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LGALS3 (lectin, galactoside-binding, soluble, 3)

Written2010-10Pratima Nangia-Makker, Vitaly Balan, Avraham Raz
Karmanos Cancer Institute, Wayne State University, 110 E Warren Avenue, Detroit, MI 48201, USA

(Note : for Links provided by Atlas : click)

Identity

Other aliasCBP35
GAL3
GALBP
GALIG
L31
LGALS2
MAC2
LocusID (NCBI) 3958
Atlas_Id 44396
Location 14q22.3  [Link to chromosome band 14q22]
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)
FBXO34 (14q22.3) / LGALS3 (14q22.3)LGALS3 (14q22.3) / ATG12 (5q22.3)LGALS3 (14q22.3) / LGALS3 (14q22.3)
TBC1D17 (19q13.33) / LGALS3 (14q22.3)

DNA/RNA

Description Size 16277 bases.
Consists of at least 6 exons.
Transcription Two transcription initiation sites were identified in human LGALS3. These transcripts arise from an internal gene embedded within LGALS3, named galig (galectin-3 internal gene) (Barondes et al., 1994; Hirayabashi and Kasai, 1998).
Pseudogene None.

Protein

Description 250 amino acids; 26152 Da; The initial 12 amino acid N-terminal peptide sequence also called small N-terminal, precede the proline/glycin-rich repetitive domain consisting of about 100 amino acids. C-terminal consists of about 130 amino acids encoding carbohydrate-binding domain. Galectin-3 is the only chimeric protein among a family of 15 galectins known so far (Hirayabashi and Kasai, 1998).
Localisation In adults, galectin-3 is ubiquitously expressed and localizes to the extracellular matrix, the cytoplasm and the nucleus (Hirayabashi and Kasai, 1998; Krzeslak and Lipinska, 2004).
Function Galectin-3 is a carbohydrate-binding protein: a characteristic that it shares with other members of galectin family. The collagen alpha like N terminal sequence can be cleaved by Matrix metalloproteinases and the cleavage results in an enhanced binding efficiency to carbohydrates (Ochieng et al.,1994; Shekhar et al., 2004). Intra-cellularly it functions as an anti-apototic protein because of the presence of Asp-Trp-Gly-Arg (NWGR) motif at the C terminal (Akahani et al., 1997; Nakahara et al., 2005; Yang et al., 1996). NWGR is designated as the anti-death motif characteristic of the BCL2 family. Extra-cellular protein however, functions as a pro-apoptotic entity on T cells (Fukumori et al., 2003). Galectin-3 has also exhibited pro-angiogenic properties (Nangia-Makker et al., 2000).
Homology N-terminal domain has 33.5% identity with collagen alpha1 (II) chain of bovine cartilage, so it is also designated as a collagen-like N-terminal domain. The C-terminal domain of galectin-3, forming a globular structure, accommodates whole carbohydrate-binding site, and is very similar to CRD of other lectins.

Mutations

Germinal P64H (rs4644), T98P (rs4652), R183K (rs10148371).
Functional germline mutation in the galectin-3 gene at position 191 (rs4644) substituting proline with histidine (P64H), which results in susceptibility to matrix metalloproteinase cleavage and acquisition of resistance to drug-induced apoptosis. This substitution correlates with incidence of breast cancer and racial disparity (Balan et al., 2008). Rs10148371 is localized in the anti-apoptotic motif NWGR.
Somatic None.

Implicated in

Note
  
Entity Various cancers
Disease Over-expression of galectin-3 was reported in the metastatic cell lines compared to their non-metastatic counterparts. Galectin-3 concentrations were significantly higher in the serum of patients with melanoma and breast cancer compared to the normal controls. In the tumor tissues, upregulation and/or redistribution of galectin-3 was shown in thyroid, colon, breast, gastric, prostate, melanoma and head and neck cancers, however, the data in some cases are not consistent (Dumic et al., 2006; Yang et al., 2008). Recently, it was reported in breast and prostate cancer that after cleavage by Matrix metalloproteases galectin-3 is not recognized by the commonly used monoclonal antibody TIB166 (Nangia-Makker et al., 2007; Wang et al., 2009), which could explain some of the discrepancy in the earlier reports.
  
  
Entity Autoimmune disease
Disease Galectin-3 plays a role in pathogenesis of autoimmune disease. Endogenous protein promotes inflammatory response in asthma, pharmacological application of galectin-3 might suppress it (del Pozo et al., 2002; Zuberi et al., 2004), thus opening a new approach for future treatment of the disease. In Crohn's disease and systemic lupus, erythematosus and polymyositis/dermatomyositis anti-galectin-3 auto-antibodies were identified (Jensen-Jarolim et al., 2001; Lim et al., 2002). In sera and synovial fluid from rheumatoid arthritis (RA) patients, galectin-3 level was found to be elevated (Ohshima et al., 2003).
Prognosis Galectin-3 is differentially expressed in thyroid carcinoma compared with benign and normal thyroid specimens, suggesting that Galectin-3 is a good diagnostic marker for thyroid cancer (Chiu et al., 2010).
Oncogenesis Galectin-3 is not an oncogene, but helps in cancer progression once it is initiated.
  

To be noted

Acknowledgements: Supported by the National Institutes of Health (R37CA46120-19 to A.R).

Bibliography

Galectin-3: a novel antiapoptotic molecule with a functional BH1 (NWGR) domain of Bcl-2 family.
Akahani S, Nangia-Makker P, Inohara H, Kim HR, Raz A.
Cancer Res. 1997 Dec 1;57(23):5272-6.
PMID 9393748
 
Racial disparity in breast cancer and functional germ line mutation in galectin-3 (rs4644): a pilot study.
Balan V, Nangia-Makker P, Schwartz AG, Jung YS, Tait L, Hogan V, Raz T, Wang Y, Yang ZQ, Wu GS, Guo Y, Li H, Abrams J, Couch FJ, Lingle WL, Lloyd RV, Ethier SP, Tainsky MA, Raz A.
Cancer Res. 2008 Dec 15;68(24):10045-50.
PMID 19074869
 
Galectins. Structure and function of a large family of animal lectins.
Barondes SH, Cooper DN, Gitt MA, Leffler H.
J Biol Chem. 1994 Aug 19;269(33):20807-10. (REVIEW)
PMID 8063692
 
Diagnostic utility of galectin-3 in thyroid cancer.
Chiu CG, Strugnell SS, Griffith OL, Jones SJ, Gown AM, Walker B, Nabi IR, Wiseman SM.
Am J Pathol. 2010 May;176(5):2067-81. Epub 2010 Apr 2.
PMID 20363921
 
Galectin-3: an open-ended story.
Dumic J, Dabelic S, Flogel M.
Biochim Biophys Acta. 2006 Apr;1760(4):616-35. Epub 2006 Jan 18. (REVIEW)
PMID 16478649
 
CD29 and CD7 mediate galectin-3-induced type II T-cell apoptosis.
Fukumori T, Takenaka Y, Yoshii T, Kim HR, Hogan V, Inohara H, Kagawa S, Raz A.
Cancer Res. 2003 Dec 1;63(23):8302-11.
PMID 14678989
 
Evolution of animal lectins.
Hirabayashi J, Kasai KI.
Prog Mol Subcell Biol. 1998;19:45-88. (REVIEW)
PMID 15898188
 
Anti-Galectin-3 IgG autoantibodies in patients with Crohn's disease characterized by means of phage display peptide libraries.
Jensen-Jarolim E, Neumann C, Oberhuber G, Gscheidlinger R, Neuchrist C, Reinisch W, Zuberi RI, Penner E, Liu FT, Boltz-Nitulescu G.
J Clin Immunol. 2001 Sep;21(5):348-56.
PMID 11720007
 
Galectin-3 as a multifunctional protein.
Krzes'lak A, Lipin'ska A.
Cell Mol Biol Lett. 2004;9(2):305-28. (REVIEW)
PMID 15213811
 
Identification of autoantibodies associated with systemic lupus erythematosus.
Lim Y, Lee DY, Lee S, Park SY, Kim J, Cho B, Lee H, Kim HY, Lee E, Song YW, Jeoung DI.
Biochem Biophys Res Commun. 2002 Jul 5;295(1):119-24.
PMID 12083777
 
On the role of galectin-3 in cancer apoptosis.
Nakahara S, Oka N, Raz A.
Apoptosis. 2005 Mar;10(2):267-75. (REVIEW)
PMID 15843888
 
Galectin-3 cleavage: a novel surrogate marker for matrix metalloproteinase activity in growing breast cancers.
Nangia-Makker P, Raz T, Tait L, Hogan V, Fridman R, Raz A.
Cancer Res. 2007 Dec 15;67(24):11760-8.
PMID 18089806
 
Galectin-3 is a novel substrate for human matrix metalloproteinases-2 and -9.
Ochieng J, Fridman R, Nangia-Makker P, Kleiner DE, Liotta LA, Stetler-Stevenson WG, Raz A.
Biochemistry. 1994 Nov 29;33(47):14109-14.
PMID 7947821
 
Galectin 3 and its binding protein in rheumatoid arthritis.
Ohshima S, Kuchen S, Seemayer CA, Kyburz D, Hirt A, Klinzing S, Michel BA, Gay RE, Liu FT, Gay S, Neidhart M.
Arthritis Rheum. 2003 Oct;48(10):2788-95.
PMID 14558084
 
Alterations in galectin-3 expression and distribution correlate with breast cancer progression: functional analysis of galectin-3 in breast epithelial-endothelial interactions.
Shekhar MP, Nangia-Makker P, Tait L, Miller F, Raz A.
Am J Pathol. 2004 Dec;165(6):1931-41.
PMID 15579437
 
Regulation of prostate cancer progression by galectin-3.
Wang Y, Nangia-Makker P, Tait L, Balan V, Hogan V, Pienta KJ, Raz A.
Am J Pathol. 2009 Apr;174(4):1515-23. Epub 2009 Mar 12.
PMID 19286570
 
Expression of galectin-3 modulates T-cell growth and apoptosis.
Yang RY, Hsu DK, Liu FT.
Proc Natl Acad Sci U S A. 1996 Jun 25;93(13):6737-42.
PMID 8692888
 
Galectins: structure, function and therapeutic potential.
Yang RY, Rabinovich GA, Liu FT.
Expert Rev Mol Med. 2008 Jun 13;10:e17. (REVIEW)
PMID 18549522
 
Critical role for galectin-3 in airway inflammation and bronchial hyperresponsiveness in a murine model of asthma.
Zuberi RI, Hsu DK, Kalayci O, Chen HY, Sheldon HK, Yu L, Apgar JR, Kawakami T, Lilly CM, Liu FT.
Am J Pathol. 2004 Dec;165(6):2045-53.
PMID 15579447
 
Gene therapy with galectin-3 inhibits bronchial obstruction and inflammation in antigen-challenged rats through interleukin-5 gene downregulation.
del Pozo V, Rojo M, Rubio ML, Cortegano I, Cardaba B, Gallardo S, Ortega M, Civantos E, Lopez E, Martin-Mosquero C, Peces-Barba G, Palomino P, Gonzalez-Mangado N, Lahoz C.
Am J Respir Crit Care Med. 2002 Sep 1;166(5):732-7.
PMID 12204873
 

Citation

This paper should be referenced as such :
Nangia-Makker, P ; Balan, V ; Raz, A
LGALS3 (lectin, galactoside-binding, soluble, 3)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(6):499-501.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/LGALS3ID44396ch14q22.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 2 ]
  Head and Neck: Laryngeal tumors: an overview
FBXO34/LGALS3 (14q22)


External links

Nomenclature
Cards
AtlasLGALS3ID44396ch14q22.txt
Aliases
Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)3958
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
Miscellaneous
canSAR (ICR) (select the gene name)
Probes
Litterature
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed


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indexed on : Thu Oct 18 17:41:20 CEST 2018

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