INTS6 (integrator complex subunit 6)

2006-11-01   Ilse Wieland 

Institut 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.

Bibliography

Pubmed IDLast YearTitleAuthors
162391442005Integrator, a multiprotein mediator of small nuclear RNA processing, associates with the C-terminal repeat of RNA polymerase II.Baillat D et al
169144952006Deleted in cancer 1 (DICE1) is an essential protein controlling the topology of the inner mitochondrial membrane in C. elegans.Han SM et al
162719642005Absence of mutations in DICE1/DDX26 gene in human cancer cell lines with frequent 13q14 deletions.Hernández M et al
94733441998DBI-1, a novel gene related to the notch family, modulates mitogenic response to insulin-like growth factor 1.Hoff HB 3rd et al
125279012003Allelic loss on chromosome 13q14 and mutation in deleted in cancer 1 gene in esophageal squamous cell carcinoma.Li WJ et al
103667191999Analysis 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
160071642005Promoter CpG hypermethylation and downregulation of DICE1 expression in prostate cancer.Röpke A et al
123887432002Distribution and evolution of von Willebrand/integrin A domains: widely dispersed domains with roles in cell adhesion and elsewhere.Whittaker CA et al
104673971999Isolation of DICE1: a gene frequently affected by LOH and downregulated in lung carcinomas.Wieland I et al
119394132001Molecular characterization of the DICE1 (DDX26) tumor suppressor gene in lung carcinoma cells.Wieland I et al
152546792004Ectopic 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

Gene IDTranscript IDUniprot
ENSG00000102786ENST00000311234Q9UL03
ENSG00000102786ENST00000311234A0A024RDU0
ENSG00000102786ENST00000398119Q9UL03
ENSG00000102786ENST00000442263Q9UL03
ENSG00000102786ENST00000469430F8WAV7
ENSG00000102786ENST00000483288C9J885
ENSG00000102786ENST00000483746C9JAV7
ENSG00000102786ENST00000485178C9K0V7
ENSG00000102786ENST00000488009C9JXP6
ENSG00000102786ENST00000490542G5E9X1
ENSG00000102786ENST00000491189C9JVX2
ENSG00000102786ENST00000497989B3KQH5

Expression (GTEx)

0
5
10
15

Pathways

PathwaySourceExternal ID
Gene ExpressionREACTOMER-HSA-74160
RNA polymerase II transcribes snRNA genesREACTOMER-HSA-6807505

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
232808232013Targeting of DICE1 tumor suppressor by Epstein-Barr virus-encoded miR-BART3* microRNA in nasopharyngeal carcinoma.36
256868402015Pseudogene INTS6P1 regulates its cognate gene INTS6 through competitive binding of miR-17-5p in hepatocellular carcinoma.27
223604202012Proteomic analysis identifies dysfunction in cellular transport, energy, and protein metabolism in different brain regions of atypical frontotemporal lobar degeneration.18
239864772013A core hSSB1-INTS complex participates in the DNA damage response.16
119394132001Molecular characterization of the DICE1 (DDX26) tumor suppressor gene in lung carcinoma cells.10
125279012003Allelic loss on chromosome 13q14 and mutation in deleted in cancer 1 gene in esophageal squamous cell carcinoma.9
152546792004Ectopic expression of DICE1 suppresses tumor cell growth.7
288993522017Integrator complex subunit 6 (INTS6) inhibits hepatocellular carcinoma growth by Wnt pathway and serve as a prognostic marker.6
162719642005Absence of mutations in DICE1/DDX26 gene in human cancer cell lines with frequent 13q14 deletions.4
256600972015Genetic Variants of DICE1/INTS6 in German Prostate Cancer Families with Linkage to 13q14.2

Citation

Ilse Wieland

INTS6 (integrator complex subunit 6)

Atlas Genet Cytogenet Oncol Haematol. 2006-11-01

Online version: http://atlasgeneticsoncology.org/gene/40287/ints6