ID LEG9_RAT Reviewed; 354 AA. AC P97840; O08588; O35866; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 15-JUL-1998, sequence version 2. DT 24-JAN-2024, entry version 148. DE RecName: Full=Galectin-9; DE Short=Gal-9; DE AltName: Full=36 kDa beta-galactoside-binding lectin; DE AltName: Full=Urate transporter/channel; DE Short=UAT; GN Name=Lgals9; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT). RC STRAIN=Sprague-Dawley; TISSUE=Kidney, and Small intestine; RX PubMed=9038233; DOI=10.1074/jbc.272.9.6078; RA Wada J., Kanwar Y.S.; RT "Identification and characterization of galectin-9, a novel beta- RT galactoside-binding mammalian lectin."; RL J. Biol. Chem. 272:6078-6086(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), AND FUNCTION. RC STRAIN=Sprague-Dawley; TISSUE=Kidney; RX PubMed=8995305; DOI=10.1074/jbc.272.1.617; RA Leal-Pinto E., Tao W., Rappaport J., Richardson M., Knorr B.A., RA Abramson R.G.; RT "Molecular cloning and functional reconstitution of a urate RT transporter/channel."; RL J. Biol. Chem. 272:617-625(1997). RN [3] RP FUNCTION, AND INDUCTION. RX PubMed=25158758; DOI=10.1186/s12974-014-0144-0; RA Steelman A.J., Li J.; RT "Astrocyte galectin-9 potentiates microglial TNF secretion."; RL J. Neuroinflamm. 11:144-144(2014). CC -!- FUNCTION: Binds galactosides (By similarity). Has high affinity for the CC Forssman pentasaccharide (By similarity). Ligand for HAVCR2/TIM3 (By CC similarity). Binding to HAVCR2 induces T-helper type 1 lymphocyte (Th1) CC death (By similarity). Also stimulates bactericidal activity in CC infected macrophages by causing macrophage activation and IL1B CC secretion which restricts intracellular bacterial growth (By CC similarity). Ligand for P4HB; the interaction retains P4HB at the cell CC surface of Th2 T helper cells, increasing disulfide reductase activity CC at the plasma membrane, altering the plasma membrane redox state and CC enhancing cell migration (By similarity). Ligand for CD44; the CC interaction enhances binding of SMAD3 to the FOXP3 promoter, leading to CC up-regulation of FOXP3 expression and increased induced regulatory T CC (iTreg) cell stability and suppressive function (By similarity). CC Promotes ability of mesenchymal stromal cells to suppress T-cell CC proliferation (By similarity). Expands regulatory T-cells and induces CC cytotoxic T-cell apoptosis following virus infection (By similarity). CC Activates ERK1/2 phosphorylation inducing cytokine (IL-6, IL-8, IL-12) CC and chemokine (CCL2) production in mast and dendritic cells (By CC similarity). Inhibits degranulation and induces apoptosis of mast cells CC (By similarity). Induces maturation and migration of dendritic cells CC (By similarity). Inhibits natural killer (NK) cell function (By CC similarity). Can transform NK cell phenotype from peripheral to CC decidual during pregnancy (By similarity). Astrocyte derived galectin-9 CC enhances microglial TNF production (PubMed:25158758). May play a role CC in thymocyte-epithelial interactions relevant to the biology of the CC thymus. May provide the molecular basis for urate flux across cell CC membranes, allowing urate that is formed during purine metabolism to CC efflux from cells and serving as an electrogenic transporter that plays CC an important role in renal and gastrointestinal urate excretion CC (PubMed:8995305). Highly selective to the anion urate (PubMed:8995305). CC {ECO:0000250|UniProtKB:O00182, ECO:0000250|UniProtKB:O08573, CC ECO:0000269|PubMed:25158758, ECO:0000269|PubMed:8995305}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:O00182}. Nucleus CC {ECO:0000250|UniProtKB:O00182}. Secreted CC {ECO:0000250|UniProtKB:O00182}. Note=May also be secreted by a non- CC classical secretory pathway. Secreted by mesenchymal stromal cells upon CC IFNG stimulation. {ECO:0000250|UniProtKB:O00182, CC ECO:0000250|UniProtKB:O08573}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Comment=Additional isoforms seem to exist.; CC Name=Long; CC IsoId=P97840-1; Sequence=Displayed; CC Name=Short; CC IsoId=P97840-2; Sequence=VSP_003098; CC -!- TISSUE SPECIFICITY: The isoform Long is expressed exclusively in the CC small intestine. CC -!- INDUCTION: By viral mimic polyinosinic:polycytidylic acid (poly I:C) CC and lipopolysaccharides (LPS) in microglia. CC {ECO:0000269|PubMed:25158758}. CC -!- DOMAIN: Contains two homologous but distinct carbohydrate-binding CC domains. CC -!- MISCELLANEOUS: The LGALS9-like proteins are encoded by a duplicated CC regions on chromosome 17; there are at least 3 genes coding for CC galectin-9-like proteins. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U59462; AAB51192.1; -; mRNA. DR EMBL; U72741; AAB68592.1; -; mRNA. DR EMBL; U67958; AAB48591.1; -; mRNA. DR RefSeq; NP_037109.1; NM_012977.1. DR AlphaFoldDB; P97840; -. DR SMR; P97840; -. DR STRING; 10116.ENSRNOP00000017042; -. DR TCDB; 9.B.9.1.1; the urate transporter (uat) family. DR iPTMnet; P97840; -. DR PhosphoSitePlus; P97840; -. DR jPOST; P97840; -. DR PaxDb; 10116-ENSRNOP00000017042; -. DR GeneID; 25476; -. DR KEGG; rno:25476; -. DR AGR; RGD:3005; -. DR CTD; 3965; -. DR RGD; 3005; Lgals9. DR eggNOG; KOG3587; Eukaryota. DR InParanoid; P97840; -. DR OrthoDB; 4125409at2759; -. DR PhylomeDB; P97840; -. DR PRO; PR:P97840; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0005737; C:cytoplasm; ISO:RGD. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0005615; C:extracellular space; ISO:RGD. DR GO; GO:0005634; C:nucleus; ISO:RGD. DR GO; GO:0005886; C:plasma membrane; IEA:GOC. DR GO; GO:0030246; F:carbohydrate binding; ISS:UniProtKB. DR GO; GO:0048030; F:disaccharide binding; ISO:RGD. DR GO; GO:0019899; F:enzyme binding; ISO:RGD. DR GO; GO:0016936; F:galactoside binding; ISO:RGD. DR GO; GO:0043539; F:protein serine/threonine kinase activator activity; ISO:RGD. DR GO; GO:0005102; F:signaling receptor binding; ISO:RGD. DR GO; GO:0071346; P:cellular response to type II interferon; ISO:RGD. DR GO; GO:0098586; P:cellular response to virus; ISO:RGD. DR GO; GO:0070371; P:ERK1 and ERK2 cascade; ISO:RGD. DR GO; GO:0007565; P:female pregnancy; ISO:RGD. DR GO; GO:0006954; P:inflammatory response; ISO:RGD. DR GO; GO:0045185; P:maintenance of protein location; ISO:RGD. DR GO; GO:0060135; P:maternal process involved in female pregnancy; ISO:RGD. DR GO; GO:0006811; P:monoatomic ion transport; IEA:UniProtKB-KW. DR GO; GO:0002519; P:natural killer cell tolerance induction; ISO:RGD. DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; ISO:RGD. DR GO; GO:2000562; P:negative regulation of CD4-positive, alpha-beta T cell proliferation; ISO:RGD. DR GO; GO:0032682; P:negative regulation of chemokine production; ISO:RGD. DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD. DR GO; GO:0050728; P:negative regulation of inflammatory response; ISO:RGD. DR GO; GO:0043305; P:negative regulation of mast cell degranulation; ISO:RGD. DR GO; GO:0032815; P:negative regulation of natural killer cell activation; ISO:RGD. DR GO; GO:0043322; P:negative regulation of natural killer cell degranulation; ISO:RGD. DR GO; GO:0045953; P:negative regulation of natural killer cell mediated cytotoxicity; ISO:RGD. DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; ISO:RGD. DR GO; GO:0032689; P:negative regulation of type II interferon production; ISO:RGD. DR GO; GO:0038066; P:p38MAPK cascade; ISO:RGD. DR GO; GO:0070241; P:positive regulation of activated T cell autonomous cell death; ISO:RGD. DR GO; GO:2000563; P:positive regulation of CD4-positive, alpha-beta T cell proliferation; ISO:RGD. DR GO; GO:0032834; P:positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation involved in immune response; ISO:RGD. DR GO; GO:0032722; P:positive regulation of chemokine production; ISO:RGD. DR GO; GO:0001819; P:positive regulation of cytokine production; ISO:RGD. DR GO; GO:1900426; P:positive regulation of defense response to bacterium; ISO:RGD. DR GO; GO:2000670; P:positive regulation of dendritic cell apoptotic process; ISO:RGD. DR GO; GO:2000510; P:positive regulation of dendritic cell chemotaxis; ISO:RGD. DR GO; GO:2001200; P:positive regulation of dendritic cell differentiation; ISO:RGD. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD. DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD. DR GO; GO:0045089; P:positive regulation of innate immune response; ISO:RGD. DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISO:RGD. DR GO; GO:0032732; P:positive regulation of interleukin-1 production; ISO:RGD. DR GO; GO:0032733; P:positive regulation of interleukin-10 production; ISO:RGD. DR GO; GO:0032735; P:positive regulation of interleukin-12 production; ISO:RGD. DR GO; GO:0032736; P:positive regulation of interleukin-13 production; ISO:RGD. DR GO; GO:0032753; P:positive regulation of interleukin-4 production; ISO:RGD. DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:RGD. DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:RGD. DR GO; GO:0043032; P:positive regulation of macrophage activation; ISO:RGD. DR GO; GO:0071639; P:positive regulation of monocyte chemotactic protein-1 production; ISO:RGD. DR GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; ISO:RGD. DR GO; GO:0045591; P:positive regulation of regulatory T cell differentiation; ISO:RGD. DR GO; GO:0060391; P:positive regulation of SMAD protein signal transduction; ISO:RGD. DR GO; GO:2001190; P:positive regulation of T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cell; ISO:RGD. DR GO; GO:2000406; P:positive regulation of T cell migration; ISO:RGD. DR GO; GO:0071636; P:positive regulation of transforming growth factor beta production; ISO:RGD. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:RGD. DR GO; GO:0032729; P:positive regulation of type II interferon production; ISO:RGD. DR GO; GO:0046598; P:positive regulation of viral entry into host cell; ISO:RGD. DR GO; GO:0043113; P:receptor clustering; ISO:RGD. DR GO; GO:0032823; P:regulation of natural killer cell differentiation; ISO:RGD. DR GO; GO:0070555; P:response to interleukin-1; ISO:RGD. DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:RGD. DR GO; GO:0034138; P:toll-like receptor 3 signaling pathway; IMP:UniProtKB. DR GO; GO:0007179; P:transforming growth factor beta receptor signaling pathway; ISO:RGD. DR CDD; cd00070; GLECT; 2. DR Gene3D; 2.60.120.200; -; 2. DR InterPro; IPR013320; ConA-like_dom_sf. DR InterPro; IPR044156; Galectin-like. DR InterPro; IPR001079; Galectin_CRD. DR PANTHER; PTHR11346; GALECTIN; 1. DR PANTHER; PTHR11346:SF80; GALECTIN-9C; 1. DR Pfam; PF00337; Gal-bind_lectin; 2. DR SMART; SM00908; Gal-bind_lectin; 2. DR SMART; SM00276; GLECT; 2. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 2. DR PROSITE; PS51304; GALECTIN; 2. PE 2: Evidence at transcript level; KW Alternative splicing; Cytoplasm; Immunity; Ion transport; Lectin; Nucleus; KW Reference proteome; Repeat; Secreted; Transport. FT CHAIN 1..354 FT /note="Galectin-9" FT /id="PRO_0000076948" FT DOMAIN 17..147 FT /note="Galectin 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00639" FT DOMAIN 226..354 FT /note="Galectin 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00639" FT BINDING 47 FT /ligand="a beta-D-galactoside" FT /ligand_id="ChEBI:CHEBI:28034" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 60 FT /ligand="a beta-D-galactoside" FT /ligand_id="ChEBI:CHEBI:28034" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 64 FT /ligand="a beta-D-galactoside" FT /ligand_id="ChEBI:CHEBI:28034" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 74 FT /ligand="a beta-D-galactoside" FT /ligand_id="ChEBI:CHEBI:28034" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 81..87 FT /ligand="a beta-D-galactoside" FT /ligand_id="ChEBI:CHEBI:28034" FT /ligand_label="1" FT /evidence="ECO:0000250" FT BINDING 266 FT /ligand="a beta-D-galactoside" FT /ligand_id="ChEBI:CHEBI:28034" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 270 FT /ligand="a beta-D-galactoside" FT /ligand_id="ChEBI:CHEBI:28034" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 280 FT /ligand="a beta-D-galactoside" FT /ligand_id="ChEBI:CHEBI:28034" FT /ligand_label="2" FT /evidence="ECO:0000250" FT BINDING 286..292 FT /ligand="a beta-D-galactoside" FT /ligand_id="ChEBI:CHEBI:28034" FT /ligand_label="2" FT /evidence="ECO:0000250" FT VAR_SEQ 148..179 FT /note="Missing (in isoform Short)" FT /evidence="ECO:0000303|PubMed:8995305, FT ECO:0000303|PubMed:9038233" FT /id="VSP_003098" SQ SEQUENCE 354 AA; 39946 MW; 6574F960B2EAF37C CRC64; MAFFSTQPPY MNPVIPFTGI IQGGLQNGLQ ITLQGTVHPF PNRIAVNFQT GFSGNDIAFH FNPRFEEGGY VVCNTKQNGK WGPEERKMQM PFQKGMPFEL CFLVQRSEFK VMVNKNFFVQ YSHRVPYHLV DTISVSGCLH LSFINFQNST AAPVQPVFST MQFSQPVQFP RMPKGRKQRT QGFQPALQAP VAQTIIHTVH SIPGQMLSTP GIPPMAYPTP AYTIPFFTSI PNGFYPSKSI NISGVVLPDA KRFHINLRCG GDIAFHLNPR FNEKVVVRNT QINNSWGPEE RSLPGRMPFN RGQSFSVWIL CEGHCFKVAV DGQHICEYYH RLKNLPDINT LEVAGDIQLT HVQT //