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    INTS6 integrator complex subunit 6 [ Homo sapiens (human) ]

    Gene ID: 26512, updated on 10-Dec-2024

    Summary

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    Official Symbol
    INTS6provided by HGNC
    Official Full Name
    integrator complex subunit 6provided by HGNC
    Primary source
    HGNC:HGNC:14879
    See related
    Ensembl:ENSG00000102786 MIM:604331; AllianceGenome:HGNC:14879
    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
    HDB; INT6; DBI-1; DDX26; DICE1; DDX26A; Notchl2
    Summary
    DEAD box proteins, characterized by the conserved motif Asp-Glu-Ala-Asp (DEAD), are putative RNA helicases. The protein encoded by this gene is a DEAD box protein that is part of a complex that interacts with the C-terminus of RNA polymerase II and is involved in 3' end processing of snRNAs. In addition, this gene is a candidate tumor suppressor and is located in the critical region of loss of heterozygosity (LOH). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2015]
    Expression
    Broad expression in testis (RPKM 13.0), thyroid (RPKM 3.7) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See INTS6 in Genome Data Viewer
    Location:
    13q14.3
    Exon count:
    24
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (51334405..51453036, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (50555225..50667956, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (51935713..52027172, complement)

    Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107984554 Neighboring gene PRELI domain containing 3B pseudogene 2 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:51795682-51796472 Neighboring gene family with sequence similarity 124 member A Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:51817288-51817877 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:51817878-51818466 Neighboring gene Sharpr-MPRA regulatory region 8165 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:51832547-51833096 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:51833097-51833644 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:51837267-51837785 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:51854236-51854892 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:51854893-51855548 Neighboring gene Sharpr-MPRA regulatory region 8155 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr13:51902755-51903254 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7772 Neighboring gene serpin family E member 3 Neighboring gene microRNA 5693 Neighboring gene H3K27ac hESC enhancer GRCh37_chr13:51944817-51945316 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5367 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5368 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5369 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5370 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5371 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5372 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7773 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5373 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5374 Neighboring gene INTS6 antisense RNA 1 Neighboring gene ribosomal protein S4X pseudogene 16

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. Small RNA-induced INTS6 gene up-regulation suppresses castration-resistant prostate cancer cells by regulating β-catenin signaling. Chen H, et al. Cell Cycle, 2018. PMID 29895194, Free PMC Article
    2. Absence of mutations in DICE1/DDX26 gene in human cancer cell lines with frequent 13q14 deletions. Hernández M, et al. Cancer Genet Cytogenet, 2005 Nov. PMID 16271964
    3. INTS6 promotes colorectal cancer progression by activating of AKT and ERK signaling. Ding X, et al. Exp Cell Res, 2021 Oct 15. PMID 34508742
    4. Allelic loss on chromosome 13q14 and mutation in deleted in cancer 1 gene in esophageal squamous cell carcinoma. Li WJ, et al. Oncogene, 2003 Jan 16. PMID 12527901
    5. Molecular characterization of the DICE1 (DDX26) tumor suppressor gene in lung carcinoma cells. Wieland I, et al. Oncol Res, 2001. PMID 11939413

    See all (73) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. The PP2A-Integrator-CDK9 axis fine-tunes transcription and can be targeted therapeutically in cancer.
      Title: The PP2A-Integrator-CDK9 axis fine-tunes transcription and can be targeted therapeutically in cancer.
    2. INTS6 promotes colorectal cancer progression by activating of AKT and ERK signaling.
      Title: INTS6 promotes colorectal cancer progression by activating of AKT and ERK signaling.
    3. Downregulation of Wnt/beta-catenin signaling was observed during the activation period, and the impairment of beta-catenin degradation reversed the tumor suppressor effects of INTS6.
      Title: Small RNA-induced INTS6 gene up-regulation suppresses castration-resistant prostate cancer cells by regulating β-catenin signaling.
    4. the results of our study show that down-regulated INTS6 expression is associated with a poorer prognosis in hepatocellular carcinoma (HCC) patients. This newly identified INTS6/WIF-1 axis indicates the molecular mechanism of HCC and may represent a therapeutic target in HCC patients.
      Title: Integrator complex subunit 6 (INTS6) inhibits hepatocellular carcinoma growth by Wnt pathway and serve as a prognostic marker.
    5. DICE1 appears to be involved in prostate cancer progression rather than in the initiation of prostate cancer.
      Title: Genetic Variants of DICE1/INTS6 in German Prostate Cancer Families with Linkage to 13q14.
    6. Findings demonstrate INTS6P1 and INTS6 exert the tumor suppressive roles through competing for oncomiR-17-5p.
      Title: Pseudogene INTS6P1 regulates its cognate gene INTS6 through competitive binding of miR-17-5p in hepatocellular carcinoma.
    7. In response to the DNA damage response, INTS3-hSSB1-INTS6 complex relocates to the DNA damage sites.
      Title: A core hSSB1-INTS complex participates in the DNA damage response.
    8. Findings suggest that EBV encoded miR-BART3* miRNA targets DICE1 tumor suppressor to promote cellular growth and transformation in nasopharyngeal cancer(NPC).
      Title: Targeting of DICE1 tumor suppressor by Epstein-Barr virus-encoded miR-BART3* microRNA in nasopharyngeal carcinoma.
    9. A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration.
      Title: Proteomic analysis identifies dysfunction in cellular transport, energy, and protein metabolism in different brain regions of atypical frontotemporal lobar degeneration.
    10. Molecular characterization of the tumor suppressor gene in lung carcinoma cells
      Title: Molecular characterization of the DICE1 (DDX26) tumor suppressor gene in lung carcinoma cells.
    Submit: New GeneRIF Correction See all GeneRIFs (13)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of integrator complex subunit 6 (INTS6) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1 PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • DKFZp434B105

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables transmembrane signaling receptor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in regulation of transcription elongation by RNA polymerase II NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    involved_in snRNA 3'-end processing IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in snRNA processing IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in snRNA processing NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in actin cytoskeleton IDA
    Inferred from Direct Assay
    more info
    		  
    part_of integrator complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of integrator complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of integrator complex NAS
    Non-traceable Author Statement
    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 IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nucleus NAS
    Non-traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    integrator complex subunit 6
    Names
    DEAD box protein
    DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 26
    RNA helicase HDB
    protein deleted in cancer 1

    NCBI Reference Sequences (RefSeq)

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    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_001039937.2 → NP_001035026.1  integrator complex subunit 6 isoform b

      See identical proteins and their annotated locations for NP_001035026.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) is missing a segment in the the 5' coding region, and uses an in-frame downstream start codon compared to variant 1. This results in an isoform (b) with a shorter N-terminus compared to isoform a.
      Source sequence(s)
      AF097645, AL137780, AL833524
      Consensus CDS
      CCDS41890.1
      UniProtKB/Swiss-Prot
      Q9UL03
      Related
      ENSP00000381187.2, ENST00000398119.6
      Conserved Domains (2) summary
      cd00198
      Location:8 → 118
      vWFA; Von Willebrand factor type A (vWA) domain was originally found in the blood coagulation protein von Willebrand factor (vWF). Typically, the vWA domain is made up of approximately 200 amino acid residues folded into a classic a/b para-rossmann type of ...
      pfam15300
      Location:796 → 855
      INT_SG_DDX_CT_C; INTS6/SAGE1/DDX26B/CT45 C-terminus

    2. NM_001039938.2 → NP_001035027.1  integrator complex subunit 6 isoform c

      See identical proteins and their annotated locations for NP_001035027.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) is missing many 3' exons and contains an alternative segment at the 3' end compared to variant 1. This results in a shorter isoform (c) with a distinct C-terminus compared to isoform a.
      Source sequence(s)
      AL354820, AL833524, BC032386
      Consensus CDS
      CCDS45048.1
      UniProtKB/Swiss-Prot
      Q9UL03
      Related
      ENSP00000411245.3, ENST00000442263.4
      Conserved Domains (1) summary
      pfam13519
      Location:4 → 103
      VWA_2; von Willebrand factor type A domain

    3. NM_001306091.2 → NP_001293020.1  integrator complex subunit 6 isoform 4

      See identical proteins and their annotated locations for NP_001293020.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) contains two alternate internal exons, and uses an in-frame downstream start codon compared to variant 1. This results in an isoform (4) with a shorter N-terminus compared to isoform a.
      Source sequence(s)
      AA251444, AA262171, AF097645, AK128795, AL833524, AW967611, BC039829, BC094745, BE160101, BG621629, BM699545, BU754174, BX116410, DA182797, FN136361
      Consensus CDS
      CCDS76636.1
      UniProtKB/TrEMBL
      A0A024RDZ5, A1MXB9, B3KU90, G5E9X1
      Related
      ENSP00000419871.1, ENST00000497989.5
      Conserved Domains (1) summary
      pfam15300
      Location:631 → 690
      INT_SG_DDX_CT_C; INTS6/SAGE1/DDX26B/CT45 C-terminus

    4. NM_012141.3 → NP_036273.1  integrator complex subunit 6 isoform a

      See identical proteins and their annotated locations for NP_036273.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (a).
      Source sequence(s)
      AF097645, AL137780, AL354820, AL833524
      Consensus CDS
      CCDS9428.1
      UniProtKB/Swiss-Prot
      Q0P664, Q6PJP4, Q9UFK0, Q9UL03, Q9Y5M9
      Related
      ENSP00000310260.4, ENST00000311234.9
      Conserved Domains (2) summary
      pfam13519
      Location:4 → 103
      VWA_2; von Willebrand factor type A domain
      pfam15300
      Location:809 → 868
      INT_SG_DDX_CT_C; INTS6/SAGE1/DDX26B/CT45 C-terminus

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000013.11 Reference GRCh38.p14 Primary Assembly

      Range
      51334405..51453036 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011535040.4 → XP_011533342.1  integrator complex subunit 6 isoform X1

      See identical proteins and their annotated locations for XP_011533342.1

      UniProtKB/Swiss-Prot
      Q0P664, Q6PJP4, Q9UFK0, Q9UL03, Q9Y5M9
      Conserved Domains (2) summary
      pfam13519
      Location:4 → 103
      VWA_2; von Willebrand factor type A domain
      pfam15300
      Location:809 → 868
      INT_SG_DDX_CT_C; INTS6/SAGE1/DDX26B/CT45 C-terminus

    2. XM_047430264.1 → XP_047286220.1  integrator complex subunit 6 isoform X2

      UniProtKB/TrEMBL
      A0A024RDZ5, G5E9X1
      Related
      ENSP00000419984.1, ENST00000490542.5

    3. XM_047430265.1 → XP_047286221.1  integrator complex subunit 6 isoform X3

      UniProtKB/TrEMBL
      B4E2C8

    RNA

    1. XR_007063673.1 RNA Sequence

    2. XR_007063676.1 RNA Sequence

    3. XR_007063675.1 RNA Sequence

    4. XR_007063674.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060937.1 Alternate T2T-CHM13v2.0

      Range
      50555225..50667956 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054374439.1 → XP_054230414.1  integrator complex subunit 6 isoform X1

      UniProtKB/Swiss-Prot
      Q0P664, Q6PJP4, Q9UFK0, Q9UL03, Q9Y5M9

    2. XM_054374440.1 → XP_054230415.1  integrator complex subunit 6 isoform X2

      UniProtKB/TrEMBL
      A0A024RDZ5, G5E9X1

    3. XM_054374441.1 → XP_054230416.1  integrator complex subunit 6 isoform X3

      UniProtKB/TrEMBL
      B4E2C8

    RNA

    1. XR_008488752.1 RNA Sequence

    2. XR_008488754.1 RNA Sequence

    3. XR_008488753.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9UL03.1 GenPept UniProtKB/Swiss-Prot:Q9UL03

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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