Affinage

COL1A2

Collagen alpha-2(I) chain · UniProt P08123

Length
1366 aa
Mass
129.3 kDa
Annotated
2026-04-28
100 papers in source corpus 32 papers cited in narrative 32 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

COL1A2 encodes the pro-α2(I) chain of type I collagen, a major structural protein of bone, skin, tendon, and other connective tissues, and its expression is controlled by one of the most extensively characterized transcriptional regulatory systems among extracellular matrix genes. TGF-β activates COL1A2 transcription through both a Smad3/Smad4–Sp1 complex at a proximal CAGA box and a non-canonical pathway involving JunB/cJun exchange at a far-upstream enhancer (~17–20 kb) where STAT3 recruits RNA polymerase II, while IFN-γ represses transcription via an RFX5/RFXB/RFXAP complex that recruits CIITA and HDAC2/mSin3B to the transcription start site, and TNF-α represses through NF-κB (p50/p65) binding at the proximal promoter (PMID:11007770, PMID:19561194, PMID:29142074, PMID:12968017, PMID:15247294, PMID:10201951). Glycine-substituting mutations in the triple-helical domain disrupt collagen helix formation and cause osteogenesis imperfecta, while splice-site mutations deleting the N-proteinase cleavage site cause Ehlers-Danlos syndrome type VIIB (PMID:2777764, PMID:1556139). Germline loss of Col1a2 in mice produces defective cardiac ECM, pathological fibroblast activation, TGF-β pathway upregulation, and progressive cardiomyopathy, establishing that the α2(I) chain is essential for normal cardiac collagen architecture and function (PMID:37681905).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1989 High

    Identifying a glycine-to-serine substitution in the triple-helical domain of pro-α2(I) as the cause of lethal perinatal osteogenesis imperfecta established that the Gly-X-Y repeat is indispensable for collagen helix formation and that COL1A2 mutations cause heritable connective tissue disease.

    Evidence Chemical mismatch cleavage of mRNA:cDNA heteroduplexes and sequencing in affected patients

    PMID:2777764

    Open questions at the time
    • Genotype-phenotype correlation across different glycine substitution positions not yet resolved
    • Mechanism by which mutant chains exert dominant-negative effects on heterotrimer not fully defined
  2. 1992 High

    Identification of a splice-acceptor mutation activating a cryptic splice site and deleting the N-proteinase cleavage site from pro-α2(I) provided the molecular basis for EDS type VIIB and demonstrated that post-translational processing of the N-propeptide is essential for normal collagen fibril assembly.

    Evidence Protein sequencing, cDNA and genomic DNA sequencing in an EDS VIIB patient

    PMID:1556139

    Open questions at the time
    • Whether tissue-specific effects of retained N-propeptide differ was not addressed
  3. 1996 High

    Mapping the AP-1 site at -265/-241 of the COL1A2 promoter as necessary for TGF-β upregulation and TNF-α antagonism established the first cis-regulatory element mediating cytokine-responsive COL1A2 transcription.

    Evidence Deletion reporters, EMSA, mutagenesis, c-jun co-transfection in fibroblasts

    PMID:8621730

    Open questions at the time
    • Identity of specific AP-1 dimer bound in vivo not determined
    • Downstream signaling cascade from TGF-β to AP-1 not delineated
  4. 1996 High

    Demonstrating that shortened α2(I) chains from multiexon deletions are incorporated into bone but not skin collagen matrix revealed tissue-specific quality control of mutant collagen incorporation.

    Evidence Radiolabeled proline incorporation and SDS-PAGE in osteoblast vs. fibroblast cultures

    PMID:8702873

    Open questions at the time
    • Molecular basis of tissue-specific exclusion of mutant chains not identified
  5. 1999 High

    Identifying an NF-κB (p50/p65) site overlapping the AP-1 element at -265/-241 as the mediator of TNF-α repression resolved how pro-inflammatory signaling directly suppresses COL1A2 transcription.

    Evidence EMSA with NF-κB supershift antibodies and site-directed mutagenesis of the NF-κB half-site

    PMID:10201951

    Open questions at the time
    • Whether NF-κB and AP-1 compete for overlapping sites or bind simultaneously was not resolved
  6. 2000 High

    Demonstrating that TGF-β stimulates COL1A2 via cooperative Smad3/Smad4 and Sp1 binding at a CAGA box defined the canonical Smad-dependent pathway for fibrogenic collagen induction.

    Evidence Recombinant Smad binding assays, dominant-negative Smad constructs, reconstitution in Sp1-deficient Drosophila cells

    PMID:11007770

    Open questions at the time
    • Relative contribution of Smad-dependent vs. Smad-independent TGF-β pathways to endogenous COL1A2 not quantified
  7. 2001 High

    Characterization of the far-upstream enhancer (~20 kb) with DNase I hypersensitive sites HS3-5 revealed that tissue-specific high-level COL1A2 expression depends on distal regulatory elements beyond the proximal promoter.

    Evidence DNase I hypersensitivity mapping, footprinting, and transgenic mouse reporters

    PMID:11279244

    Open questions at the time
    • Transcription factors binding the 12 footprinted areas (FU1-12) not all identified
    • Three-dimensional chromatin looping between enhancer and promoter not directly demonstrated
  8. 2002 High

    Identifying RFX1 and RFX5 as transcriptional repressors binding the COL1A2 start site — with RFX5 mediating IFN-γ repression through CIITA recruitment — established a dedicated repressor pathway counterbalancing pro-fibrotic activation.

    Evidence EMSA, in vitro transcription, ChIP, and reporter assays in fibroblasts

    PMID:11986307

    Open questions at the time
    • Whether RFX1/RFX5 regulation operates in non-fibroblast collagen-producing cells not tested
  9. 2004 High

    Defining the full RFX5/RFXB/RFXAP complex plus CIITA as IFN-γ effectors that displace RNA polymerase II from the COL1A2 start site provided a complete picture of the IFN-γ repression mechanism, while demonstrating that CIITA's N-terminal domains are required for repression.

    Evidence ChIP for Pol II and CIITA, shRNA knockdown, dominant-negative RFX5 mutants

    PMID:12968017 PMID:15247294

    Open questions at the time
    • Whether CIITA displaces Pol II through steric occlusion or active chromatin remodeling not determined
  10. 2004 High

    Transgenic mutagenesis of promoter elements showed that Sp1 sites are required for osteoblast expression and CBF/NFY for dermis/fascia expression, establishing combinatorial cis-element usage for tissue-specific COL1A2 activation, while the far-upstream enhancer was shown to reactivate upon injury and fibrogenic stimulation.

    Evidence Site-directed mutagenesis in transgenic mouse reporters; injury and cytokine injection models

    PMID:15062855 PMID:15516691

    Open questions at the time
    • Full map of enhancer-promoter element combinations for each tissue type not completed
  11. 2005 High

    Identification of GATA-4 binding at the HS2 element (~-2.3 kb) and at an intronic repressor element (+647 to +760, alongside IRF-1/IRF-2) revealed additional layers of transcriptional repression that constrain COL1A2 expression in fibroblasts.

    Evidence DNase I footprinting, EMSA, ChIP, reporter assays, transgenic mouse mutagenesis

    PMID:15982862 PMID:16091368

    Open questions at the time
    • Physiological signals that regulate GATA-4 and IRF occupancy at these elements not identified
  12. 2006 High

    Dissecting two distinct HDAC-containing co-repressor complexes — RFX5/HDAC2/mSin3B (IFN-γ-responsive) and RFX1/HDAC1/mSin3A (methylation-sensitive) — at the COL1A2 start site showed how epigenetic and cytokine cues converge on parallel deacetylation mechanisms to silence collagen transcription.

    Evidence Reciprocal co-IP, ChIP, HDAC activity assays, TSA treatment

    PMID:16464847

    Open questions at the time
    • Whether histone or non-histone substrates of HDAC1/2 are the critical targets for COL1A2 silencing not resolved
  13. 2009 High

    Demonstrating that TGF-β activates COL1A2 through a Smad-independent pathway involving JunB-for-cJun exchange at the far-upstream enhancer, and that TGF-β antagonizes IFN-γ repression by modulating RFXB/RFXBSV ratios to limit HDAC2 recruitment, revealed two non-canonical mechanisms by which TGF-β overrides repressive signals.

    Evidence Transgenic mice, ChIP, lentiviral RFXB/RFXBSV overexpression, siRNA in vascular smooth muscle cells

    PMID:19465385 PMID:19561194

    Open questions at the time
    • Signaling cascade from TGF-β receptor to JunB/cJun exchange not elucidated
    • Whether RFXBSV splice variant regulation occurs in all fibroblast lineages not tested
  14. 2016 High

    Identifying HIF-1α binding at -335 and its cooperation with Smad3 to activate COL1A2 independently of hypoxia linked collagen transcription to the HIF pathway and provided a mechanism for TGF-β-driven fibrosis in renal glomerulosclerosis.

    Evidence ChIP, Smad3-null MEFs, promoter-reporters, knockout mouse glomerulosclerosis model

    PMID:27503806

    Open questions at the time
    • Whether HIF-1α/Smad3 cooperation operates in non-renal fibrosis contexts not established
  15. 2017 High

    STAT3 was shown to bind the far-upstream enhancer and recruit RNA polymerase II for TGF-β-induced COL1A2 expression during myofibroblast differentiation, additionally regulating COL1A2 post-transcriptionally via IL-6 trans-signaling, while UV-induced DNA methylation at a p300 binding site was found to suppress COL1A2 by reducing H3K27ac and Smad2/3 recruitment.

    Evidence ChIP for STAT3 and Pol II, STAT3 inhibition/knockdown, pyrosequencing for methylation, p300 HAT inhibitor treatment

    PMID:28237615 PMID:29142074

    Open questions at the time
    • Post-transcriptional mechanism of STAT3-mediated COL1A2 protein regulation not defined
    • Whether UV-induced methylation at -1406 is relevant in non-skin tissues unknown
  16. 2023 High

    Germline Col1a2 knockout in mice established that the α2(I) chain is essential for cardiac ECM integrity: its loss led to compensatory fibroblast activation, TGF-β pathway upregulation, and progressive cardiomyopathy, while acute myofibroblast-specific deletion reduced collagen deposition and attenuated pressure-overload hypertrophy.

    Evidence Germline and conditional (Postn-MerCreMer) Col1a2 knockout mice with echocardiography, microCT, and proteomics

    PMID:37681905

    Open questions at the time
    • Whether homotrimeric α1(I)₃ collagen produced in absence of α2(I) is inherently dysfunctional or simply insufficient not resolved
    • Bone and tendon phenotypes of germline Col1a2 knockout not characterized in this study

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis for how α2(I) incorporation modulates collagen fibril mechanics, the full identity of transcription factors at all 12 far-upstream enhancer footprints, and how the multiple transcriptional and post-transcriptional regulatory inputs are integrated in a cell-type- and stimulus-specific manner in vivo.
  • No structural model of α1(I)₂α2(I) heterotrimer assembly vs. α1(I)₃ homotrimer
  • Comprehensive enhancer-promoter interactome (e.g., Hi-C/capture-C) not reported
  • In vivo single-cell transcriptional dynamics of COL1A2 regulatory switching not characterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005198 structural molecule activity 3
Localization
GO:0005576 extracellular region 2 GO:0031012 extracellular matrix 2
Pathway
R-HSA-1474244 Extracellular matrix organization 3 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 2
Partners
CIITACOL1A1HDAC2RFX5SMAD3SMAD4SP1STAT3
Complex memberships
type I collagen heterotrimer (α1(I)₂α2(I))

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 An AP-1 binding sequence located between nucleotides -265 and -241 of the COL1A2 promoter is essential for TGF-β up-regulation and mediates TNF-α antagonism of TGF-β effects. Gel mobility shift assays showed nuclear factor binding competed by AP-1 oligonucleotides. Overexpression of c-jun in co-transfection experiments blocked the TGF-β response, implicating AP-1 in COL1A2 transcriptional regulation. 5' deletion promoter/CAT reporter constructs, gel mobility shift assays, site-directed mutagenesis, co-transfection with c-jun expression plasmid The Journal of biological chemistry High 8621730
1999 TNF-α inhibits COL1A2 transcription through an NF-κB (p50/p65 heterodimer) binding element located between -265 and -241 in the COL1A2 promoter. A 2-bp substitution in the NF-κB1 binding half site abolished TNF-α effect. EMSA and supershift assays demonstrated rapid nuclear translocation of NF-κB upon TNF-α stimulation. 5' deletion promoter/CAT reporter constructs, EMSA, supershift assays with NF-κB antibodies, site-directed mutagenesis Journal of immunology High 10201951
2000 TGF-β1 stimulates COL1A2 transcription through cooperative binding of a Smad3/Smad4 complex and Sp1 to a CAGA box within the TGF-β responsive element (TbRE). Recombinant Smad3 and Smad4 bind in vitro to the CAGA box; TGF-β treatment induces Smad3/Smad4 binding to TbRE in fibroblasts; dominant negative Smad3 or Smad4 abolishes TGF-β-induced COL1A2 up-regulation. In vitro binding assays with recombinant Smad3/Smad4, transient and stable transfection with dominant negative Smad constructs, co-transfection in Sp1-deficient Drosophila cells, gel shift assays The Journal of biological chemistry High 11007770
2001 A far-upstream enhancer (~20 kb upstream) of the human COL1A2 gene contains DNase I hypersensitive sites (HS3-5) that confer high, tissue-specific expression in transgenic mice. The enhancer region contains 12 footprinted areas (FU1-12) and shows functional differences from the mouse counterpart; AluI repeats augment position-independent expression. DNase I hypersensitivity mapping, DNase I footprinting, transgenic mouse reporter assays The Journal of biological chemistry High 11279244
2002 RFX1 forms homodimers and heterodimers with RFX2 at the COL1A2 transcription start site and acts as a transcriptional repressor. Methylation at +7 on the coding strand increases RFX1 complex formation. An RFX5 complex also binds the collagen RFX site in a methylation-insensitive manner and represses COL1A2 transcription; IFN-γ enhances RFX5 binding and CIITA is recruited to the RFX5 complex to repress COL1A2. Gel shift assays, in vitro transcription assays, co-transfection reporter assays, chromatin immunoprecipitation The Journal of biological chemistry High 11986307
2003 The full RFX5 complex (RFX5, RFXB/RFXANK, RFXAP) mediates IFN-γ repression of COL1A2 transcription. All three components are required for maximum repression; mutations in RFX5 complex formation act as dominant negatives to activate collagen expression and reverse IFN-γ repression. IFN-γ increases expression and nuclear translocation of RFX5 and all three complex proteins accumulate at the COL1A2 transcription start site. Co-transfection reporter assays, dominant negative mutants, chromatin immunoprecipitation, Western blotting The Journal of biological chemistry High 12968017
2004 CIITA, recruited by RFX5 to the COL1A2 transcription start site, is a key mediator of IFN-γ repression of COL1A2. IFN-γ promotes CIITA occupancy at the COL1A2 start site with coordinate decrease of RNA polymerase II occupancy. CIITA repression requires its N-terminal acidic and proline/serine/threonine domains; shRNA knockdown of CIITA alleviates COL1A2 repression. Chromatin immunoprecipitation, shRNA knockdown, co-transfection with deletion mutants, DNA affinity chromatography The Journal of biological chemistry High 15247294
2004 Cooperation between the far-upstream enhancer and proximal promoter elements (Sp1 sites around -300, TC-rich boxes around -160/-125, and CBF/NFY site around -80) is essential for tissue-specific COL1A2 expression in vivo. Mutations of individual elements reduced transgene activity in specific cell types (Sp1 sites required for osteoblasts; CBF/NFY site required for ventral fascia/head dermis). Site-directed mutagenesis of promoter/enhancer elements, transgenic mouse reporter assays The Journal of biological chemistry High 15516691
2004 The Col1a2 far-upstream enhancer (~-17 kb) drives collagen gene expression during embryonic development (from E11.5) and is reactivated in adult tissues by physical injury or fibrogenic cytokine injection, establishing its central role in COL1A2 activation in tissue fibrosis. Transgenic mice with -17 kb Col1a2 promoter/reporter, histological mapping, injury models Matrix biology High 15062855
2004 IL-4-induced STAT6 binds to sequences within the COL1A2 promoter and activates COL1A2 transcription in human lung fibroblasts. Combined action of SP1, NFκB, and STAT6 contributes to IL-4-mediated COL1A2 gene activation; IL-4 treatment increased luciferase activity driven by COL1A2 promoter by ~70%. 5' deletion promoter/luciferase reporter constructs, transient transfection in human lung fibroblasts Journal of cellular physiology Medium 14603527
2005 S-adenosylmethionine (AdoMet) blocks TGF-β induction of COL1A2 promoter activity by preventing phosphorylation of ERK1/2 and blocking Sp1 binding to the TGF-β-responsive element. AdoMet represses basal and TGF-β-induced reporter activity in stellate cells and prevents activation of the -378 bp COL1A2 promoter region. Transgenic mouse model (COL1A2 promoter/β-gal), stellate cell transfection with promoter deletion constructs, Sp1 binding assays, β-galactosidase activity measurement The Journal of biological chemistry High 15983038
2005 GATA-4 binds to two GATA consensus sequences within a hairpin structure at the HS2 element (~-2.3 kb) of the human COL1A2 gene and represses transcription in fibroblasts. Forced overexpression of GATA-4 decreased transcription from COL1A2 promoter constructs and reduced endogenous collagen gene expression; ChIP confirmed GATA-4 binding at HS2 in vivo. DNase I footprinting, gel mobility shift assays, luciferase reporter assays, co-transfection with GATA-4 expression construct, chromatin immunoprecipitation Matrix biology High 15982862
2005 The first intron of human COL1A2 contains a repressor element (nucleotides +647 to +760) that inhibits transgene expression in a position-independent manner. GATA-4 and IRF-1/IRF-2 bind to this intron sequence; mutations in the footprinted regions (FI1-3) partially restore transgenic expression, indicating concerted repression by GATA and IRF proteins. DNase I footprinting, gel mobility shift assays, chromatin immunoprecipitation, transgenic mouse reporter assays with site-directed mutations The Journal of biological chemistry High 16091368
2006 RFX1 and RFX5 repress COL1A2 through two distinct co-repressor pathways: RFX5 specifically interacts with HDAC2 and mSin3B, whereas RFX1 preferentially interacts with HDAC1 and mSin3A. IFN-γ promotes recruitment of RFX5/HDAC2/mSin3B to the COL1A2 transcription start site. RFX1 binds methylated COL1A2 sequence with higher affinity, recruiting more HDAC1/mSin3A. Both RFX1 and RFX5 are acetylated in vivo, and TSA-stimulated acetylation activates COL1A2 promoter. Co-immunoprecipitation, chromatin immunoprecipitation, reporter assays, HDAC activity assays The Journal of biological chemistry High 16464847
2009 TGF-β activates COL1A2 via a non-canonical (Smad-independent) signaling pathway requiring enhancer/promoter cooperation. This involves exchange of cJun for JunB at a critical enhancer site, stabilizing enhancer/promoter coalescence. Interference with this mechanism abolishes COL1A2 fibroblast expression in vivo in transgenic mice. Transgenic mouse model, chromatin immunoprecipitation, promoter/enhancer deletion constructs, TGF-β treatment of fibroblasts Nucleic acids research High 19561194
2009 TGF-β antagonizes IFN-γ repression of COL1A2 transcription in vascular smooth muscle cells by altering the relative expression of RFXB and its splice variant RFXBSV. RFXBSV does not bind the collagen promoter but competes with RFXB for co-repressor HDAC2, limiting HDAC2 recruitment to the COL1A2 transcription start site. Lentiviral overexpression of RFXB enhanced HDAC2 enlistment and blocked TGF-β antagonism, a pattern reversed by RFXBSV infection. Lentiviral infection, chromatin immunoprecipitation, reporter assays, siRNA silencing Nucleic acids research High 19465385
2012 SIRT1 deacetylates RFX5, disrupting its repression of COL1A2 promoter. SIRT1 forms a complex with RFX5; overexpression of SIRT1 or activation with resveratrol decreases RFX5 acetylation and reduces RFX5-mediated repression of COL1A2. SIRT1 antagonizes RFX5 by promoting its nuclear expulsion and proteasomal degradation. IFN-γ represses COL1A2 in smooth muscle cells by down-regulating SIRT1. Co-immunoprecipitation, overexpression/knockdown of SIRT1, NAMPT, reporter assays, SIRT1 agonist/inhibitor treatments Biochemical and biophysical research communications Medium 23079621
2014 Sp7/Osterix binds to the second G/C-rich sequence from the transcription start site of the mouse Col1a2 proximal promoter and induces Col1a2 expression in osteoblastic cells. Substitution mutation of this G/C-rich sequence specifically decreased promoter activity in osteoblastic cells; Sp7/Osterix overexpression and siRNA knockdown confirmed this element mediates osteoblast-specific Col1a2 expression. Luciferase reporter assays with promoter mutations, Sp7/Osterix overexpression and siRNA knockdown, ChIP (binding assay) Biochemical and biophysical research communications Medium 25172663
2016 HIF-1α directly binds a functional hypoxia-responsive element (HRE) at -335 of the COL1A2 promoter and activates its transcription independently of hypoxia. TGF-β enhances HIF-1α binding to the COL1A2 promoter and HIF-1α transactivation domain activity. Smad3 is required for TGF-β effects on HIF-1α and forms an HIF-1α-Smad3 transcriptional complex at the -335 HRE. Smad3-null fibroblasts blocked TGF-β enhancement of HIF-1α-mediated COL1A2 activation. ChIP assays, Smad3-null mouse embryonic fibroblasts, HIF-1α binding assays, promoter-reporter assays, knockout mouse glomerulosclerosis model Kidney international High 27503806
2017 STAT3 binds the COL1A2 far-upstream enhancer and is essential for RNA polymerase II recruitment without affecting JunB binding. STAT3 is required for increased COL1A2 expression in myofibroblasts. Inhibiting STAT3 blocks TGF-β signaling, matrix remodeling, and TGF-β-induced myofibroblast differentiation. STAT3 also regulates COL1A2 protein expression post-transcriptionally, as IL-6 trans-signaling increased protein but not mRNA levels. ChIP assays, STAT3 inhibition/knockdown, TGF-β stimulation assays, RNA polymerase II ChIP, reporter assays Molecular biology of the cell High 29142074
2017 circRNA_000203 acts as a sponge for miR-26b-5p in cardiac fibroblasts, preventing miR-26b-5p from binding the 3'UTR of Col1a2 and CTGF, thereby de-repressing Col1a2 expression and promoting fibrosis. miR-26b-5p directly interacts with 3'UTRs of Col1a2 and CTGF as shown by dual luciferase assay; circRNA_000203 blocks these interactions. RNA pull-down, RT-qPCR, dual luciferase reporter assay, miR-26b-5p transfection Scientific reports Medium 28079129
2019 TBX3 directly binds and activates the COL1A2 promoter, and AKT1 regulates TBX3 levels with pseudo-phosphorylation at an AKT consensus serine site enhancing TBX3 ability to activate COL1A2. COL1A2 mediates the pro-migratory effect of TBX3 in chondrosarcoma cells and anti-migratory effect in fibrosarcoma cells, establishing an AKT1/TBX3/COL1A2 axis in sarcomagenesis. qRT-PCR, Western blotting, luciferase reporter assays, chromatin immunoprecipitation, cell migration assays with knockdown/overexpression Cancer letters Medium 31202624
2022 TWIST1 and EP300 bind the COL1A2 promoter (at an H3K27ac modification site) and synergistically activate COL1A2 expression. Knockdown of EP300 or TWIST1 inhibited COL1A2 expression and promoted sensitivity of gastric cancer cells to apatinib. Chromatin immunoprecipitation, luciferase reporter assays, siRNA knockdown, Western blotting Analytical cellular pathology Medium 35242497
2023 Germline deletion of Col1a2 in mice produces defective type I collagen in the heart, leading to altered ECM mechanical properties, activation of cardiac fibroblasts, TGFβ pathway activation, progressive fibrotic response, and cardiac hypertrophy with reduced functional performance by 9 months. Acute myofibroblast-specific deletion of Col1a2 (via Postn-MerCreMer) reduced total collagen deposition and attenuated pressure overload-induced cardiac hypertrophy acutely. Germline knockout, conditional Cre-mediated deletion (Postn-MerCreMer), microCT, echocardiography, proteomics, TGFβ pathway analysis Cells High 37681905
1992 A mutation at the splice acceptor site of intron 5 (AG to AC) of COL1A2 inactivates the normal splice site and activates a cryptic splice site at +14/+15 of exon 6, causing deletion of 15 nucleotides including the N-proteinase cleavage site from pro-α2(I). The resulting pN-α2(I)' chains retain the N-propeptide and produce abnormal collagen cross-linking in EDS type VIIB. Amino acid sequencing of tryptic peptides, cDNA PCR amplification and sequencing, genomic DNA sequencing The Journal of biological chemistry High 1556139
1989 Point mutations substituting glycine residues in the triple helical domain of pro-α2(I) chain (e.g., Gly865 to Ser in COL1A2) cause lethal perinatal osteogenesis imperfecta, demonstrating the critical importance of the Gly-X-Y repeat for normal collagen helix formation. Chemical mismatch cleavage of mRNA:cDNA heteroduplexes, PCR amplification and sequencing of mismatched regions The Journal of biological chemistry High 2777764
1996 Shortened α2(I) chains from COL1A2 multiexon deletions are incorporated into bone extracellular matrix by osteoblasts but not into the mature collagenous matrix of skin fibroblasts, demonstrating tissue-specific differential incorporation of mutant collagen into the ECM. RT-PCR of α2(I) cDNA, genomic DNA analysis, radiolabeled proline incorporation, SDS-PAGE, long-term fibroblast and osteoblast cultures, collagen extraction from bone and skin The Journal of biological chemistry High 8702873
2015 A novel COL1A2-PDGFB chromosomal translocation fusion gene was identified in one DFSP tumor lacking the canonical COL1A1-PDGFB fusion, demonstrating that COL1A2 regulatory sequences can drive constitutive PDGFB expression in dermatofibrosarcoma protuberans. RT-PCR with gene-specific primers, immunohistochemistry for PDGFB expression, molecular genetic analysis JAMA dermatology Medium 26332510
1999 Two dinucleotide repeats in the COL1A2 gene—one in the 5'-flanking region (poly(dC-dA)/poly(dC-dG)) and one in intron 1 (poly(dG-dT))—act cooperatively as enhancers of COL1A2 transcription. Neither repeat alone increases transcription; specific combinations of repeat alleles produce different transcriptional activities. Luciferase reporter gene assays with constructs containing various allele combinations Gene Medium 10571035
1998 COL1A2 is downstream of RAS and is specifically repressed by EGF-induced transformation, identifying it as a growth repressor regulated by the EGF/EGF receptor signal transduction pathway. Retroviral gene trap strategy selecting for EGF-repressed genes in HER1-expressing NIH3T3 cells The Journal of biological chemistry Medium 9593730
2019 COL1A2 inhibition in glioblastoma cells causes G1 cell cycle arrest by downregulating cyclin D1, CDK1, and CDK4. COL1A2 inhibition decreased Akt phosphorylation, and PI3K inhibitor reduced COL1A2 expression, suggesting COL1A2 acts partially upstream of Akt phosphorylation. siRNA and shRNA knockdown of COL1A2, flow cytometry, Western blotting for cell cycle proteins and pAkt, in vivo xenograft model Journal of neurosurgery Medium 35932265
2017 UV irradiation induces DNA methylation in the COL1A2 promoter at a p300 binding site (-1406/-1393), reducing H3K27 acetylation, p300, and Smad2/3 recruitment to this region. Anacardic acid (p300 HAT inhibitor) reverses UV-induced DNA methylation and restores histone acetylation and transcription factor recruitment at the COL1A2 promoter. Chromatin immunoprecipitation (H3K27ac, p300, Smad2/3), pyrosequencing for DNA methylation, 5-AZA treatment The Journal of investigative dermatology Medium 28237615

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 An AP-1 binding sequence is essential for regulation of the human alpha2(I) collagen (COL1A2) promoter activity by transforming growth factor-beta. The Journal of biological chemistry 277 8621730
2017 CircRNA_000203 enhances the expression of fibrosis-associated genes by derepressing targets of miR-26b-5p, Col1a2 and CTGF, in cardiac fibroblasts. Scientific reports 239 28079129
2000 Synergistic cooperation between Sp1 and Smad3/Smad4 mediates transforming growth factor beta1 stimulation of alpha 2(I)-collagen (COL1A2) transcription. The Journal of biological chemistry 197 11007770
1998 Analysis of the COL1A1 and COL1A2 genes by PCR amplification and scanning by conformation-sensitive gel electrophoresis identifies only COL1A1 mutations in 15 patients with osteogenesis imperfecta type I: identification of common sequences of null-allele mutations. American journal of human genetics 143 9443882
1990 Consistent linkage of dominantly inherited osteogenesis imperfecta to the type I collagen loci: COL1A1 and COL1A2. American journal of human genetics 126 1967900
1999 Nuclear factor-kappa B mediates TNF-alpha inhibitory effect on alpha 2(I) collagen (COL1A2) gene transcription in human dermal fibroblasts. Journal of immunology (Baltimore, Md. : 1950) 102 10201951
2010 Variable bone fragility associated with an Amish COL1A2 variant and a knock-in mouse model. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 92 19594296
2006 Mutation analysis of COL1A1 and COL1A2 in patients diagnosed with osteogenesis imperfecta type I-IV. Human mutation 80 16786509
1989 Characterization of point mutations in the collagen COL1A1 and COL1A2 genes causing lethal perinatal osteogenesis imperfecta. The Journal of biological chemistry 76 2777764
2016 Hypoxia-inducible factor-1α promotes glomerulosclerosis and regulates COL1A2 expression through interactions with Smad3. Kidney international 72 27503806
2011 Cross-platform array screening identifies COL1A2, THBS1, TNFRSF10D and UCHL1 as genes frequently silenced by methylation in melanoma. PloS one 70 22028813
2004 Collagen type I alpha2 (COL1A2) is the susceptible gene for intracranial aneurysms. Stroke 70 14739420
2020 Circular RNA COL1A2 promotes angiogenesis via regulating miR-29b/VEGF axis in diabetic retinopathy. Life sciences 68 32497630
2007 Gene targeting of mutant COL1A2 alleles in mesenchymal stem cells from individuals with osteogenesis imperfecta. Molecular therapy : the journal of the American Society of Gene Therapy 65 17955022
2017 STAT3 controls COL1A2 enhancer activation cooperatively with JunB, regulates type I collagen synthesis posttranscriptionally, and is essential for lung myofibroblast differentiation. Molecular biology of the cell 59 29142074
2004 Transcriptional activation of the type I collagen genes COL1A1 and COL1A2 in fibroblasts by interleukin-4: analysis of the functional collagen promoter sequences. Journal of cellular physiology 59 14603527
2011 The identification of novel mutations in COL1A1, COL1A2, and LEPRE1 genes in Chinese patients with osteogenesis imperfecta. Journal of bone and mineral metabolism 58 21667357
2004 Col1a2 enhancer regulates collagen activity during development and in adult tissue repair. Matrix biology : journal of the International Society for Matrix Biology 55 15062855
1992 Recurrence of lethal osteogenesis imperfecta due to parental mosaicism for a mutation in the COL1A2 gene of type I collagen. The mosaic parent exhibits phenotypic features of a mild form of the disease. Human mutation 53 1301191
2006 Transcriptional regulation of the human alpha2(I) collagen gene (COL1A2), an informative model system to study fibrotic diseases. Matrix biology : journal of the International Society for Matrix Biology 52 16815696
2004 Major histocompatibility class II transactivator (CIITA) mediates repression of collagen (COL1A2) transcription by interferon gamma (IFN-gamma). The Journal of biological chemistry 50 15247294
2018 The inhibitory effects of COL1A2 on colorectal cancer cell proliferation, migration, and invasion. Journal of Cancer 49 30123364
2002 The RFX family interacts at the collagen (COL1A2) start site and represses transcription. The Journal of biological chemistry 49 11986307
2008 Global analysis of the medulloblastoma epigenome identifies disease-subgroup-specific inactivation of COL1A2. Neuro-oncology 47 18664619
2015 A Novel Chromosomal Translocation Associated With COL1A2-PDGFB Gene Fusion in Dermatofibrosarcoma Protuberans: PDGF Expression as a New Diagnostic Tool. JAMA dermatology 46 26332510
2006 Regulatory factor for X-box family proteins differentially interact with histone deacetylases to repress collagen alpha2(I) gene (COL1A2) expression. The Journal of biological chemistry 45 16464847
2005 S-adenosylmethionine blocks collagen I production by preventing transforming growth factor-beta induction of the COL1A2 promoter. The Journal of biological chemistry 45 15983038
1999 Transcriptional regulation of the human type I collagen alpha2 (COL1A2) gene by the combination of two dinucleotide repeats. Gene 45 10571035
1996 Multiexon deletions in the type I collagen COL1A2 gene in osteogenesis imperfecta type IB. Molecules containing the shortened alpha2(I) chains show differential incorporation into the bone and skin extracellular matrix. The Journal of biological chemistry 44 8702873
1988 The gene CYP3 encoding P450pcn1 (nifedipine oxidase) is tightly linked to the gene COL1A2 encoding collagen type 1 alpha on 7q21-q22.1. American journal of human genetics 42 2901225
2021 LncRNA LIFR-AS1 promotes proliferation and invasion of gastric cancer cell via miR-29a-3p/COL1A2 axis. Cancer cell international 41 33407453
2001 Characterization of an evolutionarily conserved far-upstream enhancer in the human alpha 2(I) collagen (COL1A2) gene. The Journal of biological chemistry 41 11279244
1998 Gene trapping identifies inhibitors of oncogenic transformation. The tissue inhibitor of metalloproteinases-3 (TIMP3) and collagen type I alpha2 (COL1A2) are epidermal growth factor-regulated growth repressors. The Journal of biological chemistry 41 9593730
2016 Skeletal phenotypes in adult patients with osteogenesis imperfecta-correlations with COL1A1/COL1A2 genotype and collagen structure. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 39 27256333
2011 Interstitial fibrosis is associated with increased COL1A2 transcription in AA-injured renal tubular epithelial cells in vivo. Matrix biology : journal of the International Society for Matrix Biology 39 21864682
2001 Thirty-three novel COL1A1 and COL1A2 mutations in patients with osteogenesis imperfecta types I-IV. Human mutation 39 11317364
2017 COL1A2 is a Novel Biomarker to Improve Clinical Prediction in Human Gastric Cancer: Integrating Bioinformatics and Meta-Analysis. Pathology oncology research : POR 38 28401451
2017 Mutational analysis of COL1A1 and COL1A2 genes among Estonian osteogenesis imperfecta patients. Human genomics 38 28810924
2016 Mutation analysis of the COL1A1 and COL1A2 genes in Vietnamese patients with osteogenesis imperfecta. Human genomics 38 27519266
2011 Hypermethylation of collagen α2 (I) gene (COL1A2) is an independent predictor of survival in head and neck cancer. Cancer biomarkers : section A of Disease markers 37 22674299
1986 Marfan syndrome: exclusion of genetic linkage to the COL1A2 gene. Clinical genetics 37 2879657
2017 LncRNA COL1A2-AS1 inhibits the scar fibroblasts proliferation via regulating miR-21/Smad7 pathway. Biochemical and biophysical research communications 35 29117538
2002 Halofuginone inhibition of COL1A2 promoter activity via a c-Jun-dependent mechanism. Arthritis and rheumatism 35 12384935
1992 A base substitution at the splice acceptor site of intron 5 of the COL1A2 gene activates a cryptic splice site within exon 6 and generates abnormal type I procollagen in a patient with Ehlers-Danlos syndrome type VII. The Journal of biological chemistry 35 1556139
2012 SIRT1 deacetylates RFX5 and antagonizes repression of collagen type I (COL1A2) transcription in smooth muscle cells. Biochemical and biophysical research communications 33 23079621
2004 Proposed association between the COL1A1 and COL1A2 genes and otosclerosis is not supported by a case-control study in Spain. American journal of medical genetics. Part A 33 15211650
2003 Interferon gamma repression of collagen (COL1A2) transcription is mediated by the RFX5 complex. The Journal of biological chemistry 33 12968017
2019 A feature-based analysis identifies COL1A2 as a regulator in pancreatic cancer. Journal of enzyme inhibition and medicinal chemistry 32 30734598
1991 Exclusion of COL1A1, COL1A2, and COL3A1 genes as candidate genes for Ehlers-Danlos syndrome type I in one large family. Human genetics 32 1684560
1998 A proximal element within the human alpha 2(I) collagen (COL1A2) promoter, distinct from the tumor necrosis factor-alpha response element, mediates transcriptional repression by interferon-gamma. Matrix biology : journal of the International Society for Matrix Biology 31 9550262
2016 Bone mineral properties in growing Col1a2(+/G610C) mice, an animal model of osteogenesis imperfecta. Bone 29 27083399
2015 Two Rare Mutations in the COL1A2 Gene Associate With Low Bone Mineral Density and Fractures in Iceland. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 29 26235824
2009 RFXB and its splice variant RFXBSV mediate the antagonism between IFNgamma and TGFbeta on COL1A2 transcription in vascular smooth muscle cells. Nucleic acids research 29 19465385
2001 Canine COL1A2 mutation resulting in C-terminal truncation of pro-alpha2(I) and severe osteogenesis imperfecta. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 29 11393792
2022 Bisphenol S promotes the progression of prostate cancer by regulating the expression of COL1A1 and COL1A2. Toxicology 28 35405288
2022 COL1A2 inhibition suppresses glioblastoma cell proliferation and invasion. Journal of neurosurgery 27 35932265
2009 JunB mediates enhancer/promoter activity of COL1A2 following TGF-beta induction. Nucleic acids research 27 19561194
2020 Colorectal cancer screening: Assessment of CEACAM6, LGALS4, TSPAN8 and COL1A2 as blood markers in faecal immunochemical test negative subjects. Journal of advanced research 26 32257432
2019 A novel mutation in COL1A2 leads to osteogenesis imperfecta/Ehlers-Danlos overlap syndrome with brachydactyly. Genes & diseases 25 31193991
2018 Mutations in the COL1A1 and COL1A2 genes associated with osteogenesis imperfecta (OI) types I or III. Acta biochimica Polonica 25 29543922
2017 Amplified 7q21-22 gene MCM7 and its intronic miR-25 suppress COL1A2 associated genes to sustain intestinal gastric cancer features. Molecular carcinogenesis 25 28059478
2014 Mutation spectrum of COL1A1 and COL1A2 genes in Indian patients with osteogenesis imperfecta. American journal of medical genetics. Part A 25 24668929
2022 STAT4 and COL1A2 are potential diagnostic biomarkers and therapeutic targets for heart failure comorbided with depression. Brain research bulletin 24 35367598
2012 Novel PAX9 and COL1A2 missense mutations causing tooth agenesis and OI/DGI without skeletal abnormalities. PloS one 24 23227268
2003 Tests of linkage and association of the COL1A2 gene with bone phenotypes' variation in Chinese nuclear families. Bone 24 14555266
1986 Linkage of cystic fibrosis to the pro alpha 2(I) collagen gene, COL1A2, on chromosome 7. Cytogenetics and cell genetics 24 3011363
2022 Radiation increases COL1A1, COL3A1, and COL1A2 expression in breast cancer. Open medicine (Warsaw, Poland) 23 35274048
2019 Cardiac valvular Ehlers-Danlos syndrome is a well-defined condition due to recessive null variants in COL1A2. American journal of medical genetics. Part A 23 30821104
2021 MicroRNA-513b-5p targets COL1A1 and COL1A2 associated with the formation and rupture of intracranial aneurysm. Scientific reports 22 34290266
2019 COL1A2 is a TBX3 target that mediates its impact on fibrosarcoma and chondrosarcoma cell migration. Cancer letters 21 31202624
2014 Sp7/Osterix induces the mouse pro-α2(I) collagen gene (Col1a2) expression via the proximal promoter in osteoblastic cells. Biochemical and biophysical research communications 21 25172663
2006 Extracellular matrix containing mutated fibrillin-1 (Fbn1) down regulates Col1a1, Col1a2, Col3a1, Col5a1, and Col5a2 mRNA levels in Tsk/+ and Tsk/Tsk embryonic fibroblasts. Amino acids 21 16583319
2000 Association of functional microsatellites in the human type I collagen alpha2 chain (COL1A2) gene with systemic sclerosis. Biochemical and biophysical research communications 21 10872800
2000 Partial COL1A2 gene duplication produces features of osteogenesis imperfecta and Ehlers-Danlos syndrome type VII. Human genetics 21 10982177
2023 Col1a2-Deleted Mice Have Defective Type I Collagen and Secondary Reactive Cardiac Fibrosis with Altered Hypertrophic Dynamics. Cells 20 37681905
2016 Clinical characteristics and the identification of novel mutations of COL1A1 and COL1A2 in 61 Chinese patients with osteogenesis imperfecta. Molecular medicine reports 20 27748872
2022 TGF-β2-induced circ-PRDM5 regulates migration, invasion, and EMT through the miR-92b-3p/COL1A2 pathway in human lens epithelial cells. Journal of molecular histology 19 35083632
2022 TWIST1-EP300 Expedites Gastric Cancer Cell Resistance to Apatinib by Activating the Expression of COL1A2. Analytical cellular pathology (Amsterdam) 19 35242497
2021 Rare functional genetic variants in COL7A1, COL6A5, COL1A2 and COL5A2 frequently occur in Chiari Malformation Type 1. PloS one 18 33974636
2016 Identification of a p.Arg708Gln variant in COL1A2 in atypical femoral fractures. Joint bone spine 18 28017821
2013 Analysis of the association between an insertion/deletion polymorphism within the 3' untranslated region of COL1A2 and chronic venous insufficiency. Annals of vascular surgery 18 23849651
2015 Collagenase 1A2 (COL1A2) gene A/C polymorphism in relation to severity of dental fluorosis. Community dentistry and oral epidemiology 17 26564713
2022 Single-cell transcriptomics identifies Col1a1 and Col1a2 as hub genes in obesity-induced cardiac fibrosis. Biochemical and biophysical research communications 16 35714568
2019 lnc-SAMD14-4 can regulate expression of the COL1A1 and COL1A2 in human chondrocytes. PeerJ 16 31534838
2017 Inhibition of DNA Methylation in the COL1A2 Promoter by Anacardic Acid Prevents UV-Induced Decrease of Type I Procollagen Expression. The Journal of investigative dermatology 16 28237615
2017 Characterization of Mesenchymal-Fibroblast Cells Using the Col1a2 Promoter/Enhancer. Methods in molecular biology (Clifton, N.J.) 16 28836200
2005 GATA-4 binds to an upstream element of the human alpha2(I) collagen gene (COL1A2) and inhibits transcription in fibroblasts. Matrix biology : journal of the International Society for Matrix Biology 16 15982862
2018 Dental fluorosis and a polymorphism in the COL1A2 gene in Mexican children. Archives of oral biology 15 30172079
2017 Collagen Type I Alpha 2 (COL1A2) Polymorphism Contributes to Intracranial Aneurysm Susceptibility: A Meta-Analysis. Medical science monitor : international medical journal of experimental and clinical research 15 28671939
2008 Polymorphism rs42524 of COL1A2 and sporadic intracranial aneurysms in the Chinese population. Journal of neurosurgery 15 19035720
2005 Identification of a repressor in the first intron of the human alpha2(I) collagen gene (COL1A2). The Journal of biological chemistry 15 16091368
2004 Cooperativity between far upstream enhancer and proximal promoter elements of the human {alpha}2(I) collagen (COL1A2) gene instructs tissue specificity in transgenic mice. The Journal of biological chemistry 15 15516691
1994 EcoRI, RsaI, and MspI RFLPs of the COL1A2 gene (type I collagen) in the Cayapa, a Native American population of Ecuador. Human biology 15 7835877
2023 Circular RNA COL1A2 Mediates High Glucose-Induced Oxidative Stress and Pyroptosis by Regulating MiR-424-5p/SGK1 in Diabetic Nephropathy. Applied biochemistry and biotechnology 14 37079269
2011 A novel DHPLC-based procedure for the analysis of COL1A1 and COL1A2 mutations in osteogenesis imperfecta. The Journal of molecular diagnostics : JMD 14 21884818
2019 Mutation spectrum of COL1A1/COL1A2 screening by high-resolution melting analysis of Chinese patients with osteogenesis imperfecta. Journal of bone and mineral metabolism 13 31414283
2018 Bone Marrow Transplantation for Treatment of the Col1a2+/G610C Osteogenesis Imperfecta Mouse Model. Calcified tissue international 13 30535573
2016 Influence of COL1A2 gene variants on the incidence of hypertensive intracerebral hemorrhage in a Chinese population. Genetics and molecular research : GMR 13 26910001
2008 Allele dependent silencing of COL1A2 using small interfering RNAs. International journal of medical sciences 13 19015742
1997 Mutation producing alternative splicing of exon 26 in the COL1A2 gene causes type IV osteogenesis imperfecta with intrafamilial clinical variability. American journal of medical genetics 13 9268111