SERPINH1

UniProt ID: P50454
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

SERPINH1 (Serpin H1, better known as HSP47, also called colligin / gp46) is an endoplasmic reticulum-resident, collagen-specific molecular chaperone. Although it belongs to the serpin superfamily by fold, it is non-inhibitory and does not act as a protease inhibitor. In the ER lumen HSP47 binds specifically to the folded triple-helical region of procollagen, stabilizing the nascent triple helix, preventing local unfolding and premature aggregation, and serving as a quality-control factor in collagen biosynthesis. HSP47 accompanies procollagen from the ER to the ER-Golgi intermediate compartment/cis-Golgi, where the lower pH triggers its release; it then recycles back to the ER through its C-terminal RDEL retrieval signal. It is heat-shock inducible. Loss-of-function variants cause autosomal-recessive osteogenesis imperfecta type X (OI10), underscoring its essential role in collagen maturation.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0004867 serine-type endopeptidase inhibitor activity
IBA
GO_REF:0000033 		MARK AS OVER ANNOTATED
Summary: Phylogenetic transfer of serpin protease-inhibitor activity. HSP47 is a well-documented non-inhibitory serpin that functions as a collagen chaperone, not a protease inhibitor.
Reason: Inferred from the serpin fold/family, but HSP47/SERPINH1 lacks functional protease-inhibitory activity; its characterized role is collagen binding/chaperoning.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen.
GO:0005783 endoplasmic reticulum
IBA
GO_REF:0000033 		ACCEPT
Summary: HSP47 acts in the endoplasmic reticulum, where it chaperones procollagen. ER localization is well established.
Reason: Consistent with UniProt subcellular location (ER lumen) and multiple experimental annotations; the ER is the genuine site of HSP47 action.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.
GO:0030199 collagen fibril organization
IBA
GO_REF:0000033 		KEEP AS NON CORE
Summary: HSP47 contributes to collagen biogenesis; proper fibril organization downstream depends on correctly matured procollagen. HSP47 itself acts in the ER, upstream of extracellular fibril assembly.
Reason: Collagen fibril organization is a downstream/extracellular consequence of HSP47's ER chaperone activity; a reasonable process annotation but not its direct molecular role.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen.
GO:0004867 serine-type endopeptidase inhibitor activity
IEA
GO_REF:0000002 		MARK AS OVER ANNOTATED
Summary: InterPro serpin-family transfer of protease-inhibitor activity. HSP47 is non-inhibitory.
Reason: Domain-based transfer; HSP47/SERPINH1 does not function as a serine protease inhibitor despite its serpin fold.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen.
GO:0005518 collagen binding
IEA
GO_REF:0000002 		ACCEPT
Summary: HSP47 binds specifically to collagen (folded triple helix); this is its defining, core molecular function.
Reason: Directly supported by UniProt FUNCTION and by extensive literature; collagen binding is the central molecular activity of HSP47.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
Binds specifically to collagen.
GO:0005788 endoplasmic reticulum lumen
IEA
GO_REF:0000044 		ACCEPT
Summary: Automated (UniProt SubCell) annotation of ER lumen, the precise compartment where HSP47 chaperones procollagen.
Reason: Matches UniProt subcellular location exactly; ER lumen is the genuine and specific HSP47 compartment.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.
GO:0006457 protein folding
IEA
GO_REF:0000108 		KEEP AS NON CORE
Summary: Process annotation inferred from the protein folding chaperone MF. HSP47 stabilizes already-folded triple-helical procollagen and prevents aggregation rather than catalyzing folding de novo.
Reason: HSP47 is a holdase-type collagen chaperone, not a foldase; protein folding is a reasonable downstream process but non-core relative to collagen binding.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
Could be involved as a chaperone in the biosynthetic pathway of collagen.
GO:0005515 protein binding
IPI
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative ... 		KEEP AS NON CORE
Summary: Large-scale neurodegeneration interactome screen capturing many HSP47 interactions with diverse partners (e.g. CDH1, ETS2), none of which are collagen. Bare protein binding is uninformative and does not reflect HSP47's collagen-specific function.
Reason: High-throughput interactome partners unrelated to HSP47's characterized collagen-chaperone role; uninformative protein binding term.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
Binds specifically to collagen.
GO:0005737 cytoplasm
IEA
GO_REF:0000107 		MARK AS OVER ANNOTATED
Summary: Ensembl ortholog-based cytoplasm annotation. HSP47 is an ER-lumenal protein; the cytoplasm term is a coarse parent localization inconsistent with its specific ER-lumen residence.
Reason: Conflicts with the well-established ER-lumen localization; cytoplasm is an over-general/ortholog-transfer localization for this secretory-pathway protein.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.
GO:0005783 endoplasmic reticulum
IEA
GO_REF:0000107 		ACCEPT
Summary: Ensembl ortholog-based ER localization, consistent with HSP47's documented ER residence.
Reason: Agrees with UniProt and experimental ER annotations; the genuine compartment of HSP47.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.
GO:0044183 protein folding chaperone
IEA
GO_REF:0000107 		ACCEPT
Summary: HSP47 is a collagen-specific molecular chaperone; the generic chaperone MF is correct but the precise, informative MF is collagen binding.
Reason: HSP47 functions as a molecular chaperone for procollagen; supported by UniProt FUNCTION. Captured more specifically by collagen binding in core_functions.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
Could be involved as a chaperone in the biosynthetic pathway of collagen.
GO:0005783 endoplasmic reticulum
IDA
GO_REF:0000052 		ACCEPT
Summary: Direct immunofluorescence (HPA) evidence for ER localization, consistent with HSP47's role as an ER collagen chaperone.
Reason: IDA-supported ER localization corroborating UniProt; genuine HSP47 compartment.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.
GO:0031012 extracellular matrix
HDA
PMID:28327460
Comprehensive proteomic characterization of stem cell-derive... 		KEEP AS NON CORE
Summary: High-throughput matrisome/ECM proteomics detection. HSP47 is ER-resident; ECM detection likely reflects co-secretion with collagen or proteomic carryover, not a core localization.
Reason: HDA ECM detection is peripheral to HSP47's documented ER-lumen site of action.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.
GO:0031012 extracellular matrix
HDA
PMID:28675934
Characterization of the Extracellular Matrix of Normal and D... 		KEEP AS NON CORE
Summary: High-throughput ECM proteomics detection of HSP47, peripheral to its ER chaperone role.
Reason: HDA matrisome detection; not the core ER-lumen localization of HSP47.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.
GO:0031012 extracellular matrix
HDA
PMID:25037231
Extracellular matrix signatures of human primary metastatic ... 		KEEP AS NON CORE
Summary: High-throughput ECM proteomics detection of HSP47, peripheral to its ER chaperone role.
Reason: HDA matrisome detection; not the core ER-lumen localization of HSP47.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.
GO:0045121 membrane raft
IDA
PMID:25204797
Flotillin-1 facilitates toll-like receptor 3 signaling in hu... 		KEEP AS NON CORE
Summary: Reported cell-surface/membrane-raft pool of HSP47 in a specific context. A minor, non-canonical localization relative to its predominant ER-lumen residence.
Reason: A specialized, context-dependent localization; peripheral to HSP47's core ER collagen-chaperone function.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.
GO:0003723 RNA binding
HDA
PMID:22658674
Insights into RNA biology from an atlas of mammalian mRNA-bi... 		MARK AS OVER ANNOTATED
Summary: mRNA-interactome-capture detection of HSP47 as an RNA-binder. There is no characterized RNA-dependent function for HSP47; this is a generic proteome-wide capture result.
Reason: High-throughput RNA-interactome capture without a validated functional role; not part of HSP47's collagen-chaperone function.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
Binds specifically to collagen.
GO:0005788 endoplasmic reticulum lumen
TAS
Reactome:R-HSA-2022073 		ACCEPT
Summary: Curated (Reactome) ER lumen localization, matching the precise compartment of HSP47.
Reason: Consistent with UniProt ER-lumen location; the genuine and specific HSP47 compartment.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.
GO:0005788 endoplasmic reticulum lumen
TAS
Reactome:R-HSA-2089971 		ACCEPT
Summary: Curated (Reactome) ER lumen localization, matching the precise compartment of HSP47.
Reason: Consistent with UniProt ER-lumen location; the genuine and specific HSP47 compartment.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.
GO:0004867 serine-type endopeptidase inhibitor activity
TAS
PMID:1309665
Cloning of a human collagen-binding protein, and its homolog... 		MARK AS OVER ANNOTATED
Summary: Author-stated serpin-family inhibitor classification. HSP47 is a non-inhibitory serpin; the inhibitory activity is a historical fold-based attribution.
Reason: HSP47/SERPINH1 does not function as a protease inhibitor despite the serpin fold; its characterized function is collagen chaperoning.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
Binds specifically to collagen.
GO:0005518 collagen binding
NAS
PMID:1309665
Cloning of a human collagen-binding protein, and its homolog... 		ACCEPT
Summary: Author-stated collagen binding, HSP47's defining molecular function.
Reason: Collagen binding is the core, well-established molecular activity of HSP47; supported by UniProt and literature.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
Binds specifically to collagen.
GO:0005783 endoplasmic reticulum
TAS
PMID:1309665
Cloning of a human collagen-binding protein, and its homolog... 		ACCEPT
Summary: Author-stated ER localization, consistent with HSP47's documented ER residence.
Reason: Agrees with UniProt and experimental evidence; genuine HSP47 compartment.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.
GO:0005783 endoplasmic reticulum
TAS
PMID:7656593
Isolation, characterization and chromosomal assignment of hu... 		ACCEPT
Summary: Author-stated ER localization, consistent with HSP47's documented ER residence.
Reason: Agrees with UniProt and experimental evidence; genuine HSP47 compartment.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.
GO:0006986 response to unfolded protein
TAS
PMID:1309665
Cloning of a human collagen-binding protein, and its homolog... 		KEEP AS NON CORE
Summary: HSP47 is heat-shock inducible, historically framed as a stress/UPR-associated chaperone. However it is collagen-specific and not a general unfolded-protein-response chaperone.
Reason: HSP47 is stress-inducible but its substrate specificity is collagen, not general unfolded proteins; this process annotation is peripheral to its core role.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
INDUCTION: By heat shock.
GO:0005793 endoplasmic reticulum-Golgi intermediate compartment
IDA
PMID:15308636
Proteomics of endoplasmic reticulum-Golgi intermediate compa... 		ACCEPT
Summary: Direct evidence that HSP47 localizes to the ER-Golgi intermediate compartment, consistent with its pH-dependent procollagen escort and recycling itinerary.
Reason: IDA-supported ERGIC localization matching the established HSP47 trafficking cycle (procollagen escort to ERGIC/cis-Golgi, pH-triggered release, RDEL-mediated return).
Supporting Evidence:
file:human/SERPINH1/SERPINH1-goa.tsv
GO:0005793 endoplasmic reticulum-Golgi intermediate compartment
GO:0005518 collagen binding
NAS
PMID:7656593
Isolation, characterization and chromosomal assignment of hu... 		ACCEPT
Summary: Author-stated collagen binding, HSP47's defining molecular function.
Reason: Collagen binding is the core, well-established molecular activity of HSP47.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
Binds specifically to collagen.
GO:0005783 endoplasmic reticulum
NAS
PMID:7656593
Isolation, characterization and chromosomal assignment of hu... 		ACCEPT
Summary: Author-stated ER localization, consistent with HSP47's documented ER residence.
Reason: Agrees with UniProt and experimental evidence; genuine HSP47 compartment.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.
GO:0006986 response to unfolded protein
TAS
PMID:10023073
The human genome has only one functional hsp47 gene (CBP2) a... 		KEEP AS NON CORE
Summary: Heat-shock/stress-associated chaperone framing of HSP47. HSP47 is collagen-specific rather than a general UPR chaperone.
Reason: Stress-inducible but collagen-specific; this process annotation is peripheral to HSP47's core collagen-chaperone role.
Supporting Evidence:
file:human/SERPINH1/SERPINH1-uniprot.txt
INDUCTION: By heat shock.

Core Functions

ER-resident collagen-specific molecular chaperone that binds the folded triple-helical region of procollagen, stabilizing it and preventing premature aggregation during collagen biosynthesis.

Molecular Function:
collagen binding
Cellular Locations:
endoplasmic reticulum lumen
Supporting Evidence:
  • file:human/SERPINH1/SERPINH1-uniprot.txt
    Binds specifically to collagen.
  • file:human/SERPINH1/SERPINH1-uniprot.txt
    Could be involved as a chaperone in the biosynthetic pathway of collagen.

Collagen-dedicated chaperone activity within the early secretory pathway; HSP47 escorts procollagen from the ER to the ER-Golgi intermediate compartment, where pH-dependent release allows HSP47 to recycle back to the ER.

Molecular Function:
protein folding chaperone
Cellular Locations:
endoplasmic reticulum lumen endoplasmic reticulum-Golgi intermediate compartment
Supporting Evidence:
  • file:human/SERPINH1/SERPINH1-uniprot.txt
    Could be involved as a chaperone in the biosynthetic pathway of collagen.
  • file:human/SERPINH1/SERPINH1-goa.tsv
    GO:0005793 endoplasmic reticulum-Golgi intermediate compartment

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 based on UniProtKB Subcellular Location vocabulary mapping
GO_REF:0000052
Gene Ontology annotation based on curation of immunofluorescence data
GO_REF:0000107
Automatic transfer of experimentally verified manual GO annotation data to orthologs by Ensembl Compara
GO_REF:0000108
Automatic assignment of GO terms using logical inference, based on on inter-ontology links
PMID:10023073
The human genome has only one functional hsp47 gene (CBP2) and a pseudogene (pshsp47).
PMID:1309665
Cloning of a human collagen-binding protein, and its homology with rat gp46, chick hsp47 and mouse J6 proteins.
PMID:15308636
Proteomics of endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membranes from brefeldin A-treated HepG2 cells identifies ERGIC-32, a new cycling protein that interacts with human Erv46.
  • HSP47 localizes to the ER-Golgi intermediate compartment, consistent with pH-dependent escort and recycling of procollagen.
PMID:22658674
Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
PMID:25037231
Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver.
PMID:25204797
Flotillin-1 facilitates toll-like receptor 3 signaling in human endothelial cells.
PMID:28327460
Comprehensive proteomic characterization of stem cell-derived extracellular matrices.
PMID:28675934
Characterization of the Extracellular Matrix of Normal and Diseased Tissues Using Proteomics.
PMID:32814053
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
PMID:7656593
Isolation, characterization and chromosomal assignment of human colligin-2 gene (CBP2).
Reactome:R-HSA-2022073
Collagen biosynthesis and modifying enzymes
Reactome:R-HSA-2089971
Collagen biosynthesis pathway
file:human/SERPINH1/SERPINH1-uniprot.txt
UniProt entry P50454 (SERPH_HUMAN), Serpin H1 / HSP47
  • HSP47 binds specifically to collagen and acts as a chaperone in collagen biosynthesis; it resides in the ER lumen, is heat-shock inducible, belongs to the serpin family (non-inhibitory), and its loss causes osteogenesis imperfecta type 10.

Suggested Questions for Experts

Q: What is the precise structural basis and pH threshold for HSP47 release from procollagen in the ERGIC/cis-Golgi, and how is this coupled to its RDEL-mediated ER retrieval?

Q: Beyond fibrillar collagens, which collagen types and other ER clients (if any) does HSP47 chaperone, and how does substrate specificity arise from triple-helix recognition?

Q: How do OI10-causing SERPINH1 variants mechanistically impair collagen maturation (loss of binding, mislocalization, or destabilization)?

Suggested Experiments

Experiment: Quantitative in vitro binding/turbidity assays with purified HSP47 and triple-helical vs unfolded collagen peptides across a pH gradient to map binding affinity and the pH-dependent release transition.

Experiment: Knock-in of OI10 patient variants in osteoblast or fibroblast models followed by collagen secretion, triple-helix stability, and ER-stress assays.

Experiment: Proximity-labeling (BioID/APEX) of HSP47 in the secretory pathway to define its client repertoire and trafficking-machinery partners during collagen transport.

📚 Additional Documentation

Notes

(SERPINH1-notes.md)

SERPINH1 (HSP47 / Serpin H1 / colligin / gp46) — research notes

UniProt: P50454 (SERPH_HUMAN). Member of the serpin family but NON-INHIBITORY.

Core identity

ER-resident, collagen-specific molecular chaperone. Despite the serpin fold, it
does NOT act as a protease inhibitor; it is a dedicated chaperone for procollagen.

  • [file:human/SERPINH1/SERPINH1-uniprot.txt "FUNCTION: Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen."]
  • [file:human/SERPINH1/SERPINH1-uniprot.txt "SUBCELLULAR LOCATION: Endoplasmic reticulum lumen."]
  • [file:human/SERPINH1/SERPINH1-uniprot.txt "INDUCTION: By heat shock."]
  • [file:human/SERPINH1/SERPINH1-uniprot.txt "SIMILARITY: Belongs to the serpin family."]

Mechanism (well-established in literature)

HSP47 binds the folded triple-helical procollagen in the ER, stabilizing it and
preventing local unfolding/aggregation, and acting in quality control / preventing
premature aggregation. It travels with procollagen to the ER-Golgi intermediate
compartment (ERGIC)/cis-Golgi, where the lower pH triggers its release; HSP47 then
cycles back to the ER via its C-terminal RDEL ER-retrieval signal. It recognizes the
folded triple helix (Arg residues in Gly-Xaa-Arg repeats), not unfolded chains — so it
is a collagen-specific chaperone, NOT a general foldase or general unfolded-protein
chaperone.

  • ERGIC localization directly shown: PMID:15308636 (IDA GO:0005793 ER-Golgi intermediate compartment).
  • The serpin-family TAS annotation of "serine-type endopeptidase inhibitor activity"
    (PMID:1309665, PMID:7656593) and the IBA/IEA serpin-inhibitor transfers are based on
    the serpin FOLD; HSP47 is a well-documented non-inhibitory serpin and should not be
    annotated as a functional protease inhibitor. -> MARK_AS_OVER_ANNOTATED.

Disease

  • [file:human/SERPINH1/SERPINH1-uniprot.txt "DISEASE: Osteogenesis imperfecta 10 (OI10) [MIM:613848]"] — autosomal recessive OI; reflects the essential role of HSP47 in collagen biogenesis.

GO annotation review notes (goa.tsv)

  • GO:0004867 serine-type endopeptidase inhibitor activity (IBA, IEA, TAS x3): serpin-fold
    transfer. HSP47 is non-inhibitory. -> MARK_AS_OVER_ANNOTATED (all).
  • GO:0005518 collagen binding (IEA InterPro, NAS PMID:1309665, NAS PMID:7656593): CORE MF.
    ACCEPT.
  • GO:0005783 endoplasmic reticulum (IBA, IDA, IEA, TAS, NAS): CORE localization. ACCEPT
    the experimentally supported ones; ER lumen (GO:0005788) is the precise compartment.
  • GO:0005788 endoplasmic reticulum lumen (IEA SubCell, TAS Reactome x2): precise CORE
    localization matching UniProt. ACCEPT.
  • GO:0030199 collagen fibril organization (IBA): downstream process of collagen
    biogenesis; HSP47 chaperones procollagen in ER. KEEP_AS_NON_CORE (it acts upstream in
    ER, fibril organization is extracellular/downstream).
  • GO:0006457 protein folding (IEA from GO:0044183): HSP47 stabilizes folded procollagen
    rather than catalyzing folding. KEEP_AS_NON_CORE.
  • GO:0044183 protein folding chaperone (IEA, by similarity to mouse): HSP47 is a
    collagen-specific chaperone. Reasonable but generic; the precise MF is collagen binding /
    collagen-specific chaperone. KEEP as MF but specific term is collagen binding. ACCEPT
    (it is a chaperone) — but core MF best captured as collagen binding.
  • GO:0006986 response to unfolded protein (TAS PMID:1309665, PMID:10023073): HSP47 is heat-
    shock-induced; but it is collagen-specific and not a generic UPR chaperone. The "response
    to unfolded protein" framing is partly historical. KEEP_AS_NON_CORE.
  • GO:0031012 extracellular matrix (HDA x3): HSP47 is ER-resident; ECM detection is from
    matrisome/secretome proteomics (some HSP47 co-secreted with collagen or detected in ECM
    preps). Peripheral. KEEP_AS_NON_CORE.
  • GO:0045121 membrane raft (IDA PMID:25204797): cell-surface HSP47 reported in some
    contexts; minor/peripheral. KEEP_AS_NON_CORE.
  • GO:0003723 RNA binding (HDA PMID:22658674): mRNA-interactome capture; generic, not a
    characterized function. MARK_AS_OVER_ANNOTATED.
  • GO:0005793 ERGIC (IDA PMID:15308636): directly shown; matches the pH-dependent
    release/recycling itinerary. ACCEPT.
  • GO:0005515 protein binding (IPI PMID:32814053): large HT neurodegeneration interactome
    with many partners (CDH1, ETS2, etc., none of them collagen). Uninformative; not core.
    MARK_AS_OVER_ANNOTATED.
  • GO:0005737 cytoplasm (IEA Ensembl ortholog): HSP47 is ER-lumenal; cytoplasm is a coarse
    parent / ortholog transfer. MARK_AS_OVER_ANNOTATED (conflicts with ER-lumen specificity).

Core function synthesis

  1. Collagen-specific molecular chaperone (GO:0044183 / GO:0005518 collagen binding):
    binds folded triple-helical procollagen in ER lumen, stabilizes it, prevents
    aggregation, QC of collagen biogenesis.
  2. Localization: ER lumen (GO:0005788), cycling through ERGIC (GO:0005793) via RDEL.
  3. NOT a functional protease inhibitor despite serpin fold.

Pn Notes

(SERPINH1-pn-notes.md)

SERPINH1 PN Consistency Notes

  • Generated: 2026-06-18
  • Project: PROTEOSTASIS
  • Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
  • UniProt: P50454
  • 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: SERPINH1 (Serpin H1, better known as HSP47, also called colligin / gp46) is an endoplasmic reticulum-resident, collagen-specific molecular chaperone. Although it belongs to the serpin superfamily by fold, it is non-inhibitory and does not act as a protease inhibitor. In the ER lumen HSP47 binds specifically to the folded triple-helical region of procollagen, stabilizing the nascent triple helix, preventing local unfolding and premature aggregation, and serving as a quality-control factor in collagen biosynthesis. HSP47 accompanies procollagen from the ER to the ER-Golgi intermediate compartment/cis-Golgi, where the lower pH triggers its release; it then recycles back to the ER through its C-terminal RDEL retrieval signal. It is heat-shock inducible. Loss-of-function variants cause autosomal-recessive osteogenesis imperfecta type X (OI10), underscoring its essential role in collagen maturation.
  • Existing/core annotation action counts: ACCEPT: 14; KEEP_AS_NON_CORE: 9; MARK_AS_OVER_ANNOTATED: 5

PN Consistency Summary

  • Consistency: Strong. Review, notes and PN all describe HSP47 as an ER-resident, collagen-specific (non-inhibitory serpin) chaperone that binds the triple-helical procollagen region. Core MFs = collagen binding (GO:0005518) and protein folding chaperone (GO:0044183), in ER lumen/ERGIC. Review correctly MARKS_AS_OVER_ANNOTATED the inherited serpin protease-inhibitor activity. Fully consistent with the PN collagen-folding node.
  • PN story / NEW pressure: PN asserts collagen biosynthetic process (GO:0032964, OLS-verified real, goa_status=new_to_goa — GOA confirms only GO:0030199 collagen fibril organization present, not GO:0032964). HSP47 is genuinely dedicated to collagen maturation (OI10 disease confirms essentiality), so a collagen-process BP is defensible. The review already has GO:0030199 (collagen fibril organization, KEEP_AS_NON_CORE) as its process annotation. GO:0032964 is a reasonable, slightly more upstream alternative/addition. Conclude: ADD defensible but largely already captured by GO:0030199 — marginal value.
  • Evidence alignment: PN row carries no reference titles; review cites UniProt + collagen-chaperone literature. No conflict.
  • Verdict: Consistent and high-quality. Recommended edits: optionally add GO:0032964 collagen biosynthetic process (KEEP_AS_NON_CORE) to align with PN, since it captures HSP47's ER-upstream role better than the existing GO:0030199 fibril-organization term [YAML]; otherwise no change.

Full Consistency Review

  • UniProt: P50454 (HSP47) · batch: proteostasis-batch-2026-06-07b · review status: COMPLETE
  • PN placement: ER proteostasis|Maturation and folding of specific substrates|ER collagen processing and folding ; PN-node mapping: mapped → GO:0032964 (collagen biosynthetic process, new_to_goa)
  • Consistency: Strong. Review, notes and PN all describe HSP47 as an ER-resident, collagen-specific (non-inhibitory serpin) chaperone that binds the triple-helical procollagen region. Core MFs = collagen binding (GO:0005518) and protein folding chaperone (GO:0044183), in ER lumen/ERGIC. Review correctly MARKS_AS_OVER_ANNOTATED the inherited serpin protease-inhibitor activity. Fully consistent with the PN collagen-folding node.
  • PN story / NEW pressure: PN asserts collagen biosynthetic process (GO:0032964, OLS-verified real, goa_status=new_to_goa — GOA confirms only GO:0030199 collagen fibril organization present, not GO:0032964). HSP47 is genuinely dedicated to collagen maturation (OI10 disease confirms essentiality), so a collagen-process BP is defensible. The review already has GO:0030199 (collagen fibril organization, KEEP_AS_NON_CORE) as its process annotation. GO:0032964 is a reasonable, slightly more upstream alternative/addition. Conclude: ADD defensible but largely already captured by GO:0030199 — marginal value.
  • Mapping strategy: Single clean node; status=mapped scope=ok is appropriate. GO:0032964 is neither broader nor narrower than the review's GO:0030199 (sibling process emphasising biosynthesis vs extracellular fibril assembly); HSP47 acts upstream in the ER, so GO:0032964 arguably fits HSP47's ER role better than fibril organization. No mapping change needed.
  • Evidence alignment: PN row carries no reference titles; review cites UniProt + collagen-chaperone literature. No conflict.
  • Verdict: Consistent and high-quality. Recommended edits: optionally add GO:0032964 collagen biosynthetic process (KEEP_AS_NON_CORE) to align with PN, since it captures HSP47's ER-upstream role better than the existing GO:0030199 fibril-organization term [YAML]; otherwise no change.

PN Dossier Context

  • review_batch: proteostasis-batch-2026-06-07b
  • review_yaml: genes/human/SERPINH1/SERPINH1-ai-review.yaml
  • PN workbook rows: 1

PN row 1: ER proteostasis | Maturation and folding of specific substrates | ER collagen processing and folding

  • UniProt: P50454
  • In branches: ER
  • PN-node mapping records (path + ancestors):
    • [group] ER proteostasis|Maturation and folding of specific substrates|ER collagen processing and folding
      status=mapped scope=ok_for_propagation_to_go GO=[GO:0032964 collagen biosynthetic process]
      rationale: This PN group contains ER factors dedicated to collagen maturation, processing, and folding. Collagen biosynthetic process captures the shared substrate-specific pathway context.
    • [class] ER proteostasis|Maturation and folding of specific substrates
      status=no_mapping scope= GO=[]
      rationale: Reviewed as a broad PN category rather than a single GO class. The member genes span multiple activities, complexes, or contexts, so direct propagation from this node would overstate the shared biology.
    • [branch] ER 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:0032964 collagen biosynthetic process | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=ER proteostasis|Maturation and folding of specific substrates|ER collagen processing and folding

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: P50454
gene_symbol: SERPINH1
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: SERPINH1 (Serpin H1, better known as HSP47, also called colligin / gp46) is an endoplasmic reticulum-resident, collagen-specific molecular chaperone. Although it belongs to the serpin superfamily by fold, it is non-inhibitory and does not act as a protease inhibitor. In the ER lumen HSP47 binds specifically to the folded triple-helical region of procollagen, stabilizing the nascent triple helix, preventing local unfolding and premature aggregation, and serving as a quality-control factor in collagen biosynthesis. HSP47 accompanies procollagen from the ER to the ER-Golgi intermediate compartment/cis-Golgi, where the lower pH triggers its release; it then recycles back to the ER through its C-terminal RDEL retrieval signal. It is heat-shock inducible. Loss-of-function variants cause autosomal-recessive osteogenesis imperfecta type X (OI10), underscoring its essential role in collagen maturation.
existing_annotations:
- term:
    id: GO:0004867
    label: serine-type endopeptidase inhibitor activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: Phylogenetic transfer of serpin protease-inhibitor activity. HSP47 is a well-documented non-inhibitory serpin that functions as a collagen chaperone, not a protease inhibitor.
    action: MARK_AS_OVER_ANNOTATED
    reason: Inferred from the serpin fold/family, but HSP47/SERPINH1 lacks functional protease-inhibitory activity; its characterized role is collagen binding/chaperoning.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: HSP47 acts in the endoplasmic reticulum, where it chaperones procollagen. ER localization is well established.
    action: ACCEPT
    reason: Consistent with UniProt subcellular location (ER lumen) and multiple experimental annotations; the ER is the genuine site of HSP47 action.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.'
- term:
    id: GO:0030199
    label: collagen fibril organization
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: HSP47 contributes to collagen biogenesis; proper fibril organization downstream depends on correctly matured procollagen. HSP47 itself acts in the ER, upstream of extracellular fibril assembly.
    action: KEEP_AS_NON_CORE
    reason: Collagen fibril organization is a downstream/extracellular consequence of HSP47's ER chaperone activity; a reasonable process annotation but not its direct molecular role.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen.
- term:
    id: GO:0004867
    label: serine-type endopeptidase inhibitor activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro serpin-family transfer of protease-inhibitor activity. HSP47 is non-inhibitory.
    action: MARK_AS_OVER_ANNOTATED
    reason: Domain-based transfer; HSP47/SERPINH1 does not function as a serine protease inhibitor despite its serpin fold.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: Binds specifically to collagen. Could be involved as a chaperone in the biosynthetic pathway of collagen.
- term:
    id: GO:0005518
    label: collagen binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: HSP47 binds specifically to collagen (folded triple helix); this is its defining, core molecular function.
    action: ACCEPT
    reason: Directly supported by UniProt FUNCTION and by extensive literature; collagen binding is the central molecular activity of HSP47.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: Binds specifically to collagen.
- term:
    id: GO:0005788
    label: endoplasmic reticulum lumen
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Automated (UniProt SubCell) annotation of ER lumen, the precise compartment where HSP47 chaperones procollagen.
    action: ACCEPT
    reason: Matches UniProt subcellular location exactly; ER lumen is the genuine and specific HSP47 compartment.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.'
- term:
    id: GO:0006457
    label: protein folding
  evidence_type: IEA
  original_reference_id: GO_REF:0000108
  qualifier: involved_in
  review:
    summary: Process annotation inferred from the protein folding chaperone MF. HSP47 stabilizes already-folded triple-helical procollagen and prevents aggregation rather than catalyzing folding de novo.
    action: KEEP_AS_NON_CORE
    reason: HSP47 is a holdase-type collagen chaperone, not a foldase; protein folding is a reasonable downstream process but non-core relative to collagen binding.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: Could be involved as a chaperone in the biosynthetic pathway of collagen.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32814053
  qualifier: enables
  review:
    summary: Large-scale neurodegeneration interactome screen capturing many HSP47 interactions with diverse partners (e.g. CDH1, ETS2), none of which are collagen. Bare protein binding is uninformative and does not reflect HSP47's collagen-specific function.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interactome partners unrelated to HSP47's characterized collagen-chaperone role; uninformative protein binding term.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: Binds specifically to collagen.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Ensembl ortholog-based cytoplasm annotation. HSP47 is an ER-lumenal protein; the cytoplasm term is a coarse parent localization inconsistent with its specific ER-lumen residence.
    action: MARK_AS_OVER_ANNOTATED
    reason: Conflicts with the well-established ER-lumen localization; cytoplasm is an over-general/ortholog-transfer localization for this secretory-pathway protein.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.'
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: located_in
  review:
    summary: Ensembl ortholog-based ER localization, consistent with HSP47's documented ER residence.
    action: ACCEPT
    reason: Agrees with UniProt and experimental ER annotations; the genuine compartment of HSP47.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.'
- term:
    id: GO:0044183
    label: protein folding chaperone
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: enables
  review:
    summary: HSP47 is a collagen-specific molecular chaperone; the generic chaperone MF is correct but the precise, informative MF is collagen binding.
    action: ACCEPT
    reason: HSP47 functions as a molecular chaperone for procollagen; supported by UniProt FUNCTION. Captured more specifically by collagen binding in core_functions.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: Could be involved as a chaperone in the biosynthetic pathway of collagen.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: Direct immunofluorescence (HPA) evidence for ER localization, consistent with HSP47's role as an ER collagen chaperone.
    action: ACCEPT
    reason: IDA-supported ER localization corroborating UniProt; genuine HSP47 compartment.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.'
- term:
    id: GO:0031012
    label: extracellular matrix
  evidence_type: HDA
  original_reference_id: PMID:28327460
  qualifier: colocalizes_with
  review:
    summary: High-throughput matrisome/ECM proteomics detection. HSP47 is ER-resident; ECM detection likely reflects co-secretion with collagen or proteomic carryover, not a core localization.
    action: KEEP_AS_NON_CORE
    reason: HDA ECM detection is peripheral to HSP47's documented ER-lumen site of action.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.'
- term:
    id: GO:0031012
    label: extracellular matrix
  evidence_type: HDA
  original_reference_id: PMID:28675934
  qualifier: located_in
  review:
    summary: High-throughput ECM proteomics detection of HSP47, peripheral to its ER chaperone role.
    action: KEEP_AS_NON_CORE
    reason: HDA matrisome detection; not the core ER-lumen localization of HSP47.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.'
- term:
    id: GO:0031012
    label: extracellular matrix
  evidence_type: HDA
  original_reference_id: PMID:25037231
  qualifier: located_in
  review:
    summary: High-throughput ECM proteomics detection of HSP47, peripheral to its ER chaperone role.
    action: KEEP_AS_NON_CORE
    reason: HDA matrisome detection; not the core ER-lumen localization of HSP47.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.'
- term:
    id: GO:0045121
    label: membrane raft
  evidence_type: IDA
  original_reference_id: PMID:25204797
  qualifier: located_in
  review:
    summary: Reported cell-surface/membrane-raft pool of HSP47 in a specific context. A minor, non-canonical localization relative to its predominant ER-lumen residence.
    action: KEEP_AS_NON_CORE
    reason: A specialized, context-dependent localization; peripheral to HSP47's core ER collagen-chaperone function.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.'
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22658674
  qualifier: enables
  review:
    summary: mRNA-interactome-capture detection of HSP47 as an RNA-binder. There is no characterized RNA-dependent function for HSP47; this is a generic proteome-wide capture result.
    action: MARK_AS_OVER_ANNOTATED
    reason: High-throughput RNA-interactome capture without a validated functional role; not part of HSP47's collagen-chaperone function.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: Binds specifically to collagen.
- term:
    id: GO:0005788
    label: endoplasmic reticulum lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2022073
  qualifier: located_in
  review:
    summary: Curated (Reactome) ER lumen localization, matching the precise compartment of HSP47.
    action: ACCEPT
    reason: Consistent with UniProt ER-lumen location; the genuine and specific HSP47 compartment.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.'
- term:
    id: GO:0005788
    label: endoplasmic reticulum lumen
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-2089971
  qualifier: located_in
  review:
    summary: Curated (Reactome) ER lumen localization, matching the precise compartment of HSP47.
    action: ACCEPT
    reason: Consistent with UniProt ER-lumen location; the genuine and specific HSP47 compartment.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.'
- term:
    id: GO:0004867
    label: serine-type endopeptidase inhibitor activity
  evidence_type: TAS
  original_reference_id: PMID:1309665
  qualifier: enables
  review:
    summary: Author-stated serpin-family inhibitor classification. HSP47 is a non-inhibitory serpin; the inhibitory activity is a historical fold-based attribution.
    action: MARK_AS_OVER_ANNOTATED
    reason: HSP47/SERPINH1 does not function as a protease inhibitor despite the serpin fold; its characterized function is collagen chaperoning.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: Binds specifically to collagen.
- term:
    id: GO:0005518
    label: collagen binding
  evidence_type: NAS
  original_reference_id: PMID:1309665
  qualifier: enables
  review:
    summary: Author-stated collagen binding, HSP47's defining molecular function.
    action: ACCEPT
    reason: Collagen binding is the core, well-established molecular activity of HSP47; supported by UniProt and literature.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: Binds specifically to collagen.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: TAS
  original_reference_id: PMID:1309665
  qualifier: located_in
  review:
    summary: Author-stated ER localization, consistent with HSP47's documented ER residence.
    action: ACCEPT
    reason: Agrees with UniProt and experimental evidence; genuine HSP47 compartment.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.'
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: TAS
  original_reference_id: PMID:7656593
  qualifier: located_in
  review:
    summary: Author-stated ER localization, consistent with HSP47's documented ER residence.
    action: ACCEPT
    reason: Agrees with UniProt and experimental evidence; genuine HSP47 compartment.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.'
- term:
    id: GO:0006986
    label: response to unfolded protein
  evidence_type: TAS
  original_reference_id: PMID:1309665
  qualifier: involved_in
  review:
    summary: HSP47 is heat-shock inducible, historically framed as a stress/UPR-associated chaperone. However it is collagen-specific and not a general unfolded-protein-response chaperone.
    action: KEEP_AS_NON_CORE
    reason: HSP47 is stress-inducible but its substrate specificity is collagen, not general unfolded proteins; this process annotation is peripheral to its core role.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: 'INDUCTION: By heat shock.'
- term:
    id: GO:0005793
    label: endoplasmic reticulum-Golgi intermediate compartment
  evidence_type: IDA
  original_reference_id: PMID:15308636
  qualifier: located_in
  review:
    summary: Direct evidence that HSP47 localizes to the ER-Golgi intermediate compartment, consistent with its pH-dependent procollagen escort and recycling itinerary.
    action: ACCEPT
    reason: IDA-supported ERGIC localization matching the established HSP47 trafficking cycle (procollagen escort to ERGIC/cis-Golgi, pH-triggered release, RDEL-mediated return).
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-goa.tsv
      supporting_text: GO:0005793 endoplasmic reticulum-Golgi intermediate compartment
- term:
    id: GO:0005518
    label: collagen binding
  evidence_type: NAS
  original_reference_id: PMID:7656593
  qualifier: enables
  review:
    summary: Author-stated collagen binding, HSP47's defining molecular function.
    action: ACCEPT
    reason: Collagen binding is the core, well-established molecular activity of HSP47.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: Binds specifically to collagen.
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: NAS
  original_reference_id: PMID:7656593
  qualifier: located_in
  review:
    summary: Author-stated ER localization, consistent with HSP47's documented ER residence.
    action: ACCEPT
    reason: Agrees with UniProt and experimental evidence; genuine HSP47 compartment.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum lumen.'
- term:
    id: GO:0006986
    label: response to unfolded protein
  evidence_type: TAS
  original_reference_id: PMID:10023073
  qualifier: involved_in
  review:
    summary: Heat-shock/stress-associated chaperone framing of HSP47. HSP47 is collagen-specific rather than a general UPR chaperone.
    action: KEEP_AS_NON_CORE
    reason: Stress-inducible but collagen-specific; this process annotation is peripheral to HSP47's core collagen-chaperone role.
    supported_by:
    - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
      supporting_text: 'INDUCTION: By heat shock.'
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 based on UniProtKB Subcellular Location vocabulary mapping
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs by Ensembl Compara
  findings: []
- id: GO_REF:0000108
  title: Automatic assignment of GO terms using logical inference, based on on inter-ontology links
  findings: []
- id: PMID:10023073
  title: 'The human genome has only one functional hsp47 gene (CBP2) and a pseudogene (pshsp47).'
  findings: []
- id: PMID:1309665
  title: 'Cloning of a human collagen-binding protein, and its homology with rat gp46, chick hsp47 and mouse J6 proteins.'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: GOA-anchored (this PMID supports GO:0005518 collagen binding and GO:0005783 ER in SERPINH1-goa.tsv); early characterization of Serpin H1/HSP47 as the collagen-binding ER stress protein, supporting the collagen-binding core molecular function.
- id: PMID:15308636
  title: Proteomics of endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membranes from brefeldin A-treated HepG2 cells identifies ERGIC-32, a new cycling protein that interacts with human Erv46.
  findings:
  - statement: HSP47 localizes to the ER-Golgi intermediate compartment, consistent with pH-dependent escort and recycling of procollagen.
    reference_section_type: RESULTS
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: ERGIC proteomics study supporting HSP47's ER/ERGIC cycling localization during collagen biosynthesis. Title corrected to verbatim PubMed (previously an HSP47-specific paraphrase).
- id: PMID:22658674
  title: Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
  findings: []
- id: PMID:25037231
  title: Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver.
  findings: []
- id: PMID:25204797
  title: "Flotillin-1 facilitates toll-like receptor 3 signaling in human endothelial cells."
  findings: []
- id: PMID:28327460
  title: Comprehensive proteomic characterization of stem cell-derived extracellular matrices.
  findings: []
- id: PMID:28675934
  title: Characterization of the Extracellular Matrix of Normal and Diseased Tissues Using Proteomics.
  findings: []
- id: PMID:32814053
  title: Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
  findings: []
- id: PMID:7656593
  title: 'Isolation, characterization and chromosomal assignment of human colligin-2 gene (CBP2).'
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: GOA-anchored (this PMID supports GO:0005518 collagen binding and GO:0005783 ER in SERPINH1-goa.tsv); seminal evidence establishing HSP47/SERPINH1 as the ER-resident collagen-specific molecular chaperone - its core function.
- id: Reactome:R-HSA-2022073
  title: Collagen biosynthesis and modifying enzymes
  findings: []
- id: Reactome:R-HSA-2089971
  title: Collagen biosynthesis pathway
  findings: []
- id: file:human/SERPINH1/SERPINH1-uniprot.txt
  title: UniProt entry P50454 (SERPH_HUMAN), Serpin H1 / HSP47
  findings:
  - statement: HSP47 binds specifically to collagen and acts as a chaperone in collagen biosynthesis; it resides in the ER lumen, is heat-shock inducible, belongs to the serpin family (non-inhibitory), and its loss causes osteogenesis imperfecta type 10.
    reference_section_type: OTHER
core_functions:
- description: ER-resident collagen-specific molecular chaperone that binds the folded triple-helical region of procollagen, stabilizing it and preventing premature aggregation during collagen biosynthesis.
  molecular_function:
    id: GO:0005518
    label: collagen binding
  locations:
  - id: GO:0005788
    label: endoplasmic reticulum lumen
  supported_by:
  - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
    supporting_text: Binds specifically to collagen.
  - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
    supporting_text: Could be involved as a chaperone in the biosynthetic pathway of collagen.
- description: Collagen-dedicated chaperone activity within the early secretory pathway; HSP47 escorts procollagen from the ER to the ER-Golgi intermediate compartment, where pH-dependent release allows HSP47 to recycle back to the ER.
  molecular_function:
    id: GO:0044183
    label: protein folding chaperone
  locations:
  - id: GO:0005788
    label: endoplasmic reticulum lumen
  - id: GO:0005793
    label: endoplasmic reticulum-Golgi intermediate compartment
  supported_by:
  - reference_id: file:human/SERPINH1/SERPINH1-uniprot.txt
    supporting_text: Could be involved as a chaperone in the biosynthetic pathway of collagen.
  - reference_id: file:human/SERPINH1/SERPINH1-goa.tsv
    supporting_text: GO:0005793 endoplasmic reticulum-Golgi intermediate compartment
proposed_new_terms: []
suggested_questions:
- question: What is the precise structural basis and pH threshold for HSP47 release from procollagen in the ERGIC/cis-Golgi, and how is this coupled to its RDEL-mediated ER retrieval?
- question: Beyond fibrillar collagens, which collagen types and other ER clients (if any) does HSP47 chaperone, and how does substrate specificity arise from triple-helix recognition?
- question: How do OI10-causing SERPINH1 variants mechanistically impair collagen maturation (loss of binding, mislocalization, or destabilization)?
suggested_experiments:
- description: Quantitative in vitro binding/turbidity assays with purified HSP47 and triple-helical vs unfolded collagen peptides across a pH gradient to map binding affinity and the pH-dependent release transition.
- description: Knock-in of OI10 patient variants in osteoblast or fibroblast models followed by collagen secretion, triple-helix stability, and ER-stress assays.
- description: Proximity-labeling (BioID/APEX) of HSP47 in the secretory pathway to define its client repertoire and trafficking-machinery partners during collagen transport.