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P08571

- CD14_HUMAN

UniProt

P08571 - CD14_HUMAN

Protein

Monocyte differentiation antigen CD14

Gene

CD14

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 158 (01 Oct 2014)
      Sequence version 2 (27 Mar 2002)
      Previous versions | rss
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    Functioni

    In concert with LBP, binds to monomeric lipopolysaccharide and delivers it to the MD-2/TLR4 complex, thereby mediating the innate immune response to bacterial lipopolysaccharide (LPS). Acts via MyD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Up-regulates cell surface molecules, including adhesion molecules.1 Publication

    GO - Molecular functioni

    1. lipopolysaccharide binding Source: MGI
    2. lipoteichoic acid binding Source: MGI
    3. opsonin receptor activity Source: BHF-UCL
    4. peptidoglycan receptor activity Source: ProtInc
    5. protein binding Source: IntAct

    GO - Biological processi

    1. apoptotic process Source: ProtInc
    2. cell surface receptor signaling pathway Source: ProtInc
    3. cellular response to lipopolysaccharide Source: MGI
    4. cellular response to lipoteichoic acid Source: MGI
    5. I-kappaB kinase/NF-kappaB signaling Source: Reactome
    6. inflammatory response Source: UniProtKB-KW
    7. innate immune response Source: Reactome
    8. MyD88-dependent toll-like receptor signaling pathway Source: Reactome
    9. MyD88-independent toll-like receptor signaling pathway Source: Reactome
    10. phagocytosis Source: ProtInc
    11. positive regulation of cytokine secretion Source: Ensembl
    12. positive regulation of endocytosis Source: Ensembl
    13. positive regulation of tumor necrosis factor production Source: MGI
    14. response to ethanol Source: Ensembl
    15. response to heat Source: Ensembl
    16. response to magnesium ion Source: Ensembl
    17. response to tumor necrosis factor Source: Ensembl
    18. toll-like receptor 2 signaling pathway Source: Reactome
    19. toll-like receptor 3 signaling pathway Source: Reactome
    20. toll-like receptor 4 signaling pathway Source: Reactome
    21. toll-like receptor signaling pathway Source: Reactome
    22. toll-like receptor TLR1:TLR2 signaling pathway Source: Reactome
    23. toll-like receptor TLR6:TLR2 signaling pathway Source: Reactome
    24. TRIF-dependent toll-like receptor signaling pathway Source: Reactome

    Keywords - Biological processi

    Immunity, Inflammatory response, Innate immunity

    Enzyme and pathway databases

    ReactomeiREACT_150361. TRIF-mediated programmed cell death.
    REACT_25148. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
    REACT_25351. TRAF6 mediated induction of TAK1 complex.
    REACT_25374. IKK complex recruitment mediated by RIP1.
    REACT_6788. MyD88:Mal cascade initiated on plasma membrane.
    REACT_6822. Transfer of LPS from LBP carrier to CD14.
    REACT_6894. Toll Like Receptor 4 (TLR4) Cascade.
    REACT_8005. Toll Like Receptor TLR1:TLR2 Cascade.
    REACT_8006. Toll Like Receptor TLR6:TLR2 Cascade.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Monocyte differentiation antigen CD14
    Alternative name(s):
    Myeloid cell-specific leucine-rich glycoprotein
    CD_antigen: CD14
    Cleaved into the following 2 chains:
    Gene namesi
    Name:CD14
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:1628. CD14.

    Subcellular locationi

    GO - Cellular componenti

    1. anchored component of membrane Source: UniProtKB-KW
    2. cell surface Source: Ensembl
    3. endosome membrane Source: Reactome
    4. extracellular region Source: Reactome
    5. extracellular space Source: UniProt
    6. extracellular vesicular exosome Source: UniProt
    7. membrane raft Source: Ensembl
    8. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Cell membrane, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA26188.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1919Add
    BLAST
    Chaini20 – 367348Monocyte differentiation antigen CD14, urinary formPRO_0000020884Add
    BLAST
    Chaini20 – 345326Monocyte differentiation antigen CD14, membrane-bound formPRO_0000020885Add
    BLAST
    Propeptidei346 – 37530Removed in mature formSequence AnalysisPRO_0000020886Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Disulfide bondi25 ↔ 361 Publication
    Disulfide bondi34 ↔ 511 Publication
    Glycosylationi37 – 371N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi151 – 1511N-linked (GlcNAc...)1 Publication
    Disulfide bondi187 ↔ 2171 Publication
    Disulfide bondi241 ↔ 2721 Publication
    Glycosylationi282 – 2821N-linked (GlcNAc...)1 Publication
    Glycosylationi323 – 3231N-linked (GlcNAc...)1 Publication
    Glycosylationi336 – 3361O-linked (GalNAc...)1 Publication
    Lipidationi345 – 3451GPI-anchor amidated asparagineSequence Analysis

    Post-translational modificationi

    N- and O- glycosylated. O-glycosylated with a core 1 or possibly core 8 glycan.3 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein, GPI-anchor, Lipoprotein

    Proteomic databases

    MaxQBiP08571.
    PaxDbiP08571.
    PeptideAtlasiP08571.
    PRIDEiP08571.

    PTM databases

    PhosphoSiteiP08571.

    Miscellaneous databases

    PMAP-CutDBP08571.

    Expressioni

    Tissue specificityi

    Expressed strongly on the surface of monocytes and weakly on the surface of granulocytes; also expressed by most tissue macrophages.

    Gene expression databases

    ArrayExpressiP08571.
    BgeeiP08571.
    CleanExiHS_CD14.
    GenevestigatoriP08571.

    Organism-specific databases

    HPAiHPA001887.
    HPA002127.

    Interactioni

    Subunit structurei

    Belongs to the lipopolysaccharide (LPS) receptor, a multi-protein complex containing at least CD14, MD-2 and TLR4.

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    FSTL1Q128413EBI-3905196,EBI-2349801

    Protein-protein interaction databases

    BioGridi107367. 9 interactions.
    DIPiDIP-1030N.
    IntActiP08571. 8 interactions.
    MINTiMINT-7990664.
    STRINGi9606.ENSP00000304236.

    Structurei

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4GLPX-ray4.00A26-335[»]
    ProteinModelPortaliP08571.
    SMRiP08571. Positions 26-335.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati54 – 8229LRR 1Add
    BLAST
    Repeati83 – 11836LRR 2Add
    BLAST
    Repeati119 – 14426LRR 3Add
    BLAST
    Repeati145 – 17228LRR 4Add
    BLAST
    Repeati173 – 19624LRR 5Add
    BLAST
    Repeati197 – 22428LRR 6Add
    BLAST
    Repeati225 – 25127LRR 7Add
    BLAST
    Repeati252 – 27827LRR 8Add
    BLAST
    Repeati279 – 29921LRR 9Add
    BLAST
    Repeati300 – 32122LRR 10Add
    BLAST
    Repeati322 – 34928LRR 11Add
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni42 – 8948Ligand-binding pocket rimAdd
    BLAST

    Sequence similaritiesi

    Contains 11 LRR (leucine-rich) repeats.Curated

    Keywords - Domaini

    Leucine-rich repeat, Repeat, Signal

    Phylogenomic databases

    eggNOGiNOG86091.
    HOGENOMiHOG000237268.
    HOVERGENiHBG005269.
    InParanoidiP08571.
    KOiK04391.
    OMAiWATGGAW.
    OrthoDBiEOG751NFQ.
    PhylomeDBiP08571.
    TreeFamiTF338550.

    Family and domain databases

    InterProiIPR001611. Leu-rich_rpt.
    IPR016337. Monocyte_diff_Ag_CD14.
    [Graphical view]
    PfamiPF00560. LRR_1. 1 hit.
    [Graphical view]
    PIRSFiPIRSF002017. CD14. 1 hit.
    PROSITEiPS51450. LRR. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    P08571-1 [UniParc]FASTAAdd to Basket

    « Hide

    MERASCLLLL LLPLVHVSAT TPEPCELDDE DFRCVCNFSE PQPDWSEAFQ    50
    CVSAVEVEIH AGGLNLEPFL KRVDADADPR QYADTVKALR VRRLTVGAAQ 100
    VPAQLLVGAL RVLAYSRLKE LTLEDLKITG TMPPLPLEAT GLALSSLRLR 150
    NVSWATGRSW LAELQQWLKP GLKVLSIAQA HSPAFSCEQV RAFPALTSLD 200
    LSDNPGLGER GLMAALCPHK FPAIQNLALR NTGMETPTGV CAALAAAGVQ 250
    PHSLDLSHNS LRATVNPSAP RCMWSSALNS LNLSFAGLEQ VPKGLPAKLR 300
    VLDLSCNRLN RAPQPDELPE VDNLTLDGNP FLVPGTALPH EGSMNSGVVP 350
    ACARSTLSVG VSGTLVLLQG ARGFA 375
    Length:375
    Mass (Da):40,076
    Last modified:March 27, 2002 - v2
    Checksum:i1746CDB41F394F8D
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti187 – 1871C → Y in CAA29999. (PubMed:2453848)Curated
    Sequence conflicti303 – 3031D → E in AAC83816. 1 PublicationCurated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti204 – 2041N → D.
    Corresponds to variant rs2228049 [ dbSNP | Ensembl ].
    VAR_024302
    Natural varianti341 – 3411E → K.
    Corresponds to variant rs11556179 [ dbSNP | Ensembl ].
    VAR_050771

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X06882 Genomic DNA. Translation: CAA29999.1.
    X13334 mRNA. Translation: CAA31711.1.
    M86511 mRNA. Translation: AAA51930.1.
    AF097942 mRNA. Translation: AAC83816.1.
    AB446505 mRNA. Translation: BAG55282.1.
    BT007331 mRNA. Translation: AAP35995.1.
    CH471062 Genomic DNA. Translation: EAW62037.1.
    BC010507 mRNA. Translation: AAH10507.1.
    AY044269 mRNA. Translation: AAL02401.1.
    CCDSiCCDS4232.1.
    PIRiA27637. TDHUM4.
    RefSeqiNP_000582.1. NM_000591.3.
    NP_001035110.1. NM_001040021.2.
    NP_001167575.1. NM_001174104.1.
    NP_001167576.1. NM_001174105.1.
    UniGeneiHs.163867.

    Genome annotation databases

    EnsembliENST00000302014; ENSP00000304236; ENSG00000170458.
    ENST00000401743; ENSP00000385519; ENSG00000170458.
    GeneIDi929.
    KEGGihsa:929.
    UCSCiuc003lgi.2. human.

    Polymorphism databases

    DMDMi20141203.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Wikipedia

    CD14 entry

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X06882 Genomic DNA. Translation: CAA29999.1 .
    X13334 mRNA. Translation: CAA31711.1 .
    M86511 mRNA. Translation: AAA51930.1 .
    AF097942 mRNA. Translation: AAC83816.1 .
    AB446505 mRNA. Translation: BAG55282.1 .
    BT007331 mRNA. Translation: AAP35995.1 .
    CH471062 Genomic DNA. Translation: EAW62037.1 .
    BC010507 mRNA. Translation: AAH10507.1 .
    AY044269 mRNA. Translation: AAL02401.1 .
    CCDSi CCDS4232.1.
    PIRi A27637. TDHUM4.
    RefSeqi NP_000582.1. NM_000591.3.
    NP_001035110.1. NM_001040021.2.
    NP_001167575.1. NM_001174104.1.
    NP_001167576.1. NM_001174105.1.
    UniGenei Hs.163867.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4GLP X-ray 4.00 A 26-335 [» ]
    ProteinModelPortali P08571.
    SMRi P08571. Positions 26-335.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107367. 9 interactions.
    DIPi DIP-1030N.
    IntActi P08571. 8 interactions.
    MINTi MINT-7990664.
    STRINGi 9606.ENSP00000304236.

    Chemistry

    ChEMBLi CHEMBL3038513.

    PTM databases

    PhosphoSitei P08571.

    Polymorphism databases

    DMDMi 20141203.

    Proteomic databases

    MaxQBi P08571.
    PaxDbi P08571.
    PeptideAtlasi P08571.
    PRIDEi P08571.

    Protocols and materials databases

    DNASUi 929.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000302014 ; ENSP00000304236 ; ENSG00000170458 .
    ENST00000401743 ; ENSP00000385519 ; ENSG00000170458 .
    GeneIDi 929.
    KEGGi hsa:929.
    UCSCi uc003lgi.2. human.

    Organism-specific databases

    CTDi 929.
    GeneCardsi GC05M139991.
    HGNCi HGNC:1628. CD14.
    HPAi HPA001887.
    HPA002127.
    MIMi 158120. gene.
    neXtProti NX_P08571.
    PharmGKBi PA26188.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG86091.
    HOGENOMi HOG000237268.
    HOVERGENi HBG005269.
    InParanoidi P08571.
    KOi K04391.
    OMAi WATGGAW.
    OrthoDBi EOG751NFQ.
    PhylomeDBi P08571.
    TreeFami TF338550.

    Enzyme and pathway databases

    Reactomei REACT_150361. TRIF-mediated programmed cell death.
    REACT_25148. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
    REACT_25351. TRAF6 mediated induction of TAK1 complex.
    REACT_25374. IKK complex recruitment mediated by RIP1.
    REACT_6788. MyD88:Mal cascade initiated on plasma membrane.
    REACT_6822. Transfer of LPS from LBP carrier to CD14.
    REACT_6894. Toll Like Receptor 4 (TLR4) Cascade.
    REACT_8005. Toll Like Receptor TLR1:TLR2 Cascade.
    REACT_8006. Toll Like Receptor TLR6:TLR2 Cascade.

    Miscellaneous databases

    GeneWikii CD14.
    GenomeRNAii 929.
    NextBioi 3850.
    PMAP-CutDB P08571.
    PROi P08571.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P08571.
    Bgeei P08571.
    CleanExi HS_CD14.
    Genevestigatori P08571.

    Family and domain databases

    InterProi IPR001611. Leu-rich_rpt.
    IPR016337. Monocyte_diff_Ag_CD14.
    [Graphical view ]
    Pfami PF00560. LRR_1. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF002017. CD14. 1 hit.
    PROSITEi PS51450. LRR. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "The monocyte differentiation antigen, CD14, is anchored to the cell membrane by a phosphatidylinositol linkage."
      Haziot A., Chen S., Ferrero E., Low M.G., Silber R., Goyert S.M.
      J. Immunol. 141:547-552(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    2. "Nucleotide sequence of the gene encoding the monocyte differentiation antigen, CD14."
      Ferrero E., Goyert S.M.
      Nucleic Acids Res. 16:4173-4173(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Tissue: Lymphocyte.
    3. "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].
      Tissue: Macrophage.
    4. "Monocyte antigen CD14 is a phospholipid anchored membrane protein."
      Simmons D.L., Tan S., Tenen D.G., Nicholson-Weller A., Seed B.
      Blood 73:284-289(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    5. "Cloning and sequencing of human CD14 gene."
      Long J.Y., Xue Y.N., Sun L., Wang H.X.
      Sheng Wu Hua Xue Yu Sheng Wu Wu Li Jin Zhan 25:377-378(1998)
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Promyelocytic leukemia.
    6. "Natural selection in the TLR-related genes in the course of primate evolution."
      Nakajima T., Ohtani H., Satta Y., Uno Y., Akari H., Ishida T., Kimura A.
      Immunogenetics 60:727-735(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    7. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    9. "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].
      Tissue: Brain.
    10. "Expression and secretion of CD14 in glial neoplasms of the brain."
      Deininger M.H., Meyermann R., Schluesener H.J.
      Submitted (JUL-2001) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-125.
      Tissue: Glioblastoma.
    11. "Structural relationship between the soluble and membrane-bound forms of human monocyte surface glycoprotein CD14."
      Bazil V., Baudys M., Hilgert I., Stefanova I., Low M.G., Zbrozek J., Horejsi V.
      Mol. Immunol. 26:657-662(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEIN SEQUENCE OF 362-367.
    12. "Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
      Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J., Smith R.D.
      J. Proteome Res. 4:2070-2080(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-151 AND ASN-282.
      Tissue: Plasma.
    13. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
      Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
      J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-323.
      Tissue: Liver.
    14. "Enrichment of glycopeptides for glycan structure and attachment site identification."
      Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G., Larson G.
      Nat. Methods 6:809-811(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT THR-336, STRUCTURE OF CARBOHYDRATES.
      Tissue: Cerebrospinal fluid.
    15. "The crystal structure of human soluble CD14 reveals a bent solenoid with a hydrophobic amino-terminal pocket."
      Kelley S.L., Lukk T., Nair S.K., Tapping R.I.
      J. Immunol. 190:1304-1311(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (4.0 ANGSTROMS) OF 26-335, DISULFIDE BONDS, FUNCTION.

    Entry informationi

    Entry nameiCD14_HUMAN
    AccessioniPrimary (citable) accession number: P08571
    Secondary accession number(s): Q53XT5
    , Q96FR6, Q96L99, Q9UNS3
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1988
    Last sequence update: March 27, 2002
    Last modified: October 1, 2014
    This is version 158 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human cell differentiation molecules
      CD nomenclature of surface proteins of human leucocytes and list of entries
    2. Human chromosome 5
      Human chromosome 5: entries, gene names and cross-references to MIM
    3. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    4. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    5. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    6. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3