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

Gene ID: 26512, updated on 3-Apr-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
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Genomic context

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Location:
13q14.3
Exon count:
24
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (51334405..51453036, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (50555225..50667956, complement)
105.20220307 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: 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

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Related articles in PubMed

  1. INTS6 promotes colorectal cancer progression by activating of AKT and ERK signaling. Ding X, et al. Exp Cell Res, 2021 Oct 15. PMID 34508742
  2. 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
  3. Genetic Variants of DICE1/INTS6 in German Prostate Cancer Families with Linkage to 13q14. Böhm M, et al. Urol Int, 2015. PMID 25660097
  4. Targeting of DICE1 tumor suppressor by Epstein-Barr virus-encoded miR-BART3* microRNA in nasopharyngeal carcinoma. Lei T, et al. Int J Cancer, 2013 Jul. PMID 23280823
  5. 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

See all (67) 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)

Genotypes

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
  
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_2023_10

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

    Related
    ENSP00000419984.1, ENST00000490542.5

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

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

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

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

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