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

2010-10-01   Pratima Nangia-Makker , Vitaly Balan , Avraham Raz 

Karmanos Cancer Institute, Wayne State University, 110 E Warren Avenue, Detroit, MI 48201, USA

Identity

HGNC
LOCATION
14q22.3
LOCUSID
ALIAS
CBP35,GAL3,GALBP,GALIG,L31,LGALS2,MAC2
FUSION GENES

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.

Proteins

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

Entity name
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 name
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 Crohns 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.

Bibliography

Pubmed IDLast YearTitleAuthors
93937481997Galectin-3: a novel antiapoptotic molecule with a functional BH1 (NWGR) domain of Bcl-2 family.Akahani S et al
190748692008Racial disparity in breast cancer and functional germ line mutation in galectin-3 (rs4644): a pilot study.Balan V et al
80636921994Galectins. Structure and function of a large family of animal lectins.Barondes SH et al
203639212010Diagnostic utility of galectin-3 in thyroid cancer.Chiu CG et al
164786492006Galectin-3: an open-ended story.Dumic J et al
146789892003CD29 and CD7 mediate galectin-3-induced type II T-cell apoptosis.Fukumori T et al
158981881998Evolution of animal lectins.Hirabayashi J et al
117200072001Anti-Galectin-3 IgG autoantibodies in patients with Crohn's disease characterized by means of phage display peptide libraries.Jensen-Jarolim E et al
152138112004Galectin-3 as a multifunctional protein.Krześlak A et al
120837772002Identification of autoantibodies associated with systemic lupus erythematosus.Lim Y et al
158438882005On the role of galectin-3 in cancer apoptosis.Nakahara S et al
180898062007Galectin-3 cleavage: a novel surrogate marker for matrix metalloproteinase activity in growing breast cancers.Nangia-Makker P et al
79478211994Galectin-3 is a novel substrate for human matrix metalloproteinases-2 and -9.Ochieng J et al
145580842003Galectin 3 and its binding protein in rheumatoid arthritis.Ohshima S et al
155794372004Alterations in galectin-3 expression and distribution correlate with breast cancer progression: functional analysis of galectin-3 in breast epithelial-endothelial interactions.Shekhar MP et al
192865702009Regulation of prostate cancer progression by galectin-3.Wang Y et al
86928881996Expression of galectin-3 modulates T-cell growth and apoptosis.Yang RY et al
185495222008Galectins: structure, function and therapeutic potential.Yang RY et al
155794472004Critical role for galectin-3 in airway inflammation and bronchial hyperresponsiveness in a murine model of asthma.Zuberi RI et al
122048732002Gene therapy with galectin-3 inhibits bronchial obstruction and inflammation in antigen-challenged rats through interleukin-5 gene downregulation.del Pozo V et al

Other Information

Locus ID:

NCBI: 3958
MIM: 153619
HGNC: 6563
Ensembl: ENSG00000131981

Variants:

dbSNP: 3958
ClinVar: 3958
TCGA: ENSG00000131981
COSMIC: LGALS3

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000131981ENST00000254301P17931
ENSG00000131981ENST00000254301A0A024R693
ENSG00000131981ENST00000553493G3V407
ENSG00000131981ENST00000554715G3V3R6

Expression (GTEx)

0
100
200
300
400
500
600
700

Pathways

PathwaySourceExternal ID
Immune SystemREACTOMER-HSA-168256
Innate Immune SystemREACTOMER-HSA-168249
Advanced glycosylation endproduct receptor signalingREACTOMER-HSA-879415
Neutrophil degranulationREACTOMER-HSA-6798695

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA164712406AntibioticsChemicalClinicalAnnotationassociatedPD25869013
PA444546HypersensitivityDiseaseClinicalAnnotationassociatedPD25869013

References

Pubmed IDYearTitleCitations
165497832006Galectin-3 regulates myofibroblast activation and hepatic fibrosis.137
211890922011Predictive value of plasma galectin-3 levels in heart failure with reduced and preserved ejection fraction.119
170905432007Galectin-3 interaction with Thomsen-Friedenreich disaccharide on cancer-associated MUC1 causes increased cancer cell endothelial adhesion.101
118397552002Galectin-3 translocates to the perinuclear membranes and inhibits cytochrome c release from the mitochondria. A role for synexin in galectin-3 translocation.90
178896712007The MUC1 and galectin-3 oncoproteins function in a microRNA-dependent regulatory loop.88
152054672004Galectin-3 augments K-Ras activation and triggers a Ras signal that attenuates ERK but not phosphoinositide 3-kinase activity.86
195562442009Association of cell surface mucins with galectin-3 contributes to the ocular surface epithelial barrier.85
199131212009Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.85
170821912007Visualization of galectin-3 oligomerization on the surface of neutrophils and endothelial cells using fluorescence resonance energy transfer.80
201308882010Prognostic value of galectin-3, a novel marker of fibrosis, in patients with chronic heart failure: data from the DEAL-HF study.78

Citation

Pratima Nangia-Makker ; Vitaly Balan ; Avraham Raz

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

Atlas Genet Cytogenet Oncol Haematol. 2010-10-01

Online version: http://atlasgeneticsoncology.org/gene/44396/lgals3