LEG9_RAT
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 03-AUG-2022, entry version 143.
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_012977.1.
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; P97840; -.
DR GeneID; 25476; -.
DR KEGG; rno:25476; -.
DR CTD; 3965; -.
DR RGD; 3005; Lgals9.
DR eggNOG; KOG3587; Eukaryota.
DR InParanoid; P97840; -.
DR OrthoDB; 829777at2759; -.
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: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 interferon-gamma; 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:0006811; P:ion transport; IEA:UniProtKB-KW.
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: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:0032689; P:negative regulation of interferon-gamma production; 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: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:2001269; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway; 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:0032729; P:positive regulation of interferon-gamma production; 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:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:RGD.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO:RGD.
DR GO; GO:0051353; P:positive regulation of oxidoreductase activity; ISO:RGD.
DR GO; GO:0010862; P:positive regulation of pathway-restricted SMAD protein phosphorylation; ISO:RGD.
DR GO; GO:0045591; P:positive regulation of regulatory T cell differentiation; 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:2000679; P:positive regulation of transcription regulatory region DNA binding; 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:0046598; P:positive regulation of viral entry into host cell; 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 CDD; cd00070; GLECT; 2.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR044156; Galectin-like.
DR InterPro; IPR001079; Galectin_CRD.
DR PANTHER; PTHR11346; PTHR11346; 1.
DR Pfam; PF00337; Gal-bind_lectin; 2.
DR SMART; SM00908; Gal-bind_lectin; 2.
DR SMART; SM00276; GLECT; 2.
DR SUPFAM; SSF49899; SSF49899; 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
