COL1A1 (collagen, type I, alpha 1)

2001-02-01   Marie-Pierre Simon , Georges Maire , Florence Pedeutour 

Laboratoire de Genetique, Hopital de lArchet, 151 route de Saint Antoine de Ginestiere BP 3079, 06202 Nice Cedex 3, France

Identity

HGNC
LOCATION
17q21.33
IMAGE
Atlas Image
LEGEND
COL1A1 (17q21) - Courtesy Mariano Rocchi, Resources for Molecular Cytogenetics.
LOCUSID
ALIAS
CAFYD,EDSARTH1,EDSC,OI1,OI2,OI3,OI4
FUSION GENES

DNA/RNA

Atlas Image

Description

The COL1A1 gene is 18 kb in size and is composed of 52 exons. Exons 6 to 49 encode the alpha helical domain. Most of these exons were 45 bp, 54 bp or multiple of 45 bp or 54 bp

Transcription

Two RNA of 5,8 kb and 4,8 kb differing by their 3 terminus non coding sequence and giving rise to a single 140 kDa protein

Proteins

Atlas Image

Description

1464 amino acids. The a1 (I) chains of the type I collagen are synthesised as procollagen molecules containing amino and carboxy-terminal propeptides, wich are removed by site-specific endopeptidase. The central triple helical domain is formed by 338 repeats of a Gly-X-Y triplet where X and Y are often a proline.

Expression

Type I collagen is the most abundant protein in vertebrates and a constituent of the extra cellular matrix in connective tissue of bone, skin, tendon, ligament and dentine. It is mostly produced and secreted by fibroblasts and osteoblasts.

Localisation

Extra-cellular matrix

Function

Two pro a1 (I) chain associate in trimers with one pro a2 (I) chain to form the type I collagen fibrils after proteolysis.

Homology

Member of the collagen family.

Implicated in

Entity name
  • Dermatofibrosarcoma Protuberans (DP), also called Darier Ferrand tumour or Darier-Hoffmann tumour. , 
  • Giant cell fibrosarcoma (GCF) (juvenile form of DP). , 
  • Bednar tumour (pigmented variant of DP)
  • Disease
    Infiltrative skin tumours of intermediate malignancy
    Prognosis
    The prognosis is usually favourable. These tumours are locally aggressive and highly recurrent, but metastases or tumour-related deaths are extremely rare.
    Cytogenetics
    Dermatofibrosarcoma Protuberans, Giant Cell fibrosarcoma and Bednar tumours present specific cytogenetic features such as reciprocal translocations t(17;22)(q22;q13.1) ( Fig A) or, more often, supernumerary ring chromosomes derived from t(17;22) (B). As shown by FISH analysis, the ring chromosomes contain chromosome 22 centromere and low-level amplification of 22cen-q13.1 and 17q22-qter sequences. To note, in most cases, the derivative chromosome 17 is not present. In contrast, several copies of the derivative chromosome 22 are generally observed.in addition to two apparently normal chromosomes 17
    Hybrid gene
  • Both rings and der(22) translocated chromosomes present a same molecular rearrangement that fuses the collagen type I alpha 1(COL1A1) and the platelet-derived growth factor B chain (PDGFB) genes (C).
  • In all DP and GCF cases studied, the t(17;22)translocation results in chimerical COL1A1/PDGFB mRNA production, in which the PDGFB exon 1 is deleted and replaced by a variable segment of COL1A1 mRNA sequence. In the 32 cases tested the fusion mRNA was an in-frame fusion of one of the COL1A1 exons (varying from exon 7 to exon 47) to PDGFB exon 2 (D).
  • Atlas Image
    Fusion protein
  • COL1A1 and PDGFB are both encoded as pro-peptides, which are processed by proteolytic cleavage at N and C-terminus, to give mature proteins. Sequences analyses of the chimerical COL1A1/PDGFB fusion transcripts showed that the COL1A1/PDGFB putative proteins displayed a pro-peptide structure, which preserved the N-terminus COL1A1 pro-peptide containing the signal peptide and the N and C-terminus PDGFB maturation cleavage sites.
  • The functional and structural properties of the COL1A1/PDGFB fusion protein were characterized by generating stable fibroblastic cell lines that expressed tumour-derived COL1A1/PDGFB chimerical genes. The diagram herein given presents the COL1A1/PDGFB chimerical protein encoded by the T94796 tumour-derived chimerical COL1A1/PDGFB cDNA sequence
  • Atlas Image
    A chimerical COL1A1/PDGFB cDNA sequence fusing COL1A1 exon 29 to PDGFB exon 2 was isolated from the DP T94796 tumour and stably transfected in the Chinese hamster lung fibroblastic cell line PS200 (E).
    The T94796 COL1A1/PDGFB chimerical protein sequence retained the COL1A1 N-terminus processing site encoded by the COL1A1 exon 6 and the N and C-terminus PDGFB processing sites encoded by the PDGFB exons 3 and 6 respectively (F).
    Mutagenesis experiments and immunodetection with anti-PDGFBB and specific anti-COL1A1/PDGFB antibodies showed that COL1A1/PDGFB expressing cells produced 116 kD chimerical COL1A1/PDGFB precursors chains, which formed dimers and were processed to give active 30 kD PDGFB-like dimers (G).
    Oncogenesis
  • Transfected cells lines expressing the chimerical T94796-COL1A1/PDGFB proteins became independent upon growth factors, including PDGFB, and induced tumours formation in nude mice. In addition, it was shown that the COL1A1/PDGFB stable clones cells contained activated PDGF b-receptors and that the conditioned media from COL1A1/PDGFB transfected cells were able to stimulate fibroblastic cells growth. Anti-PDGFBB antibodies neutralized this effect.
  • These results strongly suggest that the COL1A1/PDGFB chimerical gene expression associated with DP, contributes to tumour formation through ectopic production of mature PDGFB and the formation of an autocrine loop.
  • Breakpoints

    Atlas Image
    Atlas Image

    Bibliography

    Pubmed IDLast YearTitleAuthors
    22380871990Brittle bones--fragile molecules: disorders of collagen gene structure and expression.Byers PH et al
    90165321997The human type I collagen mutation database.Dalgleish R et al
    85997391996Soft tissue sarcomas in dermatology.Fish FS et al
    97719751998Transforming activity of the chimeric sequence formed by the fusion of collagen gene COL1A1 and the platelet derived growth factor b-chain gene in dermatofibrosarcoma protuberans.Greco A et al
    95917281998Fibrosarcomatous ("high-grade") dermatofibrosarcoma protuberans: clinicopathologic and immunohistochemical study of a series of 41 cases with emphasis on prognostic significance.Mentzel T et al
    97905081998COL1A1-PDGFB fusion in a ring chromosome 4 found in a dermatofibrosarcoma protuberans.Navarro M et al
    111702902001Supernumerary ring chromosome in a Bednar tumor (pigmented dermatofibrosarcoma protuberans) is composed of interspersed sequences from chromosomes 17 and 22: a fluorescence in situ hybridization and comparative genomic hybridization analysis.Nishio J et al
    97390231998Various regions within the alpha-helical domain of the COL1A1 gene are fused to the second exon of the PDGFB gene in dermatofibrosarcomas and giant-cell fibroblastomas.O'Brien KP et al
    89787651996Translocation, t(17;22)(q22;q13), in dermatofibrosarcoma protuberans: a new tumor-associated chromosome rearrangement.Pedeutour F et al
    104469871999The dermatofibrosarcoma protuberans-associated collagen type Ialpha1/platelet-derived growth factor (PDGF) B-chain fusion gene generates a transforming protein that is processed to functional PDGF-BB.Shimizu A et al
    114207092001Structural and functional analysis of a chimeric protein COL1A1-PDGFB generated by the translocation t(17;22)(q22;q13.1) in Dermatofibrosarcoma protuberans (DP).Simon MP et al
    89881771997Deregulation of the platelet-derived growth factor B-chain gene via fusion with collagen gene COL1A1 in dermatofibrosarcoma protuberans and giant-cell fibroblastoma.Simon MP et al
    105656811999Detection of COL1A1-PDGFB fusion transcripts in dermatofibrosarcoma protuberans by reverse transcription-polymerase chain reaction using archival formalin-fixed, paraffin-embedded tissues.Wang J et al

    Other Information

    Locus ID:

    NCBI: 1277
    MIM: 120150
    HGNC: 2197
    Ensembl: ENSG00000108821

    Variants:

    dbSNP: 1277
    ClinVar: 1277
    TCGA: ENSG00000108821
    COSMIC: COL1A1

    RNA/Proteins

    Gene IDTranscript IDUniprot
    ENSG00000108821ENST00000225964P02452
    ENSG00000108821ENST00000507689I3L3H7

    Expression (GTEx)

    0
    500
    1000
    1500
    2000
    2500
    3000
    3500
    4000

    Pathways

    PathwaySourceExternal ID
    Focal adhesionKEGGko04510
    ECM-receptor interactionKEGGko04512
    Focal adhesionKEGGhsa04510
    ECM-receptor interactionKEGGhsa04512
    AmoebiasisKEGGko05146
    AmoebiasisKEGGhsa05146
    Protein digestion and absorptionKEGGko04974
    Protein digestion and absorptionKEGGhsa04974
    PI3K-Akt signaling pathwayKEGGhsa04151
    PI3K-Akt signaling pathwayKEGGko04151
    Platelet activationKEGGhsa04611
    Vesicle-mediated transportREACTOMER-HSA-5653656
    Binding and Uptake of Ligands by Scavenger ReceptorsREACTOMER-HSA-2173782
    Scavenging by Class A ReceptorsREACTOMER-HSA-3000480
    Extracellular matrix organizationREACTOMER-HSA-1474244
    Collagen formationREACTOMER-HSA-1474290
    Collagen biosynthesis and modifying enzymesREACTOMER-HSA-1650814
    Assembly of collagen fibrils and other multimeric structuresREACTOMER-HSA-2022090
    AGE-RAGE signaling pathway in diabetic complicationsKEGGko04933
    AGE-RAGE signaling pathway in diabetic complicationsKEGGhsa04933
    Collagen chain trimerizationREACTOMER-HSA-8948216

    Protein levels (Protein atlas)

    Not detected
    Low
    Medium
    High

    PharmGKB

    Entity IDNameTypeEvidenceAssociationPKPDPMIDs
    PA179GP1BBGenePathwayassociated20938371
    PA204ITGA2GenePathwayassociated20938371
    PA26212CD36GenePathwayassociated20938371
    PA28823GP5GenePathwayassociated20938371
    PA28824GP6GenePathwayassociated20938371
    PA28825GP9GenePathwayassociated20938371
    PA444065EpilepsyDiseaseClinicalAnnotationassociatedPD26727275
    PA445190OsteoporosisDiseaseVariantAnnotationassociated8841196
    PA451446somatropin recombinantChemicalClinicalAnnotationassociatedPD22026923
    PA451846valproic acidChemicalClinicalAnnotationassociatedPD26727275

    References

    Pubmed IDYearTitleCitations
    167237012006Decreased collagen production in chronologically aged skin: roles of age-dependent alteration in fibroblast function and defective mechanical stimulation.114
    222492492012Candidate DNA methylation drivers of acquired cisplatin resistance in ovarian cancer identified by methylome and expression profiling.86
    199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
    186695832008Gene expression profiling identifies genes predictive of oral squamous cell carcinoma.80
    170282622007Prostaglandin E(2) inhibits collagen expression and proliferation in patient-derived normal lung fibroblasts via E prostanoid 2 receptor and cAMP signaling.67
    203796142010Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.62
    199134962010Suppression of type I collagen production by microRNA-29b in cultured human stellate cells.55
    204891572010Metastatic outgrowth encompasses COL-I, FN1, and POSTN up-regulation and assembly to fibrillar networks regulating cell adhesion, migration, and growth.47
    217468802011A novel role of vimentin filaments: binding and stabilization of collagen mRNAs.45
    171797262007Candidate-gene association study of mothers with pre-eclampsia, and their infants, analyzing 775 SNPs in 190 genes.44

    Citation

    Marie-Pierre Simon ; Georges Maire ; Florence Pedeutour

    COL1A1 (collagen, type I, alpha 1)

    Atlas Genet Cytogenet Oncol Haematol. 2001-02-01

    Online version: http://atlasgeneticsoncology.org/gene/186/col1a1