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   02-SEP-2026, entry version 154.
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.
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DR   EMBL; U59462; AAB51192.1; -; mRNA.
DR   EMBL; U72741; AAB68592.1; -; mRNA.
DR   EMBL; U67958; AAB48591.1; -; mRNA.
DR   RefSeq; NP_037109.1; NM_012977.2.
DR   AlphaFoldDB; P97840; -.
DR   SMR; P97840; -.
DR   FunCoup; P97840; 132.
DR   STRING; 10116.ENSRNOP00000017042; -.
DR   TCDB; 9.B.9.1.1; the urate transporter (uat) family.
DR   GlyGen; P97840; 1 site.
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; 5795596at2759; -.
DR   PhylomeDB; P97840; -.
DR   PRO; PR:P97840; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0030246; F:carbohydrate binding; ISS:UniProtKB.
DR   GO; GO:0016936; F:galactoside binding; IBA:GO_Central.
DR   GO; GO:2000562; P:negative regulation of CD4-positive, alpha-beta T cell proliferation; IBA:GO_Central.
DR   GO; GO:0032689; P:negative regulation of type II interferon production; IBA:GO_Central.
DR   GO; GO:0010628; P:positive regulation of gene expression; IBA:GO_Central.
DR   GO; GO:0034138; P:toll-like receptor 3 signaling pathway; IMP:UniProtKB.
DR   CDD; cd00070; GLECT; 2.
DR   FunFam; 2.60.120.200:FF:000023; Galectin; 1.
DR   FunFam; 2.60.120.200:FF:000078; Galectin; 1.
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
//