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    CCNT1 cyclin T1 [ Homo sapiens (human) ]

    Gene ID: 904, updated on 19-Jul-2021

    Summary

    Official Symbol
    CCNT1provided by HGNC
    Official Full Name
    cyclin T1provided by HGNC
    Primary source
    HGNC:HGNC:1599
    See related
    Ensembl:ENSG00000129315 MIM:143055
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    CCNT; CYCT1; HIVE1
    Summary
    This gene encodes a member of the highly conserved cyclin C subfamily. The encoded protein tightly associates with cyclin-dependent kinase 9, and is a major subunit of positive transcription elongation factor b (p-TEFb). In humans, there are multiple forms of positive transcription elongation factor b, which may include one of several different cyclins along with cyclin-dependent kinase 9. The complex containing the encoded cyclin and cyclin-dependent kinase 9 acts as a cofactor of human immunodeficiency virus type 1 (HIV-1) Tat protein, and is both necessary and sufficient for full activation of viral transcription. This cyclin and its kinase partner are also involved in triggering transcript elongation through phosphorylation of the carboxy-terminal domain of the largest RNA polymerase II subunit. Overexpression of this gene is implicated in tumor growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2013]
    Expression
    Ubiquitous expression in bone marrow (RPKM 11.5), testis (RPKM 9.4) and 25 other tissues See more
    Orthologs
    NEW
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    Genomic context

    See CCNT1 in Genome Data Viewer
    Location:
    12q13.11-q13.12
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    109.20210514 current GRCh38.p13 (GCF_000001405.39) 12 NC_000012.12 (48688458..48716707, complement)
    105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (49082241..49110490, complement)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene KAT8 regulatory NSL complex subunit 2 Neighboring gene small nucleolar RNA, H/ACA box 2A Neighboring gene small nucleolar RNA, H/ACA box 2B Neighboring gene testis expressed 49 Neighboring gene adenylate cyclase 6 Neighboring gene microRNA 4701

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Clozapine-induced agranulocytosis is associated with rare HLA-DQB1 and HLA-B alleles.
    GeneReviews: Not available

    HIV-1 interactions

    Replication interactions

    Interaction Pubs
    HIV transcription is restricted by the dissociation of a functional P-TEFb complex (CCNT1-CDK9) caused by PPP1R10 (PNUTS) PubMed
    HIV-1 infection increases CCNT1 (Cyclin T1) expression in monocyte derived macrophages PubMed
    Knockdown of cyclin T1 (CCNT1) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells PubMed
    Knockdown of cyclin T1 (CCNT1) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Pr55(Gag) gag CCNT1 isoform b inhibits HIV-1 RT activity in the media and HIV-1 Gag protein expression in the cell lysate in a dose-dependent manner PubMed
    gag Expression of CycT1 increases Gag production 20-50 fold in rat T cells. Expression of both CRM1 and CycT1 factors synergistically enhances Gag production to levels approximately 10-40% of those detected in human cells PubMed
    Tat tat HIV-1 Tat binds to CDK9 and CCNT1 (CycT1) in an additive manner as shown through Fluoppi (fluorescent-based technology detecting protein-protein interactions) PubMed
    tat The N-terminus (amino acids 1-48, including activation domain) of HIV-1 Tat binds to P-TEFb through a direct interaction with the N-terminus (amino acids 1-290) of cyclin T1 during Tat-mediated transactivation of the HIV-1 LTR promoter PubMed
    tat Cyclin T1 mutant N60A fails to bind to HIV-1 Tat and impairs the effect on Tat-mediated transactivation, but H183A mutant exhibits Tat-binding activity and partially disrupts Tat-mediated transactivation PubMed
    tat PKR-mediated Tat phosphorylation inhibits Tat nuclear localization, and disrupts Tat binding to HIV-1 TAR RNA and interaction with cyclin T1 in HeLa cells PubMed
    tat A La-related protein, LARP7, is associated with P-TEFb, HEXIM1/2, MEPCE, and 7SK RNA in a large stable complex form. Knockdown of LARP7 decreases the steady-state level of 7SK, but increases free P-TEFb and enhances Tat-mediated transcription PubMed
    tat Amino acids Q46, Q50 and F176 of human CycT1 protein are involved in its binding to HIV-1 Tat. A triple-mutant containing Q46A, Q50A and F176A mutations in CycT1 completely abolishes the transcriptional activity PubMed
    tat HIV-1 Tat recruits P-TEFb to the HIV-1 Transcription Activation Response (TAR) RNA during Tat-mediated transactivation of the HIV-1 LTR promoter PubMed
    tat P-TEFb interacts with HIV-1 Tat as part of both the HIV-1 transcription preinitiation and elongation complexes PubMed
    tat Cyclin T1 (CCNT1) is identified to interact with HIV-1 Tat mutant Nullbasic in HeLa cells by LC MS/MS PubMed
    tat A homogeneous assay in AlphaLISA indicates that the affinity between HIV-1 Tat and pTEFb is determined to be approximately 20pM, and only 7% of purified Tat is found to be active in forming tertiary complex with pTEFb PubMed
    tat Cyclin T1 V107E mutant that exhibits no binding to CDK9 or HEXIM1 has weak interaction with HIV-1 Tat, and inhibits Tat-mediated transactivation in human cells PubMed
    tat Cyclin T1 N60K mutant that binds weakly with CDK9, but not with HEXIM1 and AFF4, has weak interaction with HIV-1 Tat and inhibits Tat-mediated transactivation in human cells PubMed
    tat Cyclin T1 Y175E and Y175S mutants exhibit no binding to HEXIM1 and HIV-1 Tat, leading to impair Tat-dependent transactivation of HIV LTR PubMed
    tat CDK9-CycT1-AFF1 is stimulated by HIV-1 Tat and transferred as a single complex unit to BRD4 upon stress-induced disruption of AFF1-containing 7SK snRNP (HEMX1, MEPCE, LARP7, 7SK RNA, CDK9, CycT1, and AFF1) PubMed
    tat AFF1 enhances the affinity of HIV-1 Tat for CycT1, which competitively dissociates HEXIM1 and is responsible for AFF1's promotion of Tat's extraction of CDK9/CycT1 from 7SK snRNP PubMed
    tat Brd4 inhibits HIV-1 Tat-human super elongation complex (components AFF4, ELL2, CycT1, and CDK9) by competing with HIV-1 Tat for binding to P-TEFb on HIV-1 promoter PubMed
    tat TAR binds Tat and P-TEFb as it emerges on the nascent transcript, competitively displacing the inhibitory 7SK snRNP (HEXIM1 and LARP7) and activating the P-TEFb kinase PubMed
    tat HIV-1 Tat displaces HEXIM1 from Cyclin T1 in the context of the native 7SK snRNP by interacting with the Cyclin T1-binding domain (amino acid 255-359) of HEXIM1 PubMed
    tat The interaction of HIV-1 Tat with HIV-1 Transcription Activation Response (TAR) RNA is enhanced by the interaction of Tat with P-TEFb, and TAR RNA also enhances the interaction between Tat and cyclin T1 PubMed
    tat During HIV-1 Tat mediated transactivation of the HIV-1 LTR promoter, Tat stimulates the phosphorylation of the C-terminal domain (CTD) of RNA polymerase II by P-TEFb, leading to transcription elongation PubMed
    tat ZASC1, a cellular transcription factor, interacts with HIV-1 Tat and cellular proteins CDK9/Cyclin T1 (P-TEFb) in a TAR-independent manner, suggesting that the Tat/P-TEFb complex in the transcriptional elongation site is promoted by ZASC1 PubMed
    tat Binding of isolated AFF1(1-308) CBS to CDK9/CycT1 prevents HIV-1 Tat from activating HIV transcription and assembling complete SECs (AFF1, AFF4, ELL2, and ENL). The AFF1(1-308) M60A/L61A mutant shows no suppression of Tat transactivation PubMed
    tat The crystal structure provides a structural basis for the modulation of TAR RNA binding by acetylation of Lys28 in Tat and for involvement of Asn257 in Cyclin T1 PubMed
    tat The crystal structure demonstrates that Met55Thr substitution in AFF4 forms a hydrogen bond with Glu246 of Cyclin T1, which is not as favorable for HIV-1 Tat docking PubMed
    tat The Tat-AFF4-P-TEFb complex containing HIV-1 Tat (residues 1-48), human Cyclin T1 (residues 1-266), human Cdk9 (residues 7-332), and human AFF4 (residues 27-69) is determined by the crystal structure analysis PubMed
    tat HIV-1 Tat recruits PPM1G phosphatase protein to dephosphorylate the T loop of CDK9 and release P-TEFb from the 7SK snRNP complex PubMed
    tat The interaction of Tip110 with HIV-1 Tat and the RNAPII C-terminal domain leads to the recruitment of increased CDK9/CycT1 to the transcription complex PubMed
    tat HIV-1 Tat forms at least two distinct P-TEFb-containing complexes. Tatcom1 is composed of P-TEFb, AF9, ENL, ELL, AFF1, AFF4, and PAF1, presenting strong CTD-kinase activity, while Tatcom2 consists of 7SK, LARP7, and MEPCE with two molecules of Tat/P-TEFb PubMed
    tat A small molecule compound C3 inhibits HIV-1 replication by suppressing HIV-1 Tat-mediated HIV-1 LTR-driven gene expression and phosphorylation of RNAPII through inhibition of Tat binding to CycT1 PubMed
    tat Small molecule ligands disrupt the CDK9/Cyclin T1/Tat complex and dissociate CDK9 away from the HIV-1 transcription complex PubMed
    tat Phosphorylation of CDK9 at position Ser175 regulates the competition between HIV-1 Tat and BRD4 for P-TEFb binding PubMed
    tat Yeast two-hybrid assay shows that CCNT1 isoform b loss the ability of binding to HIV-1 Tat PubMed
    tat JQ1, a small molecule inhibitor of Brd4, increases CDK9 T-loop phosphorylation in a Tat-dependent manner and partially dissociates P-TEFb from 7SK snRNP in Jurkat cells PubMed
    tat CCNT1 that lacks exon 7 inhibits HIV-1 replication through the attenuation of HIV-1 Tat/long terminal repeat (LTR)-driven transcription PubMed
    tat HIV-1 Tat mutations at positions Y26 and K28 show the most defect in the Tat:TAR:P-TEFb complex formation, but Tat:P-TEFb assembly is not abolished PubMed
    tat HIV-1 Tat mutations at positions P3, P6, W11, K12, T20, T23, V36, I39, T40, and Y47 show decreased Tat activity and P-TEFb assembly/Cdk9 activation, with three residues P3, P6, and W11 possibly involved in Cdk9 interactions PubMed
    tat Coexpression of RNA-binding domain deficient Tat (T-RS) and two fusion proteins CycT1N-Rev and Cdk9-Rev synergistically stimulates transcription when P-TEFb is tethered to RNA through Rev, and thus T-RS is no longer an inhibitor PubMed
    tat An RNA-binding domain deficient Tat excludes wild-type Tat from the promoter by preferentially assembling with P-TEFb through the Tat activation domain, but can not facilitate transfer of P-TEFb to TAR, thus blocking transition to elongation PubMed
    tat The P-TEFb binding region (amino acids 1209-1362) of BRD4 is required for HIV-1 Tat-mediated release of P-TEFb from the 7SK snRNP PubMed
    tat HIV-1 Tat-mediated release of P-TEFb from the 7SK sn RNP results in a conformational change in 7SK RNA and release of HEXIM1 from the complex PubMed
    tat P-TEFb is required for HIV-1 Tat-mediated transcriptional activation PubMed
    tat HIV-1 Tat stimulates the phosphorylation of SPT5 by P-TEFb during transactivation of the HIV-1 LTR promoter PubMed
    tat Expression of human cyclin T1 in transgenic mice is sufficient to support HIV-1 Tat-mediated transactivation in primary mouse CD4 T lymphocytes and monocytes/macrophages and increases in vitro and in vivo HIV-1 production PubMed
    tat HIV-1 Q35L mutant fails to efficiently bind either CDK9 or CycT1 resulting in the defective gene expression. However, the I39Q mutation rescues the Q35L mutant's loss of function PubMed
    tat Mutant CycT1-U7, which contains four substitutions and one deletion in the N-terminal cyclin box (67HRFYM71 to IIWE), binds HIV-1 Tat to inhibit HIV transcription. The CycT1-U7 protein fails to interact with Cdk9 or HEXIM1 PubMed
    tat SKIP is required for Tat transactivation in vivo and stimulates HIV-1 transcription elongation by associating with CycT1:CDK9 (P-TEFb) and Tat:P-TEFb complexes both in nuclear extracts and in recombinant Tat:P-TEFb:TAR RNA complexes in vitro PubMed
    tat HIV-1 Tat and P-TEFb undergo constant association and dissociation cycles with TAR and the elongating polymerase in living cells PubMed
    tat Mutant CycT1-U7 shows a potent dominant negative effect on Tat-dependent HIV transcription by specifically targeting Tat into the proteasome degradation pathway PubMed
    tat HIV-1 Tat Lys-28 is required for CycT1-dependent RNA binding. Asn 250, but not Asn-257, in the TRM region of CycT1 is important for unacetylated Tat binding PubMed
    tat Tat-SF1 is a required cofactor for HIV-1 Tat activity that complexes with P-TEFb and Tat, and stimulates Tat-mediated activation of the HIV-1 LTR promoter PubMed
    tat Hsp70 and Hsp90/Cdc37 stabilize CDK9 as well as the assembly of an active P-TEFb complex which is stimulated by HIV-1 Tat during HIV-1 transcriptional activation PubMed
    tat HIV-1 Tat competes with CIITA for the binding to P-TEFb, leading to the downregulation of MHC class II gene expression PubMed
    tat MAQ1 and 7SK RNA interact with P-TEFb and compete with the binding of HIV-1 Tat to cyclin T1, suggesting the TAR RNA/Tat lentivirus system evolved to subvert the cellular 7SK RNA/MAQ1 system PubMed
    tat The p160 nuclear receptor co-activator GRIP1 binds to the N-terminal region of HIV-1 Tat, bridging HIV-1 LTR promoter-bound factors to the Tat-P-TEFb complex and enhancing the transactivating activity of Tat PubMed
    tat The human I-mfa domain-containing protein (HIC) interacts with both P-TEFb and HIV-1 Tat, and modulates Tat transactivation of the HIV-1 LTR promoter PubMed
    tat Cyclin T1 is capable of recruiting CDK9 and HIV-1 Tat to splicing factor-rich nuclear speckle regions, suggesting nuclear speckles are a site of P-TEFb and Tat function PubMed
    tat The up and downregulation of expression of CDK9 and cyclin T1 or sequestration of cyclin T1 in infected cells may regulate HIV-1 latency by up or downregulating HIV-1 Tat transcriptional activation PubMed
    tat Amino acids 260-263 of cyclin T1 are critical for HIV-1 Tat-mediated transcriptional activation, and mediate the species specificity of cyclin T1 and P-TEFb binding to Tat PubMed
    tat P-TEFb regulates HIV-1 Tat-mediated activation of transcription through two built-in auto inhibitory mechanisms, autophosphorylation of CDK9 and cyclin T1 binding to the transcription elongation factor Tat-SF1 PubMed
    tat Mutant CycT1 protein containing triple T-to-A mutations in the N-terminal region (amino acids T143, T149, and T155) associates with CDK9 and HIV-1 Tat as a kinase-negative complex and blocks HIV transactivation PubMed
    tat Undetectable CycT1 protein and un-phosphorylation of CDK9 in undifferentiated monocytes result in the lack of Tat transactivation of the LTR promoter in early viral life cycle PubMed
    tat The growth factor granulin and the promyelocytic leukemia (PML) protein regulate HIV-1 Tat-mediated transcriptional activation by competing with the Tat interaction with cyclin T1/P-TEFb PubMed
    tat HIV-1 Tat-mediated stimulation of RNA polymerase II C-terminal domain phosphorylation by P-TEFb leads to stimulation of co-transcriptional capping of HIV-1 mRNA PubMed
    tat Acetylation of HIV-1 Tat by cellular histone acetyltransferases regulates the binding of Tat to P-TEFb PubMed
    tat Interaction of P-TEFb with histone H1 results in its phosphorylation at position Ser-183 in a Tat-dependent manner, which is necessary for transcription from the HIV-1 LTR PubMed
    tat PARP1 negatively regulates HIV-1 transcription by directly competing with Tat-P-TEFb complex for binding to TAR RNA PubMed
    tat PRMT6-mediated arginine methylation of HIV-1 Tat negatively affects Tat-TAR-cyclin T1 ternary complex formation and diminishes cyclin T1-dependent Tat transcriptional activation PubMed
    tat Cyclin T1-P-TEFb is important for prostratin stimulation of HIV-1 virus expression in the presence of functional Tat PubMed
    tat IL-10 inhibits HIV-1 gene expression in an HIV-1 Tat-dependent manner by downregulating cyclin T1 expression through the induction of proteasome-mediated proteolysis in human macrophages PubMed
    tat HIV-1 Tat interaction with cyclin T1 is required for the repression of mannose receptor (MR) and bone morphogenetic protein receptor-2 (BMPR2) promoters PubMed
    tat P-TEFb, Puralpha and HIV-1 Tat cooperate to activate the TNFalpha promoter PubMed
    Vpr vpr HIV-1 Vpr binds to cyclin T1 (amino acids 300-479) in a ternary complex of HIV-1 Tat, Vpr, Cyclin T1, and CDK9, and enhances Tat transactivation of the viral LTR promoter PubMed
    reverse transcriptase gag-pol CCNT1 isoform b inhibits HIV-1 RT activity in the media and HIV-1 Gag protein expression in the cell lysate in a dose-dependent manner PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Clone Names

    • FLJ11223, DKFZp313A1331, DKFZp313N0919, DKFZp313O1211

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 7SK snRNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables RNA polymerase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables chromatin binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables cyclin-dependent protein serine/threonine kinase activator activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables cyclin-dependent protein serine/threonine kinase regulator activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein kinase binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables transcription cis-regulatory region binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables transcription factor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Component Evidence Code Pubs
    part_of P-TEFb complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of cyclin/CDK positive transcription elongation factor complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    part_of cyclin/CDK positive transcription elongation factor complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
     
    NOT located_in nucleolus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
     
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 

    General protein information

    Preferred Names
    cyclin-T1
    Names
    CDK9-associated C-type protein
    MLLT10/CCNT1 fusion
    cyclin C-related protein
    human immunodeficiency virus type 1 (HIV-1) expression (elevated) 1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    mRNA and Protein(s)

    1. NM_001240.4NP_001231.2  cyclin-T1 isoform a

      See identical proteins and their annotated locations for NP_001231.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (a, also known as FL and CycT1a) represents the longer transcript and encodes the longer isoform (a).
      Source sequence(s)
      AC079951, AF045161, BX098766
      Consensus CDS
      CCDS8766.1
      UniProtKB/Swiss-Prot
      O60563
      Related
      ENSP00000261900.3, ENST00000261900.8
      Conserved Domains (1) summary
      pfam00134
      Location:13149
      Cyclin_N; Cyclin, N-terminal domain
    2. NM_001277842.2NP_001264771.1  cyclin-T1 isoform b

      See identical proteins and their annotated locations for NP_001264771.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (b, also known as dE7 and CycT1b) lacks an exon in the coding region, which results in a frameshift and an early stop codon, compared to variant a. The encoded isoform (b) has a shorter and distinct C-terminus, compared to isoform a. While this variant may be considered a candidate for nonsense-mediated decay, experimental evidence suggests that it is protein coding (PMID: 23569210 and PMID: 22692005).
      Source sequence(s)
      AC079951, AK290990, EF688064
      Consensus CDS
      CCDS61109.1
      UniProtKB/Swiss-Prot
      O60563
      UniProtKB/TrEMBL
      A8K4M5
      Related
      ENSP00000481035.1, ENST00000618666.4
      Conserved Domains (2) summary
      cd00043
      Location:38109
      CYCLIN; Cyclin box fold. Protein binding domain functioning in cell-cycle and transcription control. Present in cyclins, TFIIB and Retinoblastoma (RB).The cyclins consist of 8 classes of cell cycle regulators that regulate cyclin dependent kinases (CDKs). TFIIB ...
      cl28538
      Location:1153
      CCL1; Cdk activating kinase (CAK)/RNA polymerase II transcription initiation/nucleotide excision repair factor TFIIH/TFIIK, cyclin H subunit [Cell division and chromosome partitioning / Transcription / DNA replication, recombination, and repair]

    RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p13 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p13 Primary Assembly

      Range
      48688458..48716707 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017020197.2XP_016875686.1  cyclin-T1 isoform X1

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