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

Summary

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

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_000013.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues 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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D13S315 (e-PCR)
- UniSTS:148530

WI-22746 (e-PCR)
- UniSTS:70978

RH103325 (e-PCR)
- UniSTS:97656

RH47936 (e-PCR)
- UniSTS:73107

DDX26_9492 (e-PCR)
- UniSTS:468373

SHGC-84699 (e-PCR)
- UniSTS:104096

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)

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
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
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
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