Affinage

SERPINH1

Serpin H1 · UniProt P50454

Length
418 aa
Mass
46.4 kDa
Annotated
2026-06-10
100 papers in source corpus 27 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SERPINH1/HSP47 is an ER-resident, collagen-specific molecular chaperone that recognizes the folded triple-helical conformation of procollagens and stabilizes the thermally labile elongating triple helix at body temperature (PMID:16484215, PMID:31758055). Although it belongs to the serpin superfamily, it lacks the active-site residues for serine protease inhibition and instead carries a C-terminal RDEL ER-retention signal that recycles it to the ER (PMID:2072906). HSP47 recognizes its substrate by binding Arg at the Yaa position of Gly-Xaa-Arg triplets through a conserved aspartic acid, with two molecules engaging a single collagen triple helix head-to-head; collagen primary structure and flanking residues tune affinity and complex stoichiometry (PMID:16484215, PMID:22847422, PMID:34487762, PMID:34356607). By binding the assembling helix it prevents post-translational overmodification and aggregation and times procollagen secretion, while a histidine cluster provides the structural basis for pH-dependent substrate release in the cis-Golgi/ERGIC (PMID:9722680, PMID:22847422, PMID:31758055). Live imaging localizes HSP47/procollagen sorting to ER exit sites, with HSP47 excluded from the transport carriers that export procollagen (PMID:32562852). HSP47 is required for the folding, assembly, and secretion of multiple collagen types — I, II, III, IV, VI, and the transmembrane collagen XVII — acting in concert with other ER folding factors including cyclophilin B, BiP/GRP94, and FKBP65 (PMID:7629154, PMID:8834444, PMID:22492985, PMID:32716577, PMID:25510505). Loss of HSP47 function causes intracellular procollagen retention, ER stress, and collagen overmodification, and a missense SERPINH1 mutation causes autosomal recessive osteogenesis imperfecta (PMID:19629171, PMID:26004778). Beyond its biosynthetic role, HSP47 is the principal driver of myofibroblast-dependent tissue fibrosis by enabling fibrillar collagen deposition, is induced by TGF-β1/Smad2/3 signaling, and acts at the cell surface in platelets to enhance GPVI-collagen signaling and thrombosis; in cancer it promotes collagen-dependent platelet recruitment, metastatic colonization, and an immunosuppressive niche (PMID:29512284, PMID:31393098, PMID:31664133, PMID:32015106, PMID:38744278).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1991 High

    Established the molecular identity of HSP47 as a heat-inducible, ER-retained member of the serpin family that lacks protease-inhibitory activity, framing it as a chaperone rather than an enzyme.

    Evidence cDNA cloning, sequence homology analysis, and nuclear run-on assays

    PMID:2072906

    Open questions at the time
    • Substrate specificity not yet defined
    • No direct demonstration of chaperone activity
  2. 1995 Medium

    Showed HSP47 stays bound to procollagen from ER into pre-Golgi intermediates and that its release tracks triple-helix maturation, linking HSP47 dissociation to collagen folding state.

    Evidence pulse-chase, reciprocal immunoprecipitation, and pharmacological trafficking inhibition; complemented by co-IP showing HSP47/BiP/GRP94 heteromeric complexes on collagen IV (1996)

    PMID:7629154 PMID:8834444

    Open questions at the time
    • Release trigger not molecularly defined
    • Single-lab co-IP evidence for chaperone complexes
  3. 1998 Medium

    Demonstrated functionally that HSP47 delays procollagen III secretion and prevents backbone overmodification, defining its quality-control role in the secretory pathway.

    Evidence heterologous reconstitution in 293 cells with cross-link co-IP, secretion and thermal stability assays

    PMID:9722680

    Open questions at the time
    • Recognition motif still unknown
    • Single heterologous system
  4. 2006 High

    Defined the molecular recognition code: HSP47 reads Arg at the Yaa position of Gly-Xaa-Arg triplets plus the Yaa-3 residue on the same strand, explaining triple-helix specificity.

    Evidence systematic synthetic collagen-model peptide binding and competition assays

    PMID:16484215

    Open questions at the time
    • Structural basis of recognition not yet resolved
    • Native collagen binding-site distribution unknown
  5. 2009 High

    Established SERPINH1 as a disease gene by linking a conserved-domain missense mutation to autosomal recessive osteogenesis imperfecta.

    Evidence homozygosity mapping and candidate-gene analysis in affected Dachshunds

    PMID:19629171

    Open questions at the time
    • Cellular consequence of the mutation not yet defined
    • Animal model only at this stage
  6. 2012 High

    Provided the structural mechanism: crystal structures showed two HSP47 molecules bind a triple helix head-to-head via a conserved aspartate engaging the key Arg, and a histidine cluster rationalizes pH-dependent release.

    Evidence X-ray crystallography of free HSP47 and HSP47-collagen peptide complexes; genetic ablation in chondrocytes (Col2a1-Cre) establishing requirement for type II/XI procollagen folding

    PMID:22492985 PMID:22847422

    Open questions at the time
    • pH-release model not directly tested in cells
    • Stoichiometry on native heterotrimeric collagens unresolved
  7. 2015 Medium

    Connected HSP47 dysfunction to a shared OI pathway with FKBP65 and dissected the cellular pathology of the OI mutation (ER retention, ER stress, collagen overmodification).

    Evidence patient/mutant fibroblast biochemistry, co-IP, immunofluorescence, mass spectrometry, ER-stress immunoblotting in the Dachshund model

    PMID:25510505 PMID:26004778

    Open questions at the time
    • Direct vs. secondary nature of FKBP65 disruption needs further dissection
    • Single-lab co-IP for HSP47-FKBP65 interaction
  8. 2019 High

    Demonstrated the essential chaperone function is thermal stabilization of the elongating triple helix: lowering temperature to 33°C fully rescued the procollagen defects of HSP47-null fibroblasts.

    Evidence temperature-rescue experiments in hsp47-null MEFs with modification and secretion assays

    PMID:31758055

    Open questions at the time
    • Does not address sorting/release steps
    • Single-lab study
  9. 2019 High

    Established HSP47 as the dominant cell-autonomous driver of myofibroblast-mediated fibrosis downstream of TGF-β1/Smad2/3, required for fibrillar collagen deposition and scar formation.

    Evidence myofibroblast/cardiomyocyte/endothelial cell-specific conditional knockouts in pressure-overload and MI models; TGF-β1/Smad pathway and functional fibroblast assays; therapeutic siRNA in vocal fold scar

    PMID:31100613 PMID:31393098 PMID:31664133

    Open questions at the time
    • Mechanism coupling collagen secretion to myofibroblast proliferation unclear
    • Human in vivo efficacy of HSP47 silencing not established
  10. 2020 High

    Refined the trafficking model, showing procollagen and HSP47 sort at ER exit sites with HSP47 excluded from export carriers, correcting prior interpretations of HSP47/procollagen puncta.

    Evidence live-cell super-resolution imaging, FRAP, ARF1 inhibition, RDEL-deletion, ERGIC53 colocalization

    PMID:32562852

    Open questions at the time
    • Molecular machinery sorting HSP47 away from procollagen at ERES unidentified
    • Timing relative to pH-dependent release not integrated
  11. 2020 High

    Expanded the substrate range and mechanism, showing HSP47 is needed for assembly of collagens VI and XVII and for procollagen I secretion via direct N-terminal binding, with recombinant HSP47 rescuing folding in null membranes.

    Evidence keratinocyte-specific knockout, isolated membrane vesicle reconstitution with recombinant HSP47, EM and assembly assays

    PMID:32716577

    Open questions at the time
    • Assembly vs. secretion roles differ by collagen type and not fully reconciled
    • Single-lab reconstitution
  12. 2021 High

    Refined the recognition rules at structural resolution, showing flanking hydrophobic residues alter binding affinity and switch HSP47:collagen stoichiometry from 2:1 to 1:1, and mapped sparse native binding sites clustered near the collagen N-terminus.

    Evidence collagen peptide library binding/ELISA, X-ray crystallography of HSP47-Phe/Leu peptide complexes, molecular modeling and virtual inhibitor screening

    PMID:34356607 PMID:34487762

    Open questions at the time
    • Functional consequence of variable stoichiometry in cells unknown
    • Inhibitor efficacy in vivo not established
  13. 2020 High

    Defined extracellular/surface roles of HSP47 in platelet collagen signaling and cancer metastasis, mediated by type I collagen and platelet recruitment.

    Evidence platelet-specific Hsp47 knockout with flow/thrombosis assays; Hsp47 overexpression in MECs with collagen-blocking antibody and platelet depletion; integrin/NF-κB and microglia studies in brain metastasis

    PMID:29512284 PMID:32015106 PMID:38744278

    Open questions at the time
    • Mechanism of HSP47 export to the cell surface despite RDEL signal unresolved
    • Some downstream tumor signaling (ERK/CCL2) only low-confidence

Open questions

Synthesis pass · forward-looking unresolved questions
  • How HSP47 reaches the platelet and cancer cell surface despite its RDEL ER-retention signal, and how surface/extracellular HSP47 functionally relates to its canonical ER chaperone role, remains unresolved.
  • No trafficking mechanism for surface localization identified
  • Relationship between intracellular chaperone and extracellular signaling activities undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 3 GO:0044183 protein folding chaperone 3 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005783 endoplasmic reticulum 4 GO:0005886 plasma membrane 2
Pathway
R-HSA-1474244 Extracellular matrix organization 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-1643685 Disease 2 R-HSA-109582 Hemostasis 1
Partners
CD9COL1A1COL2A1COL3A1FKBP10GP6HSPA5PPIB

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1991 HSP47 (SERPINH1) contains a C-terminal RDEL sequence functioning as an ER-retention signal, belongs to the serpin superfamily but lacks the active site required for serine protease inhibition, and is transcriptionally regulated by heat shock elements in its promoter. Its suppression after Rous sarcoma virus transformation is regulated at the transcriptional level. cDNA cloning, Northern blot, nuclear run-on assay, amino acid sequence homology analysis Molecular and cellular biology High 2072906
1995 HSP47 and cyclophilin B remain associated with procollagen I as it traverses from the ER into pre-Golgi intermediate vesicles. Cyclosporin A treatment diminished CyPB bound to procollagen and slowed the rate of HSP47 release from procollagen and the rate of procollagen secretion, suggesting HSP47 release is coupled to triple-helix formation. Pulse-chase metabolic labeling, immunoprecipitation, immunofluorescence, pharmacological inhibition of G proteins and vesicular trafficking The Journal of biological chemistry Medium 7629154
1996 Hsp47, GRP78 (BiP), and GRP94 form heteromeric complexes with each other and with nascent chains of collagen type IV in the ER. ATP depletion increased the association of newly synthesized collagen IV with all three chaperones simultaneously. Co-immunoprecipitation in mouse teratocarcinoma cells, ATP depletion experiments Connective tissue research Medium 8834444
1998 HSP47 transiently binds to procollagen III in the ER (confirmed by chemical cross-linking immunoprecipitation), delays secretion of type III procollagen, and prevents overmodification of procollagen chains. In cells expressing HSP47, the electrophoretic mobility and melting temperature of type III procollagen matched those of normal collagen-producing cells, indicating HSP47 prevents overmodification of the procollagen backbone. Stable transfection of 293 cells with procollagen III ± HSP47, chemical cross-linking (DSP) immunoprecipitation, pulse-chase secretion assays, thermal stability measurements Journal of biochemistry Medium 9722680
2001 Recombinant mouse Hsp47 exists as both a structurally mesostable monomer (with a 5-strand A-sheet) and a hyperstable trimer; both states have biological activity. Hsp47 can bind a monomeric, partially folded collagen mimic peptide (PPG)10 and induce it to adopt a polyproline type II conformation, promoting higher-order assembly similar to collagen-like structures. The peptide-binding site does not reside in strand 4 of sheet A. Biophysical analysis of recombinant mouse Hsp47 including circular dichroism, analytical ultracentrifugation, peptide-binding assays The Journal of biological chemistry Medium 11592970
2006 HSP47 specifically recognizes the collagen triple helix by binding Arg residues at the Yaa position (Arg0) of Gly-Xaa-Arg triplets, and also contacts the residue at the Yaa-3 position on the same peptide strand. Maximal binding affinity occurs when Yaa-3 is Thr. The two key residues must be on the same strand of the triple helix for recognition by HSP47. Binding assays with synthetic heterotrimeric collagen-model peptides with systematic amino-acid substitutions, competitive inhibition assays The Journal of biological chemistry High 16484215
2009 A missense mutation in SERPINH1 (c.977C>T, p.L326P) in an evolutionarily conserved domain causes autosomal recessive osteogenesis imperfecta in Dachshunds, establishing SERPINH1 as a causative OI gene (the fifth identified). Homozygosity mapping with SNP chip, haplotype analysis, candidate gene mutation analysis in affected vs. control Dachshunds PLoS genetics High 19629171
2012 Crystal structures of Hsp47 free and in complex with homotrimeric synthetic collagen model peptides reveal that two Hsp47 molecules bind head-to-head to a collagen triple helix, each occupying one of two Arg-containing binding sites. A conserved aspartic acid on Hsp47 recognizes the key arginine in the Xaa-Arg-Gly triplet. A cluster of histidine residues in the structure provides the structural basis for pH-dependent substrate release in cis-Golgi/ERGIC. The structures explain triple-helix stabilization and inhibition of collagen-bundle formation by Hsp47. X-ray crystallography of Hsp47 alone and in complex with synthetic collagen peptides Proceedings of the National Academy of Sciences of the United States of America High 22847422
2012 Conditional knockout of Hsp47 specifically in chondrocytes (Col2a1-Cre) causes severe chondrodysplasia with reduced type II and XI collagen levels, accumulation of misaligned type I collagen, and loss of type II collagen fibers. This establishes Hsp47 as indispensable for correct folding of type II and type XI procollagens and for cartilage/endochondral bone formation. Conditional gene knockout (Hsp47 floxed × Col2a1-Cre), second-harmonic generation analysis, electron microscopy, immunohistochemistry, skeletal staining Journal of cell science High 22492985
2014 HSP47 and FKBP65 cooperate in posttranslational maturation of type I procollagen. An OI-causing SERPINH1 mutation destabilizes and mislocalizes HSP47, secondarily disrupting FKBP65 localization and preventing normal HSP47-FKBP65 interaction, revealing a common cellular pathway for OI caused by HSP47 and FKBP65 deficiency. Patient fibroblast biochemical assays, immunofluorescence localization, co-immunoprecipitation, analysis of procollagen processing Human molecular genetics Medium 25510505
2015 In the Dachshund OI model (HSP47 L326P mutation), HSP47 chaperone function is impaired in the ER, leading to intracellular procollagen retention with ER dilation and activation of ER stress markers (GRP78, phospho-eIF2α), post-translational overmodification of type I collagen chains, and higher pyridinoline crosslink content in bone collagen. Biochemical assays on mutant and control skin fibroblasts and bone, SDS-PAGE electrophoretic mobility analysis, tandem mass spectrometry, electron microscopy, ER stress marker immunoblotting The Journal of biological chemistry High 26004778
2015 Hsp47 silencing in breast cancer cells reprogrammed them to form growth-arrested and non-invasive structures in 3D cultures and reduced collagen and fibronectin deposition. miR-29b and miR-29c directly repress Hsp47 expression along with multiple ECM network genes. Ectopic expression of miR-29b suppressed malignant phenotypes. Hsp47 siRNA knockdown in 3D culture and xenograft assays, coexpression network analysis, miRNA overexpression, luciferase reporter assays for miR-29 targeting Cancer research Medium 25744716
2015 In zebrafish fin regeneration, serpinh1b (Hsp47) acts downstream of the gap junction protein Cx43 to regulate collagen-based actinotrichia organization, cell proliferation, and joint formation. Knockdown of Hsp47 recapitulates the short-fin phenotype with reduced fin/segment length and disrupted actinotrichia. Morpholino knockdown in zebrafish regenerating fin, short fin (sof) mutant analysis, epistasis experiments Mechanisms of development Medium 26103547
2016 SERPINH1 is a direct target of miR-29a as validated by luciferase reporter assay. miR-29a restoration suppressed cancer cell aggressiveness and fibroblast migration in lung cancer cells. Luciferase reporter assay for direct miRNA targeting, miR-29a restoration experiments in lung cancer cells and lung fibroblasts Journal of human genetics Medium 27488440
2018 HSP47 is present on the platelet surface where it binds collagen and modulates GPVI-collagen interaction. Deletion or inhibition of HSP47 in platelets specifically reduces collagen-induced (but not thrombin-induced) platelet activation, GPVI signaling, thrombus formation under arterial flow, and in vivo thrombosis in cremaster arterioles. Platelet-specific Hsp47 knockout mouse, flow-based thrombus assays, GPVI-collagen binding assays, laser-induced thrombosis, tail bleeding time Journal of thrombosis and haemostasis : JTH High 29512284
2019 Myofibroblast-specific ablation of Hsp47 blocks cardiac fibrosis and deposition of collagens type I, III, and V after pressure overload and reduces cardiac hypertrophy. Cardiomyocyte- or endothelial-specific deletion of Hsp47 has no effect on cardiac fibrosis. Fibroblast-specific Hsp47 deletion causes lethality after myocardial infarction due to failed scar formation and ventricular wall rupture. Deletion of Hsp47 from myofibroblasts reduced fibrillar collagen mRNA and attenuated myofibroblast proliferation without affecting paracrine secretory activity. Cell-type-specific conditional knockout (myofibroblast, cardiomyocyte, endothelial cell-specific Cre lines), pressure overload and MI models, histological fibrosis assessment, mRNA analysis JCI insight High 31393098
2019 Knockdown of Serpinh1 using siRNA in fibrotic vocal fold mucosa reversed scar-associated collagen accumulation within 4 weeks. Transcriptome analysis showed evidence of cell cycle upregulation, catabolism, matrix disassembly, and morphogenesis as therapeutic outcomes. Liposome-mediated siRNA delivery in vitro (naive and scar fibroblasts) and in vivo (rat VF mucosa), transcriptome analysis Molecular therapy. Nucleic acids Medium 31100613
2019 TGF-β1-induced HSP47 expression in nasal fibroblasts occurs via the Smad2/3 signaling pathway, and HSP47 is required for TGF-β1-induced myofibroblast differentiation, ECM production, fibroblast migration and contraction. siRNA knockdown of HSP47, Smad2/3 pathway inhibitor experiments, migration and collagen gel contraction assays, immunofluorescence, western blotting Scientific reports Medium 31664133
2019 Lowering culture temperature to 33°C corrects all procollagen biosynthesis defects in hsp47-/- fibroblasts, including ER accumulation, over-modification (prolyl/lysyl hydroxylation and glycosylation), and secretion of type I collagen homotrimer. This demonstrates that the essential function of HSP47 is to stabilize the elongating, thermally unstable triple helix of procollagen at body temperature. hsp47-null mouse embryo fibroblasts cultured at 37°C vs. 33°C, procollagen modification analysis, secretion assays, ER accumulation assessment Scientific reports High 31758055
2020 Live cell imaging with fluorescently tagged procollagen and HSP47 demonstrated that bona fide ER-to-Golgi transport carriers delivering procollagen contain no HSP47 (unless HSP47's RDEL ER-retention signal is deleted). Procollagen co-localizes with HSP47 and ERGIC53 at ER exit sites (ERESs), but co-localizes with ERGIC53 without HSP47 in Golgi-bound transport intermediates. Previously reported HSP47/procollagen puncta were identified as dilated ER regions, ERESs, or autophagic structures rather than transport vesicles. This indicates procollagen and HSP47 sorting occurs at ERES before ER export. Live cell fluorescence imaging with up to 120 nm spatial / 500 ms time resolution, FRAP, ARF1 inhibition, deletion of RDEL signal, colocalization with ERGIC53 and lysosomal markers Matrix biology : journal of the International Society for Matrix Biology High 32562852
2020 Hsp47 expression induces mesenchymal phenotypes in mammary epithelial cells, enhances platelet recruitment to cancer cells, and promotes lung retention and colonization of circulating tumor cells. Type I collagen was identified as the key mediator of Hsp47-induced cancer cell-platelet interaction by rescue experiments and functional blocking antibodies. Hsp47-dependent collagen deposition facilitated cancer cell clustering and extravasation. Hsp47 overexpression in MECs, platelet depletion in vivo, functional blocking antibodies against type I collagen, rescue experiments, lung retention assays Proceedings of the National Academy of Sciences of the United States of America High 32015106
2020 HSP47 ablation does not majorly impact collagen VI secretion but specifically impairs its lateral assembly. In keratinocytes, Hsp47 ablation impairs transmembrane collagen XVII triple-helix formation at the C-terminus; application of recombinant HSP47 to isolated Hsp47-null keratinocyte membrane vesicles fully restores collagen XVII C-terminal folding. HSP47 also binds the N-terminal region of procollagen I and is essential for its secretion. HSP47 ablation in murine keratinocytes (specific Cre), membrane vesicle isolation, application of recombinant HSP47, electron microscopy, collagen secretion/assembly assays FASEB journal : official publication of the Federation of American Societies for Experimental Biology High 32716577
2021 Collagen's primary structure determines the stoichiometry of the HSP47:collagen complex. Many predicted binding sites have low affinity due to negatively charged flanking amino acids, while large hydrophobic residues (Phe, Leu) at certain positions increase binding strength. Crystal structures of HSP47 bound to Phe- or Leu-containing collagen peptides reveal conformational rearrangements at the binding site and a 1:1 (rather than 2:1) complex stoichiometry due to steric clashes caused by the large hydrophobic side chain on the trailing strand. Collagen II peptide library binding assays, X-ray crystallography of HSP47-peptide complexes, molecular modeling The Journal of biological chemistry High 34487762
2021 Mapping HSP47 binding sites on native collagen types II and III using collagen toolkit peptide ELISA revealed that HSP47 binds only a few GXR motifs, with most high-affinity binding sites near the N-terminal part of the triple-helical region. Molecular modelling showed flanking residues beyond the key Arg also determine binding affinity. Two novel small-molecule HSP47-collagen interaction inhibitors were identified by virtual screening targeting the Arg binding site. ELISA binding assay with collagen toolkit synthetic peptides, molecular modeling, binding energy calculation, virtual screening, bioassay of inhibitor candidates Biomolecules Medium 34356607
2024 HSP47-mediated collagen deposition in brain metastatic niches promotes microglial polarization to the M2 phenotype via the α2β1 integrin/NF-κB pathway, upregulating anti-inflammatory cytokines and repressing CD8+ T cell anti-tumor responses. Microglial depletion reverses HSP47-induced CD8+ T cell inactivation and abolishes brain metastasis. HSP47 overexpression/knockdown in tumor cells, microglial depletion experiments, integrin blocking, NF-κB pathway analysis, CD8+ T cell functional assays, in vivo brain metastasis models Cell reports. Medicine Medium 38744278
1999 On the surface of tumor cells, Hsp47 (colligin) associates with the tetraspanin protein CD9 in a membrane complex. Cell lines with constitutively high surface Hsp47 showed the lowest invasion and migration indices; incorporation of anti-Hsp47 antibodies into migration assays increased invasion indices, suggesting surface Hsp47 moderates tumor cell invasion. Protein cross-linking followed by immunoprecipitation, cytometric analysis, Boyden chamber invasion assay, colloidal gold migration assay Journal of cellular biochemistry Low 10227388
2021 HSP47 promotes angiogenesis in bladder cancer by activating the ERK pathway and inducing CCL2 expression. HSP47 downregulation suppresses angiogenesis in vitro and in vivo. HSP47 knockdown/overexpression, ERK pathway inhibition, CCL2 measurement, angiogenesis assays, correlation with clinical samples Cellular signalling Low 34000383

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Hsp47: a collagen-specific molecular chaperone. Trends in biochemical sciences 220 8848834
2016 Biology of Hsp47 (Serpin H1), a collagen-specific molecular chaperone. Seminars in cell & developmental biology 194 27838364
2020 SERPINH1 regulates EMT and gastric cancer metastasis via the Wnt/β-catenin signaling pathway. Aging 175 32091407
2000 Identification and characterization of a highly conserved calcineurin binding protein, CBP1/calcipressin, in Cryptococcus neoformans. The EMBO journal 147 10899116
2018 Roles of the endoplasmic reticulum-resident, collagen-specific molecular chaperone Hsp47 in vertebrate cells and human disease. The Journal of biological chemistry 133 30541925
2007 Pirfenidone inhibits the expression of HSP47 in TGF-beta1-stimulated human lung fibroblasts. Life sciences 133 18093617
2012 Molecular basis for the action of the collagen-specific chaperone Hsp47/SERPINH1 and its structure-specific client recognition. Proceedings of the National Academy of Sciences of the United States of America 129 22847422
1991 HSP47: a tissue-specific, transformation-sensitive, collagen-binding heat shock protein of chicken embryo fibroblasts. Molecular and cellular biology 120 2072906
2015 Chaperone Hsp47 Drives Malignant Growth and Invasion by Modulating an ECM Gene Network. Cancer research 115 25744716
2011 Hsp47 as a collagen-specific molecular chaperone. Methods in enzymology 113 21683254
2020 Hsp47 promotes cancer metastasis by enhancing collagen-dependent cancer cell-platelet interaction. Proceedings of the National Academy of Sciences of the United States of America 112 32015106
1995 Hsp47 and cyclophilin B traverse the endoplasmic reticulum with procollagen into pre-Golgi intermediate vesicles. A role for Hsp47 and cyclophilin B in the export of procollagen from the endoplasmic reticulum. The Journal of biological chemistry 111 7629154
2003 HSP47 as a collagen-specific molecular chaperone: function and expression in normal mouse development. Seminars in cell & developmental biology 105 14986857
2006 The collagen-specific molecular chaperone HSP47: is there a role in fibrosis? Trends in molecular medicine 98 17169614
2009 A missense mutation in the SERPINH1 gene in Dachshunds with osteogenesis imperfecta. PLoS genetics 94 19629171
2001 Upregulation of HSP47 and collagen type III in the dermal fibrotic disease, keloid. Biochemical and biophysical research communications 94 11162672
2001 The molecular interactions of heat shock protein 47 (Hsp47) and their implications for collagen biosynthesis. The Journal of biological chemistry 92 11592970
2019 Cell-specific ablation of Hsp47 defines the collagen-producing cells in the injured heart. JCI insight 83 31393098
1989 CBP2 protein promotes in vitro excision of a yeast mitochondrial group I intron. Molecular and cellular biology 73 2685564
2002 A novel gene, CBP1, encoding a putative extracellular chitin-binding protein, may play an important role in the hydrophobic surface sensing of Magnaporthe grisea during appressorium differentiation. Molecular plant-microbe interactions : MPMI 72 12036274
2022 Circular RNA circ-TNPO3 inhibits clear cell renal cell carcinoma metastasis by binding to IGF2BP2 and destabilizing SERPINH1 mRNA. Clinical and translational medicine 68 35876041
2005 Hsp47 a novel collagen binding serpin chaperone, autoantigen and therapeutic target. Frontiers in bioscience : a journal and virtual library 64 15574354
2006 Specific recognition of the collagen triple helix by chaperone HSP47. II. The HSP47-binding structural motif in collagens and related proteins. The Journal of biological chemistry 62 16484215
1982 Identification and cloning of a yeast nuclear gene (CBP1) involved in expression of mitochondrial cytochrome b. Proceedings of the National Academy of Sciences of the United States of America 62 7043464
2022 Splicing factor derived circular RNA circCAMSAP1 accelerates nasopharyngeal carcinoma tumorigenesis via a SERPINH1/c-Myc positive feedback loop. Molecular cancer 61 35227262
1999 The possible role of colligin/HSP47, a collagen-binding protein, in the pathogenesis of human and experimental fibrotic diseases. Histology and histopathology 60 10506936
2015 Effects of heat stress on respiratory burst, oxidative damage and SERPINH1 (HSP47) mRNA expression in rainbow trout Oncorhynchus mykiss. Fish physiology and biochemistry 59 26614500
2021 HSP47: a potential target for fibrotic diseases and implications for therapy. Expert opinion on therapeutic targets 54 33287600
2011 Modulation of CRISPR locus transcription by the repeat-binding protein Cbp1 in Sulfolobus. Nucleic acids research 54 22139923
2016 Regulation of LOXL2 and SERPINH1 by antitumor microRNA-29a in lung cancer with idiopathic pulmonary fibrosis. Journal of human genetics 53 27488440
2018 Vitamin A-coupled liposomes containing siRNA against HSP47 ameliorate skin fibrosis in chronic graft-versus-host disease. Blood 52 29363541
2014 HSP47 and FKBP65 cooperate in the synthesis of type I procollagen. Human molecular genetics 50 25510505
1998 Histoplasma acquisition of calcium and expression of CBP1 during intracellular parasitism. Molecular microbiology 50 9489665
2005 Expression of HSP47, a collagen-specific chaperone, in normal and diseased human liver. Laboratory investigation; a journal of technical methods and pathology 49 15806139
1991 Binding of the CBP2 protein to a yeast mitochondrial group I intron requires the catalytic core of the RNA. Genes & development 48 1916266
2004 The mitochondrial message-specific mRNA protectors Cbp1 and Pet309 are associated in a high-molecular weight complex. Molecular biology of the cell 47 15047869
1998 Probing the yeast phase-specific expression of the CBP1 gene in Histoplasma capsulatum. Journal of bacteriology 45 9537376
2016 HSP47 Promotes Glioblastoma Stemlike Cell Survival by Modulating Tumor Microenvironment Extracellular Matrix through TGF-β Pathway. ACS chemical neuroscience 44 27696866
2012 The molecular chaperone Hsp47 is essential for cartilage and endochondral bone formation. Journal of cell science 43 22492985
2003 Prevalence of HSP47 antigen and autoantibodies to HSP47 in the sera of patients with mixed connective tissue disease. Biochemical and biophysical research communications 43 12659832
1984 Assembly of the mitochondrial membrane system. Nucleotide sequence of a yeast nuclear gene (CBP1) involved in 5' end processing of cytochrome b pre-mRNA. The Journal of biological chemistry 42 6325407
2002 Cbp1 is required for translation of the mitochondrial cytochrome b mRNA of Saccharomyces cerevisiae. The Journal of biological chemistry 40 12149267
2015 Macrophage cell death and transcriptional response are actively triggered by the fungal virulence factor Cbp1 during H. capsulatum infection. Molecular microbiology 39 26288377
2005 Expression of HSP47 in usual interstitial pneumonia and nonspecific interstitial pneumonia. Respiratory research 39 15955241
2015 Molecular Consequences of the SERPINH1/HSP47 Mutation in the Dachshund Natural Model of Osteogenesis Imperfecta. The Journal of biological chemistry 38 26004778
2005 Calcineurin-binding protein Cbp1 directs the specificity of calcineurin-dependent hyphal elongation during mating in Cryptococcus neoformans. Eukaryotic cell 38 16151246
1989 The yeast CBP1 gene produces two differentially regulated transcripts by alternative 3'-end formation. Molecular and cellular biology 38 2573826
2022 Targeting HSP47 and HSP70: promising therapeutic approaches in liver fibrosis management. Journal of translational medicine 35 36435779
2019 TGF-β1-induced HSP47 regulates extracellular matrix accumulation via Smad2/3 signaling pathways in nasal fibroblasts. Scientific reports 34 31664133
1987 Nuclearly-encoded CBP1 interacts with the 5' end of mitochondrial cytochrome b pre-mRNA. Current genetics 34 3329053
2019 Up-regulation of SNHG6 activates SERPINH1 expression by competitive binding to miR-139-5p to promote hepatocellular carcinoma progression. Cell cycle (Georgetown, Tex.) 33 31258024
1993 Generation of temperature-sensitive cbp1 strains of Saccharomyces cerevisiae by PCR mutagenesis and in vivo recombination: characteristics of the mutant strains imply that CBP1 is involved in stabilization and processing of cytochrome b pre-mRNA. Genetics 33 8307338
2024 Targeting the HSP47-collagen axis inhibits brain metastasis by reversing M2 microglial polarization and restoring anti-tumor immunity. Cell reports. Medicine 31 38744278
2020 Mechanisms of procollagen and HSP47 sorting during ER-to-Golgi trafficking. Matrix biology : journal of the International Society for Matrix Biology 31 32562852
2018 The chaperone protein HSP47: a platelet collagen binding protein that contributes to thrombosis and hemostasis. Journal of thrombosis and haemostasis : JTH 31 29512284
2016 Tissue Degeneration following Loss of Schistosoma mansoni cbp1 Is Associated with Increased Stem Cell Proliferation and Parasite Death In Vivo. PLoS pathogens 31 27812220
2009 High expression of HSP47 in ulcerative colitis-associated carcinomas: proteomic approach. British journal of cancer 31 19603022
2007 Alpha-defensin enhances expression of HSP47 and collagen-1 in human lung fibroblasts. Life sciences 31 17367817
2015 Activation of the signalling mucin MoMsb2 and its functional relationship with Cbp1 in Magnaporthe oryzae. Environmental microbiology 30 25808678
1999 Cell surface colligin/Hsp47 associates with tetraspanin protein CD9 in epidermoid carcinoma cell lines. Journal of cellular biochemistry 29 10227388
2020 Small molecule inhibitor of HSP47 prevents pro-fibrotic mechanisms of fibroblasts in vitro. Biochemical and biophysical research communications 27 32747092
2018 Heat stress-induced renal damage in poultry and the protective effects of HSP60 and HSP47. Cell stress & chaperones 27 29779133
1996 Hsp47 and other ER-resident molecular chaperones form heterocomplexes with each other and with collagen type IV chains. Connective tissue research 26 8834444
2015 The tRNA Splicing Endonuclease Complex Cleaves the Mitochondria-localized CBP1 mRNA. The Journal of biological chemistry 25 25971974
1990 Identification of the CBP1 polypeptide in mitochondrial extracts from Saccharomyces cerevisiae. The Journal of biological chemistry 25 2104848
2023 HSP47: A Therapeutic Target in Pulmonary Fibrosis. Biomedicines 24 37760828
1998 HSP47, a collagen-specific molecular chaperone, delays the secretion of type III procollagen transfected in human embryonic kidney cell line 293: a possible role for HSP47 in collagen modification. Journal of biochemistry 24 9722680
2020 Regulation of aberrantly expressed SERPINH1 by antitumor miR-148a-5p inhibits cancer cell aggressiveness in gastric cancer. Journal of human genetics 22 32235846
2019 Reversal of Vocal Fold Mucosal Fibrosis Using siRNA against the Collagen-Specific Chaperone Serpinh1. Molecular therapy. Nucleic acids 22 31100613
1997 Premature 3'-end formation of CBP1 mRNA results in the downregulation of cytochrome b mRNA during the induction of respiration in Saccharomyces cerevisiae. Molecular and cellular biology 22 9234677
2022 Cbp1, a fungal virulence factor under positive selection, forms an effector complex that drives macrophage lysis. PLoS pathogens 21 35731824
2015 Hsp47 mediates Cx43-dependent skeletal growth and patterning in the regenerating fin. Mechanisms of development 21 26103547
1991 Yeast CBP1 mRNA 3' end formation is regulated during the induction of mitochondrial function. Molecular and cellular biology 20 1990285
2019 Lowering the culture temperature corrects collagen abnormalities caused by HSP47 gene knockout. Scientific reports 19 31758055
1997 Specific expression of HSP47 in human tumor cell lines in vitro. In vivo (Athens, Greece) 19 9067768
1997 Genetic evidence for interaction between Cbp1 and specific nucleotides in the 5' untranslated region of mitochondrial cytochrome b mRNA in Saccharomyces cerevisiae. Molecular and cellular biology 19 9343381
1995 Cotranscriptional splicing of a group I intron is facilitated by the Cbp2 protein. Molecular and cellular biology 19 8524264
2022 MiR-29a Increase in Aging May Function as a Compensatory Mechanism Against Cardiac Fibrosis Through SERPINH1 Downregulation. Frontiers in cardiovascular medicine 18 35118144
2002 Collagen-binding heat shock protein HSP47 expression during healing of fetal skin wounds. International journal of oral and maxillofacial surgery 18 12102417
1995 Isolation, characterization and chromosomal assignment of human colligin-2 gene (CBP2). Cytogenetics and cell genetics 18 7656593
2022 Hsp47 Inhibitor Col003 Attenuates Collagen-Induced Platelet Activation and Cerebral Ischemic-Reperfusion Injury in Rats. Frontiers in pharmacology 17 35082674
2022 H19 may regulate the immune cell infiltration in carcinogenesis of gastric cancer through miR-378a-5p/SERPINH1 signaling. World journal of surgical oncology 17 36104825
2022 MicroRNA-29a inhibits collagen expression and induces apoptosis in human fetal scleral fibroblasts by targeting the Hsp47/Smad3 signaling pathway. Experimental eye research 17 36206860
2020 New specific HSP47 functions in collagen subfamily chaperoning. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 17 32716577
2000 Binding motifs of CBP2 a potential cell surface target for carcinoma cells. Journal of cellular biochemistry 17 10842320
2000 CBP1 associates with the Dictyostelium cytoskeleton and is important for normal cell aggregation under certain developmental conditions. Experimental cell research 17 10896781
1996 Expression of 47 kDa heat shock protein (HSP47) during development of mouse cornea. Experimental eye research 17 8944545
1990 CBP1 function is required for stability of a hybrid cob-oli1 transcript in yeast mitochondria. Current genetics 17 2150347
2015 Overexpression of HSP47 in esophageal squamous cell carcinoma: clinical implications and functional analysis. Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus 16 25953518
2007 Coexpression of HSP47 gene and type I and type III collagen genes in LPS-induced pulmonary fibrosis in rats. Lung 16 17310300
2024 HSP47 in human diseases: Navigating pathophysiology, diagnosis and therapy. Clinical and translational medicine 15 39135385
2021 HSP47 contributes to angiogenesis by induction of CCL2 in bladder cancer. Cellular signalling 15 34000383
2021 Identification of HSP47 Binding Site on Native Collagen and Its Implications for the Development of HSP47 Inhibitors. Biomolecules 15 34356607
2008 A 12-bp deletion in the 5'-flanking region of the SERPINH1 gene affects promoter activity and protects against preterm premature rupture of membranes in African Americans. Human mutation 15 18205191
2006 The molecular chaperone HSP47 rapidly senses gravitational changes in myoblasts. Genes to cells : devoted to molecular & cellular mechanisms 15 17054723
2022 A CCaMK/Cyclops response element in the promoter of Lotus japonicus calcium-binding protein 1 (CBP1) mediates transcriptional activation in root symbioses. The New phytologist 14 35318667
2021 Collagen's primary structure determines collagen:HSP47 complex stoichiometry. The Journal of biological chemistry 14 34487762
2017 Ancestry & molecular evolutionary analyses of heat shock protein 47 kDa (HSP47/SERPINH1). Scientific reports 14 28871169
2011 Heat shock protein 47 (HSP47) antisense oligonucleotides reduce cardiac remodeling and improve cardiac function in a rat model of myocardial infarction. The Thoracic and cardiovascular surgeon 14 21412710
2008 Proliferation of HSP47-positive skin fibroblasts in dermatofibroma. Journal of cutaneous pathology 14 18095990

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