LGALS3 (lectin, galactoside-binding, soluble, 3)
2010-10-01 Pratima Nangia-Makker , Vitaly Balan , Avraham Raz AffiliationKarmanos 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.
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.
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.
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 9393748 | 1997 | Galectin-3: a novel antiapoptotic molecule with a functional BH1 (NWGR) domain of Bcl-2 family. | Akahani S et al |
| 19074869 | 2008 | Racial disparity in breast cancer and functional germ line mutation in galectin-3 (rs4644): a pilot study. | Balan V et al |
| 8063692 | 1994 | Galectins. Structure and function of a large family of animal lectins. | Barondes SH et al |
| 20363921 | 2010 | Diagnostic utility of galectin-3 in thyroid cancer. | Chiu CG et al |
| 16478649 | 2006 | Galectin-3: an open-ended story. | Dumic J et al |
| 14678989 | 2003 | CD29 and CD7 mediate galectin-3-induced type II T-cell apoptosis. | Fukumori T et al |
| 15898188 | 1998 | Evolution of animal lectins. | Hirabayashi J et al |
| 11720007 | 2001 | Anti-Galectin-3 IgG autoantibodies in patients with Crohn's disease characterized by means of phage display peptide libraries. | Jensen-Jarolim E et al |
| 15213811 | 2004 | Galectin-3 as a multifunctional protein. | Krześlak A et al |
| 12083777 | 2002 | Identification of autoantibodies associated with systemic lupus erythematosus. | Lim Y et al |
| 15843888 | 2005 | On the role of galectin-3 in cancer apoptosis. | Nakahara S et al |
| 18089806 | 2007 | Galectin-3 cleavage: a novel surrogate marker for matrix metalloproteinase activity in growing breast cancers. | Nangia-Makker P et al |
| 7947821 | 1994 | Galectin-3 is a novel substrate for human matrix metalloproteinases-2 and -9. | Ochieng J et al |
| 14558084 | 2003 | Galectin 3 and its binding protein in rheumatoid arthritis. | Ohshima S et al |
| 15579437 | 2004 | Alterations 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 |
| 19286570 | 2009 | Regulation of prostate cancer progression by galectin-3. | Wang Y et al |
| 8692888 | 1996 | Expression of galectin-3 modulates T-cell growth and apoptosis. | Yang RY et al |
| 18549522 | 2008 | Galectins: structure, function and therapeutic potential. | Yang RY et al |
| 15579447 | 2004 | Critical role for galectin-3 in airway inflammation and bronchial hyperresponsiveness in a murine model of asthma. | Zuberi RI et al |
| 12204873 | 2002 | Gene 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 ID | Transcript ID | Uniprot |
|---|---|---|
| ENSG00000131981 | ENST00000254301 | P17931 |
| ENSG00000131981 | ENST00000254301 | A0A024R693 |
| ENSG00000131981 | ENST00000553493 | G3V407 |
| ENSG00000131981 | ENST00000554715 | G3V3R6 |
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA164712406 | Antibiotics | Chemical | ClinicalAnnotation | associated | PD | 25869013 | |
| PA444546 | Hypersensitivity | Disease | ClinicalAnnotation | associated | PD | 25869013 |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37815932 | 2024 | Galectin-3 does not interact with RNA directly. | 0 |
| 37988169 | 2024 | Galectin-3 aggravates microglial activation and tau transmission in tauopathy. | 1 |
| 38151436 | 2024 | Association between galectin-3 and the prognosis of patients with stroke: A meta-analysis of observational studies. | 0 |
| 38172822 | 2024 | Inter-relationships of galectin-3 and NLR family pyrin domain containing 3 inflammasomes with oral lichen planus: a preliminary cross-sectional in vitro study. | 0 |
| 38216266 | 2024 | Circulating Galectin-3 levels in women with polycystic ovary syndrome: A meta-analysis. | 0 |
| 38237765 | 2024 | Cigarette smoke-induced galectin-3 as a diagnostic biomarker and therapeutic target in lung tissue remodeling. | 1 |
| 38251657 | 2024 | The Role of Galectin3, Tubulinβ, and Maspin in Promoting Tumor Budding in Colorectal Carcinoma and Their Clinical Implications. | 0 |
| 38310085 | 2024 | Combination of serum alpha-fetoprotein, PIVKA-Ⅱ and glypican-3 in diagnosis of hepatocellular carcinoma: a meta-analysis. | 0 |
| 38310352 | 2024 | Placental expression quantitative trait loci in an East Asian population. | 0 |
| 38371379 | 2024 | Galectin-3 promotes fibrosis in ovarian endometriosis. | 0 |
| 38438589 | 2024 | Targeting Galectin 3 illuminates its contributions to the pathology of uterine serous carcinoma. | 0 |
| 38471823 | 2024 | Galectin-3, Metabolic Risk, and Incident Heart Failure: The ARIC Study. | 0 |
| 38474141 | 2024 | Biophysical and Structural Characterization of the Interaction between Human Galectin-3 and the Lipopolysaccharide from Pseudomonas aeruginosa. | 0 |
| 38474195 | 2024 | BAP31 Promotes Angiogenesis via Galectin-3 Upregulation in Neuroblastoma. | 0 |
| 38561725 | 2024 | Role of Galectin-3 in intervertebral disc degeneration: an experimental study. | 0 |
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
