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{{Infobox_gene}}
{{PBB_Controls
'''CD14''' ([[cluster of differentiation]] 14) is a human [[gene]].<ref name="pmid2472171">{{cite journal | vauthors = Setoguchi M, Nasu N, Yoshida S, Higuchi Y, Akizuki S, Yamamoto S | title = Mouse and human CD14 (myeloid cell-specific leucine-rich glycoprotein) primary structure deduced from cDNA clones | journal = Biochimica et Biophysica Acta | volume = 1008 | issue = 2 | pages = 213–22 | date = July 1989 | pmid = 2472171 | doi = 10.1016/0167-4781(80)90012-3 }}</ref><ref name="pmid2462937">{{cite journal | vauthors = Simmons DL, Tan S, Tenen DG, Nicholson-Weller A, Seed B | title = Monocyte antigen CD14 is a phospholipid anchored membrane protein | journal = Blood | volume = 73 | issue = 1 | pages = 284–9 | date = January 1989 | pmid = 2462937 }}</ref>
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
The [[protein]] encoded by this gene is a component of the [[innate immune system]]. CD14 exists in two forms, one anchored to the membrane by a [[glycosylphosphatidylinositol]] tail (mCD14), the other a soluble form (sCD14). Soluble CD14 either appears after shedding of mCD14 (48 [[kDa]]) or is directly secreted from intracellular vesicles (56 kDa).<ref name="pmid9575549">{{cite journal | vauthors = Kirkland TN, Viriyakosol S | title = Structure-function analysis of soluble and membrane-bound CD14 | journal = Progress in Clinical and Biological Research | volume = 397 | issue =  | pages = 79–87 | year = 1998 | pmid = 9575549 | doi =  }}</ref>
{{GNF_Protein_box
| image = 
| image_source = 
| PDB =
| Name = CD14 molecule
| HGNCid = 1628
| Symbol = CD14
| AltSymbols =;
| OMIM = 158120
| ECnumber = 
| Homologene = 493
| MGIid = 88318
| GeneAtlas_image1 = PBB_GE_CD14_201743_at_tn.png
| Function = {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0016019 |text = peptidoglycan receptor activity}} {{GNF_GO|id=GO:0048503 |text = GPI anchor binding}}
| Component = {{GNF_GO|id=GO:0005886 |text = plasma membrane}} {{GNF_GO|id=GO:0019898 |text = extrinsic to membrane}}
| Process = {{GNF_GO|id=GO:0006909 |text = phagocytosis}} {{GNF_GO|id=GO:0006915 |text = apoptosis}} {{GNF_GO|id=GO:0006954 |text = inflammatory response}} {{GNF_GO|id=GO:0006955 |text = immune response}} {{GNF_GO|id=GO:0007166 |text = cell surface receptor linked signal transduction}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 929
    | Hs_Ensembl = ENSG00000170458
    | Hs_RefseqProtein = NP_000582
    | Hs_RefseqmRNA = NM_000591
    | Hs_GenLoc_db =   
    | Hs_GenLoc_chr = 5
    | Hs_GenLoc_start = 139991522
    | Hs_GenLoc_end = 139993157
    | Hs_Uniprot = P08571
    | Mm_EntrezGene = 12475
    | Mm_Ensembl = ENSMUSG00000051439
    | Mm_RefseqmRNA = NM_009841
    | Mm_RefseqProtein = NP_033971
    | Mm_GenLoc_db =   
    | Mm_GenLoc_chr = 18
    | Mm_GenLoc_start = 36851038
    | Mm_GenLoc_end = 36852628
    | Mm_Uniprot = Q3TE16
  }}
}}


The x-ray crystal structure of human CD14 (4GLP.pdb) reveals a monomeric, bent solenoid structure containing a hydrophobic amino-terminal pocket.<ref name="pmid23264655">{{cite journal | vauthors = Kelley SL, Lukk T, Nair SK, Tapping RI | title = The crystal structure of human soluble CD14 reveals a bent solenoid with a hydrophobic amino-terminal pocket | journal = Journal of Immunology | volume = 190 | issue = 3 | pages = 1304–11 | date = February 2013 | pmid = 23264655 | doi = 10.4049/jimmunol.1202446 | pmc=3552104}}</ref>


'''CD14''' is a membrane-associated  [[glycosylphosphatidylinositol]]-linked [[protein]] expressed at the surface of cells, especially [[macrophages]].
CD14 was the first described [[pattern recognition receptor]]<!-- The page for CRP (http://en.wikipedia.org/wiki/C-reactive_protein) says that CRP was the first PRR to be identified. Which is it? -->.


CD14 takes its name from its inclusion in the [[cluster of differentiation]] group of cell surface marker proteins.
== Function ==
CD14 acts as a co-receptor (along with the [[Toll-like receptor]] [[TLR 4]] and [[Ly96|MD-2]]) for the detection of bacterial [[lipopolysaccharide]] (LPS).<ref name="pmid10608082">{{cite journal | vauthors = Kitchens RL | title = Role of CD14 in cellular recognition of bacterial lipopolysaccharides | journal = Chemical Immunology | volume = 74 | issue =  | pages = 61–82 | year = 2000 | pmid = 10608082 | doi = 10.1159/000058750 | isbn = 3-8055-6917-3 | series = Chemical Immunology and Allergy }}</ref><ref name="pmid10608084">{{cite journal | vauthors = Tapping RI, Tobias PS | title = Soluble CD14-mediated cellular responses to lipopolysaccharide | journal = Chemical Immunology | volume = 74 | issue =  | pages = 108–21 | year = 2000 | pmid = 10608084 | doi = 10.1159/000058751 | isbn = 3-8055-6917-3 | series = Chemical Immunology and Allergy }}</ref> CD14 can bind LPS only in the presence of [[lipopolysaccharide-binding protein]] (LBP).
Although LPS is considered its main [[ligand]], CD14 also recognizes other pathogen-associated molecular patterns such as lipoteichoic acid.<ref name="pmid23430250">{{cite journal | vauthors = Ranoa DR, Kelley SL, Tapping RI | title = Human lipopolysaccharide-binding protein (LBP) and CD14 independently deliver triacylated lipoproteins to Toll-like receptor 1 (TLR1) and TLR2 and enhance formation of the ternary signaling complex | journal = The Journal of Biological Chemistry | volume = 288 | issue = 14 | pages = 9729–41 | date = April 2013 | pmid = 23430250 | doi = 10.1074/jbc.M113.453266 | pmc=3617275}}</ref>


CD14 was the first described [[pattern recognition receptor]].
[[Image:Toll-like receptor pathways revised.jpg|thumbnail|left|500px|Signaling pathway of toll-like receptors. Dashed grey lines represent unknown associations]]
{{Clear}}


==Function==
==Tissue distribution==
CD14 acts as a co-receptor (along with the [[Toll-like receptor]] [[TLR 4]] and [[Ly96|MD-2]]) for the detection of bacterial [[lipopolysaccharide]].
CD14 is expressed mainly by [[macrophages]] and (at 10-times lesser extent) by [[neutrophil]]s. It is also expressed by [[dendritic cells]]. The soluble form of the receptor (sCD14) is secreted by the [[liver]] and [[monocyte]]s and is sufficient in low concentrations to confer LPS-responsiveness to cells not expressing CD14. mCD14 and sCD14 are also present on enterocytes.<ref>{{cite journal|title=CD14 Is Expressed and Released as Soluble CD14 by Human Intestinal Epithelial Cells In Vitro: Lipopolysaccharide Activation of Epithelial Cells Revisited}}</ref> sCD14 is also present in human milk, where it is believed to regulate microbial growth in the infant gut.


[[Image:Toll-like receptor pathways revised.jpg|thumbnail|center|500px|Signaling pathway of toll-like receptors. Dashed grey lines represent unknown associations]]
==Differentiation==
'''CD14+''' [[monocytes]]  can differentiate into a host of different cells, including [[dendritic cell]]s, a differentiation pathway encouraged by [[cytokines]], including [[GM-CSF]] and [[Interleukin-4|IL-4]].


==Production==
== Interactions ==
A soluble form '''sCD14''' is secreted by the [[liver]] and [[monocyte]]s and is sufficient in low concentrations to confer LPS-responsiveness to cells which otherwise do not express CD14.


==Differentiation==
CD14 has been shown to [[Protein-protein interaction|interact]] with lipopolysaccharide-binding protein.<ref name=pmid12417309>{{cite journal | vauthors = Thomas CJ, Kapoor M, Sharma S, Bausinger H, Zyilan U, Lipsker D, Hanau D, Surolia A | title = Evidence of a trimolecular complex involving LPS, LPS binding protein and soluble CD14 as an effector of LPS response | journal = FEBS Letters | volume = 531 | issue = 2 | pages = 184–8 | date = November 2002 | pmid = 12417309 | doi = 10.1016/S0014-5793(02)03499-3 }}</ref><ref name=pmid7583357>{{cite journal | vauthors = Yu B, Wright SD | title = LPS-dependent interaction of Mac-2-binding protein with immobilized CD14 | journal = Journal of Inflammation | volume = 45 | issue = 2 | pages = 115–25 | year = 1995 | pmid = 7583357 }}</ref>
'''CD14+''' are [[monocytes]] that can differentiate into a host of different cells. (A '+' sign refers to the presence of the CD14 protein on a cell. )


One type of cell is the [[dendritic cell]], where differentiation is encouraged by [[cytokines]]. Examples of cytokines that will cause dendritic cell differentiation includes [[GM-CSF]] and [[Interleukin-4|IL-4]].
== References ==
{{Reflist|2}}


==External links==
== External links ==
* {{UCSC gene info|CD14}}
* {{MeshName|CD14+Antigens}}
* {{MeshName|CD14+Antigens}}
* [http://www.ebioscience.com/resources/mouse-cd-chart.htm]
* [http://www.ebioscience.com/resources/human-cd-chart.htm]
* [http://www.jimmunol.org/content/early/2012/12/21/jimmunol.1202446.abstract]
* [http://www.jbc.org/content/early/2013/02/19/jbc.M113.453266.abstract]


==References==
{{Clusters of differentiation}}
{{reflist|2}}
{{Clusters of differentiation by lineage}}
{{TLR signaling pathway}}


{{DEFAULTSORT:Cd14}}
[[Category:Clusters of differentiation]]


==Further reading==
{{refbegin | 2}}
{{PBB_Further_reading
| citations =
*{{cite journal  | author=Todd RF, Petty HR |title=Beta 2 (CD11/CD18) integrins can serve as signaling partners for other leukocyte receptors. |journal=J. Lab. Clin. Med. |volume=129 |issue= 5 |pages= 492-8 |year= 1997 |pmid= 9142045 |doi=  }}
}}
{{refend}}
{{protein-stub}}
{{Clusters of differentiation}}
{{Immune receptors}}
{{protein-stub}}
[[Category:Clusters of differentiation]]


[[ca:CD14]]
{{gene-5-stub}}
{{WikiDoc Sources}}

Latest revision as of 08:19, 7 March 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

CD14 (cluster of differentiation 14) is a human gene.[1][2]

The protein encoded by this gene is a component of the innate immune system. CD14 exists in two forms, one anchored to the membrane by a glycosylphosphatidylinositol tail (mCD14), the other a soluble form (sCD14). Soluble CD14 either appears after shedding of mCD14 (48 kDa) or is directly secreted from intracellular vesicles (56 kDa).[3]

The x-ray crystal structure of human CD14 (4GLP.pdb) reveals a monomeric, bent solenoid structure containing a hydrophobic amino-terminal pocket.[4]

CD14 was the first described pattern recognition receptor.

Function

CD14 acts as a co-receptor (along with the Toll-like receptor TLR 4 and MD-2) for the detection of bacterial lipopolysaccharide (LPS).[5][6] CD14 can bind LPS only in the presence of lipopolysaccharide-binding protein (LBP). Although LPS is considered its main ligand, CD14 also recognizes other pathogen-associated molecular patterns such as lipoteichoic acid.[7]

Signaling pathway of toll-like receptors. Dashed grey lines represent unknown associations

Tissue distribution

CD14 is expressed mainly by macrophages and (at 10-times lesser extent) by neutrophils. It is also expressed by dendritic cells. The soluble form of the receptor (sCD14) is secreted by the liver and monocytes and is sufficient in low concentrations to confer LPS-responsiveness to cells not expressing CD14. mCD14 and sCD14 are also present on enterocytes.[8] sCD14 is also present in human milk, where it is believed to regulate microbial growth in the infant gut.

Differentiation

CD14+ monocytes can differentiate into a host of different cells, including dendritic cells, a differentiation pathway encouraged by cytokines, including GM-CSF and IL-4.

Interactions

CD14 has been shown to interact with lipopolysaccharide-binding protein.[9][10]

References

  1. ↑ Setoguchi M, Nasu N, Yoshida S, Higuchi Y, Akizuki S, Yamamoto S (July 1989). "Mouse and human CD14 (myeloid cell-specific leucine-rich glycoprotein) primary structure deduced from cDNA clones". Biochimica et Biophysica Acta. 1008 (2): 213–22. doi:10.1016/0167-4781(80)90012-3. PMID 2472171.
  2. ↑ Simmons DL, Tan S, Tenen DG, Nicholson-Weller A, Seed B (January 1989). "Monocyte antigen CD14 is a phospholipid anchored membrane protein". Blood. 73 (1): 284–9. PMID 2462937.
  3. ↑ Kirkland TN, Viriyakosol S (1998). "Structure-function analysis of soluble and membrane-bound CD14". Progress in Clinical and Biological Research. 397: 79–87. PMID 9575549.
  4. ↑ Kelley SL, Lukk T, Nair SK, Tapping RI (February 2013). "The crystal structure of human soluble CD14 reveals a bent solenoid with a hydrophobic amino-terminal pocket". Journal of Immunology. 190 (3): 1304–11. doi:10.4049/jimmunol.1202446. PMC 3552104. PMID 23264655.
  5. ↑ Kitchens RL (2000). "Role of CD14 in cellular recognition of bacterial lipopolysaccharides". Chemical Immunology. Chemical Immunology and Allergy. 74: 61–82. doi:10.1159/000058750. ISBN 3-8055-6917-3. PMID 10608082.
  6. ↑ Tapping RI, Tobias PS (2000). "Soluble CD14-mediated cellular responses to lipopolysaccharide". Chemical Immunology. Chemical Immunology and Allergy. 74: 108–21. doi:10.1159/000058751. ISBN 3-8055-6917-3. PMID 10608084.
  7. ↑ Ranoa DR, Kelley SL, Tapping RI (April 2013). "Human lipopolysaccharide-binding protein (LBP) and CD14 independently deliver triacylated lipoproteins to Toll-like receptor 1 (TLR1) and TLR2 and enhance formation of the ternary signaling complex". The Journal of Biological Chemistry. 288 (14): 9729–41. doi:10.1074/jbc.M113.453266. PMC 3617275. PMID 23430250.
  8. ↑ "CD14 Is Expressed and Released as Soluble CD14 by Human Intestinal Epithelial Cells In Vitro: Lipopolysaccharide Activation of Epithelial Cells Revisited".
  9. ↑ Thomas CJ, Kapoor M, Sharma S, Bausinger H, Zyilan U, Lipsker D, Hanau D, Surolia A (November 2002). "Evidence of a trimolecular complex involving LPS, LPS binding protein and soluble CD14 as an effector of LPS response". FEBS Letters. 531 (2): 184–8. doi:10.1016/S0014-5793(02)03499-3. PMID 12417309.
  10. ↑ Yu B, Wright SD (1995). "LPS-dependent interaction of Mac-2-binding protein with immobilized CD14". Journal of Inflammation. 45 (2): 115–25. PMID 7583357.

External links


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