RARRES1 (retinoic acid receptor responder (tazarotene induced) 1)

2007-01-01 Kwok-Wai Lo , Grace TY Chung Affiliation

State Key Laboratory in Cancer in South China, Department of Anatomical and Cellular Pathology, Prinve of Wales Hospital, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China

Identity

HGNC

RARRES1

LOCATION

3q25.32

LOCUSID

5918

ALIAS

LXNL,PERG-1,TIG1

FUSION GENES

Show Gene Fusions

DNA/RNA

Two transcript variants (isoform 1: NM_206963.1 and isoform 2: NM_002888.2) are shown. Black boxes represent the exons of RARRES1. CpG: location of CpG island.

Description

The RARRES1 gene contains 6 exons and spans 35377 bases.

Transcription

Two alternatively spliced transcripts were identified (isoform 1 and isoform 2). Exons 1 to 4 are common to both isoforms. Exon 5 and 6 are present in isoform 1 (NM_206963.1) only. The cDNA of isoform 1 is 1545 bp while isoform 2 is 886 bp.

Pseudogene

No known pseudogenes

Proteins

The gray box indicates the single membrane-spanning hydrophobic region. Lataxin domain for 2 RARRES1 isoforms is shown as black box.

Description

Called Retinoic acid receptor responder protein 1 (synonyms: Tazarotene-induced gene 1 protein/RAR-responsive protein TIG1); Two isoform, isoform 1 (NP_996846) and isoform 2 (NP_002879), produced by alternative splicing were reported. Isoforms 1 and 2 contain 294 and 228 amino acids respectively. Molecular weight of Isoform 1 is 33258 Da. The two isoforms show difference in the 3end-region. RARRES1 is predicted to be a transmembrane protein with a small N-terminal intracellular regions, a single membrane-spanning hydrophobic region, and a large C-terminal extracellular region containing a glycosylation signal.

Expression

High level of RARRES1 transcripts was detected in multiple tissues including prostate, heart, lung, liver, colon and small intestine. Expression of RARRES1 protein was demonstrated in colorectal tissues.

Localisation

Based on the predicted amino acid sequence, RARRES1 is suspected to be a transmembrane protein. However, immunohistochemical analysis showed that RARRES1 protein localizes at the supranuclear regions of colorectal adenocarcinoma, adenoma and adjacent normal epithelial cells. The precise localization of RARRES1 protein needed to be further investigated.

Function

RARRES1 was suggested to be a tumor suppressor of a variety of human cancers. Inactivation of RARRES1 is involved in the malignant progression of prostate cancer. Restoration of RARRES1 expression in malignant prostate cell lines led to a decrease of invasiveness and tumorigenicity in nude mice. It is speculated that RARRES1 may function as a cell adhesion molecule. Since the protein shows sequence similarity to Latexin, the only known mammalian carboxypeptidase inhibitor, RARRES1 may also have protease inhibitor activity and inhibit the degradation of extracellular matrix.

Homology

RARRES1 belongs to the proteinase inhibitor I47 (latexin) family, its c-terminal region shows 30% sequence similarity with Latexin.

Mutations

Note

No germline or somatic mutation associated with disease is reported.

Implicated in

Entity name

A variety of human cancers

Note

The association of RARRES1 with human cancer was first revealed by the subtractive differential gene display analysis of benign and malignant prostate cell lines. The gene was expressed in benign prostate cell lines and not in malignant ones. It is now considered as a putative tumor suppressor gene in a variety of human cancers although its function remains unclear. Its expression is commonly suppressed in prostate carcinoma, lung cancer, nasopharyngeal carcinoma, and leukemia by promoter hypermethylation. Restoring RARRES1 expression in prostate cancer cells resulted in decrease of in vitro invasiveness and in vivo tumorigenicity. RARRES1 also implicated in therapeutic effects of retinoic acid in psoriasis.

Disease

prostate carcinoma, nasopharyngeal carcinoma, head and neck cancer, lung cancer, gastric carcinoma, colorectal adenocarcinoma, endometrial cancer, breast cancer, acute myeloid leukemia, Chronic myeloid leukemia.

Prognosis

down-regulation of RARRES1 is significantly related with the late stage colorectal adenocarcinoma (Dukess stage D). However, no difference in survival was found comparing patient with negative, weak and strong RARRES1 expression in tumors.

Cytogenetics

No translocations and amplifications of this gene have been reported

Hybrid gene

No hybrid gene involving RARRES1 has been described.

Breakpoints

Note

No breakpoints involving this gene have been described.

Bibliography

Pubmed ID	Last Year	Title	Authors
15698574	2005	An inflammatory role for the mammalian carboxypeptidase inhibitor latexin: relationship to cystatins and the tumor suppressor TIG1.	Aagaard A et al
9270552	1997	Molecular mechanisms of tazarotene action in psoriasis.	Duvic M et al
11493603	2001	Ovocalyxin-32, a novel chicken eggshell matrix protein. isolation, amino acid sequencing, cloning, and immunocytochemical localization.	Gautron J et al
12952168	2003	Purification of ovocalyxin-32, a novel chicken eggshell matrix protein.	Hincke MT et al
11929948	2002	Tazarotene-induced gene 1 (TIG1) expression in prostate carcinomas and its relationship to tumorigenicity.	Jing C et al
15455391	2005	Silencing of the retinoid response gene TIG1 by promoter hypermethylation in nasopharyngeal carcinoma.	Kwong J et al
11929940	2002	Is TIG1 a new tumor suppressor in prostate cancer?	Lotan R et al
16128742	2005	DNA methylation of genes linked to retinoid signaling in squamous cell carcinoma of the esophagus: DNA methylation of CRBP1 and TIG1 is associated with tumor stage.	Mizuiri H et al
14987796	2004	Microdissection, mRNA amplification and microarray: a study of pleural mesothelial and malignant mesothelioma cells.	Mohr S et al
8601727	1996	Tazarotene-induced gene 1 (TIG1), a novel retinoic acid receptor-responsive gene in skin.	Nagpal S et al
16322291	2005	Promoter hypermethylation as an independent prognostic factor for relapse in patients with prostate cancer following radical prostatectomy.	Rosenbaum E et al
16134180	2005	DNA methylation of genes linked with retinoid signaling in gastric carcinoma: expression of the retinoid acid receptor beta, cellular retinol-binding protein 1, and tazarotene-induced gene 1 genes is associated with DNA methylation.	Shutoh M et al
16952303	2006	Multiple tumor suppressor genes are increasingly methylated with age in non-neoplastic gastric epithelia.	So K et al
15886297	2005	Discovery of epigenetically masked tumor suppressor genes in endometrial cancer.	Takai N et al
15328191	2004	Optimal use of a panel of methylation markers with GSTP1 hypermethylation in the diagnosis of prostate adenocarcinoma.	Tokumaru Y et al
16728587	2006	Effects of oestrogen on gene expression in epithelium and stroma of normal human breast tissue.	Wilson CL et al
14996990	2004	DNA microarray analysis of vitamin D-induced gene expression in a human colon carcinoma cell line.	Wood RJ et al
16426842	2006	RARRES1 expression is significantly related to tumour differentiation and staging in colorectal adenocarcinoma.	Wu CC et al
15059893	2004	Hypermethylation and silencing of the putative tumor suppressor Tazarotene-induced gene 1 in human cancers.	Youssef EM et al
14691453	2004	Methylation of the retinoid response gene TIG1 in prostate cancer correlates with methylation of the retinoic acid receptor beta gene.	Zhang J et al
15897880	2005	All-trans retinoic acid treatment of Wilms tumor cells reverses expression of genes associated with high risk and relapse in vivo.	Zirn B et al

Other Information

Locus ID:

NCBI: 5918
MIM: 605090
HGNC: 9867
Ensembl: ENSG00000118849

Variants:

dbSNP: 5918
ClinVar: 5918
TCGA: ENSG00000118849
COSMIC: RARRES1

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000118849	ENST00000237696	P49788
ENSG00000118849	ENST00000479756	P49788

Expression (GTEx)

100

150

200

250

300

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
21303978	2011	Tumor suppressor RARRES1 interacts with cytoplasmic carboxypeptidase AGBL2 to regulate the α-tubulin tyrosination cycle.	31
15059893	2004	Hypermethylation and silencing of the putative tumor suppressor Tazarotene-induced gene 1 in human cancers.	28
19834535	2009	Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging.	27
19737656	2009	Role of the RARRES1 gene in nasopharyngeal carcinoma.	18
24014597	2013	TIG1 promotes the development and progression of inflammatory breast cancer through activation of Axl kinase.	17
16128742	2005	DNA methylation of genes linked to retinoid signaling in squamous cell carcinoma of the esophagus: DNA methylation of CRBP1 and TIG1 is associated with tumor stage.	16
16134180	2005	DNA methylation of genes linked with retinoid signaling in gastric carcinoma: expression of the retinoid acid receptor beta, cellular retinol-binding protein 1, and tazarotene-induced gene 1 genes is associated with DNA methylation.	16
21575264	2011	G protein-coupled receptor kinase 5 mediates Tazarotene-induced gene 1-induced growth suppression of human colon cancer cells.	15
27286452	2016	Breast cancer subtype dictates DNA methylation and ALDH1A3-mediated expression of tumor suppressor RARRES1.	12
22126303	2011	Tazarotene-induced gene 1 inhibits prostaglandin E2-stimulated HCT116 colon cancer cell growth.	11

Citation

Kwok-Wai Lo ; Grace TY Chung

RARRES1 (retinoic acid receptor responder (tazarotene induced) 1)

Atlas Genet Cytogenet Oncol Haematol. 2007-01-01

Online version: http://atlasgeneticsoncology.org/gene/42050/rarres1