Galectin-9 (LGALS9)

The protein contains 355 amino acids for an estimated molecular weight of 39518 Da.

 

Binds galactosides (PubMed:18005988). Has high affinity for the Forssman pentasaccharide (PubMed:18005988). Ligand for HAVCR2/TIM3 (PubMed:16286920). Binding to HAVCR2 induces T-helper type 1 lymphocyte (Th1) death (PubMed:16286920). Also stimulates bactericidal activity in infected macrophages by causing macrophage activation and IL1B secretion which restricts intracellular bacterial growth (By similarity). Ligand for P4HB; the interaction retains P4HB at the cell surface of Th2 T-helper cells, increasing disulfide reductase activity at the plasma membrane, altering the plasma membrane redox state and enhancing cell migration (PubMed:21670307). Ligand for CD44; the interaction enhances binding of SMAD3 to the FOXP3 promoter, leading to up-regulation of FOXP3 expression and increased induced regulatory T (iTreg) cell stability and suppressive function (By similarity). Promotes ability of mesenchymal stromal cells to suppress T-cell proliferation (PubMed:23817958). Expands regulatory T-cells and induces cytotoxic T-cell apoptosis following virus infection (PubMed:20209097). Activates ERK1/2 phosphorylation inducing cytokine (IL-6, IL-8, IL-12) and chemokine (CCL2) production in mast and dendritic cells (PubMed:24465902, PubMed:16116184). Inhibits degranulation and induces apoptosis of mast cells (PubMed:24465902). Induces maturation and migration of dendritic cells (PubMed:25754930, PubMed:16116184). Inhibits natural killer (NK) cell function (PubMed:23408620). Can transform (updated: Nov. 22, 2017)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. 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.
  3. 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.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  6. 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.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

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.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 83%
Model score: 37

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VariantDescription
dbSNP:rs3751093

Biological Process

Cellular response to interferon-gamma GO Logo
Cellular response to virus GO Logo
Chemotaxis GO Logo
ERK1 and ERK2 cascade GO Logo
Female pregnancy GO Logo
Inflammatory response GO Logo
Maternal process involved in female pregnancy GO Logo
Natural killer cell tolerance induction GO Logo
Negative regulation of activated T cell proliferation GO Logo
Negative regulation of CD4-positive, alpha-beta T cell proliferation GO Logo
Negative regulation of chemokine production GO Logo
Negative regulation of gene expression GO Logo
Negative regulation of interferon-gamma production GO Logo
Negative regulation of mast cell degranulation GO Logo
Negative regulation of natural killer cell mediated cytotoxicity GO Logo
Negative regulation of tumor necrosis factor production GO Logo
P38MAPK cascade GO Logo
Positive regulation of activated T cell autonomous cell death GO Logo
Positive regulation of CD4-positive, alpha-beta T cell proliferation GO Logo
Positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation involved in immune response GO Logo
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway GO Logo
Positive regulation of dendritic cell apoptotic process GO Logo
Positive regulation of dendritic cell chemotaxis GO Logo
Positive regulation of dendritic cell differentiation GO Logo
Positive regulation of ERK1 and ERK2 cascade GO Logo
Positive regulation of gene expression GO Logo
Positive regulation of I-kappaB kinase/NF-kappaB signaling GO Logo
Positive regulation of interferon-gamma production GO Logo
Positive regulation of interferon-gamma secretion GO Logo
Positive regulation of interleukin-1 beta production GO Logo
Positive regulation of interleukin-1 beta secretion GO Logo
Positive regulation of interleukin-10 production GO Logo
Positive regulation of interleukin-10 secretion GO Logo
Positive regulation of interleukin-12 production GO Logo
Positive regulation of interleukin-12 secretion GO Logo
Positive regulation of interleukin-13 production GO Logo
Positive regulation of interleukin-13 secretion GO Logo
Positive regulation of interleukin-4 production GO Logo
Positive regulation of interleukin-6 production GO Logo
Positive regulation of interleukin-6 secretion GO Logo
Positive regulation of interleukin-8 production GO Logo
Positive regulation of interleukin-8 secretion GO Logo
Positive regulation of monocyte chemotactic protein-1 production GO Logo
Positive regulation of NF-kappaB import into nucleus GO Logo
Positive regulation of NF-kappaB transcription factor activity GO Logo
Positive regulation of NIK/NF-kappaB signaling GO Logo
Positive regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell GO Logo
Positive regulation of transforming growth factor beta production GO Logo
Positive regulation of tumor necrosis factor production GO Logo
Positive regulation of tumor necrosis factor secretion GO Logo
Positive regulation of viral entry into host cell GO Logo
Response to interleukin-1 GO Logo
Response to lipopolysaccharide GO Logo
Signal transduction GO Logo

The reference OMIM entry for this protein is 601879

Lectin, galactoside-binding, soluble, 9; lgals9
Galectin 9 ecalectin, included

DESCRIPTION

Specific interactions between carbohydrate moieties and their putative binding proteins (i.e., lectins) play a critical role in various developmental, physiologic, and pathologic processes. Mammalian lectins are classified into 4 categories: C-type lectins (including selectins), P-type lectins, pentraxins, and galectins. Wada et al. (1997) stated that 10 mammalian galectins had been cloned, sequenced, and functionally characterized, namely galectin-1 to -10 (see 150570).

CLONING

Galectin-9 was isolated from mouse embryonic kidney and characterized by Wada and Kanwar (1997). From studies of its expression in embryonic, newborn, and adult mouse tissues, Wada et al. (1997) demonstrated that its expression is widely distributed and developmentally regulated. Its expression was accentuated in liver and thymus of embryonic mice. In postnatal mice, antigalectin-9 immunoreactivity was observed in various tissues, including thymic epithelial cells. Galectin-9 induced apoptosis in thymocytes but not in hepatocytes. Wada et al. (1997) concluded that galectin-9 plays a role in thymocyte-epithelial interactions relevant to the biology of the thymus. Tureci et al. (1997) used autologous serum to immunoscreen a cDNA expression library derived from tissue involved by Hodgkin disease (236000). They detected a 36-kD protein with the galactoside-binding characteristics of galectins. This human galectin, galectin-9, has a predicted length of 323 amino acids and shares sequence similarity with other galectins. Ecalectin is an eosinophil chemoattractant (ECA) produced by antigen-activated T cells. Matsumoto et al. (1998) partially purified ecalectin from the conditioned medium of a human T cell-derived cell line. By screening a human T-cell cDNA expression library with antibodies against ecalectin, they isolated cDNAs encoding ecalectin. The deduced ecalectin protein has 323 amino acids. Although ecalectin is secreted, it lacks a predicted hydrophobic signal peptide. Ecalectin is not related to any known cytokine or chemokine but rather is related to the galectin family of carbohydrate-binding proteins. Matsumoto et al. (1998) stated that ecalectin and galectin-9 are likely 2 allelic variants of the same gene because they encode deduced proteins that differ by only a few amino acids, they have identical 5-prime untranslated regions (UTRs), their 3-prime UTRs differ by only 1 nucleotide, and both are expressed in peripheral blood cells. Recombinant ecalectin expressed in COS cells or insect cells exhibited potent ECA activity and attracted eosinophils in vitro and in vivo in a dose-dependent manner; ecalectin did not induce chemotaxis of neutrophils, lymphocytes, or monocytes. Northern blot analysis of human tissues detected an approximately 1.8-kb ecalectin transcript that was expressed most abundantly in lymphoid tissues, namely spleen and peripheral blood lymphocytes, and at lower levels in stomach, small intestine, and lung. Ecalectin expression increased substantially in antigen-activated peripheral blood mononuclear cells. Matsumoto et al. (1998) suggested that ecalectin is an important T cell-derived regulator of eosinophil recruitment in tissues during inflammatory reactions. ... More on the omim web site

Subscribe to this protein entry history

Feb. 10, 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

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 25, 2017: Additional information
No protein expression data in P. Mayeux work for LGALS9

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 601879 was added.

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed