CD14_MOUSE
ID CD14_MOUSE Reviewed; 366 AA.
AC P10810;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Monocyte differentiation antigen CD14;
DE AltName: Full=Myeloid cell-specific leucine-rich glycoprotein;
DE AltName: CD_antigen=CD14;
DE Flags: Precursor;
GN Name=Cd14;
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 [GENOMIC DNA].
RC STRAIN=BALB/cJ; TISSUE=Liver;
RX PubMed=2467257; DOI=10.1093/nar/17.5.2132;
RA Miyazaki Y., Setoguchi M., Yoshida S., Higuchi Y., Akizuki S., Yamamoto S.;
RT "Nucleotide and amino acid sequences of the mouse CD14 gene.";
RL Nucleic Acids Res. 17:2132-2132(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=ICR; TISSUE=Macrophage;
RX PubMed=2472171; DOI=10.1016/0167-4781(80)90012-3;
RA Setoguchi M., Nasu N., Yoshida S., Higuchi Y., Akizuki S., Yamamoto S.;
RT "Mouse and human CD14 (myeloid cell-specific leucine-rich glycoprotein)
RT primary structure deduced from cDNA clones.";
RL Biochim. Biophys. Acta 1008:213-222(1989).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1694207;
RA Ferrero E., Hsieh C.L., Francke U., Goyert S.M.;
RT "CD14 is a member of the family of leucine-rich proteins and is encoded by
RT a gene syntenic with multiple receptor genes.";
RL J. Immunol. 145:331-336(1990).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NMRI; TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP DISRUPTION PHENOTYPE, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=8612135; DOI=10.1016/s1074-7613(00)80254-x;
RA Haziot A., Ferrero E., Kontgen F., Hijiya N., Yamamoto S., Silver J.,
RA Stewart C.L., Goyert S.M.;
RT "Resistance to endotoxin shock and reduced dissemination of gram-negative
RT bacteria in CD14-deficient mice.";
RL Immunity 4:407-414(1996).
RN [6]
RP FUNCTION.
RX PubMed=16148141; DOI=10.4049/jimmunol.175.6.3940;
RA Gangloff S.C., Zahringer U., Blondin C., Guenounou M., Silver J.,
RA Goyert S.M.;
RT "Influence of CD14 on ligand interactions between lipopolysaccharide and
RT its receptor complex.";
RL J. Immunol. 175:3940-3945(2005).
RN [7]
RP FUNCTION, AND DOMAIN.
RX PubMed=15895089; DOI=10.1038/ni1207;
RA Jiang Z., Georgel P., Du X., Shamel L., Sovath S., Mudd S., Huber M.,
RA Kalis C., Keck S., Galanos C., Freudenberg M., Beutler B.;
RT "CD14 is required for MyD88-independent LPS signaling.";
RL Nat. Immunol. 6:565-570(2005).
RN [8]
RP FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Macrophage;
RX PubMed=19362712; DOI=10.1016/j.cellimm.2009.03.008;
RA Drage M.G., Pecora N.D., Hise A.G., Febbraio M., Silverstein R.L.,
RA Golenbock D.T., Boom W.H., Harding C.V.;
RT "TLR2 and its co-receptors determine responses of macrophages and dendritic
RT cells to lipoproteins of Mycobacterium tuberculosis.";
RL Cell. Immunol. 258:29-37(2009).
RN [9]
RP FUNCTION, INTERACTION WITH LPAR1, AND SUBCELLULAR LOCATION.
RX PubMed=21821728; DOI=10.1152/ajplung.00058.2011;
RA Zhao J., He D., Su Y., Berdyshev E., Chun J., Natarajan V., Zhao Y.;
RT "Lysophosphatidic acid receptor 1 modulates lipopolysaccharide-induced
RT inflammation in alveolar epithelial cells and murine lungs.";
RL Am. J. Physiol. 301:L547-L556(2011).
RN [10]
RP FUNCTION.
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 [11]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 20-329, DISULFIDE BONDS,
RP GLYCOSYLATION AT ASN-147; ASN-180 AND ASN-276, AND DOMAINS LEUCINE-RICH
RP REPEATS.
RX PubMed=15644310; DOI=10.1074/jbc.m414607200;
RA Kim J.I., Lee C.J., Jin M.S., Lee C.H., Paik S.G., Lee H., Lee J.O.;
RT "Crystal structure of CD14 and its implications for lipopolysaccharide
RT signaling.";
RL J. Biol. Chem. 280:11347-11351(2005).
CC -!- FUNCTION: Coreceptor for bacterial lipopolysaccharide. In concert with
CC LBP, binds to monomeric lipopolysaccharide and delivers it to the
CC LY96/TLR4 complex, thereby mediating the innate immune response to
CC bacterial lipopolysaccharide (LPS) (PubMed:16148141). Acts via MyD88,
CC TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion
CC and the inflammatory response (PubMed:8612135, PubMed:15895089). Acts
CC as a coreceptor for TLR2:TLR6 heterodimer in response to diacylated
CC lipopeptides and for TLR2:TLR1 heterodimer in response to triacylated
CC lipopeptides, these clusters trigger signaling from the cell surface
CC and subsequently are targeted to the Golgi in a lipid-raft dependent
CC pathway (By similarity). Acts as an accessory receptor for
CC M.tuberculosis lipoproteins LprA, LprG and LpqH, in conjunction with
CC coreceptors TLR2 and TLR1. The lipoproteins act as agonists to modulate
CC antigen presenting cell functions in response to the pathogen
CC (PubMed:19362712). Binds electronegative LDL (LDL(-)) and mediates the
CC cytokine release induced by LDL(-) (By similarity).
CC {ECO:0000250|UniProtKB:P08571, ECO:0000269|PubMed:15895089,
CC ECO:0000269|PubMed:16148141, ECO:0000269|PubMed:19362712,
CC ECO:0000269|PubMed:21821728, ECO:0000269|PubMed:8612135}.
CC -!- SUBUNIT: Belongs to the lipopolysaccharide (LPS) receptor, a multi-
CC protein complex containing at least CD14, LY96 and TLR4 (By
CC similarity). Interacts with LPS-bound LPB. Interacts with LPAR1
CC (PubMed:21821728). Interacts with the TLR2:TLR6 or TLR2:TLR1
CC heterodimers; upon interaction with ligands such as diacylated
CC lipopeptides and triacylated lipopeptides, respectively. Interacts with
CC MYO18A (By similarity). Interacts with FSTL1 (By similarity).
CC {ECO:0000250|UniProtKB:P08571, ECO:0000269|PubMed:21821728}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21821728,
CC ECO:0000269|PubMed:8612135}; Lipid-anchor, GPI-anchor
CC {ECO:0000250|UniProtKB:P08571}. Secreted
CC {ECO:0000250|UniProtKB:P08571}. Membrane raft
CC {ECO:0000250|UniProtKB:P08571}. Golgi apparatus
CC {ECO:0000250|UniProtKB:P08571}. Note=Soluble, secreted forms seem to
CC exist. They may arise by cleavage of the GPI anchor.
CC {ECO:0000250|UniProtKB:P08571}.
CC -!- TISSUE SPECIFICITY: Detected on peritoneal macrophages (at protein
CC level) (PubMed:8612135). Cell surface expression detected in lung
CC alveolar macrophages, dendritic macrophages and lung macrophages (at
CC protein level) (PubMed:19362712). {ECO:0000269|PubMed:19362712,
CC ECO:0000269|PubMed:8612135}.
CC -!- DOMAIN: The C-terminal leucine-rich repeat (LRR) region is required for
CC responses to smooth LPS. {ECO:0000269|PubMed:15895089}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Mice are fertile and appear
CC healthy when kept in a clean, microbe-free environment. Mice do not
CC respond to bacterial smooth lipopolysaccharide (LPS). Contrary to wild-
CC type, they do not develop toxic shock or secrete TNF in response to
CC LPS. Surprisingly, they have fewer live bacteria in their lungs and
CC bloodstream after inoculation with bacteria and are not killed by an
CC inoculum that is lethal to wild-type; they are killed when the inoculum
CC is further increased. {ECO:0000269|PubMed:8612135}.
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DR EMBL; X13987; CAA32166.1; -; Genomic_DNA.
DR EMBL; X13333; CAA31710.1; -; mRNA.
DR EMBL; M34510; AAA37387.1; -; Genomic_DNA.
DR EMBL; BC057889; AAH57889.1; -; mRNA.
DR CCDS; CCDS29159.1; -.
DR PIR; S03605; TDMSM4.
DR RefSeq; NP_033971.1; NM_009841.4.
DR PDB; 1WWL; X-ray; 2.50 A; A/B=20-329.
DR PDBsum; 1WWL; -.
DR AlphaFoldDB; P10810; -.
DR SMR; P10810; -.
DR BioGRID; 198573; 2.
DR STRING; 10090.ENSMUSP00000056669; -.
DR ChEMBL; CHEMBL2384896; -.
DR GlyGen; P10810; 5 sites.
DR iPTMnet; P10810; -.
DR PhosphoSitePlus; P10810; -.
DR SwissPalm; P10810; -.
DR PaxDb; P10810; -.
DR PeptideAtlas; P10810; -.
DR PRIDE; P10810; -.
DR ProteomicsDB; 279962; -.
DR Antibodypedia; 798; 3677 antibodies from 56 providers.
DR DNASU; 12475; -.
DR Ensembl; ENSMUST00000061829; ENSMUSP00000056669; ENSMUSG00000051439.
DR GeneID; 12475; -.
DR KEGG; mmu:12475; -.
DR UCSC; uc008eof.2; mouse.
DR CTD; 929; -.
DR MGI; MGI:88318; Cd14.
DR VEuPathDB; HostDB:ENSMUSG00000051439; -.
DR eggNOG; ENOG502SNYQ; Eukaryota.
DR GeneTree; ENSGT00390000005689; -.
DR HOGENOM; CLU_062152_0_0_1; -.
DR InParanoid; P10810; -.
DR OMA; PSSSCQW; -.
DR OrthoDB; 1097023at2759; -.
DR PhylomeDB; P10810; -.
DR TreeFam; TF338550; -.
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-166020; Transfer of LPS from LBP carrier to CD14.
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-6798695; Neutrophil degranulation.
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-975163; IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation.
DR BioGRID-ORCS; 12475; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Cd14; mouse.
DR EvolutionaryTrace; P10810; -.
DR PRO; PR:P10810; -.
DR Proteomes; UP000000589; Chromosome 18.
DR RNAct; P10810; protein.
DR Bgee; ENSMUSG00000051439; Expressed in thoracic mammary gland and 136 other tissues.
DR ExpressionAtlas; P10810; baseline and differential.
DR Genevisible; P10810; MM.
DR GO; GO:0031362; C:anchored component of external side of plasma membrane; ISS:UniProtKB.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0046696; C:lipopolysaccharide receptor complex; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0071723; F:lipopeptide binding; ISO:MGI.
DR GO; GO:0001530; F:lipopolysaccharide binding; ISO:MGI.
DR GO; GO:0070891; F:lipoteichoic acid binding; ISO:MGI.
DR GO; GO:0071726; P:cellular response to diacyl bacterial lipopeptide; ISS:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IMP:UniProtKB.
DR GO; GO:0071223; P:cellular response to lipoteichoic acid; ISO:MGI.
DR GO; GO:0071219; P:cellular response to molecule of bacterial origin; ISO:MGI.
DR GO; GO:0071727; P:cellular response to triacyl bacterial lipopeptide; ISS:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; ISO:MGI.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IBA:GO_Central.
DR GO; GO:0001819; P:positive regulation of cytokine production; ISO:MGI.
DR GO; GO:0045807; P:positive regulation of endocytosis; IMP:UniProtKB.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IMP:UniProtKB.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; ISO:MGI.
DR GO; GO:0031666; P:positive regulation of lipopolysaccharide-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; ISO:MGI.
DR GO; GO:0034145; P:positive regulation of toll-like receptor 4 signaling pathway; IMP:UniProtKB.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:UniProtKB.
DR GO; GO:0032481; P:positive regulation of type I interferon production; IMP:CACAO.
DR GO; GO:0006898; P:receptor-mediated endocytosis; IMP:CACAO.
DR GO; GO:0009617; P:response to bacterium; IMP:UniProtKB.
DR GO; GO:0051602; P:response to electrical stimulus; IEA:Ensembl.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
DR GO; GO:0009408; P:response to heat; IEA:Ensembl.
DR GO; GO:0032026; P:response to magnesium ion; IEA:Ensembl.
DR GO; GO:0002237; P:response to molecule of bacterial origin; IDA:UniProtKB.
DR GO; GO:0034612; P:response to tumor necrosis factor; ISO:MGI.
DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; IBA:GO_Central.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR016337; Monocyte_diff_Ag_CD14.
DR PANTHER; PTHR10630; PTHR10630; 1.
DR PIRSF; PIRSF002017; CD14; 1.
DR PROSITE; PS51450; LRR; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Disulfide bond; Glycoprotein; Golgi apparatus;
KW GPI-anchor; Immunity; Inflammatory response; Innate immunity;
KW Leucine-rich repeat; Lipoprotein; Membrane; Reference proteome; Repeat;
KW Secreted; Signal.
FT SIGNAL 1..15
FT CHAIN 16..336
FT /note="Monocyte differentiation antigen CD14"
FT /id="PRO_0000020887"
FT PROPEP 337..366
FT /note="Removed in mature form"
FT /evidence="ECO:0000255"
FT /id="PRO_0000020888"
FT REPEAT 50..78
FT /note="LRR 1"
FT REPEAT 79..114
FT /note="LRR 2"
FT REPEAT 115..140
FT /note="LRR 3"
FT REPEAT 141..168
FT /note="LRR 4"
FT REPEAT 169..192
FT /note="LRR 5"
FT REPEAT 193..220
FT /note="LRR 6"
FT REPEAT 221..247
FT /note="LRR 7"
FT REPEAT 248..272
FT /note="LRR 8"
FT REPEAT 273..293
FT /note="LRR 9"
FT REPEAT 294..315
FT /note="LRR 10"
FT REPEAT 316..340
FT /note="LRR 11"
FT REGION 284..366
FT /note="Required for response to bacterial
FT lipopolysaccharide (LPS)"
FT /evidence="ECO:0000269|PubMed:15895089"
FT LIPID 336
FT /note="GPI-anchor amidated asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 33
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 147
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15644310"
FT CARBOHYD 180
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15644310"
FT CARBOHYD 276
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:15644310"
FT CARBOHYD 317
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 23..32
FT /evidence="ECO:0000269|PubMed:15644310"
FT DISULFID 30..47
FT /evidence="ECO:0000269|PubMed:15644310"
FT DISULFID 183..213
FT /evidence="ECO:0000269|PubMed:15644310"
FT DISULFID 237..266
FT /evidence="ECO:0000269|PubMed:15644310"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:1WWL"
FT HELIX 41..46
FT /evidence="ECO:0007829|PDB:1WWL"
FT STRAND 47..49
FT /evidence="ECO:0007829|PDB:1WWL"
FT STRAND 51..61
FT /evidence="ECO:0007829|PDB:1WWL"
FT HELIX 65..68
FT /evidence="ECO:0007829|PDB:1WWL"
FT HELIX 76..84
FT /evidence="ECO:0007829|PDB:1WWL"
FT STRAND 89..96
FT /evidence="ECO:0007829|PDB:1WWL"
FT HELIX 99..109
FT /evidence="ECO:0007829|PDB:1WWL"
FT STRAND 116..123
FT /evidence="ECO:0007829|PDB:1WWL"
FT STRAND 132..134
FT /evidence="ECO:0007829|PDB:1WWL"
FT STRAND 141..147
FT /evidence="ECO:0007829|PDB:1WWL"
FT STRAND 151..155
FT /evidence="ECO:0007829|PDB:1WWL"
FT HELIX 156..161
FT /evidence="ECO:0007829|PDB:1WWL"
FT STRAND 170..175
FT /evidence="ECO:0007829|PDB:1WWL"
FT TURN 183..185
FT /evidence="ECO:0007829|PDB:1WWL"
FT STRAND 194..196
FT /evidence="ECO:0007829|PDB:1WWL"
FT HELIX 204..211
FT /evidence="ECO:0007829|PDB:1WWL"
FT STRAND 222..224
FT /evidence="ECO:0007829|PDB:1WWL"
FT HELIX 233..242
FT /evidence="ECO:0007829|PDB:1WWL"
FT STRAND 248..251
FT /evidence="ECO:0007829|PDB:1WWL"
FT STRAND 274..276
FT /evidence="ECO:0007829|PDB:1WWL"
FT STRAND 291..297
FT /evidence="ECO:0007829|PDB:1WWL"
FT TURN 309..311
FT /evidence="ECO:0007829|PDB:1WWL"
FT STRAND 314..319
FT /evidence="ECO:0007829|PDB:1WWL"
FT TURN 324..326
FT /evidence="ECO:0007829|PDB:1WWL"
SQ SEQUENCE 366 AA; 39204 MW; 57C4492EC7EA3AA1 CRC64;
MERVLGLLLL LLVHASPAPP EPCELDEESC SCNFSDPKPD WSSAFNCLGA ADVELYGGGR
SLEYLLKRVD TEADLGQFTD IIKSLSLKRL TVRAARIPSR ILFGALRVLG ISGLQELTLE
NLEVTGTAPP PLLEATGPDL NILNLRNVSW ATRDAWLAEL QQWLKPGLKV LSIAQAHSLN
FSCEQVRVFP ALSTLDLSDN PELGERGLIS ALCPLKFPTL QVLALRNAGM ETPSGVCSAL
AAARVQLQGL DLSHNSLRDA AGAPSCDWPS QLNSLNLSFT GLKQVPKGLP AKLSVLDLSY
NRLDRNPSPD ELPQVGNLSL KGNPFLDSES HSEKFNSGVV TAGAPSSQAV ALSGTLALLL
GDRLFV
