Monocyte differentiation antigen CD14 (CD14)
The protein contains 375 amino acids for an estimated molecular weight of 40076 Da.
Coreceptor for bacterial lipopolysaccharide (PubMed:1698311, PubMed:23264655). 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:20133493, PubMed:23264655, PubMed:22265692). Acts via MyD88, TIRAP and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:8612135). 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 (PubMed:16880211). Binds electronegative LDL (LDL(-)) and mediates the cytokine release induced by LDL(-) (PubMed:23880187). (updated: June 2, 2021)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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| Variant | Description |
|---|---|
| dbSNP:rs2228049 | |
| dbSNP:rs11556179 |
Biological Process
Apoptotic process
Apoptotic signaling pathway
Cell surface receptor signaling pathway
Cellular response to diacyl bacterial lipopeptide
Cellular response to lipopolysaccharide
Cellular response to lipoteichoic acid
Cellular response to molecule of bacterial origin
Cellular response to triacyl bacterial lipopeptide
I-kappaB kinase/NF-kappaB signaling
Inflammatory response
Innate immune response
Lipopolysaccharide-mediated signaling pathway
MyD88-dependent toll-like receptor signaling pathway
MyD88-independent toll-like receptor signaling pathway
Necroptotic process
Negative regulation of MyD88-independent toll-like receptor signaling pathway
Neutrophil degranulation
Phagocytosis
Positive regulation of cytokine secretion
Positive regulation of endocytosis
Positive regulation of interferon-gamma production
Positive regulation of interleukin-8 production
Positive regulation of interleukin-8 secretion
Positive regulation of NIK/NF-kappaB signaling
Positive regulation of tumor necrosis factor production
Positive regulation of type I interferon production
Receptor-mediated endocytosis
Response to electrical stimulus
Response to ethanol
Response to heat
Response to magnesium ion
Response to tumor necrosis factor
Toll-like receptor 2 signaling pathway
Toll-like receptor 3 signaling pathway
Toll-like receptor 4 signaling pathway
Toll-like receptor signaling pathway
Toll-like receptor TLR1:TLR2 signaling pathway
Toll-like receptor TLR6:TLR2 signaling pathway
TRIF-dependent toll-like receptor signaling pathway
Cellular Component
Anchored component of external side of plasma membrane
Anchored component of membrane
Cell surface
Endosome membrane
External side of plasma membrane
Extracellular exosome
Extracellular region
Extracellular space
Golgi apparatus
Lipopolysaccharide receptor complex
Membrane raft
Plasma membrane
Secretory granule membrane
The reference OMIM entry for this protein is 158120
Monocyte differentiation antigen cd14; cd14
Myeloid cell-specific leucine-rich glycoprotein
DESCRIPTION
CD14 is a single-copy gene encoding 2 protein forms: a 50- to 55-kD glycosylphosphatidylinositol-anchored membrane protein (mCD14) and a monocyte or liver-derived soluble serum protein (sCD14) that lacks the anchor. Both molecules are critical for lipopolysaccharide (LPS)-dependent signal transduction, and sCD14 confers LPS sensitivity to cells lacking mCD14. Increased sCD14 levels are associated with inflammatory infectious diseases and high mortality in gram-negative shock (LeVan et al., 2001).CLONING
Differentiation of myelomonocytic cells from pluripotent stem cells to mature functioning monocytes/macrophages and granulocytes is accompanied by a variety of changes, including the expression of new cell surface antigens. One of these antigens, CD14, a 55-kD glycoprotein, is preferentially expressed on the surface of mature cells of the monocytic lineage. Goyert et al. (1988) isolated a cDNA clone encoding CD14 and isolated the CD14 gene. Ferrero et al. (1990) demonstrated that, as in man, the expression of murine CD14 is limited to the myeloid lineage. In both mouse and man, the CD14 protein contains leucine-rich motif that is repeated 10 times.BIOCHEMICAL FEATURES
Kelley et al. (2013) determined the crystal structure of human CD14 at 4-angstrom resolution. The structure revealed a bent solenoid typical of leucine-rich repeat proteins with an N-terminal pocket that likely binds acylated ligands, such as LPS. The structures of human and mouse CD14 are similar, except that human CD14 contains an expanded pocket and alternative rim residues that are probably important for LPS binding and cell activation.GENE FUNCTION
The expression profile of CD14, as well as its inclusion in the family of leucine-rich proteins and the chromosomal location of other receptor genes, supports the hypothesis that CD14 functions as a receptor. Its receptor function was indeed demonstrated by Wright (1990) who showed that it is a receptor for the lipopolysaccharide-binding protein:lipopolysaccharide complex (LBP; 151990:LPS); also see Wright et al. (1990). Gupta et al. (1996) transfected mouse 70Z/3 cells with human CD14 and showed that these cells were responsive to peptidoglycan (PGN), a polymer of alternating GlcNAc and MurNAc cross-linked by short peptides, that is present in the cell walls of all bacteria, but is particularly abundant in gram-positive bacteria. They concluded that CD14 serves as a cell-activating receptor not only for LPS but also for PGN. Cells undergoing programmed cell death (apoptosis) are cleared rapidly in vivo by phagocytes without inducing inflammation. Devitt et al. (1998) showed that the glycoprotein CD14 on the surface of human macrophages is important for the recognition and clearance of apoptotic cells. CD14 can also act as a receptor that binds bacterial LPS, triggering inflammatory responses. Overstimulation of CD14 by LPS can cause the often fatal toxic-shock syndrome. Devitt et al. (1998) showed that apoptotic cells interact with CD14, triggering phagocytosis of the apoptotic cells. This interaction depends on a region of CD14 that is identical to, or at least closely associated with, a region known to bind LPS. However, apoptotic cells, unlike LPS, do not provoke the release of proinflammatory cytokines from macrophages. These results indicated that clearance of apoptotic cells is mediated by a receptor whose interactions with 'nonself' components (LPS) and 'self ... More on the omim web site
July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for CD14
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 158120 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed