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Protein

Monocyte differentiation antigen CD14

Gene

Cd14

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Coreceptor for bacterial lipopolysaccharide. In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the LY96/TLR4 complex, thereby mediating the innate immune response to bacterial lipopolysaccharide (LPS) (PubMed:16148141). Acts via MyD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:8612135, PubMed:15895089). Acts as a coreceptor for TLR2:TLR6 heterodimer in response to diacylated lipopeptides and for TLR2:TLR1 heterodimer in response to triacylated lipopeptides, these clusters trigger signaling from the cell surface and subsequently are targeted to the Golgi in a lipid-raft dependent pathway (By similarity). Acts as an accessory receptor for M.tuberculosis lipoproteins LprA, LprG and LpqH, in conjunction with coreceptors TLR2 and TLR1. The lipoproteins act as agonits to modulate antigen presenting cell functions in response to the pathogen (PubMed:19362712). Binds electronegative LDL (LDL-) and mediates the cytokine release induced by LDL- (By similarity).By similarity5 Publications

GO - Molecular functioni

GO - Biological processi

  • cellular response to diacyl bacterial lipopeptide Source: UniProtKB
  • cellular response to lipopolysaccharide Source: UniProtKB
  • cellular response to lipoteichoic acid Source: MGI
  • cellular response to triacyl bacterial lipopeptide Source: UniProtKB
  • inflammatory response Source: UniProtKB-KW
  • innate immune response Source: UniProtKB-KW
  • lipopolysaccharide-mediated signaling pathway Source: UniProtKB
  • positive regulation of cytokine secretion Source: Ensembl
  • positive regulation of endocytosis Source: UniProtKB
  • positive regulation of interferon-gamma production Source: UniProtKB
  • positive regulation of tumor necrosis factor production Source: UniProtKB
  • positive regulation of type I interferon production Source: CACAO
  • receptor-mediated endocytosis Source: CACAO
  • response to bacterium Source: UniProtKB
  • response to electrical stimulus Source: Ensembl
  • response to ethanol Source: Ensembl
  • response to heat Source: Ensembl
  • response to magnesium ion Source: Ensembl
  • response to molecule of bacterial origin Source: UniProtKB
  • response to tumor necrosis factor Source: Ensembl
  • toll-like receptor 4 signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Enzyme and pathway databases

ReactomeiR-MMU-166016. Toll Like Receptor 4 (TLR4) Cascade.
R-MMU-166020. Transfer of LPS from LBP carrier to CD14.
R-MMU-166166. MyD88-independent TLR3/TLR4 cascade.

Names & Taxonomyi

Protein namesi
Recommended name:
Monocyte differentiation antigen CD14
Alternative name(s):
Myeloid cell-specific leucine-rich glycoprotein
CD_antigen: CD14
Gene namesi
Name:Cd14
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 18

Organism-specific databases

MGIiMGI:88318. Cd14.

Subcellular locationi

  • Cell membrane 2 Publications; Lipid-anchorGPI-anchor By similarity
  • Secreted By similarity
  • Membrane raft By similarity
  • Golgi apparatus By similarity

  • Note: Soluble, secreted forms seem to exist. They may arise by cleavage of the GPI anchor.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane, Secreted

Pathology & Biotechi

Disruption phenotypei

No visible phenotype. Mice are fertile and appear healthy when kept in a clean, microbe-free environment. Mice do not respond to bacterial smooth lipopolysaccharide (LPS). Contrary to wild-type, they do not develop toxic shock or secrete TNF in response to LPS. Surprisingly, they have fewer live bacteria in their lungs and bloodstream after inoculation with bacteria and are not killed by an inoculum that is lethal to wild-type; they are killed when the inoculum is further increased.1 Publication

Chemistry

ChEMBLiCHEMBL3038514.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1515Add
BLAST
Chaini16 – 336321Monocyte differentiation antigen CD14PRO_0000020887Add
BLAST
Propeptidei337 – 36630Removed in mature formSequence analysisPRO_0000020888Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi23 ↔ 321 Publication
Disulfide bondi30 ↔ 471 Publication
Glycosylationi33 – 331N-linked (GlcNAc...)Sequence analysis
Glycosylationi147 – 1471N-linked (GlcNAc...)1 Publication
Glycosylationi180 – 1801N-linked (GlcNAc...)1 Publication
Disulfide bondi183 ↔ 2131 Publication
Disulfide bondi237 ↔ 2661 Publication
Glycosylationi276 – 2761N-linked (GlcNAc...)1 Publication
Glycosylationi317 – 3171N-linked (GlcNAc...)Sequence analysis
Lipidationi336 – 3361GPI-anchor amidated asparagineSequence analysis

Keywords - PTMi

Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

Proteomic databases

MaxQBiP10810.
PaxDbiP10810.
PRIDEiP10810.

PTM databases

iPTMnetiP10810.
PhosphoSiteiP10810.

Miscellaneous databases

PMAP-CutDBP10810.

Expressioni

Tissue specificityi

Detected on peritoneal macrophages (at protein level) (PubMed:8612135). Cell surface expression detected in lung alveolar macrophages, dendritic macrophages and lung macrophages (at protein level) (PubMed:19362712).2 Publications

Gene expression databases

BgeeiP10810.
CleanExiMM_CD14.
ExpressionAtlasiP10810. baseline and differential.
GenevisibleiP10810. MM.

Interactioni

Subunit structurei

Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14, LY96 and TLR4 (By similarity). Interacts with LPS-bound LPB. Interacts with LPAR1 (PubMed:21821728). Interacts with the TLR2:TLR6 or TLR2:TLR1 heterodimers; upon interaction with ligands such as diacylated lipopeptides and triacylated lipopeptides, respectively (By similarity).By similarity1 Publication

Protein-protein interaction databases

BioGridi198573. 1 interaction.
STRINGi10090.ENSMUSP00000056669.

Structurei

Secondary structure

1
366
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi36 – 383Combined sources
Helixi41 – 466Combined sources
Beta strandi47 – 493Combined sources
Beta strandi51 – 6111Combined sources
Helixi65 – 684Combined sources
Helixi76 – 849Combined sources
Beta strandi89 – 968Combined sources
Helixi99 – 10911Combined sources
Beta strandi116 – 1238Combined sources
Beta strandi132 – 1343Combined sources
Beta strandi141 – 1477Combined sources
Beta strandi151 – 1555Combined sources
Helixi156 – 1616Combined sources
Beta strandi170 – 1756Combined sources
Turni183 – 1853Combined sources
Beta strandi194 – 1963Combined sources
Helixi204 – 2118Combined sources
Beta strandi222 – 2243Combined sources
Helixi233 – 24210Combined sources
Beta strandi248 – 2514Combined sources
Beta strandi274 – 2763Combined sources
Beta strandi291 – 2977Combined sources
Turni309 – 3113Combined sources
Beta strandi314 – 3196Combined sources
Turni324 – 3263Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1WWLX-ray2.50A/B20-329[»]
ProteinModelPortaliP10810.
SMRiP10810. Positions 22-329.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10810.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati50 – 7829LRR 1Add
BLAST
Repeati79 – 11436LRR 2Add
BLAST
Repeati115 – 14026LRR 3Add
BLAST
Repeati141 – 16828LRR 4Add
BLAST
Repeati169 – 19224LRR 5Add
BLAST
Repeati193 – 22028LRR 6Add
BLAST
Repeati221 – 24727LRR 7Add
BLAST
Repeati248 – 27225LRR 8Add
BLAST
Repeati273 – 29321LRR 9Add
BLAST
Repeati294 – 31522LRR 10Add
BLAST
Repeati316 – 34025LRR 11Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni284 – 36683Required for response to bacterial lipopolysaccharide (LPS)1 PublicationAdd
BLAST

Domaini

The C-terminal leucine-rich repeat (LRR) region is required for responses to smooth LPS.1 Publication

Sequence similaritiesi

Contains 11 LRR (leucine-rich) repeats.Curated

Keywords - Domaini

Leucine-rich repeat, Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IXG9. Eukaryota.
ENOG41118N2. LUCA.
HOGENOMiHOG000237268.
HOVERGENiHBG005269.
InParanoidiP10810.
KOiK04391.
OMAiLCPHKFP.
OrthoDBiEOG751NFQ.
PhylomeDBiP10810.
TreeFamiTF338550.

Family and domain databases

Gene3Di3.80.10.10. 1 hit.
InterProiIPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR016337. Monocyte_diff_Ag_CD14.
[Graphical view]
PIRSFiPIRSF002017. CD14. 1 hit.
SUPFAMiSSF52058. SSF52058. 1 hit.
PROSITEiPS51450. LRR. 3 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P10810-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MERVLGLLLL LLVHASPAPP EPCELDEESC SCNFSDPKPD WSSAFNCLGA
60 70 80 90 100
ADVELYGGGR SLEYLLKRVD TEADLGQFTD IIKSLSLKRL TVRAARIPSR
110 120 130 140 150
ILFGALRVLG ISGLQELTLE NLEVTGTAPP PLLEATGPDL NILNLRNVSW
160 170 180 190 200
ATRDAWLAEL QQWLKPGLKV LSIAQAHSLN FSCEQVRVFP ALSTLDLSDN
210 220 230 240 250
PELGERGLIS ALCPLKFPTL QVLALRNAGM ETPSGVCSAL AAARVQLQGL
260 270 280 290 300
DLSHNSLRDA AGAPSCDWPS QLNSLNLSFT GLKQVPKGLP AKLSVLDLSY
310 320 330 340 350
NRLDRNPSPD ELPQVGNLSL KGNPFLDSES HSEKFNSGVV TAGAPSSQAV
360
ALSGTLALLL GDRLFV
Length:366
Mass (Da):39,204
Last modified:July 1, 1989 - v1
Checksum:i57C4492EC7EA3AA1
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X13987 Genomic DNA. Translation: CAA32166.1.
X13333 mRNA. Translation: CAA31710.1.
M34510 Genomic DNA. Translation: AAA37387.1.
BC057889 mRNA. Translation: AAH57889.1.
CCDSiCCDS29159.1.
PIRiS03605. TDMSM4.
RefSeqiNP_033971.1. NM_009841.4.
UniGeneiMm.3460.

Genome annotation databases

EnsembliENSMUST00000061829; ENSMUSP00000056669; ENSMUSG00000051439.
GeneIDi12475.
KEGGimmu:12475.
UCSCiuc008eof.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X13987 Genomic DNA. Translation: CAA32166.1.
X13333 mRNA. Translation: CAA31710.1.
M34510 Genomic DNA. Translation: AAA37387.1.
BC057889 mRNA. Translation: AAH57889.1.
CCDSiCCDS29159.1.
PIRiS03605. TDMSM4.
RefSeqiNP_033971.1. NM_009841.4.
UniGeneiMm.3460.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1WWLX-ray2.50A/B20-329[»]
ProteinModelPortaliP10810.
SMRiP10810. Positions 22-329.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198573. 1 interaction.
STRINGi10090.ENSMUSP00000056669.

Chemistry

ChEMBLiCHEMBL3038514.

PTM databases

iPTMnetiP10810.
PhosphoSiteiP10810.

Proteomic databases

MaxQBiP10810.
PaxDbiP10810.
PRIDEiP10810.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000061829; ENSMUSP00000056669; ENSMUSG00000051439.
GeneIDi12475.
KEGGimmu:12475.
UCSCiuc008eof.2. mouse.

Organism-specific databases

CTDi929.
MGIiMGI:88318. Cd14.

Phylogenomic databases

eggNOGiENOG410IXG9. Eukaryota.
ENOG41118N2. LUCA.
HOGENOMiHOG000237268.
HOVERGENiHBG005269.
InParanoidiP10810.
KOiK04391.
OMAiLCPHKFP.
OrthoDBiEOG751NFQ.
PhylomeDBiP10810.
TreeFamiTF338550.

Enzyme and pathway databases

ReactomeiR-MMU-166016. Toll Like Receptor 4 (TLR4) Cascade.
R-MMU-166020. Transfer of LPS from LBP carrier to CD14.
R-MMU-166166. MyD88-independent TLR3/TLR4 cascade.

Miscellaneous databases

EvolutionaryTraceiP10810.
NextBioi281354.
PMAP-CutDBP10810.
PROiP10810.
SOURCEiSearch...

Gene expression databases

BgeeiP10810.
CleanExiMM_CD14.
ExpressionAtlasiP10810. baseline and differential.
GenevisibleiP10810. MM.

Family and domain databases

Gene3Di3.80.10.10. 1 hit.
InterProiIPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR016337. Monocyte_diff_Ag_CD14.
[Graphical view]
PIRSFiPIRSF002017. CD14. 1 hit.
SUPFAMiSSF52058. SSF52058. 1 hit.
PROSITEiPS51450. LRR. 3 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: BALB/cJ.
    Tissue: Liver.
  2. "Mouse and human CD14 (myeloid cell-specific leucine-rich glycoprotein) primary structure deduced from cDNA clones."
    Setoguchi M., Nasu N., Yoshida S., Higuchi Y., Akizuki S., Yamamoto S.
    Biochim. Biophys. Acta 1008:213-222(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: ICR.
    Tissue: Macrophage.
  3. "CD14 is a member of the family of leucine-rich proteins and is encoded by a gene syntenic with multiple receptor genes."
    Ferrero E., Hsieh C.L., Francke U., Goyert S.M.
    J. Immunol. 145:331-336(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: NMRI.
    Tissue: Mammary gland.
  5. "Resistance to endotoxin shock and reduced dissemination of gram-negative bacteria in CD14-deficient mice."
    Haziot A., Ferrero E., Kontgen F., Hijiya N., Yamamoto S., Silver J., Stewart C.L., Goyert S.M.
    Immunity 4:407-414(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION, SUBCELLULAR LOCATION.
  6. "Influence of CD14 on ligand interactions between lipopolysaccharide and its receptor complex."
    Gangloff S.C., Zahringer U., Blondin C., Guenounou M., Silver J., Goyert S.M.
    J. Immunol. 175:3940-3945(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  7. Cited for: FUNCTION, DOMAIN.
  8. "TLR2 and its co-receptors determine responses of macrophages and dendritic cells to lipoproteins of Mycobacterium tuberculosis."
    Drage M.G., Pecora N.D., Hise A.G., Febbraio M., Silverstein R.L., Golenbock D.T., Boom W.H., Harding C.V.
    Cell. Immunol. 258:29-37(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY.
    Tissue: Macrophage.
  9. "Lysophosphatidic acid receptor 1 modulates lipopolysaccharide-induced inflammation in alveolar epithelial cells and murine lungs."
    Zhao J., He D., Su Y., Berdyshev E., Chun J., Natarajan V., Zhao Y.
    Am. J. Physiol. 301:L547-L556(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH LPAR1, SUBCELLULAR LOCATION.
  10. "The attenuated inflammation of MPL is due to the lack of CD14-dependent tight dimerization of the TLR4/MD2 complex at the plasma membrane."
    Tanimura N., Saitoh S., Ohto U., Akashi-Takamura S., Fujimoto Y., Fukase K., Shimizu T., Miyake K.
    Int. Immunol. 26:307-314(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  11. "Crystal structure of CD14 and its implications for lipopolysaccharide signaling."
    Kim J.I., Lee C.J., Jin M.S., Lee C.H., Paik S.G., Lee H., Lee J.O.
    J. Biol. Chem. 280:11347-11351(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 20-329, DISULFIDE BONDS, GLYCOSYLATION AT ASN-147; ASN-180 AND ASN-276, DOMAINS LEUCINE-RICH REPEATS.

Entry informationi

Entry nameiCD14_MOUSE
AccessioniPrimary (citable) accession number: P10810
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: January 20, 2016
This is version 152 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.