LY96_MOUSE
ID LY96_MOUSE Reviewed; 160 AA.
AC Q9JHF9;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Lymphocyte antigen 96;
DE Short=Ly-96;
DE AltName: Full=ESOP-1 {ECO:0000303|PubMed:10891475};
DE AltName: Full=Protein MD-2;
DE Flags: Precursor;
GN Name=Ly96; Synonyms=Esop1, Md2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=10891475;
RA Kato K., Morrison A.M., Nakano T., Tashiro K., Honjo T.;
RT "ESOP-1, a secreted protein expressed in the hematopoietic, nervous, and
RT reproductive systems of embryonic and adult mice.";
RL Blood 96:362-364(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND
RP INTERACTION WITH TLR4.
RC TISSUE=Kidney;
RX PubMed=10725698; DOI=10.4049/jimmunol.164.7.3471;
RA Akashi S., Shimazu R., Ogata H., Nagai Y., Takeda K., Kimoto M., Miyake K.;
RT "Cell surface expression and lipopolysaccaride signaling via the Toll-like
RT receptor 4-MD-2 complex on mouse peritoneal macrophages.";
RL J. Immunol. 164:3471-3475(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND MUTAGENESIS OF PHE-126.
RX PubMed=20133493; DOI=10.1093/intimm/dxq005;
RA Tsukamoto H., Fukudome K., Takao S., Tsuneyoshi N., Kimoto M.;
RT "Lipopolysaccharide-binding protein-mediated Toll-like receptor 4
RT dimerization enables rapid signal transduction against lipopolysaccharide
RT stimulation on membrane-associated CD14-expressing cells.";
RL Int. Immunol. 22:271-280(2010).
RN [5]
RP FUNCTION, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=24380872; DOI=10.1093/intimm/dxt071;
RA Tanimura N., Saitoh S., Ohto U., Akashi-Takamura S., Fujimoto Y.,
RA Fukase K., Shimizu T., Miyake K.;
RT "The attenuated inflammation of MPL is due to the lack of CD14-dependent
RT tight dimerization of the TLR4/MD2 complex at the plasma membrane.";
RL Int. Immunol. 26:307-314(2014).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.84 ANGSTROMS) OF 21-155 IN COMPLEX WITH TLR4,
RP GLYCOSYLATION AT ASN-26; ASN-114 AND ASN-150, AND DISULFIDE BONDS.
RX PubMed=17803912; DOI=10.1016/j.cell.2007.08.002;
RA Kim H.M., Park B.S., Kim J.-I., Kim S.E., Lee J., Oh S.C., Enkhbayar P.,
RA Matsushima N., Lee H., Yoo O.J., Lee J.-O.;
RT "Crystal structure of the TLR4-MD-2 complex with bound endotoxin antagonist
RT Eritoran.";
RL Cell 130:906-917(2007).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.48 ANGSTROMS) OF 17-160 IN COMPLEX WITH TLR4 AND
RP LIPID X, DISULFIDE BONDS, AND INTERACTION WITH TLR4.
RX PubMed=22532668; DOI=10.1073/pnas.1201193109;
RA Ohto U., Fukase K., Miyake K., Shimizu T.;
RT "Structural basis of species-specific endotoxin sensing by innate immune
RT receptor TLR4/MD-2.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:7421-7426(2012).
CC -!- FUNCTION: Binds bacterial lipopolysaccharide (LPS) (PubMed:22532668).
CC Cooperates with TLR4 in the innate immune response to bacterial
CC lipopolysaccharide (LPS), and with TLR2 in the response to cell wall
CC components from Gram-positive and Gram-negative bacteria. Enhances
CC TLR4-dependent activation of NF-kappa-B. Cells expressing both LY96 and
CC TLR4, but not TLR4 alone, respond to LPS (PubMed:10725698).
CC {ECO:0000250|UniProtKB:Q9Y6Y9, ECO:0000269|PubMed:10725698,
CC ECO:0000269|PubMed:20133493, ECO:0000269|PubMed:24380872}.
CC -!- SUBUNIT: Heterogeneous homomer formed from homodimers; disulfide-linked
CC (By similarity). Belongs to the lipopolysaccharide (LPS) receptor, a
CC multi-protein complex containing at least CD14, LY96 and TLR4
CC (PubMed:10725698, PubMed:20133493, PubMed:24380872). Binds to the
CC extracellular domain of TLR4 (PubMed:10725698, PubMed:20133493,
CC PubMed:24380872, PubMed:17803912, PubMed:22532668). Binds to the
CC extracellular domain of TLR2 (By similarity). Ligand binding induces
CC interaction with TLR4 and oligomerization of the complex
CC (PubMed:20133493, PubMed:24380872, PubMed:22532668).
CC {ECO:0000250|UniProtKB:Q9Y6Y9, ECO:0000269|PubMed:10725698,
CC ECO:0000269|PubMed:17803912, ECO:0000269|PubMed:20133493,
CC ECO:0000269|PubMed:22532668, ECO:0000269|PubMed:24380872}.
CC -!- INTERACTION:
CC Q9JHF9; Q9QUK6: Tlr4; NbExp=8; IntAct=EBI-1534566, EBI-1534575;
CC -!- SUBCELLULAR LOCATION: Secreted, extracellular space
CC {ECO:0000269|PubMed:10725698, ECO:0000269|PubMed:20133493,
CC ECO:0000305|PubMed:24380872}. Secreted {ECO:0000269|PubMed:10891475}.
CC Note=Retained in the extracellular space at the cell surface by
CC interaction with TLR4. {ECO:0000269|PubMed:10725698,
CC ECO:0000269|PubMed:20133493, ECO:0000305|PubMed:24380872}.
CC -!- TISSUE SPECIFICITY: Highly expressed in spleen, bone marrow, thymus,
CC liver, kidney, ovary and decidua. Detected at lower levels in testis,
CC small intestine and skin. {ECO:0000269|PubMed:10891475}.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:17803912}.
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DR EMBL; AF168120; AAF89634.1; -; mRNA.
DR EMBL; AB018550; BAA93619.1; -; mRNA.
DR EMBL; AK019283; BAB31645.1; -; mRNA.
DR CCDS; CCDS14832.1; -.
DR RefSeq; NP_001153183.1; NM_001159711.1.
DR RefSeq; NP_058619.1; NM_016923.2.
DR PDB; 2Z64; X-ray; 2.84 A; C=21-155.
DR PDB; 3VQ1; X-ray; 2.70 A; C/D=17-160.
DR PDB; 3VQ2; X-ray; 2.48 A; C/D=17-160.
DR PDB; 5IJB; X-ray; 2.91 A; C/D=19-160.
DR PDB; 5IJC; X-ray; 2.57 A; C/D=19-160.
DR PDB; 5IJD; X-ray; 2.70 A; C/D=19-160.
DR PDB; 7MLM; X-ray; 2.10 A; C=19-160.
DR PDBsum; 2Z64; -.
DR PDBsum; 3VQ1; -.
DR PDBsum; 3VQ2; -.
DR PDBsum; 5IJB; -.
DR PDBsum; 5IJC; -.
DR PDBsum; 5IJD; -.
DR PDBsum; 7MLM; -.
DR AlphaFoldDB; Q9JHF9; -.
DR SMR; Q9JHF9; -.
DR DIP; DIP-38572N; -.
DR IntAct; Q9JHF9; 1.
DR STRING; 10090.ENSMUSP00000026881; -.
DR BindingDB; Q9JHF9; -.
DR ChEMBL; CHEMBL2384895; -.
DR GlyGen; Q9JHF9; 3 sites.
DR iPTMnet; Q9JHF9; -.
DR PhosphoSitePlus; Q9JHF9; -.
DR MaxQB; Q9JHF9; -.
DR PaxDb; Q9JHF9; -.
DR PRIDE; Q9JHF9; -.
DR ProteomicsDB; 290199; -.
DR Antibodypedia; 12334; 485 antibodies from 38 providers.
DR DNASU; 17087; -.
DR Ensembl; ENSMUST00000026881; ENSMUSP00000026881; ENSMUSG00000025779.
DR GeneID; 17087; -.
DR KEGG; mmu:17087; -.
DR UCSC; uc007ajz.2; mouse.
DR CTD; 23643; -.
DR MGI; MGI:1341909; Ly96.
DR VEuPathDB; HostDB:ENSMUSG00000025779; -.
DR eggNOG; ENOG502SD7W; Eukaryota.
DR GeneTree; ENSGT00390000000742; -.
DR InParanoid; Q9JHF9; -.
DR OMA; YTYCDNM; -.
DR OrthoDB; 1320082at2759; -.
DR PhylomeDB; Q9JHF9; -.
DR TreeFam; TF335876; -.
DR Reactome; R-MMU-140534; Caspase activation via Death Receptors in the presence of ligand.
DR Reactome; R-MMU-166016; Toll Like Receptor 4 (TLR4) Cascade.
DR Reactome; R-MMU-166166; MyD88-independent TLR4 cascade.
DR Reactome; R-MMU-2562578; TRIF-mediated programmed cell death.
DR Reactome; R-MMU-5686938; Regulation of TLR by endogenous ligand.
DR Reactome; R-MMU-936964; Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
DR Reactome; R-MMU-937041; IKK complex recruitment mediated by RIP1.
DR Reactome; R-MMU-937072; TRAF6-mediated induction of TAK1 complex within TLR4 complex.
DR Reactome; R-MMU-9707616; Heme signaling.
DR Reactome; R-MMU-975163; IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
DR BioGRID-ORCS; 17087; 0 hits in 74 CRISPR screens.
DR ChiTaRS; Ly96; mouse.
DR EvolutionaryTrace; Q9JHF9; -.
DR PRO; PR:Q9JHF9; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q9JHF9; protein.
DR Bgee; ENSMUSG00000025779; Expressed in granulocyte and 157 other tissues.
DR ExpressionAtlas; Q9JHF9; baseline and differential.
DR Genevisible; Q9JHF9; MM.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell.
DR GO; GO:0031226; C:intrinsic component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0046696; C:lipopolysaccharide receptor complex; IDA:UniProtKB.
DR GO; GO:0043235; C:receptor complex; ISO:MGI.
DR GO; GO:0001530; F:lipopolysaccharide binding; IEA:InterPro.
DR GO; GO:0001875; F:lipopolysaccharide immune receptor activity; ISS:UniProtKB.
DR GO; GO:0035662; F:Toll-like receptor 4 binding; IEA:InterPro.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IMP:UniProtKB.
DR GO; GO:0032497; P:detection of lipopolysaccharide; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:MGI.
DR GO; GO:0031666; P:positive regulation of lipopolysaccharide-mediated signaling pathway; IDA:MGI.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:UniProtKB.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:MGI.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; IMP:UniProtKB.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; ISO:MGI.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR039217; LY96.
DR InterPro; IPR003172; ML_dom.
DR PANTHER; PTHR15218; PTHR15218; 1.
DR Pfam; PF02221; E1_DerP2_DerF2; 1.
DR SMART; SM00737; ML; 1.
DR SUPFAM; SSF81296; SSF81296; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Glycoprotein; Immunity;
KW Inflammatory response; Innate immunity; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..160
FT /note="Lymphocyte antigen 96"
FT /id="PRO_0000018620"
FT REGION 119..123
FT /note="Interaction with lipopolysaccharide"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6Y9,
FT ECO:0000269|PubMed:22532668"
FT CARBOHYD 26
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17803912,
FT ECO:0007744|PDB:2Z64"
FT CARBOHYD 114
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17803912"
FT CARBOHYD 150
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:17803912"
FT DISULFID 25..51
FT /evidence="ECO:0000269|PubMed:17803912,
FT ECO:0000269|PubMed:22532668, ECO:0007744|PDB:2Z64,
FT ECO:0007744|PDB:3VQ1, ECO:0007744|PDB:3VQ2"
FT DISULFID 37..148
FT /evidence="ECO:0000269|PubMed:17803912,
FT ECO:0000269|PubMed:22532668, ECO:0007744|PDB:2Z64,
FT ECO:0007744|PDB:3VQ1, ECO:0007744|PDB:3VQ2"
FT DISULFID 95..105
FT /evidence="ECO:0000269|PubMed:17803912,
FT ECO:0000269|PubMed:22532668, ECO:0007744|PDB:2Z64,
FT ECO:0007744|PDB:3VQ1, ECO:0007744|PDB:3VQ2"
FT MUTAGEN 126
FT /note="F->A: Abolishes dimerization of the TLR4 complex and
FT stimulation of TNF production in response to bacterial
FT lipopolysaccharide."
FT /evidence="ECO:0000269|PubMed:24380872"
FT STRAND 23..26
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 28..37
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 45..50
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 56..65
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 74..82
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 90..94
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 97..99
FT /evidence="ECO:0007829|PDB:7MLM"
FT HELIX 103..106
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 113..122
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 128..139
FT /evidence="ECO:0007829|PDB:7MLM"
FT TURN 140..143
FT /evidence="ECO:0007829|PDB:7MLM"
FT STRAND 144..155
FT /evidence="ECO:0007829|PDB:7MLM"
SQ SEQUENCE 160 AA; 18394 MW; E224D17E5D5429E2 CRC64;
MLPFILFSTL LSPILTESEK QQWFCNSSDA IISYSYCDHL KFPISISSEP CIRLRGTNGF
VHVEFIPRGN LKYLYFNLFI SVNSIELPKR KEVLCHGHDD DYSFCRALKG ETVNTSIPFS
FEGILFPKGH YRCVAEAIAG DTEEKLFCLN FTIIHRRDVN
