HSPB7

UniProt ID: Q9UBY9
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

HSPB7 (heat shock protein beta-7), also known as cardiovascular heat shock protein (cvHsp), is a member of the small heat shock protein (sHSP / HSP20, alpha-crystallin domain) family. It is selectively and highly expressed in cardiovascular and insulin-sensitive tissues, predominantly heart and skeletal muscle. HSPB7 binds the actin-crosslinking protein filamin (alpha-filamin / actin-binding protein 280) through its core alpha-crystallin domain and forms hetero-oligomeric complexes with other small heat shock proteins including HSPB8 (HSP22), HSPB2 (MKBP) and HSPB1 (HSP27). Unlike the canonical small HSPs HSPB1 and HSPB5, HSPB7 does not promote refolding of denatured substrates; instead it acts as a non-canonical chaperone/sequestrase that binds and sequesters aggregation-prone proteins (e.g. polyglutamine-expanded and filamin clients), suppressing their aggregation. HSPB7 localizes to the cytoplasm and nucleus and constitutively resides in SC35 nuclear splicing speckles via its N-terminal region. It is implicated in cardiac biology and cardiomyopathy risk.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0005634 nucleus
IBA
GO_REF:0000033 		ACCEPT
Summary: Nuclear localization inferred phylogenetically; HSPB7 is directly documented in the nucleus and constitutively resides in SC35 nuclear splicing speckles.
Reason: Corroborated by direct experimental (IDA) evidence (PMID:19464326) and the UniProt subcellular-location record.
Supporting Evidence:
file:human/HSPB7/HSPB7-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19464326}. Nucleus
GO:0005737 cytoplasm
IBA
GO_REF:0000033 		ACCEPT
Summary: Cytoplasmic localization inferred phylogenetically; HSPB7 has a documented cytoplasmic pool in addition to its nuclear-speckle residence.
Reason: Corroborated by direct experimental (IDA) evidence (PMID:19464326) and the UniProt subcellular-location record.
Supporting Evidence:
file:human/HSPB7/HSPB7-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0005634 nucleus
IEA
GO_REF:0000044 		ACCEPT
Summary: Electronic annotation of nuclear localization, consistent with the IBA and IDA nucleus annotations.
Reason: Agrees with stronger experimental evidence (PMID:19464326) placing HSPB7 in the nucleus.
Supporting Evidence:
file:human/HSPB7/HSPB7-uniprot.txt
Nucleus {ECO:0000269|PubMed:19464326}
GO:0005737 cytoplasm
IEA
GO_REF:0000044 		ACCEPT
Summary: Electronic annotation of cytoplasmic localization, redundant with the IBA and IDA cytoplasm annotations.
Reason: Correct compartment, agreeing with stronger experimental evidence.
Supporting Evidence:
file:human/HSPB7/HSPB7-uniprot.txt
SUBCELLULAR LOCATION: Cytoplasm
GO:0007507 heart development
IEA
GO_REF:0000002 		KEEP AS NON CORE
Summary: InterPro-based electronic annotation to heart development, reflecting HSPB7's cardiac-enriched expression and family associations. No direct experimental demonstration of a role in heart morphogenesis for human HSPB7.
Reason: Plausible given the strong cardiac/cardiovascular expression of cvHsp, but derived from an InterPro-to-GO family rule rather than direct experimental evidence for this gene; retained as a non-core process.
Supporting Evidence:
PMID:10593960
selectively expressed in cardiovascular and insulin-sensitive tissues
GO:0015030 Cajal body
IEA
GO_REF:0000044 		KEEP AS NON CORE
Summary: UniProt-SubCell-derived electronic localization to Cajal bodies, consistent with HSPB7's reported sub-nuclear localization to splicing-related nuclear bodies.
Reason: Supported by the UniProt subcellular-location record (Cajal body), but sub-nuclear body localization is peripheral to HSPB7's core chaperone/sequestrase function.
Supporting Evidence:
file:human/HSPB7/HSPB7-uniprot.txt
Nucleus, Cajal body {ECO:0000269|PubMed:19464326}
GO:0005515 protein binding
IPI
PMID:14594798
Interaction of human HSP22 (HSPB8) with other small heat sho... 		MODIFY
Summary: Demonstrates that HSPB7 (cvHSP) hetero-dimerizes with the small heat shock protein HSPB8 (HSP22) through a C-C interaction. The bare protein binding term is uninformative; the interaction is with a heat shock protein.
Reason: Per curation guidelines, bare protein binding (GO:0005515) is uninformative. The documented partner here is the small HSP HSPB8, so the more informative MF is heat shock protein binding (GO:0031072).
Proposed replacements: heat shock protein binding
Supporting Evidence:
PMID:14594798
HSP22 interacts with itself, cvHSP (HSPB7), MKBP (HSPB2) and HSP27
GO:0005515 protein binding
IPI
PMID:16189514
Towards a proteome-scale map of the human protein-protein in... 		MODIFY
Summary: Proteome-scale interactome screen capturing an HSPB7-HSPB8 (Q9UJY1) interaction. The bare protein binding term is uninformative; the partner is a heat shock protein.
Reason: Bare protein binding is uninformative. The WITH partner is HSPB8 (Q9UJY1), a small heat shock protein, so heat shock protein binding (GO:0031072) is the appropriate specific term.
Proposed replacements: heat shock protein binding
Supporting Evidence:
file:human/HSPB7/HSPB7-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:16189514 UniProtKB:Q9UJY1
GO:0005515 protein binding
IPI
PMID:25416956
A proteome-scale map of the human interactome network. 		KEEP AS NON CORE
Summary: Yeast two-hybrid human interactome map capturing multiple HSPB7 interactions, including HSPB8 (Q9UJY1) and FLNA (P21333-2), alongside several non-chaperone partners. The bare protein binding term is uninformative.
Reason: This collapses many high-throughput interactions; while it includes the biologically meaningful HSPB8 and filamin partners (captured elsewhere as heat shock protein binding and filamin binding), the bare term records genuine interactions but is not itself an informative molecular function.
Supporting Evidence:
file:human/HSPB7/HSPB7-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:25416956 UniProtKB:P21333-2
GO:0005515 protein binding
IPI
PMID:28514442
Architecture of the human interactome defines protein commun... 		MODIFY
Summary: Interactome (BioPlex-type) screen capturing an HSPB7-FLNA (P21333-2) interaction, consistent with HSPB7's documented filamin binding. The bare protein binding term is uninformative.
Reason: Bare protein binding is uninformative. The WITH partner is the filamin FLNA (P21333-2), and HSPB7's filamin binding is experimentally established, so filamin binding (GO:0031005) is the appropriate specific molecular function.
Proposed replacements: filamin binding
Supporting Evidence:
file:human/HSPB7/HSPB7-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:28514442 UniProtKB:P21333-2
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome. 		KEEP AS NON CORE
Summary: Reference binary interactome map capturing many HSPB7 interactions, including the co-chaperone BAG3 (O95817), HSPB8 (Q9UJY1) and FLNA (P21333-2). The bare protein binding term is uninformative.
Reason: A large set of binary interactions collapsed under the uninformative bare term; the functionally salient partners (HSPB8, BAG3, filamin) are better captured as heat shock protein binding and filamin binding. Retained as non-core because it records genuine interactions.
Supporting Evidence:
file:human/HSPB7/HSPB7-goa.tsv
GO:0005515 protein binding molecular_function ECO:0000353 IPI PMID:32296183 UniProtKB:O95817
GO:0015629 actin cytoskeleton
IEA
GO_REF:0000107 		KEEP AS NON CORE
Summary: Ensembl-ortholog-based electronic localization to the actin cytoskeleton, consistent with HSPB7's binding to the actin-crosslinker filamin.
Reason: Plausible given the experimentally established filamin binding, but supported only by ortholog-based electronic inference; retained as a non-core localization.
Supporting Evidence:
file:human/HSPB7/HSPB7-uniprot.txt
Interacts with C-terminal domain of actin-binding protein 280.
GO:0031005 filamin binding
IEA
GO_REF:0000107 		ACCEPT
Summary: HSPB7 binds alpha-filamin (actin-binding protein 280) through its alpha-crystallin domain; this is a directly documented molecular function of cvHsp, although the GOA annotation here is by ortholog-based electronic inference.
Reason: Filamin binding is experimentally established for human cvHsp (PMID:10593960), making this electronic annotation correct and a core molecular function.
Supporting Evidence:
PMID:10593960
cvHsp interacted in both yeast two-hybrid and immunoprecipitation experiments with alpha-filamin or actin-binding protein 280
file:human/HSPB7/HSPB7-uniprot.txt
Interacts with C-terminal domain of actin-binding protein 280.
GO:0005634 nucleus
IDA
PMID:19464326
HSPB7 is a SC35 speckle resident small heat shock protein. 		ACCEPT
Summary: Direct experimental (confocal microscopy) evidence for nuclear localization; HSPB7 constitutively resides in SC35 splicing speckles.
Reason: IDA-supported nuclear localization, consistent with UniProt and the SC35-speckle residence.
Supporting Evidence:
PMID:19464326
HSPB7 constitutively localized to SC35 splicing speckles, driven by its
GO:0005737 cytoplasm
IDA
PMID:19464326
HSPB7 is a SC35 speckle resident small heat shock protein. 		ACCEPT
Summary: Direct experimental (confocal microscopy) evidence for a cytoplasmic pool of HSPB7.
Reason: IDA-supported cytoplasmic localization from the HSPB-family subcellular-distribution survey.
Supporting Evidence:
file:human/HSPB7/HSPB7-uniprot.txt
Cytoplasm {ECO:0000269|PubMed:19464326}
GO:0006986 response to unfolded protein
TAS
PMID:10593960
Identification and characterization of cvHsp. A novel human ... 		ACCEPT
Summary: HSPB7 (cvHsp) is a small stress protein of the sHSP family. It participates in the cellular response to proteotoxic stress, although notably by sequestering aggregation-prone clients rather than by promoting refolding.
Reason: Membership in the stress-responsive small heat shock protein family supports this process annotation; cvHsp was characterized as a small stress protein.
Supporting Evidence:
PMID:10593960
a novel small stress protein of 170 amino acids that we named cvHsp
GO:0008016 regulation of heart contraction
TAS
PMID:10593960
Identification and characterization of cvHsp. A novel human ... 		KEEP AS NON CORE
Summary: Annotation derived from the original cvHsp characterization, reflecting its high cardiac expression and filamin interaction. A direct role in regulating heart contraction is inferred rather than demonstrated.
Reason: Plausible given cardiac-restricted expression and filamin (cytoskeletal) binding, but the contractile-regulation role is indirect/inferential; retained as non-core.
Supporting Evidence:
PMID:10593960
selectively expressed in cardiovascular and insulin-sensitive tissues

Core Functions

Non-canonical small heat shock protein that binds aggregation-prone client proteins and small-HSP partners (e.g. HSPB8, HSPB2, HSPB1) and sequesters them to suppress aggregation, without promoting substrate refolding.

Molecular Function:
unfolded protein binding
Cellular Locations:
cytoplasm nucleus
Supporting Evidence:

Binding to the actin-crosslinking protein filamin (alpha-filamin / actin-binding protein 280) via the alpha-crystallin domain, linking HSPB7 to the cardiac/muscle cytoskeleton.

Molecular Function:
filamin binding
Cellular Locations:
cytoplasm
Supporting Evidence:
  • PMID:10593960
    cvHsp interacted in both yeast two-hybrid and immunoprecipitation experiments with alpha-filamin or actin-binding protein 280

References

GO_REF:0000002
Gene Ontology annotation through association of InterPro records with GO terms
GO_REF:0000033
Annotation inferences using phylogenetic trees
GO_REF:0000044
Gene Ontology annotation of UniProtKB entries based on the manual curation of subcellular locations
GO_REF:0000107
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
PMID:10593960
Identification and characterization of cvHsp. A novel human small stress protein selectively expressed in cardiovascular and insulin-sensitive tissues.
  • Identified cvHsp/HSPB7 as a 170-aa small stress protein highly expressed in heart and skeletal muscle that binds the C-terminal tail of alpha-filamin (actin-binding protein 280) via residues 56-119.
PMID:14594798
Interaction of human HSP22 (HSPB8) with other small heat shock proteins.
  • HSPB8 (HSP22) hetero-dimerizes with cvHSP (HSPB7) through a C-terminal to C-terminal interaction, and also interacts with HSPB2 (MKBP) and HSPB1 (HSP27), defining the small-HSP hetero-oligomer network.
PMID:16189514
Towards a proteome-scale map of the human protein-protein interaction network.
PMID:19464326
HSPB7 is a SC35 speckle resident small heat shock protein.
  • HSPB7 constitutively localizes to SC35 nuclear splicing speckles driven by its N-terminus and, unlike HSPB1/HSPB5, does not support refolding of heat-denatured substrates, indicating a non-canonical chaperone role.
PMID:25416956
A proteome-scale map of the human interactome network.
PMID:28514442
Architecture of the human interactome defines protein communities and disease networks.
PMID:32296183
A reference map of the human binary protein interactome.
file:human/HSPB7/HSPB7-uniprot.txt
UniProt entry Q9UBY9 (HSPB7_HUMAN), Heat shock protein beta-7 (cvHsp)
  • Cardiovascular small heat shock protein; binds actin-binding protein 280 (filamin); interacts with HSPB8 and BAG3; cytoplasm, nucleus and SC35 splicing speckles; heart/skeletal-muscle enriched.

Suggested Questions for Experts

Q: What is the molecular mechanism by which HSPB7 suppresses aggregation of clients such as polyglutamine-expanded proteins and mutant filamin without supporting their refolding?

Q: Does HSPB7's residence in SC35 splicing speckles reflect a role in RNA/splicing biology, or is it a storage/sequestration site distinct from its cytoskeletal function?

Q: How do HSPB7 hetero-oligomers with HSPB8/BAG3 contribute to chaperone-assisted selective autophagy in cardiomyocytes?

Suggested Experiments

Experiment: In vitro aggregation-suppression assays comparing HSPB7 with canonical HSPB1/HSPB5 on amyloidogenic and polyQ substrates, paired with refolding assays to confirm holdase/sequestrase (non-foldase) behavior.

Experiment: Domain-swap and point-mutation analysis of the HSPB7 N-terminal region (1-71) to dissect SC35-speckle targeting versus client sequestration.

Experiment: Cardiomyocyte HSPB7 knockout/knock-in models to test effects on filamin handling, proteostasis, and contractile function.

📚 Additional Documentation

Notes

(HSPB7-notes.md)

HSPB7 (Q9UBY9) research notes

Identity

  • Heat shock protein beta-7 / cardiovascular heat shock protein (cvHsp), small heat shock protein (HSP20/alpha-crystallin) family, 170 aa, ~18.6 kDa.
  • Identified as a novel small stress protein selectively expressed in cardiovascular and insulin-sensitive tissues [PMID:10593960 "a novel small stress protein of 170 amino acids that we named cvHsp"; "expression was high in heart, medium in skeletal muscle, and low in aorta or adipose tissues."].

Tissue

  • Heart-enriched; HPA group enriched (heart muscle, skeletal muscle, tongue) [file:human/HSPB7/HSPB7-uniprot.txt "HPA; ENSG00000173641; Group enriched (heart muscle, skeletal muscle, tongue)."]. Isoform 1 highly expressed in adult/fetal heart and skeletal muscle.

Molecular interactions / function

  • Binds alpha-filamin (filamin / actin-binding protein 280); residues 56-119 important PMID:10593960. UniProt SUBUNIT: "Interacts with C-terminal domain of actin-binding protein 280." GOA: filamin binding (IEA, Ensembl ortholog).
  • Forms hetero-oligomers with other small HSPs: HSPB8 (HSP22), HSPB2 (MKBP), HSPB1 (HSP27) [PMID:14594798 "HSP22 interacts with itself, cvHSP (HSPB7), MKBP (HSPB2) and HSP27"; "HSP22-cvHSP hetero-dimers through C-C interaction."]. UniProt INTERACTION list includes HSPB8 (Q9UJY1) and BAG3 (O95817).
  • Non-canonical chaperone: in the Vos HSPB-family survey, classical members HSPB1/HSPB5 refolded heat-unfolded substrate but HSPB7 did NOT support refolding [PMID:19464326 "Unlike HSPB1 and HSPB5, that chaperoned heat unfolded substrates and kept them folding competent, HSPB7 did not support refolding."; "Our data suggest a non-chaperone-like role of HSPB7 at SC35 speckles."]. HSPB7 is, however, an effective suppressor of protein aggregation (e.g. polyQ); it sequesters aggregation-prone proteins rather than refolding them (field consensus; Vos 2010 J Biol Chem).

Localization

  • Cytoplasm and nucleus; constitutively resides in SC35 nuclear splicing speckles, driven by its N-terminus (residues 1-71) [file:human/HSPB7/HSPB7-uniprot.txt "Note=Resides in sub-nuclear structures known as SC35 speckles or nuclear splicing speckles."; FT REGION 1..71 "Required for localization to SC35 splicing speckles"; PMID:19464326 "HSPB7 constitutively localized to SC35 splicing speckles, driven by its N-terminus."].
  • UniProt also lists Nucleus, Cajal body. GOA: aggresome (IDA, HPA), nucleoplasm (IDA, HPA), actin cytoskeleton (IEA ortholog).

GO review reasoning

  • protein binding (IPI, GO:0005515) x many: uninformative bare term. The informative interactions are with small HSPs and filamin. MKBP/HSPB8 interactions -> heat shock protein binding. Filamin -> filamin binding (already an IEA term). KEEP_AS_NON_CORE the generic IPI; the HSPB8 (Q9UJY1) IPIs can be MODIFY-ed to heat shock protein binding.
  • filamin binding (GO:0031005, IEA ortholog): supported by direct experimental human data (PMID:10593960). ACCEPT/MODIFY-up; this is a genuine MF for cvHsp.
  • regulation of heart contraction (GO:0008016, TAS): cvHsp is cardiac-enriched and binds filamin; plausible but indirect; KEEP_AS_NON_CORE.
  • heart development (GO:0007507, IEA InterPro): IEA ortholog/family; KEEP_AS_NON_CORE.
  • response to unfolded protein (GO:0006986, TAS): stress-protein family role; but HSPB7 specifically does NOT refold. Still a member of the stress-response sHSP family and sequesters aggregates; KEEP as ACCEPT (process-level, stress response) — note it acts via sequestration not refolding.
  • Localization terms (cytoplasm, nucleus IBA/IDA/IEA): ACCEPT. Cajal body (IEA): KEEP_AS_NON_CORE. actin cytoskeleton (IEA ortholog): KEEP_AS_NON_CORE (consistent with filamin binding).

Core functions

  1. Small-HSP holdase/sequestrase that binds aggregation-prone clients (and small-HSP partners) without refolding them -> unfolded protein binding (GO:0051082) / heat shock protein binding (GO:0031072).
  2. Filamin binding (GO:0031005) - structural/cytoskeletal cardiac role.

Pn Notes

(HSPB7-pn-notes.md)

HSPB7 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: Q9UBY9
  • AIGR review status: COMPLETE
  • Review batch: proteostasis-batch-2026-06-07b
  • Batch change status: added

Source Files Checked

Deep Research Files

  • No *-deep-research*.md file found in this gene directory.

AIGR Review Snapshot

  • Description: HSPB7 (heat shock protein beta-7), also known as cardiovascular heat shock protein (cvHsp), is a member of the small heat shock protein (sHSP / HSP20, alpha-crystallin domain) family. It is selectively and highly expressed in cardiovascular and insulin-sensitive tissues, predominantly heart and skeletal muscle. HSPB7 binds the actin-crosslinking protein filamin (alpha-filamin / actin-binding protein 280) through its core alpha-crystallin domain and forms hetero-oligomeric complexes with other small heat shock proteins including HSPB8 (HSP22), HSPB2 (MKBP) and HSPB1 (HSP27). Unlike the canonical small HSPs HSPB1 and HSPB5, HSPB7 does not promote refolding of denatured substrates; instead it acts as a non-canonical chaperone/sequestrase that binds and sequesters aggregation-prone proteins (e.g. polyglutamine-expanded and filamin clients), suppressing their aggregation. HSPB7 localizes to the cytoplasm and nucleus and constitutively resides in SC35 nuclear splicing speckles via its N-terminal region. It is implicated in cardiac biology and cardiomyopathy risk.
  • Existing/core annotation action counts: ACCEPT: 8; KEEP_AS_NON_CORE: 6; MODIFY: 3

PN Consistency Summary

  • Consistency: Notes ↔ review converge tightly — HSPB7/cvHsp is a NON-canonical sHSP that does NOT refold denatured substrate (PMID:19464326 "HSPB7 did not support refolding"); it sequesters aggregation-prone clients (polyQ, filamin) and binds alpha-filamin (PMID:10593960). Cardiac-enriched, SC35-speckle resident. This directly contradicts the PN GO:0044183 (foldase) projection.
  • PN story / NEW pressure: GOA has no folding-chaperone MF for HSPB7 (has GO:0031005 filamin binding, GO:0006986 BP). PN projects GO:0044183 protein folding chaperone (verified real, but a FOLDASE per OLS — "binds an unfolded protein to fold it"). HSPB7 is explicitly a non-foldase sequestrase, so GO:0044183 is the most over-reaching projection of the six sHSPs here. The review's genuine MFs are GO:0031005 filamin binding (ACCEPT) and GO:0051082 unfolded protein binding (holdase/sequestrase, core). The defensible MF gap, if any, is GO:0140309 unfolded protein holdase activity / GO:0051082, NOT GO:0044183.
  • Evidence alignment: PN row carries no reference titles; review PMIDs (19464326, 10593960, 14594798, plus interactome set) cover the non-refolding phenotype, filamin binding, and sHSP hetero-oligomers — no overlap to diverge, but the key review finding (no refolding) refutes the PN projection.
  • Verdict: sHSP membership correct but the GO:0044183 foldase projection is contradicted by direct evidence; over-reaches. Recommended edits: [MAP] do not project GO:0044183 protein folding chaperone onto Q9UBY9 (HSPB7 demonstrably does not refold; PMID:19464326); if a shared sHSP MF is desired use GO:0140309 unfolded protein holdase activity / GO:0051082 unfolded protein binding, and mark HSPB7 a non-canonical exception.

Full Consistency Review

  • UniProt: Q9UBY9 · batch: proteostasis-batch-2026-06-07b · review status: COMPLETE
  • PN placement: one row — Cytonuclear proteostasis|Chaperone|small HSP system|small HSP (type) ; PN-node mapping: sHSP type → mapped/ok_for_propagation_to_go GO:0044183 protein folding chaperone (new_to_goa); group/class/branch no_mapping.
  • Consistency: Notes ↔ review converge tightly — HSPB7/cvHsp is a NON-canonical sHSP that does NOT refold denatured substrate (PMID:19464326 "HSPB7 did not support refolding"); it sequesters aggregation-prone clients (polyQ, filamin) and binds alpha-filamin (PMID:10593960). Cardiac-enriched, SC35-speckle resident. This directly contradicts the PN GO:0044183 (foldase) projection.
  • PN story / NEW pressure: GOA has no folding-chaperone MF for HSPB7 (has GO:0031005 filamin binding, GO:0006986 BP). PN projects GO:0044183 protein folding chaperone (verified real, but a FOLDASE per OLS — "binds an unfolded protein to fold it"). HSPB7 is explicitly a non-foldase sequestrase, so GO:0044183 is the most over-reaching projection of the six sHSPs here. The review's genuine MFs are GO:0031005 filamin binding (ACCEPT) and GO:0051082 unfolded protein binding (holdase/sequestrase, core). The defensible MF gap, if any, is GO:0140309 unfolded protein holdase activity / GO:0051082, NOT GO:0044183.
  • Mapping strategy: This gene is the exemplar where the sHSP-family GO:0044183 mapping is wrong: HSPB7 is a poor classical holdase and an outright non-foldase. GO:0044183 is broader-and-wrong (foldase activity HSPB7 lacks). Either re-scope the sHSP "small HSP" type away from a foldase term, or flag HSPB7 as an exception on Q9UBY9.
  • Evidence alignment: PN row carries no reference titles; review PMIDs (19464326, 10593960, 14594798, plus interactome set) cover the non-refolding phenotype, filamin binding, and sHSP hetero-oligomers — no overlap to diverge, but the key review finding (no refolding) refutes the PN projection.
  • Verdict: sHSP membership correct but the GO:0044183 foldase projection is contradicted by direct evidence; over-reaches. Recommended edits: [MAP] do not project GO:0044183 protein folding chaperone onto Q9UBY9 (HSPB7 demonstrably does not refold; PMID:19464326); if a shared sHSP MF is desired use GO:0140309 unfolded protein holdase activity / GO:0051082 unfolded protein binding, and mark HSPB7 a non-canonical exception.

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07b
  • review_yaml: genes/human/HSPB7/HSPB7-ai-review.yaml
  • PN workbook rows: 1

PN row 1: Cytonuclear proteostasis | Chaperone | small HSP system | small HSP

  • UniProt: Q9UBY9
  • In branches: CY
  • PN-node mapping records (path + ancestors):
    • [type] Cytonuclear proteostasis|Chaperone|small HSP system|small HSP
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0044183 protein folding chaperone]
      rationale: This PN type denotes small heat-shock chaperones. Protein folding chaperone is the appropriate shared molecular-function term.
    • [group] Cytonuclear proteostasis|Chaperone|small HSP system
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a narrower taxonomy bucket that is already covered by a curated parent mapping or by gene-level annotations. No additional direct GO mapping is appropriate from this node.
    • [class] Cytonuclear proteostasis|Chaperone
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a broad PN category rather than a specific GO class. The member genes span multiple activities, complexes, or contexts, so propagation from this node would overstate the shared biology; use narrower child or gene-level curations.
    • [branch] Cytonuclear proteostasis
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a top-level PN branch. This is a systems/taxonomy umbrella, not a direct GO assertion; narrower child curations carry any propagating GO mappings.

Projected GO annotations (1)

  • GO:0044183 protein folding chaperone | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=Cytonuclear proteostasis|Chaperone|small HSP system|small HSP

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

 
id: Q9UBY9
gene_symbol: HSPB7
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: HSPB7 (heat shock protein beta-7), also known as cardiovascular heat shock
  protein (cvHsp), is a member of the small heat shock protein (sHSP / HSP20, alpha-crystallin
  domain) family. It is selectively and highly expressed in cardiovascular and insulin-sensitive
  tissues, predominantly heart and skeletal muscle. HSPB7 binds the actin-crosslinking
  protein filamin (alpha-filamin / actin-binding protein 280) through its core alpha-crystallin
  domain and forms hetero-oligomeric complexes with other small heat shock proteins
  including HSPB8 (HSP22), HSPB2 (MKBP) and HSPB1 (HSP27). Unlike the canonical small
  HSPs HSPB1 and HSPB5, HSPB7 does not promote refolding of denatured substrates; instead
  it acts as a non-canonical chaperone/sequestrase that binds and sequesters aggregation-prone
  proteins (e.g. polyglutamine-expanded and filamin clients), suppressing their aggregation.
  HSPB7 localizes to the cytoplasm and nucleus and constitutively resides in SC35 nuclear
  splicing speckles via its N-terminal region. It is implicated in cardiac biology
  and cardiomyopathy risk.
existing_annotations:
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Nuclear localization inferred phylogenetically; HSPB7 is directly documented
      in the nucleus and constitutively resides in SC35 nuclear splicing speckles.
    action: ACCEPT
    reason: Corroborated by direct experimental (IDA) evidence (PMID:19464326) and
      the UniProt subcellular-location record.
    supported_by:
    - reference_id: file:human/HSPB7/HSPB7-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19464326}.
        Nucleus'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: Cytoplasmic localization inferred phylogenetically; HSPB7 has a documented
      cytoplasmic pool in addition to its nuclear-speckle residence.
    action: ACCEPT
    reason: Corroborated by direct experimental (IDA) evidence (PMID:19464326) and
      the UniProt subcellular-location record.
    supported_by:
    - reference_id: file:human/HSPB7/HSPB7-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic annotation of nuclear localization, consistent with the IBA
      and IDA nucleus annotations.
    action: ACCEPT
    reason: Agrees with stronger experimental evidence (PMID:19464326) placing HSPB7
      in the nucleus.
    supported_by:
    - reference_id: file:human/HSPB7/HSPB7-uniprot.txt
      supporting_text: Nucleus {ECO:0000269|PubMed:19464326}
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic annotation of cytoplasmic localization, redundant with the
      IBA and IDA cytoplasm annotations.
    action: ACCEPT
    reason: Correct compartment, agreeing with stronger experimental evidence.
    supported_by:
    - reference_id: file:human/HSPB7/HSPB7-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0007507
    label: heart development
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: InterPro-based electronic annotation to heart development, reflecting
      HSPB7's cardiac-enriched expression and family associations. No direct experimental
      demonstration of a role in heart morphogenesis for human HSPB7.
    action: KEEP_AS_NON_CORE
    reason: Plausible given the strong cardiac/cardiovascular expression of cvHsp,
      but derived from an InterPro-to-GO family rule rather than direct experimental
      evidence for this gene; retained as a non-core process.
    supported_by:
    - reference_id: PMID:10593960
      supporting_text: selectively expressed in cardiovascular and insulin-sensitive
        tissues
- term:
    id: GO:0015030
    label: Cajal body
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: UniProt-SubCell-derived electronic localization to Cajal bodies, consistent
      with HSPB7's reported sub-nuclear localization to splicing-related nuclear bodies.
    action: KEEP_AS_NON_CORE
    reason: Supported by the UniProt subcellular-location record (Cajal body), but
      sub-nuclear body localization is peripheral to HSPB7's core chaperone/sequestrase
      function.
    supported_by:
    - reference_id: file:human/HSPB7/HSPB7-uniprot.txt
      supporting_text: Nucleus, Cajal body {ECO:0000269|PubMed:19464326}
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:14594798
  qualifier: enables
  review:
    summary: Demonstrates that HSPB7 (cvHSP) hetero-dimerizes with the small heat shock
      protein HSPB8 (HSP22) through a C-C interaction. The bare protein binding term
      is uninformative; the interaction is with a heat shock protein.
    action: MODIFY
    reason: Per curation guidelines, bare protein binding (GO:0005515) is uninformative.
      The documented partner here is the small HSP HSPB8, so the more informative MF
      is heat shock protein binding (GO:0031072).
    proposed_replacement_terms:
    - id: GO:0031072
      label: heat shock protein binding
    supported_by:
    - reference_id: PMID:14594798
      supporting_text: HSP22 interacts with itself, cvHSP (HSPB7), MKBP (HSPB2) and
        HSP27
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16189514
  qualifier: enables
  review:
    summary: Proteome-scale interactome screen capturing an HSPB7-HSPB8 (Q9UJY1) interaction.
      The bare protein binding term is uninformative; the partner is a heat shock protein.
    action: MODIFY
    reason: Bare protein binding is uninformative. The WITH partner is HSPB8 (Q9UJY1),
      a small heat shock protein, so heat shock protein binding (GO:0031072) is the
      appropriate specific term.
    proposed_replacement_terms:
    - id: GO:0031072
      label: heat shock protein binding
    supported_by:
    - reference_id: file:human/HSPB7/HSPB7-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI
        PMID:16189514 UniProtKB:Q9UJY1
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: Yeast two-hybrid human interactome map capturing multiple HSPB7 interactions,
      including HSPB8 (Q9UJY1) and FLNA (P21333-2), alongside several non-chaperone
      partners. The bare protein binding term is uninformative.
    action: KEEP_AS_NON_CORE
    reason: This collapses many high-throughput interactions; while it includes the
      biologically meaningful HSPB8 and filamin partners (captured elsewhere as heat
      shock protein binding and filamin binding), the bare term records genuine interactions
      but is not itself an informative molecular function.
    supported_by:
    - reference_id: file:human/HSPB7/HSPB7-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI
        PMID:25416956 UniProtKB:P21333-2
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:28514442
  qualifier: enables
  review:
    summary: Interactome (BioPlex-type) screen capturing an HSPB7-FLNA (P21333-2) interaction,
      consistent with HSPB7's documented filamin binding. The bare protein binding
      term is uninformative.
    action: MODIFY
    reason: Bare protein binding is uninformative. The WITH partner is the filamin
      FLNA (P21333-2), and HSPB7's filamin binding is experimentally established, so
      filamin binding (GO:0031005) is the appropriate specific molecular function.
    proposed_replacement_terms:
    - id: GO:0031005
      label: filamin binding
    supported_by:
    - reference_id: file:human/HSPB7/HSPB7-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI
        PMID:28514442 UniProtKB:P21333-2
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  qualifier: enables
  review:
    summary: Reference binary interactome map capturing many HSPB7 interactions, including
      the co-chaperone BAG3 (O95817), HSPB8 (Q9UJY1) and FLNA (P21333-2). The bare
      protein binding term is uninformative.
    action: KEEP_AS_NON_CORE
    reason: A large set of binary interactions collapsed under the uninformative bare
      term; the functionally salient partners (HSPB8, BAG3, filamin) are better captured
      as heat shock protein binding and filamin binding. Retained as non-core because
      it records genuine interactions.
    supported_by:
    - reference_id: file:human/HSPB7/HSPB7-goa.tsv
      supporting_text: GO:0005515 protein binding molecular_function ECO:0000353 IPI
        PMID:32296183 UniProtKB:O95817
- term:
    id: GO:0015629
    label: actin cytoskeleton
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Ensembl-ortholog-based electronic localization to the actin cytoskeleton,
      consistent with HSPB7's binding to the actin-crosslinker filamin.
    action: KEEP_AS_NON_CORE
    reason: Plausible given the experimentally established filamin binding, but supported
      only by ortholog-based electronic inference; retained as a non-core localization.
    supported_by:
    - reference_id: file:human/HSPB7/HSPB7-uniprot.txt
      supporting_text: Interacts with C-terminal domain of actin-binding protein 280.
- term:
    id: GO:0031005
    label: filamin binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: HSPB7 binds alpha-filamin (actin-binding protein 280) through its alpha-crystallin
      domain; this is a directly documented molecular function of cvHsp, although the
      GOA annotation here is by ortholog-based electronic inference.
    action: ACCEPT
    reason: Filamin binding is experimentally established for human cvHsp (PMID:10593960),
      making this electronic annotation correct and a core molecular function.
    supported_by:
    - reference_id: PMID:10593960
      supporting_text: cvHsp interacted in both yeast two-hybrid and immunoprecipitation
        experiments with alpha-filamin or actin-binding protein 280
    - reference_id: file:human/HSPB7/HSPB7-uniprot.txt
      supporting_text: Interacts with C-terminal domain of actin-binding protein 280.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IDA
  original_reference_id: PMID:19464326
  qualifier: located_in
  review:
    summary: Direct experimental (confocal microscopy) evidence for nuclear localization;
      HSPB7 constitutively resides in SC35 splicing speckles.
    action: ACCEPT
    reason: IDA-supported nuclear localization, consistent with UniProt and the SC35-speckle
      residence.
    supported_by:
    - reference_id: PMID:19464326
      supporting_text: HSPB7 constitutively localized to SC35 splicing speckles, driven
        by its
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:19464326
  qualifier: located_in
  review:
    summary: Direct experimental (confocal microscopy) evidence for a cytoplasmic pool
      of HSPB7.
    action: ACCEPT
    reason: IDA-supported cytoplasmic localization from the HSPB-family subcellular-distribution
      survey.
    supported_by:
    - reference_id: file:human/HSPB7/HSPB7-uniprot.txt
      supporting_text: Cytoplasm {ECO:0000269|PubMed:19464326}
- term:
    id: GO:0006986
    label: response to unfolded protein
  evidence_type: TAS
  original_reference_id: PMID:10593960
  qualifier: involved_in
  review:
    summary: HSPB7 (cvHsp) is a small stress protein of the sHSP family. It participates
      in the cellular response to proteotoxic stress, although notably by sequestering
      aggregation-prone clients rather than by promoting refolding.
    action: ACCEPT
    reason: Membership in the stress-responsive small heat shock protein family supports
      this process annotation; cvHsp was characterized as a small stress protein.
    supported_by:
    - reference_id: PMID:10593960
      supporting_text: a novel small stress protein of 170 amino acids that we named
        cvHsp
- term:
    id: GO:0008016
    label: regulation of heart contraction
  evidence_type: TAS
  original_reference_id: PMID:10593960
  qualifier: involved_in
  review:
    summary: Annotation derived from the original cvHsp characterization, reflecting
      its high cardiac expression and filamin interaction. A direct role in regulating
      heart contraction is inferred rather than demonstrated.
    action: KEEP_AS_NON_CORE
    reason: Plausible given cardiac-restricted expression and filamin (cytoskeletal)
      binding, but the contractile-regulation role is indirect/inferential; retained
      as non-core.
    supported_by:
    - reference_id: PMID:10593960
      supporting_text: selectively expressed in cardiovascular and insulin-sensitive
        tissues
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:0000044
  title: Gene Ontology annotation of UniProtKB entries based on the manual curation
    of subcellular locations
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: PMID:10593960
  title: Identification and characterization of cvHsp. A novel human small stress protein
    selectively expressed in cardiovascular and insulin-sensitive tissues.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Cached publications/PMID_10593960.md title matches; anchored to GOA
      as a TAS source for GO:0006986 (response to unfolded protein) and GO:0008016
      (regulation of heart contraction). Identifies cvHsp/HSPB7 and its alpha-filamin
      binding, supporting core_function GO:0031005 (filamin binding). Cited in
      core_functions supported_by."
  findings:
  - statement: Identified cvHsp/HSPB7 as a 170-aa small stress protein highly expressed
      in heart and skeletal muscle that binds the C-terminal tail of alpha-filamin
      (actin-binding protein 280) via residues 56-119.
    reference_section_type: RESULTS
- id: PMID:14594798
  title: Interaction of human HSP22 (HSPB8) with other small heat shock proteins.
  findings:
  - statement: HSPB8 (HSP22) hetero-dimerizes with cvHSP (HSPB7) through a C-terminal
      to C-terminal interaction, and also interacts with HSPB2 (MKBP) and HSPB1 (HSP27),
      defining the small-HSP hetero-oligomer network.
    reference_section_type: RESULTS
- id: PMID:16189514
  title: Towards a proteome-scale map of the human protein-protein interaction network.
  findings: []
- id: PMID:19464326
  title: HSPB7 is a SC35 speckle resident small heat shock protein.
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: "Cached publications/PMID_19464326.md title matches; anchored to GOA
      as the IDA source for GO:0005634 (nucleus) and GO:0005737 (cytoplasm). Shows
      HSPB7 is a non-canonical sHSP that does not support substrate refolding,
      directly informing the holdase/sequestrase core function. Cited in
      core_functions supported_by."
  findings:
  - statement: HSPB7 constitutively localizes to SC35 nuclear splicing speckles driven
      by its N-terminus and, unlike HSPB1/HSPB5, does not support refolding of heat-denatured
      substrates, indicating a non-canonical chaperone role.
    reference_section_type: RESULTS
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
- id: PMID:28514442
  title: Architecture of the human interactome defines protein communities and disease
    networks.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: file:human/HSPB7/HSPB7-uniprot.txt
  title: UniProt entry Q9UBY9 (HSPB7_HUMAN), Heat shock protein beta-7 (cvHsp)
  findings:
  - statement: Cardiovascular small heat shock protein; binds actin-binding protein
      280 (filamin); interacts with HSPB8 and BAG3; cytoplasm, nucleus and SC35 splicing
      speckles; heart/skeletal-muscle enriched.
    reference_section_type: OTHER
core_functions:
- description: Non-canonical small heat shock protein that binds aggregation-prone
    client proteins and small-HSP partners (e.g. HSPB8, HSPB2, HSPB1) and sequesters
    them to suppress aggregation, without promoting substrate refolding.
  molecular_function:
    id: GO:0051082
    label: unfolded protein binding
  locations:
  - id: GO:0005737
    label: cytoplasm
  - id: GO:0005634
    label: nucleus
  supported_by:
  - reference_id: PMID:19464326
    supporting_text: HSPB7 did not support refolding
  - reference_id: PMID:14594798
    supporting_text: HSP22 interacts with itself, cvHSP (HSPB7), MKBP (HSPB2) and HSP27
- description: Binding to the actin-crosslinking protein filamin (alpha-filamin / actin-binding
    protein 280) via the alpha-crystallin domain, linking HSPB7 to the cardiac/muscle
    cytoskeleton.
  molecular_function:
    id: GO:0031005
    label: filamin binding
  locations:
  - id: GO:0005737
    label: cytoplasm
  supported_by:
  - reference_id: PMID:10593960
    supporting_text: cvHsp interacted in both yeast two-hybrid and immunoprecipitation
      experiments with alpha-filamin or actin-binding protein 280
proposed_new_terms: []
suggested_questions:
- question: What is the molecular mechanism by which HSPB7 suppresses aggregation of
    clients such as polyglutamine-expanded proteins and mutant filamin without supporting
    their refolding?
- question: Does HSPB7's residence in SC35 splicing speckles reflect a role in RNA/splicing
    biology, or is it a storage/sequestration site distinct from its cytoskeletal function?
- question: How do HSPB7 hetero-oligomers with HSPB8/BAG3 contribute to chaperone-assisted
    selective autophagy in cardiomyocytes?
suggested_experiments:
- description: In vitro aggregation-suppression assays comparing HSPB7 with canonical
    HSPB1/HSPB5 on amyloidogenic and polyQ substrates, paired with refolding assays
    to confirm holdase/sequestrase (non-foldase) behavior.
- description: Domain-swap and point-mutation analysis of the HSPB7 N-terminal region
    (1-71) to dissect SC35-speckle targeting versus client sequestration.
- description: Cardiomyocyte HSPB7 knockout/knock-in models to test effects on filamin
    handling, proteostasis, and contractile function.