Galectin-3 (LGALS3)
The protein contains 250 amino acids for an estimated molecular weight of 26152 Da.
Galactose-specific lectin which binds IgE. May mediate with the alpha-3, beta-1 integrin the stimulation by CSPG4 of endothelial cells migration. Together with DMBT1, required for terminal differentiation of columnar epithelial cells during early embryogenesis (By similarity). In the nucleus: acts as a pre-mRNA splicing factor. Involved in acute inflammatory responses including neutrophil activation and adhesion, chemoattraction of monocytes macrophages, opsonization of apoptotic neutrophils, and activation of mast cells. Together with TRIM16, coordinates the recognition of membrane damage with mobilization of the core autophagy regulators ATG16L1 and BECN1 in response to damaged endomembranes. (updated: Nov. 7, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
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| Variant | Description |
|---|---|
| dbSNP:rs4644 | |
| dbSNP:rs4652 | |
| dbSNP:rs10148371 |
Biological Process
Antimicrobial humoral immune response mediated by antimicrobial peptide
Eosinophil chemotaxis
Epithelial cell differentiation
Extracellular matrix organization
Innate immune response
Killing of cells of other organism
Macrophage chemotaxis
Monocyte chemotaxis
Mononuclear cell migration
MRNA processing
Negative regulation of endocytosis
Negative regulation of extrinsic apoptotic signaling pathway
Negative regulation of immunological synapse formation
Negative regulation of protein tyrosine phosphatase activity
Negative regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell
Negative regulation of T cell receptor signaling pathway
Neutrophil chemotaxis
Neutrophil degranulation
Positive chemotaxis
Positive regulation of calcium ion import
Positive regulation of mononuclear cell migration
Positive regulation of protein homodimerization activity
Positive regulation of protein localization to plasma membrane
Positive regulation of protein-containing complex assembly
Regulation of extrinsic apoptotic signaling pathway via death domain receptors
Regulation of myeloid cell differentiation
Regulation of T cell apoptotic process
Regulation of T cell proliferation
RNA splicing
Skeletal system development
Cellular Component
Cell surface
Collagen-containing extracellular matrix
Cytoplasm
External side of plasma membrane
Extracellular exosome
Extracellular matrix
Extracellular region
Extracellular space
Ficolin-1-rich granule membrane
Immunological synapse
Membrane
Mitochondrial inner membrane
Nucleus
Obsolete other organism cell
Plasma membrane
Proteinaceous extracellular matrix
Secretory granule membrane
Spliceosomal complex
The reference OMIM entry for this protein is 153619
Lectin, galactoside-binding, soluble, 3; lgals3
Macrophage galactose-specific lectin; mac2
Galactoside-binding protein; galbp
Galectin 3; gal3 galectin 3 internal gene, included; galig, included
CLONING
The murine Mac2 protein is a galactose- and IgE-binding lectin secreted by inflammatory macrophages. Cherayil et al. (1990) cloned and characterized a cDNA representing the human homolog. The amino acid sequence derived therefrom indicated that the protein is evolutionarily highly conserved, especially in the C-terminal lectin domain. Human MAC2 synthesized in vitro is recognized by a monoclonal antibody to mouse Mac2 and behaves like a galactose-specific lectin in its binding to the desialylated glycoprotein asialofetuin. It also binds to purified laminin (see 150320), indicating a potential role in macrophage extracellular matrix interactions. MAC2 is also known as galectin-3 (LGALS3), as mentioned in Madsen et al., (1995). From a human fibrosarcoma cDNA library, Raz et al. (1991) cloned a galactoside-binding protein with a molecular weight of 31,000. The deduced 242-amino acid protein has the characteristics of a carbohydrate-binding protein. The deduced amino acid sequence contains 95 residues at the N terminus that are homologous to the predicted amino acid sequence of the second exon of the oncogene LMYC (164850). Huflejt et al. (1997) found that LGALS3 and LGALS4 (602518) have very different cellular localizations in human colon adenocarcinoma T84 cells, suggesting that these LGALSs have different targeting mechanisms, ligands, and functions. In confluent T84 cells, LGALS3 is concentrated mainly at the apical membrane in large granular inclusions. In subconfluent T84 cells, it is distributed along most of the cell periphery and is concentrated in the posterior part of lamellipodia. By RT-PCR of a human osteosarcoma cell line, Raimond et al. (1995) identified galectin-3 transcripts initiated from the promoter upstream of exon 1 and from the internal promoter within intron 2. Using RT-PCR and EST database analysis, Guittaut et al. (2001) obtained transcripts originating from the internal promoter in intron 2 of LGALS3 from several cDNA libraries. They concluded that these transcripts arise from a gene embedded within LGALS3 that they called 'galectin-3 internal gene,' or GALIG. The GALIG transcripts contain 2 overlapping ORFs, ORF1 and ORF2, that initiate in exon 3 of LGALS3 and are out-of-frame relative to the LGALS3 coding sequence. RT-PCR detected variable and tissue-specific expression of LGALS3 and GALIG transcripts. GALIG transcripts showed highest expression in peripheral blood leukocytes, but overall they were much less abundant than LGALS3 transcripts. In transfected osteosarcoma cells, fluorescence-tagged ORF1 localized to cytosol and nucleus, and fluorescence-tagged ORF2 localized to mitochondria.GENE FUNCTION
Galectin-3 is expressed in various tissues and organs, but is significantly absent in normal hepatocytes. However, evaluation of patient liver biopsies for galectin-3 expression revealed that hepatocellular carcinoma (HCC) frequently expressed significant levels of this lectin; 76% were immunohistochemically positive. Further investigations showed that galectin-3 expression in HCC is independent of whether the patient had prior hepatitis B virus infection (Hsu et al., 1999). Hsu et al. (1999) suggested that deregulated expression of galectin-3 can result in tumor transformation and invasiveness, or confer propensity for tumor cell survival. Using reporter gene assays, Raimond et al. (1995) showed that p53 (TP53; 191170) downregulated expression of the GALIG promoter when cotransfected ... More on the omim web site
Nov. 16, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 153619 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed