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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

CST6 Gene

protein-coding   GIFtS: 52
GCID: GC11P065779

cystatin E/M

 Explore 20 diseases affiliated with
CST6 via our new
 Human Malady Compendium 
Biological research products
for CST6
    

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section

Aliases
Cystatin E/M1 2     Cystatin-E3
Cystatin 62     Cystatin-M1
Cystatin M2     Cysteine Proteinase Inhibitor2
Cystatin M/E2     Cystatin-63
Cystatin-63     Cystatin-E3

External Ids:    HGNC: 24781   Entrez Gene: 14742   Ensembl: ENSG000001753157   OMIM: 6018915   UniProtKB: Q158283   

Export aliases for CST6 gene to outside databases

Previous GC identifers: GC11P068313 GC11P067460 GC11P066029 GC11P065554 GC11P065536 GC11P062105


(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for CST6:
The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are
active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There
are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and the
kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human
fluids and secretions, where they appear to provide protective functions. This gene encodes a cystatin from the type 2
family, which is down-regulated in metastatic breast tumor cells as compared to primary tumor cells. Loss of
expression is likely associated with the progression of a primary tumor to a metastatic phenotype. (provided by
RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: CYTM_HUMAN, Q15828
Function: Shows moderate inhibition of cathepsin B but is not active against cathepsin C

Gene Wiki entry for CST6


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000011.9  NC_018922.1  NT_167190.1  
Regulatory elements:
   SABiosciences Regulatory transcription factor binding sites in the CST6 gene promoter:
         NF-1   NF-1/L   E47   RORalpha1   STAT3   Hand1   c-Myb   FOXO1a   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): CST6 promoter sequence
   Search SABiosciences Chromatin IP Primers for CST6

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat CST6


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 11q13   Ensembl cytogenetic band:  11q13.1   HGNC cytogenetic band: 11q13

CST6 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CST6 gene location

GeneLoc information about chromosome 11         GeneLoc Exon Structure

GeneLoc location for GC11P065779:  view genomic region     (about GC identifiers)

Start:
65,779,312 bp from pter      End:
65,780,976 bp from pter
Size:
1,665 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: CYTM_HUMAN, Q15828 (See protein sequence)
Recommended Name: Cystatin-M precursor  
Size: 149 amino acids; 16511 Da
Subcellular location: Secreted
Secondary accessions: Q540N7

Explore the universe of human proteins at neXtProt for CST6: NX_Q15828

Post-translational modifications:

  • Substrate for transglutaminases. Acts as an acyl acceptor but not as an acyl donor1
  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_Q15828

  • CST6 Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

    REFSEQ proteins: NP_001314.1  
    ENSEMBL proteins: 
     ENSP00000311313  

    Human Recombinant Protein Products: 
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    Sino Biological Recombinant Protein for CST6
    ProSpec Recombinant Protein for CST6
    Uscn Proteins for CST6

    Gene Ontology (GO): 2 cellular component terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001533cornified envelope IEA--
    GO:0005576extracellular region IEA--


    CST6 for ontologies           About GeneDecksing



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    Uscn ELISAs and CLIAs for CST6


    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section

    CST6 for domains           About GeneDecksing

    3 InterPro domains/families:
     IPR018073 Prot_inh_cystat_CS
     IPR000010 Prot_inh_cystat
     IPR027214 Cystatin

    Graphical View of Domain Structure for InterPro Entry Q15828

    ProtoNet protein and cluster: Q15828

    2 Blocks protein families:
    IPB000010 Cysteine protease inhibitor
    IPB003243 Proteinase inhibitor I25A and I25B


    UniProtKB/Swiss-Prot: CYTM_HUMAN, Q15828
    Similarity: Belongs to the cystatin family


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section

    Function Summary:

         UniProtKB/Swiss-Prot: CYTM_HUMAN, Q15828
    Function: Shows moderate inhibition of cathepsin B but is not active against cathepsin C

         Genatlas biochemistry entry for CST6:
    cystatin M,member of type 2 cystatin gene family,found at high levels in saliva,tears,seminal plasma,type 2 family

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    Search Advanced Cell Diagnostics for RNAscope RNA in situ hybridization assays for CST6

    Gene Ontology (GO): 1 molecular function term (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004869cysteine-type endopeptidase inhibitor activity IEA--


    CST6 for ontologies           About GeneDecksing


    Animal Models:
         5 MGI mutant phenotypes (inferred from 1 allele(MGI details for Cst6):
     cellular  endocrine/exocrine gland  growth/size  integument  mortality/aging 

    CST6 for phenotypes           About GeneDecksing


    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
    About This Section



    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for CST6

    STRING Interaction Network Preview (showing 1 interactants - click image to see more details)

    3 Interacting proteins for CST6 (Q158282, 3 ENSP000003113134) via UniProtKB, MINT, STRING, and/or I2D
    InteractantInteraction Details
    GeneCardExternal ID(s)
    GSK3BP498412, 3MINT-8257053 I2D: score=2 
    PRKAB1Q9Y4783I2D: score=1 
    VHLENSP000002564744STRING: ENSP00000256474
    About this table

    Gene Ontology (GO): 2 biological process terms (GO ID links to tree view):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0008544epidermis development IEA--
    GO:0009653anatomical structure morphogenesis TAS9099741


    CST6 for ontologies           About GeneDecksing



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    CST6 for compounds           About GeneDecksing

    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Browse Tocris compounds for CST6
    4 Novoseek chemical compound relationships for CST6 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    cysteine 69.8 25 9099741 (3), 16150465 (3), 14676833 (2), 12839564 (1) (see all 17)
    5-aza-2'deoxycytidine 62.4 5 17043665 (1), 17099723 (1), 16912163 (1)
    matrigel 57.6 6 20074384 (2), 19503093 (1), 14676833 (1), 15466187 (1)
    kininogen 54.5 1 9099741 (1)

    Search CenterWatch for drugs/clinical trials and news about CST6 / CYTM 

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section

    REFSEQ mRNAs for CST6 gene: 
    NM_001323.3  

    Unigene Cluster for CST6:

    Cystatin E/M
    Hs.139389  [show with all ESTs]
    Unigene Representative Sequence: AK092391
    1 Ensembl transcript including schematic representation, and UCSC links where relevant:
    ENST00000312134(uc001ogr.3)

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    Inhib. RNA
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    Clone
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    Additional cDNA sequence: 

    AK092391.1 BC031334.1 CR456872.1 U62800.1 U81233.1 

    2 DOTS entries:

    DT.114401  DT.120738888 

    24/72 AceView cDNA sequences (see all 72):

    AI188465 AI333946 AA128615 BC031334 AW129328 AA418973 BE503775 AI198474 
    NM_001323 AI916287 BM761733 AI127958 BF765573 AA778147 BF198119 AI743831 
    CF529874 W58171 W56781 AI885674 AK092391 U62800 BX118301 AI431604 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    CST6 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: GTGGAGGGCA

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)

    About this image
    See CST6 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for CST6

    SOURCE GeneReport for Unigene cluster: Hs.139389

    UniProtKB/Swiss-Prot: CYTM_HUMAN, Q15828
    Tissue specificity: Restricted to the stratum granulosum of normal skin, the stratum granulosum/spinosum of psoriatic
    skin, and the secretory coils of eccrine sweat glands. Low expression levels are found in the nasal cavity

        SABiosciences Expression via Pathway-Focused PCR Array including CST6: 
              Breast Cancer in human mouse rat

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    In Situ
    Assay Products:
     

     
    Search Advanced Cell Diagnostics for RNAscope RNA in situ hybridization assays for CST6

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
    About This Section

    This gene was present in the common ancestor of chordates.

    Orthologs for CST6 gene from 1/8 species (see all 8)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    lizard
    (Anolis carolinensis)
    Reptilia CST66
    --
    41(a)
    1 ↔ 1
    GL343575.1(314864-329707)


    ENSEMBL Gene Tree for CST6 (if available)
    TreeFam Gene Tree for CST6 (if available) 

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for CST6 gene
    CST42  CST22  CST82  CSTL12  CST72  CST12  CST32  CST52  
    CST112  
    8 SIMAP similar genes for CST6 using alignment to 2 protein entries:     CYTM_HUMAN (see all proteins):
    CSTL1    CST3    CST5    CST2    CST7    CST1
    CST8    CST4

    CST6 for paralogs           About GeneDecksing



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/73 NCBI SNPs in CST6 are shown (see all 73    About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 11 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1874603381,2
    --65777539(+) TCAGCA/GTTCCA 1 -- us2k10--------
    rs6156461,2
    C,--65777544(-) TTCAGC/TGGAAT 1 -- us2k18Minor allele frequency- T:0.14NA WA CSA 133
    rs71136611,2
    C,--65777665(+) tccctA/Gaagtt 1 -- us2k10--------
    rs1905701591,2
    --65777746(+) TGACCA/GACAAT 1 -- us2k10--------
    rs790775461,2
    C,--65777754(+) AATTAA/CCTGAC 1 -- us2k10--------
    rs1871334871,2
    --65777782(+) TCCCCC/GTTTCT 1 -- us2k10--------
    rs1479827961,2
    C,--65777899(+) GTCTC-/TTGTCTT 1 -- us2k10--------
    rs1919147871,2
    --65777921(+) GTTTGC/TCCGGC 1 -- us2k10--------
    rs1478549631,2
    --65777936(+) TTCAGA/TCCCCC 1 -- us2k10--------
    rs1827096701,2
    --65777975(+) CACCAG/TGTTGG 1 -- us2k10--------

    HapMap Linkage Disequilibrium report for CST6 (65779312 - 65780976 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
          Database of Genomic Variants (DGV) variations for CST6: --

    SABiosciences Cancer Mutation PCR Assays
    QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing CST6
    DNA2.0 Custom Variant and Variant Library Synthesis for CST6

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

    CST6 for disorders           About GeneDecksing

    OMIM gene information: 601891    OMIM disorders: --

    20 diseases for CST6:    About MalaCards
    ichthyosis    atopic dermatitis    papillary thyroid carcinoma    squamous cell carcinoma
    thyroid carcinoma    breast cancer    dermatitis    breast carcinoma
    oral cancer    thyroiditis    cervical cancer    carcinoma
    cervicitis    psoriasis    pancreatic cancer    lung cancer
    prostate cancer    pancreatitis    prostatitis    melanoma

    10 Novoseek disease relationships for CST6 gene    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    harlequin ichthyosis 84.3 7 12839564 (4), 15044380 (1)
    primary tumor 51.2 13 17540367 (4), 12798398 (2), 15466187 (1), 20004178 (1) (see all 6)
    breast cancer metastatic 42.3 4 17043665 (1), 15792117 (1), 17540367 (1)
    breast cancer 40.7 31 17043665 (5), 19551853 (4), 15466187 (3), 17099723 (3) (see all 10)
    breast carcinoma 36.3 12 17099723 (6), 14676833 (1), 16912163 (1), 15792117 (1)
    metastasis 34.7 16 17540367 (4), 12798398 (2), 15466187 (2), 19503093 (1) (see all 6)
    premalignant 31.2 3 17043665 (1), 14676833 (1)
    tumors 30 43 19551853 (5), 16912163 (4), 17540367 (3), 15466187 (3) (see all 14)
    nsclc 14.4 1 17043644 (1)
    cancer 7.65 3 14676833 (1), 17099723 (1), 16912163 (1)


    Export disorders for CST6 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
    About This Section

    PubMed articles for CST6 gene, integrated from 9 sources (see all 50):
    (articles sorted by number of sources associating them with CST6)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Cystatin E is a novel human cysteine proteinase inhibitor with structural resemblance to family 2 cystatins. (PubMed id 9099741)1, 2, 3, 9 Ni J.... Gentz R. (1997)
    2. The human cystatin M/E gene (CST6): exclusion candidate gene for harlequin ichthyosis. (PubMed id 12839564)1, 2, 9 Zeeuwen P.L.... Schalkwijk J. (2003)
    3. Cystatin M/E expression is restricted to differentiated epidermal keratinocytes and sweat glands: a new skin-specific proteinase inhibitor that is a target for cross-linking by transglutaminase. (PubMed id 11348457)1, 2, 9 Zeeuwen P.L.... Schalkwijk J. (2001)
    4. Identification, cloning, and characterization of cystatin M, a novel cysteine proteinase inhibitor, down-regulated in breast cancer. (PubMed id 8995380)1, 2, 9 Sotiropoulou G.... Sager R. (1997)
    5. The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)1, 2 Gerhard D.S....Malek J. (2004)
    6. Assignment of a novel cysteine proteinase inhibitor (CST6) to 11q13 by fluorescence in situ hybridization. (PubMed id 9154125)1, 3 Stenman G....Sager R. (1997)
    7. Methylation-dependent silencing of CST6 in primary human breast tumors and metastatic lesions. (PubMed id 17540367)1, 9 Rivenbark A.G....Coleman W.B. (2007)
    8. DNA methylation-dependent silencing of CST6 in human breast cancer cell lines. (PubMed id 17043665)1, 9 Rivenbark A.G....Coleman W.B. (2006)
    9. Invasion suppressor cystatin E/M (CST6): high-level cell type-specific expression in normal brain and epigenetic silencing in gliomas. (PubMed id 18607344)1, 9 Qiu J....Robertson K.D. (2008)
    10. Frequent epigenetic inactivation of cystatin M in breast carcinoma. (PubMed id 17099723)1, 9 Schagdarsurengin U....Dammann R. (2007)

    (in PubMed, OMIM, and NCBI Bookshelf)
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    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
    About This Section
    Entrez Gene: 1474 HGNC: 2478 AceView: CST6 Ensembl:ENSG00000175315 euGenes: HUgn1474
    ECgene: CST6 H-InvDB: CST6

    (According to HUGE)
    About This Section
      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
    Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
    About This Section
    NameDescription
    PharmGKB entry for CST6 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for CST6 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for CST6 gene:
    Search GeneIP for patents involving CST6

    GeneCards and IP:
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