082 is proposed for obsoletion. Hsp27 is an sHSP holdase that binds unfolded
      proteins to prevent aggregation. GO:0140309 is not appropriate (carrier-specific).
      Retain until holdase NTR is created. Accepted as consistent with experimental evidence
      for holdase activity (PMID:16572729).
    action: ACCEPT
    reason: >-
      Retained as supported by direct experimental evidence. GO:0051082 is proposed for
      obsoletion but no suitable replacement exists yet. Hsp27 is an sHSP holdase and
      GO:0140309 (unfolded protein carrier activity) is not appropriate because it is
      carrier-specific (per go-ontology#30552). Retain until a holdase chaperone activity
      NTR is created.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'Manual review: cytoplasm is consistent with known biology of Hsp27.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0009408
    label: response to heat
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'Manual review: response to heat is consistent with known biology of Hsp27.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0042026
    label: protein refolding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'Manual review: protein refolding is consistent with known biology of Hsp27.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: 'Manual review: unfolded protein binding is consistent with known biology of Hsp27.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IDA
  original_reference_id: PMID:16572729
  review:
    summary: 'Manual review: protein folding is consistent with known biology of Hsp27.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
    supported_by:
      - reference_id: PMID:16572729
        supporting_text: "the 4 main sHsps of Drosophila share the ability to prevent heat-induced protein aggregation and are able to maintain proteins in a refoldable state, although with different efficiencies"
- term:
    id: GO:0044183
    label: protein folding chaperone
  evidence_type: IDA
  original_reference_id: PMID:16572729
  review:
    summary: 'Manual review: protein folding chaperone is consistent with known biology of Hsp27.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
    supported_by:
      - reference_id: PMID:16572729
        supporting_text: "Heat-induced aggregation of citrate synthase was decreased from 100 to 17 arbitrary units in the presence of Hsp22 and Hsp27 at a 1:1 molar ratio of sHsp to citrate synthase"
- term:
    id: GO:0034663
    label: endoplasmic reticulum chaperone complex
  evidence_type: IPI
  original_reference_id: PMID:22099462
  review:
    summary: 'Manual review: endoplasmic reticulum chaperone complex may be context-dependent or peripheral for Hsp27.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
    supported_by:
      - reference_id: PMID:22099462
        supporting_text: "XPORT is a resident ER and secretory pathway protein that interacts with TRP and Rh1, as well as with Hsp27 and Hsp90"
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: ISM
  original_reference_id: PMID:19715580
  review:
    summary: 'Manual review: protein folding is consistent with known biology of Hsp27.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
    supported_by:
      - reference_id: PMID:19715580
        supporting_text: "sHSPs primarily have chaperone activity and reflect the response machine of organisms to some extreme stresses existing in environment"
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: IDA
  original_reference_id: PMID:16572729
  review:
    summary: 'Manual review: unfolded protein binding is consistent with known biology of Hsp27.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
    supported_by:
      - reference_id: PMID:16572729
        supporting_text: "These differences in luciferase reactivation efficiency seemed related to the ability of sHsps to bind their substrate at 42 degrees C, as revealed by sedimentation analysis of sHsp and luciferase on sucrose gradients"
- term:
    id: GO:0051082
    label: unfolded protein binding
  evidence_type: ISM
  original_reference_id: PMID:19715580
  review:
    summary: 'Manual review: unfolded protein binding is consistent with known biology of Hsp27.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
    supported_by:
      - reference_id: PMID:19715580
        supporting_text: "This stable multimeric structure formed by sHSPs has the function of molecular chaperone, which binds to the proteins and prevents them from thermal denaturation"
- term:
    id: GO:0009408
    label: response to heat
  evidence_type: IDA
  original_reference_id: PMID:26705243
  review:
    summary: 'Manual review: response to heat is consistent with known biology of Hsp27.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
    supported_by:
      - reference_id: PMID:26705243
        supporting_text: "The four classical small HSPs (HSP22, HSP23, HSP26, and HSP27) were all highly induced after a heat shock"
- term:
    id: GO:0042026
    label: protein refolding
  evidence_type: IDA
  original_reference_id: PMID:26705243
  review:
    summary: 'Manual review: protein refolding is consistent with known biology of Hsp27.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
    supported_by:
      - reference_id: PMID:26705243
        supporting_text: "overexpression of the classical small HSPs (HSP23, HSP26, and HSP27) increased luciferase refolding"
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: HDA
  original_reference_id: PMID:24292889
  review:
    summary: 'Manual review: nucleus may be context-dependent or peripheral for Hsp27.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
    supported_by:
      - reference_id: PMID:24292889
        supporting_text: "we have now devised a protocol to screen for substrates of this particular ubiquitin ligase"
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: HDA
  original_reference_id: PMID:24292889
  review:
    summary: 'Manual review: cytoplasm is consistent with known biology of Hsp27.'
    action: ACCEPT
    reason: Retained as supported or plausible for this gene and evidence context.
    supported_by:
      - reference_id: PMID:24292889
        supporting_text: "we report the genetic interaction in vivo between Ube3a and the C-terminal part of Rpn10"
- term:
    id: GO:0042595
    label: behavioral response to starvation
  evidence_type: IMP
  original_reference_id: PMID:18229455
  review:
    summary: 'Manual review: behavioral response to starvation may be context-dependent or peripheral for Hsp27.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
    supported_by:
      - reference_id: PMID:18229455
        supporting_text: "a significant reduction in starvation resistance was associated with the genotype without a functional Hsp27 gene"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:9514881
  review:
    summary: 'Manual review: protein binding is too generic or over-extended for Hsp27.'
    action: MARK_AS_OVER_ANNOTATED
    reason: Marked over-annotated because more specific terms capture the biology more accurately.
    supported_by:
      - reference_id: PMID:9514881
        supporting_text: "two-hybrid system analysis reveals DmUbc9 interaction with Drosophila and mammalian Hsp27"
- term:
    id: GO:0042742
    label: defense response to bacterium
  evidence_type: IMP
  original_reference_id: PMID:21076039
  review:
    summary: 'Manual review: defense response to bacterium may be context-dependent or peripheral for Hsp27.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
    supported_by:
      - reference_id: PMID:21076039
        supporting_text: "p38-activated heat-shock factor and suppressed JNK collectively contributed to host defense against infection"
- term:
    id: GO:0050832
    label: defense response to fungus
  evidence_type: IMP
  original_reference_id: PMID:21076039
  review:
    summary: 'Manual review: defense response to fungus may be context-dependent or peripheral for Hsp27.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
    supported_by:
      - reference_id: PMID:21076039
        supporting_text: "the p38 pathway-mediated stress response contribute to Drosophila host defense against microbial infection"
- term:
    id: GO:0008340
    label: determination of adult lifespan
  evidence_type: IMP
  original_reference_id: PMID:15308776
  review:
    summary: 'Manual review: determination of adult lifespan may be context-dependent or peripheral for Hsp27.'
    action: KEEP_AS_NON_CORE
    reason: Kept as non-core to preserve potentially valid context-specific annotation without elevating it to core function.
    supported_by:
      - reference_id: PMID:15308776
        supporting_text: "Overexpression of either hsp26 or hsp27 extended the mean lifespan by 30%, and the flies also displayed increased stress resistance"
core_functions:
- description: >-
    Hsp27 functions as an ATP-independent holdase chaperone that prevents heat-induced
    protein aggregation and maintains substrates in a refoldable state. It is highly
    efficient at a 1:1 molar ratio to substrate (PMID:16572729), with approximately
    40% luciferase recovery in refolding assays. Its refolding capacity is partially
    dependent on the HSP70 machine (PMID:26705243). Hsp27 is strongly heat-inducible
    and is one of four classical Drosophila sHSPs. Note - GO:0051082 is proposed for
    obsoletion but no suitable holdase-specific replacement exists yet.
  molecular_function:
    id: GO:0051082
    label: unfolded protein binding
  directly_involved_in:
    - id: GO:0006457
      label: protein folding
    - id: GO:0009408
      label: response to heat
  locations:
    - id: GO:0005737
      label: cytoplasm
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: PMID:15308776
  title: Multiple-stress analysis for isolation of Drosophila longevity genes.
  findings: []
- id: PMID:16572729
  title: Differences in the chaperone-like activities of the four main small heat shock proteins of Drosophila melanogaster.
  findings: []
- id: PMID:18229455
  title: The Hsp27 gene is not required for Drosophila development but its activity is associated with starvation resistance.
  findings: []
- id: PMID:19715580
  title: The small heat shock protein (sHSP) genes in the silkworm, Bombyx mori, and comparative analysis with other insect sHSP genes.
  findings: []
- id: PMID:21076039
  title: Participation of the p38 pathway in Drosophila host defense against pathogenic bacteria and fungi.
  findings: []
- id: PMID:22099462
  title: XPORT-dependent transport of TRP and rhodopsin.
  findings: []
- id: PMID:24292889
  title: Ube3a, the E3 ubiquitin ligase causing Angelman syndrome and linked to autism, regulates protein homeostasis through the proteasomal shuttle Rpn10.
  findings: []
- id: PMID:26705243
  title: Specific protein homeostatic functions of small heat-shock proteins increase lifespan.
  findings: []
- id: PMID:9514881
  title: Cloning and developmental expression of a nuclear ubiquitin-conjugating enzyme (DmUbc9) that interacts with small heat shock proteins in Drosophila melanogaster.
  findings: []