Galectin-9

Details

Name
Galectin-9
Synonyms
  • Ecalectin
  • Gal-9
  • Tumor antigen HOM-HD-21
Gene Name
LGALS9
Organism
Humans
Amino acid sequence
>lcl|BSEQ0008235|Galectin-9
MAFSGSQAPYLSPAVPFSGTIQGGLQDGLQITVNGTVLSSSGTRFAVNFQTGFSGNDIAF
HFNPRFEDGGYVVCNTRQNGSWGPEERKTHMPFQKGMPFDLCFLVQSSDFKVMVNGILFV
QYFHRVPFHRVDTISVNGSVQLSYISFQNPRTVPVQPAFSTVPFSQPVCFPPRPRGRRQK
PPGVWPANPAPITQTVIHTVQSAPGQMFSTPAIPPMMYPHPAYPMPFITTILGGLYPSKS
ILLSGTVLPSAQRFHINLCSGNHIAFHLNPRFDENAVVRNTQIDNSWGSEERSLPRKMPF
VRGQSFSVWILCEAHCLKVAVDGQHLFEYYHRLRNLPTINRLEVGGDIQLTHVQT
Number of residues
355
Molecular Weight
39517.98
Theoretical pI
9.41
GO Classification
Functions
carbohydrate binding / disaccharide binding / enzyme binding / galactose binding / signal transducer activity
Processes
cellular response to interferon-gamma / cellular response to virus / chemotaxis / ERK1 and ERK2 cascade / female pregnancy / inflammatory response / maternal process involved in female pregnancy / natural killer cell tolerance induction / negative regulation of activated T cell proliferation / negative regulation of CD4-positive, alpha-beta T cell proliferation / negative regulation of chemokine production / negative regulation of gene expression / negative regulation of interferon-gamma production / negative regulation of mast cell degranulation / negative regulation of natural killer cell mediated cytotoxicity / negative regulation of tumor necrosis factor production / p38MAPK cascade / positive regulation of activated T cell autonomous cell death / positive regulation of CD4-positive, alpha-beta T cell proliferation / positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation involved in immune response / positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway / positive regulation of dendritic cell apoptotic process / positive regulation of dendritic cell chemotaxis / positive regulation of dendritic cell differentiation / positive regulation of ERK1 and ERK2 cascade / positive regulation of gene expression / positive regulation of I-kappaB kinase/NF-kappaB signaling / positive regulation of interferon-gamma secretion / positive regulation of interleukin-1 beta secretion / positive regulation of interleukin-10 secretion / positive regulation of interleukin-12 secretion / positive regulation of interleukin-13 secretion / positive regulation of interleukin-4 production / positive regulation of interleukin-6 secretion / positive regulation of interleukin-8 secretion / positive regulation of monocyte chemotactic protein-1 production / positive regulation of NF-kappaB import into nucleus / positive regulation of NF-kappaB transcription factor activity / positive regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell / positive regulation of transforming growth factor beta production / positive regulation of tumor necrosis factor secretion / positive regulation of viral entry into host cell / response to interleukin-1 / response to lipopolysaccharide
Components
cytoplasm / extracellular exosome / extracellular space / intracellular / nucleus
General Function
Signal transducer activity
Specific Function
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 NK cell phenotype from peripheral to decidual during pregnancy (PubMed:25578313). Astrocyte derived galectin-9 enhances microglial TNF production (By similarity). May play a role in thymocyte-epithelial interactions relevant to the biology of the thymus. May provide the molecular basis for urate flux across cell membranes, allowing urate that is formed during purine metabolism to efflux from cells and serving as an electrogenic transporter that plays an important role in renal and gastrointestinal urate excretion (By similarity). Highly selective to the anion urate (By similarity).Isoform 2: Acts as an eosinophil chemoattractant (PubMed:9642261). It also inhibits angiogenesis (PubMed:24333696). Suppresses IFNG production by natural killer cells (By similarity).
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasm
Gene sequence
>lcl|BSEQ0021868|Galectin-9 (LGALS9)
ATGGCCTTCAGCGGTTCCCAGGCTCCCTACCTGAGTCCAGCTGTCCCCTTTTCTGGGACT
ATTCAAGGAGGTCTCCAGGACGGACTTCAGATCACTGTCAATGGGACCGTTCTCAGCTCC
AGTGGAACCAGGTTTGCTGTGAACTTTCAGACTGGCTTCAGTGGAAATGACATTGCCTTC
CACTTCAACCCTCGGTTTGAAGATGGAGGGTACGTGGTGTGCAACACGAGGCAGAACGGA
AGCTGGGGGCCCGAGGAGAGGAAGACACACATGCCTTTCCAGAAGGGGATGCCCTTTGAC
CTCTGCTTCCTGGTGCAGAGCTCAGATTTCAAGGTGATGGTGAACGGGATCCTCTTCGTG
CAGTACTTCCACCGCGTGCCCTTCCACCGTGTGGACACCATCTCCGTCAATGGCTCTGTG
CAGCTGTCCTACATCAGCTTCCAGCCTCCCGGCGTGTGGCCTGCCAACCCGGCTCCCATT
ACCCAGACAGTCATCCACACAGTGCAGAGCGCCCCTGGACAGATGTTCTCTACTCCCGCC
ATCCCACCTATGATGTACCCCCACCCCGCCTATCCGATGCCTTTCATCACCACCATTCTG
GGAGGGCTGTACCCATCCAAGTCCATCCTCCTGTCAGGCACTGTCCTGCCCAGTGCTCAG
AGGTTCCACATCAACCTGTGCTCTGGGAACCACATCGCCTTCCACCTGAACCCCCGTTTT
GATGAGAATGCTGTGGTCCGCAACACCCAGATCGACAACTCCTGGGGGTCTGAGGAGCGA
AGTCTGCCCCGAAAAATGCCCTTCGTCCGTGGCCAGAGCTTCTCAGTGTGGATCTTGTGT
GAAGCTCACTGCCTCAAGGTGGCCGTGGATGGTCAGCACCTGTTTGAATACTACCATCGC
CTGAGGAACCTGCCCACCATCAACAGACTGGAAGTGGGGGGCGACATCCAGCTGACCCAT
GTGCAGACATAG
Chromosome Location
17
Locus
17q11.2
External Identifiers
ResourceLink
UniProtKB IDO00182
UniProtKB Entry NameLEG9_HUMAN
GenBank Protein ID1924954
GenBank Gene IDZ49107
HGNC IDHGNC:6570
General References
  1. Tureci O, Schmitt H, Fadle N, Pfreundschuh M, Sahin U: Molecular definition of a novel human galectin which is immunogenic in patients with Hodgkin's disease. J Biol Chem. 1997 Mar 7;272(10):6416-22. [Article]
  2. Matsumoto R, Matsumoto H, Seki M, Hata M, Asano Y, Kanegasaki S, Stevens RL, Hirashima M: Human ecalectin, a variant of human galectin-9, is a novel eosinophil chemoattractant produced by T lymphocytes. J Biol Chem. 1998 Jul 3;273(27):16976-84. [Article]
  3. Zody MC, Garber M, Adams DJ, Sharpe T, Harrow J, Lupski JR, Nicholson C, Searle SM, Wilming L, Young SK, Abouelleil A, Allen NR, Bi W, Bloom T, Borowsky ML, Bugalter BE, Butler J, Chang JL, Chen CK, Cook A, Corum B, Cuomo CA, de Jong PJ, DeCaprio D, Dewar K, FitzGerald M, Gilbert J, Gibson R, Gnerre S, Goldstein S, Grafham DV, Grocock R, Hafez N, Hagopian DS, Hart E, Norman CH, Humphray S, Jaffe DB, Jones M, Kamal M, Khodiyar VK, LaButti K, Laird G, Lehoczky J, Liu X, Lokyitsang T, Loveland J, Lui A, Macdonald P, Major JE, Matthews L, Mauceli E, McCarroll SA, Mihalev AH, Mudge J, Nguyen C, Nicol R, O'Leary SB, Osoegawa K, Schwartz DC, Shaw-Smith C, Stankiewicz P, Steward C, Swarbreck D, Venkataraman V, Whittaker CA, Yang X, Zimmer AR, Bradley A, Hubbard T, Birren BW, Rogers J, Lander ES, Nusbaum C: DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature. 2006 Apr 20;440(7087):1045-9. [Article]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  5. Dai SY, Nakagawa R, Itoh A, Murakami H, Kashio Y, Abe H, Katoh S, Kontani K, Kihara M, Zhang SL, Hata T, Nakamura T, Yamauchi A, Hirashima M: Galectin-9 induces maturation of human monocyte-derived dendritic cells. J Immunol. 2005 Sep 1;175(5):2974-81. [Article]
  6. Zhu C, Anderson AC, Schubart A, Xiong H, Imitola J, Khoury SJ, Zheng XX, Strom TB, Kuchroo VK: The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nat Immunol. 2005 Dec;6(12):1245-52. Epub 2005 Nov 13. [Article]
  7. Mengshol JA, Golden-Mason L, Arikawa T, Smith M, Niki T, McWilliams R, Randall JA, McMahan R, Zimmerman MA, Rangachari M, Dobrinskikh E, Busson P, Polyak SJ, Hirashima M, Rosen HR: A crucial role for Kupffer cell-derived galectin-9 in regulation of T cell immunity in hepatitis C infection. PLoS One. 2010 Mar 4;5(3):e9504. doi: 10.1371/journal.pone.0009504. [Article]
  8. Bi S, Hong PW, Lee B, Baum LG: Galectin-9 binding to cell surface protein disulfide isomerase regulates the redox environment to enhance T-cell migration and HIV entry. Proc Natl Acad Sci U S A. 2011 Jun 28;108(26):10650-5. doi: 10.1073/pnas.1017954108. Epub 2011 Jun 13. [Article]
  9. Heusschen R, Freitag N, Tirado-Gonzalez I, Barrientos G, Moschansky P, Munoz-Fernandez R, Leno-Duran E, Klapp BF, Thijssen VL, Blois SM: Profiling Lgals9 splice variant expression at the fetal-maternal interface: implications in normal and pathological human pregnancy. Biol Reprod. 2013 Jan 25;88(1):22. doi: 10.1095/biolreprod.112.105460. Print 2013 Jan. [Article]
  10. Gieseke F, Kruchen A, Tzaribachev N, Bentzien F, Dominici M, Muller I: Proinflammatory stimuli induce galectin-9 in human mesenchymal stromal cells to suppress T-cell proliferation. Eur J Immunol. 2013 Oct;43(10):2741-9. doi: 10.1002/eji.201343335. Epub 2013 Jul 23. [Article]
  11. Golden-Mason L, McMahan RH, Strong M, Reisdorph R, Mahaffey S, Palmer BE, Cheng L, Kulesza C, Hirashima M, Niki T, Rosen HR: Galectin-9 functionally impairs natural killer cells in humans and mice. J Virol. 2013 May;87(9):4835-45. doi: 10.1128/JVI.01085-12. Epub 2013 Feb 13. [Article]
  12. Tandon R, Chew GM, Byron MM, Borrow P, Niki T, Hirashima M, Barbour JD, Norris PJ, Lanteri MC, Martin JN, Deeks SG, Ndhlovu LC: Galectin-9 is rapidly released during acute HIV-1 infection and remains sustained at high levels despite viral suppression even in elite controllers. AIDS Res Hum Retroviruses. 2014 Jul;30(7):654-64. doi: 10.1089/AID.2014.0004. Epub 2014 May 28. [Article]
  13. Heusschen R, Schulkens IA, van Beijnum J, Griffioen AW, Thijssen VL: Endothelial LGALS9 splice variant expression in endothelial cell biology and angiogenesis. Biochim Biophys Acta. 2014 Feb;1842(2):284-92. doi: 10.1016/j.bbadis.2013.12.003. Epub 2013 Dec 12. [Article]
  14. Kojima R, Ohno T, Iikura M, Niki T, Hirashima M, Iwaya K, Tsuda H, Nonoyama S, Matsuda A, Saito H, Matsumoto K, Nakae S: Galectin-9 enhances cytokine secretion, but suppresses survival and degranulation, in human mast cell line. PLoS One. 2014 Jan 20;9(1):e86106. doi: 10.1371/journal.pone.0086106. eCollection 2014. [Article]
  15. Li YH, Zhou WH, Tao Y, Wang SC, Jiang YL, Zhang D, Piao HL, Fu Q, Li DJ, Du MR: The Galectin-9/Tim-3 pathway is involved in the regulation of NK cell function at the maternal-fetal interface in early pregnancy. Cell Mol Immunol. 2016 Jan;13(1):73-81. doi: 10.1038/cmi.2014.126. Epub 2015 Jan 12. [Article]
  16. Hsu YL, Wang MY, Ho LJ, Huang CY, Lai JH: Up-regulation of galectin-9 induces cell migration in human dendritic cells infected with dengue virus. J Cell Mol Med. 2015 May;19(5):1065-76. doi: 10.1111/jcmm.12500. Epub 2015 Mar 6. [Article]
  17. Nagae M, Nishi N, Nakamura-Tsuruta S, Hirabayashi J, Wakatsuki S, Kato R: Structural analysis of the human galectin-9 N-terminal carbohydrate recognition domain reveals unexpected properties that differ from the mouse orthologue. J Mol Biol. 2008 Jan 4;375(1):119-35. Epub 2007 Sep 26. [Article]
  18. Nagae M, Nishi N, Murata T, Usui T, Nakamura T, Wakatsuki S, Kato R: Structural analysis of the recognition mechanism of poly-N-acetyllactosamine by the human galectin-9 N-terminal carbohydrate recognition domain. Glycobiology. 2009 Feb;19(2):112-7. doi: 10.1093/glycob/cwn121. Epub 2008 Oct 31. [Article]
  19. Yoshida H, Teraoka M, Nishi N, Nakakita S, Nakamura T, Hirashima M, Kamitori S: X-ray structures of human galectin-9 C-terminal domain in complexes with a biantennary oligosaccharide and sialyllactose. J Biol Chem. 2010 Nov 19;285(47):36969-76. doi: 10.1074/jbc.M110.163402. Epub 2010 Sep 22. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB04472(R)-1-Para-Nitro-Phenyl-2-Azido-EthanolexperimentalunknownDetails