Atlas of Genetics and Cytogenetics in Oncology and Haematology

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

RARRES3 (retinoic acid receptor responder (tazarotene induced) 3)

Written2012-01Tiffany Scharadin, Richard L Eckert
Department of Biochemistry, Molecular Biology, University of Maryland, School of Medicine, Baltimore, Maryland 21201, USA

(Note : for Links provided by Atlas : click)


LocusID (NCBI) 5920
Atlas_Id 42051
Location 11q12.3  [Link to chromosome band 11q12]
Location_base_pair Starts at and ends at bp from pter
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
MRPL28 (16p13.3)::RARRES3 (11q12.3)RARRES3 (11q12.3)::CDC42SE1 (1q21.3)RARRES3 (11q12.3)::MYC (8q24.21)
RARRES3 (11q12.3)::SSU72 (1p36.33)
Note Reported at 11q23 (DiSepio et al., 1998) but more recent results suggest TIG3 is at 11q12 (Auer et al., 2002).


  Schematic of the TIG3 gene. Thick red boxes indicate exons.
Description DNA size: 9658 bp with 4 exons.
Transcription mRNA size: 779 bp, processed: 495 bp.


Note The C-terminus of TIG3 is believed to be a membrane-anchoring domain which is involved in driving membrane localization and is also required for centrosome localization. Removal of this domain from TIG3 causes it to distribute diffusely throughout the cytoplasm and reduces its ability to decrease cell survival (Deucher et al., 2000; Sturniolo et al., 2003; Sturniolo et al., 2005; Jans et al., 2008; Tsai et al., 2009).
  Schematic of the TIG3 protein. The purple indicates the hydrophilic N-terminus (amino acids 1-134) and green indicates the hydrophobic C-terminus (amino acids 134-164). The orange regions represent conserved elements with the H-rev107 family. Highly conserved regions are labeled.
Description 164 amino acids; 18 kDa protein; contains a hydrophilic N-terminus (1-134) and hydrophobic, membrane-anchoring domain (134-164).
Expression Ubiquitously expressed; expression is reduced in hyperproliferative diseases including cancer.
Localisation Cell membrane, centrosome (Scharadin et al., 2011).
Function TIG3 is a type II tumor suppressor gene which regulates cell proliferation and survival (DiSepio et al., 1998). Loss of TIG3 expression leads to hyperproliferative diseases including psoriasis and cancer. Restoration of TIG3 expression to cancer cell lines decreases cell cycle progression and induces apoptosis causing an overall decrease in viable cells (DiSepio et al., 1998; Huang et al., 2002; Higuchi et al., 2003; Tsai et al., 2009; Scharadin et al., 2011). Localization of TIG3 to the centrosome is believed to be responsible for this decrease in cell survival, which leads to an increase in p21 level, a G1/S phase block, an activation of the caspase cascade, and a reorganization of the microtubule network (Scharadin et al., 2011).
In contrast, expression of TIG3 in normal keratinocytes induces a process of terminal differentiation through the binding to and activation of type I transglutaminase and increase in cornified envelope formation to decrease cell survival (Sturniolo et al., 2003; Sturniolo et al., 2005; Jans et al., 2008). Localization of TIG3 to the cell membrane in keratinocytes is necessary for it to bind type I transglutaminase.
Homology TIG3 shares homology with the H-rev107 family of class II tumor suppressors and the NlpC/P60 superfamily (Hajnal et al., 1994; DiSepio et al., 1998; Husmann et al., 1998; Anantharaman and Aravind, 2003; Jahng et al., 2003).


Note No known mutations.

Implicated in

Entity Various cancers
Note TIG3 expression is reduced in several cancer including breast, skin, lymphoma, leukemia, kidney, ureter, colorectal, liver, biliary tract, ovary, and uterine.
Disease Cancer is a disease characterized by uncontrolled cell proliferation.
Prognosis Cancer prognosis is dependent upon several tumor-specific conditions, including location, size, and metastasis.
Oncogenesis Loss of TIG3 mRNA and protein expression is observed in several cancers and may be necessary for oncogenesis (DiSepio et al., 1998; Casanova et al., 2001; Duvic et al., 2003; Shyu et al., 2003; Jiang et al., 2005; Lotz et al., 2005; Shyu et al., 2005). Tazarotene treatment of skin cancers leads to increased TIG3 expression and reduced proliferation (Duvic et al., 2000; Duvic et al., 2003). The loss of TIG3 is associated with increased cell proliferation and TIG3 loss may be necessary for cancer progression.
Entity Hyperproliferative diseases
Note Loss of TIG3 expression is associated with hyperproliferative diseases including psoriasis and cancer.
TIG3 mRNA and protein levels are reduced in psoriatic lesions. Treatment with tazarotene leads to an increase in TIG3 levels and restoration of the normal epidermal condition (Duvic et al., 2000). Hypermethylation of the TIG3 promoter is a possible mechanism for reduced expression in psoriasis (Kwong et al., 2005).
Disease Psoriasis is a common disorder of the skin which is characterized by inflammation and hyperproliferation of the epidermis.
Prognosis Psoriasis is a non-fatal, chronic disorder that can be controlled with treatment.


Note No breakpoints known.


Evolutionary history, structural features and biochemical diversity of the NlpC/P60 superfamily of enzymes.
Anantharaman V, Aravind L.
Genome Biol. 2003;4(2):R11. Epub 2003 Feb 3.
PMID 12620121
The class II tumour suppressor gene RARRES3 maps to 11q12, not 11q23.
Auer RL, Bertoni F, Jones C, Cotter FE.
Leukemia. 2002 Jul;16(7):1396; author reply 1396-7.
PMID 12094268
The class II tumor-suppressor gene RARRES3 is expressed in B cell lymphocytic leukemias and down-regulated with disease progression.
Casanova B, de la Fuente MT, Garcia-Gila M, Sanz L, Silva A, Garcia-Marco JA, Garcia-Pardo A.
Leukemia. 2001 Oct;15(10):1521-6.
PMID 11587209
The carboxy-terminal hydrophobic domain of TIG3, a class II tumor suppressor protein, is required for appropriate cellular localization and optimal biological activity.
Deucher A, Nagpal S, Chandraratna RA, Di Sepio D, Robinson NA, Dashti SR, Eckert RL.
Int J Oncol. 2000 Dec;17(6):1195-203.
PMID 11078805
Identification and characterization of a retinoid-induced class II tumor suppressor/growth regulatory gene.
DiSepio D, Ghosn C, Eckert RL, Deucher A, Robinson N, Duvic M, Chandraratna RA, Nagpal S.
Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):14811-5.
PMID 9843971
Expression of a retinoid-inducible tumor suppressor, Tazarotene-inducible gene-3, is decreased in psoriasis and skin cancer.
Duvic M, Helekar B, Schulz C, Cho M, DiSepio D, Hager C, DiMao D, Hazarika P, Jackson B, Breuer-McHam J, Young J, Clayman G, Lippman SM, Chandraratna RA, Robinson NA, Deucher A, Eckert RL, Nagpal S.
Clin Cancer Res. 2000 Aug;6(8):3249-59.
PMID 10955811
Tazarotene-induced gene 3 is suppressed in basal cell carcinomas and reversed in vivo by tazarotene application.
Duvic M, Ni X, Talpur R, Herne K, Schulz C, Sui D, Ward S, Joseph A, Hazarika P.
J Invest Dermatol. 2003 Oct;121(4):902-9.
PMID 14632211
Subtraction cloning of H-rev107, a gene specifically expressed in H-ras resistant fibroblasts.
Hajnal A, Klemenz R, Schafer R.
Oncogene. 1994 Feb;9(2):479-90.
PMID 8290259
Induction of TIG3, a putative class II tumor suppressor gene, by retinoic acid in head and neck and lung carcinoma cells and its association with suppression of the transformed phenotype.
Higuchi E, Chandraratna RA, Hong WK, Lotan R.
Oncogene. 2003 Jul 24;22(30):4627-35.
PMID 12879006
The retinoid-inducible gene I: effect on apoptosis and mitogen-activated kinase signal pathways.
Huang SL, Shyu RY, Yeh MY, Jiang SY.
Anticancer Res. 2002 Mar-Apr;22(2A):799-804.
PMID 12014653
Transcriptional and translational downregulation of H-REV107, a class II tumour suppressor gene located on human chromosome 11q11-12.
Husmann K, Sers C, Fietze E, Mincheva A, Lichter P, Schafer R.
Oncogene. 1998 Sep 10;17(10):1305-12.
PMID 9771974
Lecithin retinol acyltransferase is a founder member of a novel family of enzymes.
Jahng WJ, Xue L, Rando RR.
Biochemistry. 2003 Nov 11;42(44):12805-12.
PMID 14596594
Localization of the TIG3 transglutaminase interaction domain and demonstration that the amino-terminal region is required for TIG3 function as a keratinocyte differentiation regulator.
Jans R, Sturniolo MT, Eckert RL.
J Invest Dermatol. 2008 Mar;128(3):517-29. Epub 2007 Aug 30.
PMID 17762858
Decreased expression of type II tumor suppressor gene RARRES3 in tissues of hepatocellular carcinoma and cholangiocarcinoma.
Jiang SY, Chou JM, Leu FJ, Hsu YY, Shih YL, Yu JC, Lee MS, Shyu RY.
World J Gastroenterol. 2005 Feb 21;11(7):948-53.
PMID 15742394
Silencing of the retinoid response gene TIG1 by promoter hypermethylation in nasopharyngeal carcinoma.
Kwong J, Lo KW, Chow LS, Chan FL, To KF, Huang DP.
Int J Cancer. 2005 Jan 20;113(3):386-92.
PMID 15455391
Suppression of the TIG3 tumor suppressor gene in human ovarian carcinomas is mediated via mitogen-activated kinase-dependent and -independent mechanisms.
Lotz K, Kellner T, Heitmann M, Nazarenko I, Noske A, Malek A, Gontarewicz A, Schafer R, Sers C.
Int J Cancer. 2005 Oct 10;116(6):894-902.
PMID 15856468
TIG3 tumor suppressor-dependent organelle redistribution and apoptosis in skin cancer cells.
Scharadin TM, Jiang H, Jans R, Rorke EA, Eckert RL.
PLoS One. 2011;6(8):e23230. Epub 2011 Aug 17.
PMID 21858038
Expression and regulation of retinoid-inducible gene 1 (RIG1) in breast cancer.
Shyu RY, Chang SC, Yu JC, Hsu SJ, Chou JM, Lee MS, Jiang SY.
Anticancer Res. 2005 May-Jun;25(3c):2453-60.
PMID 16080475
RARRES3 expression positively correlated to tumour differentiation in tissues of colorectal adenocarcinoma.
Shyu RY, Jiang SY, Chou JM, Shih YL, Lee MS, Yu JC, Chao PC, Hsu YJ, Jao SW.
Br J Cancer. 2003 Jul 7;89(1):146-51.
PMID 12838316
A novel transglutaminase activator forms a complex with type 1 transglutaminase.
Sturniolo MT, Chandraratna RA, Eckert RL.
Oncogene. 2005 Apr 21;24(18):2963-72.
PMID 15846304
Induction of apoptosis by the retinoid inducible growth regulator RIG1 depends on the NC motif in HtTA cervical cancer cells.
Tsai FM, Shyu RY, Lin SC, Wu CC, Jiang SY.
BMC Cell Biol. 2009 Feb 26;10:15.
PMID 19245694


This paper should be referenced as such :
Scharadin, T ; Eckert, RL
RARRES3 (retinoic acid receptor responder (tazarotene induced) 3)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(6):417-419.
Free journal version : [ pdf ]   [ DOI ]

External links

Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
BioGPS (Tissue expression)5920
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Fri Oct 8 21:26:37 CEST 2021

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us