Platelet glycoprotein 4 (CD36)
The protein contains 472 amino acids for an estimated molecular weight of 53053 Da.
Multifunctional glycoprotein that acts as receptor for a broad range of ligands. Ligands can be of proteinaceous nature like thrombospondin, fibronectin, collagen or amyloid-beta as well as of lipidic nature such as oxidized low-density lipoprotein (oxLDL), anionic phospholipids, long-chain fatty acids and bacterial diacylated lipopeptides. They are generally multivalent and can therefore engage multiple receptors simultaneously, the resulting formation of CD36 clusters initiates signal transduction and internalization of receptor-ligand complexes. The dependency on coreceptor signaling is strongly ligand specific. Cellular responses to these ligands are involved in angiogenesis, inflammatory response, fatty acid metabolism, taste and dietary fat processing in the intestine (Probable). Binds long-chain fatty acids and facilitates their transport into cells, thus participating in muscle lipid utilization, adipose energy storage, and gut fat absorption (By similarity) (PubMed:18353783, PubMed:21610069). In the small intestine, plays a role in proximal absorption of dietary fatty acid and cholesterol for optimal chylomicron formation, possibly through the activation of MAPK1/3 (ERK1/2) signaling pathway (By similarity) (PubMed:18753675). Involved in oral fat perception and preferences (PubMed:22240721, PubMed:25822988). Detection into the tongue of long-chain fatty acids leads to a rapid and sustained rise in flux and protein content of pancreatobiliary secretions (By similarit (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- 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, is predicted to be membranous by TOPCONS.
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No binding partner found
Biological Process
Amyloid fibril formation
Amyloid-beta clearance by cellular catabolic process
Antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent
Apoptotic cell clearance
Blood coagulation
Cell adhesion
Cellular response to amyloid-beta
Cellular response to diacyl bacterial lipopeptide
Cellular response to hydroperoxide
Cellular response to lipopolysaccharide
Cellular response to lipoteichoic acid
Cellular response to low-density lipoprotein particle stimulus
Cellular response to oxidised low-density lipoprotein particle stimulus
CGMP-mediated signaling
Cholesterol import
Cholesterol transport
Cytokine-mediated signaling pathway
Defense response to Gram-positive bacterium
Energy homeostasis
Fatty acid metabolic process
Interleukin-1 beta production
Interleukin-1 beta secretion
Intestinal absorption
Intestinal cholesterol absorption
Lipid metabolic process
Lipid storage
Lipid transport across blood-brain barrier
Lipoprotein transport
Long-chain fatty acid import across plasma membrane
Long-chain fatty acid import into cell
Long-chain fatty acid transport
Low-density lipoprotein particle clearance
Low-density lipoprotein particle mediated signaling
MyD88-dependent toll-like receptor signaling pathway
Negative regulation of gene expression
Negative regulation of protein import into nucleus
Negative regulation of transcription by RNA polymerase II
Neutrophil degranulation
Nitric oxide mediated signal transduction
Oxidised low-density lipoprotein particle clearance
Phagocytosis, engulfment
Phagocytosis, recognition
Plasma lipoprotein particle clearance
Platelet degranulation
Positive regulation of blood coagulation
Positive regulation of blood microparticle formation
Positive regulation of cell death
Positive regulation of cell-matrix adhesion
Positive regulation of cholesterol storage
Positive regulation of cold-induced thermogenesis
Positive regulation of cytosolic calcium ion concentration
Positive regulation of ERK1 and ERK2 cascade
Positive regulation of gene expression
Positive regulation of I-kappaB kinase/NF-kappaB signaling
Positive regulation of interleukin-1 beta production
Positive regulation of interleukin-12 production
Positive regulation of interleukin-6 production
Positive regulation of macrophage cytokine production
Positive regulation of macrophage derived foam cell differentiation
Positive regulation of NF-kappaB transcription factor activity
Positive regulation of nitric oxide biosynthetic process
Positive regulation of NLRP3 inflammasome complex assembly
Positive regulation of peptidyl-tyrosine phosphorylation
Positive regulation of phagocytosis, engulfment
Positive regulation of reactive oxygen species biosynthetic process
Positive regulation of tumor necrosis factor production
Production of molecular mediator involved in inflammatory response
Receptor internalization
Receptor-mediated endocytosis
Regulation of action potential
Regulation of lipid metabolic process
Regulation of lipopolysaccharide-mediated signaling pathway
Regulation of metabolic process
Regulation of protein-containing complex assembly
Regulation of removal of superoxide radicals
Regulation of toll-like receptor signaling pathway
Response to fatty acid
Response to linoleic acid
Response to lipid
Response to stilbenoid
Sensory perception of taste
Short-chain fatty acid transport
Toll-like receptor signaling pathway
Toll-like receptor TLR6:TLR2 signaling pathway
Triglyceride transport
Cellular Component
Apical plasma membrane
Brush border membrane
Caveola
Cell periphery
Cell surface
Cytoplasm
Endocytic vesicle membrane
External side of plasma membrane
Extracellular space
Golgi apparatus
Integral component of plasma membrane
Membrane
Membrane raft
Obsolete cell
Phagocytic vesicle
Plasma membrane
Platelet alpha granule membrane
Receptor complex
Specific granule membrane
Molecular Function
Amyloid-beta binding
High-density lipoprotein particle binding
Lipid binding
Lipoprotein particle binding
Lipoteichoic acid immune receptor activity
Long-chain fatty acid transporter activity
Low-density lipoprotein particle binding
Low-density lipoprotein particle receptor activity
Oleate transmembrane transporter activity
Oxidised low-density lipoprotein particle receptor activity
Protein-containing complex binding
Scavenger receptor activity
Short-chain fatty acid transmembrane transporter activity
Thrombospondin receptor activity
Toll-like receptor binding
Transforming growth factor beta binding
The reference OMIM entry for this protein is 173510
Cd36 antigen; cd36
Leukocyte differentiation antigen cd36
Platelet glycoprotein iv; gp4
Glycoprotein iiib; gp3b
Gp iiib
Thrombospondin receptor
Collagen receptor, platelet
Fatty acid translocase; fat
DESCRIPTION
Platelet glycoprotein IV, alternatively known as GP IIIb, is immunologically related to the leukocyte differentiation antigen CD36. It is the fourth major glycoprotein of the platelet surface and serves as a receptor for thrombospondin (188060) in platelets and various cell lines. Since thrombospondins are widely distributed proteins involved in a variety of adhesive processes, GP IV may have important functions as a cell adhesion molecule. Other platelet glycoproteins include GP Ib (606672), the platelet receptor for thrombin (176930) and von Willebrand factor (231200), and the complex of GP IIb (607759) and GP IIIa (173470), the platelet-binding site for fibrinogen and fibronectin (134820) (see review by Greenwalt et al., 1992).CLONING
Tandon et al. (1989) isolated and characterized the platelet GP IV protein. Oquendo et al. (1989) reported sequencing of the CD36 cDNA which encodes a deduced 472-amino acid protein.GENE STRUCTURE
Armesilla and Vega (1994) demonstrated that the CD36 gene contains 15 exons and spans more than 32 kb.MAPPING
Fernandez-Ruiz et al. (1993) mapped the human CD36 gene to chromosome 7q11.2 by fluorescence in situ hybridization.GENE FUNCTION
Tandon et al. (1989) demonstrated that GP IV is the primary receptor for adhesion of platelets to collagen. (See 120340 for another type of receptor involved in cell adhesion to collagen.) Oquendo et al. (1989) found that expression of a CD36 cDNA clone in COS cells supported cytoadherence of erythrocytes parasitized by Plasmodium falciparum. Van Schravendijk et al. (1992) showed that normal human erythrocytes express CD36; thus, this adhesion molecule may have a biologic role in normal individuals as well as in the pathology of falciparum malaria (see 611162). Tomiyama et al. (1990) demonstrated that the platelet-specific alloantigen Nak(a) is carried on GP IV, and noted that antibodies against GP IV may play an important role in refractoriness to platelet transfusions. Savill et al. (1992) found that CD36, using thrombospondin as a molecular bridge with ITGAV (193210), mediates macrophage scavenging of senescent polymorphonuclear cells undergoing apoptosis. Endemann et al. (1993) demonstrated that CD36 is a physiologic receptor for oxidized low density lipoprotein (LDL). Transfection of a CD36 clone into human kidney cells resulted in specific and high affinity binding of oxidized LDL, followed by its internalization and degradation. Nozaki et al. (1995) found that macrophages derived from patients with CD36 deficiency (608404) showed a 40% decrease in binding and uptake of oxidized LDL. Griffin et al. (2001) reported a glucose-mediated increase in CD36 mRNA translation efficiency that resulted in increased expression of CD36, and proposed that a link between diabetes and atherosclerosis may be indicated by the findings. Expression of CD36 was increased in endarterectomy lesions from patients with a history of hyperglycemia. Macrophages that were differentiated from human peripheral blood monocytes in the presence of high glucose concentrations showed increased expression of cell surface CD36 secondary to an increase in translational efficiency of CD36 mRNA. They obtained similar data from primary cells isolated from human vascular lesions. They concluded that increased translation of macrophage CD36 transcripts under high glucose conditions provides a mechanism for accelerated atherosclerosis in diabeti ... More on the omim web site
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 173510 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).