INTS6 (integrator complex subunit 6)
2006-11-01 Ilse Wieland AffiliationInstitut für Humangenetik, Otto-von-Guericke-Universitüt, Leipziger Str. 44, 39120 Magdeburg, Germany
Identity
HGNC
LOCATION
13q14.3
LOCUSID
ALIAS
DBI-1,DDX26,DDX26A,DICE1,HDB,INT6,Notchl2
FUSION GENES
DNA/RNA
Description
The DICE1 gene consists of 18 exons and contains a GpC-rich promoter.
Transcription
A major transcript of 4.4 kb and a minor transcript of 6.9 kb was detected in fetal and adult tissues. In adult heart, brain and skeletal muscle an additional smaller transcript of 4 kb has been detected by Northern blot analysis. The DICE1 cDNA consists of 3665 bp with a coding sequence of 2661 bp; an alternatively spliced variant generated by skipping of exon 3 has been detected specifically in brain.
Pseudogene
Presumably LOC285634 at 5p13.1
Proteins
Description
For the DICE1 protein 887 amino acids were predicted. A protein of approximately 100 kDaltons was detected by coupled in vitro transcription and translation. The Int6 protein was purified as an approximately 110 kDaltons polypeptide component of a nuclear Integrator complex.
Localisation
Mainly nuclear localisation
Function
Predicted motifs of DICE1 protein were a von willebrand factor a (VWFA) domain of nuclear proteins, nuclear sorting signals and a DEAD box of ATP-dependent helicases. Ectopic expression of DICE1 cDNA in tumour cells suppresses colony formation and in cell culture. The Int6 protein was purified as a subunit of a RNA polymerase II multiprotein complex with roles in transcriptional regulation and RNA processing.
Homology
Weak homology to members of the helicase superfamily II
Mutations
Note
Mutations in the coding sequence of DICE1/DDX26 have been infrequently detected in tumour cells.
Somatic
Frequent loss of heterozygosity (LOH) has been observed in lung, esophageal and prostate carcinomas. Promoter hypermethylation concomitant with reduced mRNA expression has been observed in lung and prostate carcinomas. In esophageal squamous cell carcinomas missense mutations V431I, R658Q have been detected. In prostate cancer cell line LNCaP missense mutation D546G has been described.
Implicated in
Entity name
Functional inactivation of the DICE1 gene has been implicated in tumorigenesis of sporadic lung carcinomas, esophagus carcinomas, prostate carcinomas and possibly other sporadic carcinomas.
Fusion protein
A 6.3 kb fusion cDNA of a Notch-like with Dice1 cDNA (DBI-1) was detected in mouse cell line TC4. Overexpression of DBI-1 cDNA in IGF-IR transformed mouse cells compromised the mitogenic response to IGF-1 and interfered with anchorage-independent growth.
Oncogenesis
Downregulation of DICE1 mRNA was detected in 7 of 8 non-small cell lung carcinoma cell lines by Northern blot analysis. Microdissected non-small cell lung carcinomas showed reduced or absent expression of DICE1 mRNA by RT-PCR. Promoter hypermethylation was found in tumour cells with downregulated DICE1 expression. Aberrantly sized transcripts were detected in two non-small cell lung carcinoma cell lines. A reduced DICE1 expression was also observed in prostate cancer cell lines DU145 and LNCaP by real-time RT-PCR. DICE1 promoter hypermethylation was detected in 6 of 10 microdissected prostate cancer samples. Ectopic expression of DICE1 cDNA inhibited colony formation of human non-small cell lung carcinoma cell lines and prostate carcinoma cell lines and suppressed anchorage-independent growth of IGF-IR transformed mouse cells.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 16239144 | 2005 | Integrator, a multiprotein mediator of small nuclear RNA processing, associates with the C-terminal repeat of RNA polymerase II. | Baillat D et al |
| 16914495 | 2006 | Deleted in cancer 1 (DICE1) is an essential protein controlling the topology of the inner mitochondrial membrane in C. elegans. | Han SM et al |
| 16271964 | 2005 | Absence of mutations in DICE1/DDX26 gene in human cancer cell lines with frequent 13q14 deletions. | Hernández M et al |
| 9473344 | 1998 | DBI-1, a novel gene related to the notch family, modulates mitogenic response to insulin-like growth factor 1. | Hoff HB 3rd et al |
| 12527901 | 2003 | Allelic loss on chromosome 13q14 and mutation in deleted in cancer 1 gene in esophageal squamous cell carcinoma. | Li WJ et al |
| 10366719 | 1999 | Analysis of the mouse MAP1B gene identifies a highly conserved 4.3 kb 3' untranslated region and provides evidence against the proposed structure of DBI-1 cDNA. | Meixner A et al |
| 16007164 | 2005 | Promoter CpG hypermethylation and downregulation of DICE1 expression in prostate cancer. | Röpke A et al |
| 12388743 | 2002 | Distribution and evolution of von Willebrand/integrin A domains: widely dispersed domains with roles in cell adhesion and elsewhere. | Whittaker CA et al |
| 10467397 | 1999 | Isolation of DICE1: a gene frequently affected by LOH and downregulated in lung carcinomas. | Wieland I et al |
| 11939413 | 2001 | Molecular characterization of the DICE1 (DDX26) tumor suppressor gene in lung carcinoma cells. | Wieland I et al |
| 15254679 | 2004 | Ectopic expression of DICE1 suppresses tumor cell growth. | Wieland I et al |
Other Information
Locus ID:
NCBI: 26512
MIM: 604331
HGNC: 14879
Ensembl: ENSG00000102786
Variants:
dbSNP: 26512
ClinVar: 26512
TCGA: ENSG00000102786
COSMIC: INTS6
RNA/Proteins
Expression (GTEx)
Pathways
| Pathway | Source | External ID |
|---|---|---|
| Gene Expression | REACTOME | R-HSA-74160 |
| RNA polymerase II transcribes snRNA genes | REACTOME | R-HSA-6807505 |
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 34004147 | 2021 | The PP2A-Integrator-CDK9 axis fine-tunes transcription and can be targeted therapeutically in cancer. | 63 |
| 34508742 | 2021 | INTS6 promotes colorectal cancer progression by activating of AKT and ERK signaling. | 5 |
| 34004147 | 2021 | The PP2A-Integrator-CDK9 axis fine-tunes transcription and can be targeted therapeutically in cancer. | 63 |
| 34508742 | 2021 | INTS6 promotes colorectal cancer progression by activating of AKT and ERK signaling. | 5 |
| 29895194 | 2018 | Small RNA-induced INTS6 gene up-regulation suppresses castration-resistant prostate cancer cells by regulating β-catenin signaling. | 6 |
| 29895194 | 2018 | Small RNA-induced INTS6 gene up-regulation suppresses castration-resistant prostate cancer cells by regulating β-catenin signaling. | 6 |
| 28899352 | 2017 | Integrator complex subunit 6 (INTS6) inhibits hepatocellular carcinoma growth by Wnt pathway and serve as a prognostic marker. | 13 |
| 28899352 | 2017 | Integrator complex subunit 6 (INTS6) inhibits hepatocellular carcinoma growth by Wnt pathway and serve as a prognostic marker. | 13 |
| 25660097 | 2015 | Genetic Variants of DICE1/INTS6 in German Prostate Cancer Families with Linkage to 13q14. | 3 |
| 25686840 | 2015 | Pseudogene INTS6P1 regulates its cognate gene INTS6 through competitive binding of miR-17-5p in hepatocellular carcinoma. | 42 |
| 25660097 | 2015 | Genetic Variants of DICE1/INTS6 in German Prostate Cancer Families with Linkage to 13q14. | 3 |
| 25686840 | 2015 | Pseudogene INTS6P1 regulates its cognate gene INTS6 through competitive binding of miR-17-5p in hepatocellular carcinoma. | 42 |
| 23280823 | 2013 | Targeting of DICE1 tumor suppressor by Epstein-Barr virus-encoded miR-BART3* microRNA in nasopharyngeal carcinoma. | 52 |
| 23986477 | 2013 | A core hSSB1-INTS complex participates in the DNA damage response. | 29 |
| 23280823 | 2013 | Targeting of DICE1 tumor suppressor by Epstein-Barr virus-encoded miR-BART3* microRNA in nasopharyngeal carcinoma. | 52 |
Citation
Ilse Wieland
INTS6 (integrator complex subunit 6)
Atlas Genet Cytogenet Oncol Haematol. 2006-11-01
Online version: http://atlasgeneticsoncology.org/gene/40287/ints6
