Summary: CD36 family
Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.
This is the Wikipedia entry entitled "CD36". More...
The Wikipedia text that you see displayed here is a download from Wikipedia. This means that the information we display is a copy of the information from the Wikipedia database. The button next to the article title ("Edit Wikipedia article") takes you to the edit page for the article directly within Wikipedia. You should be aware you are not editing our local copy of this information. Any changes that you make to the Wikipedia article will not be displayed here until we next download the article from Wikipedia. We currently download new content on a nightly basis.
Does Pfam agree with the content of the Wikipedia entry ?
Pfam has chosen to link families to Wikipedia articles. In some case we have created or edited these articles but in many other cases we have not made any direct contribution to the content of the article. The Wikipedia community does monitor edits to try to ensure that (a) the quality of article annotation increases, and (b) vandalism is very quickly dealt with. However, we would like to emphasise that Pfam does not curate the Wikipedia entries and we cannot guarantee the accuracy of the information on the Wikipedia page.
Editing Wikipedia articles
Before you edit for the first time
Wikipedia is a free, online encyclopedia. Although anyone can edit or contribute to an article, Wikipedia has some strong editing guidelines and policies, which promote the Wikipedia standard of style and etiquette. Your edits and contributions are more likely to be accepted (and remain) if they are in accordance with this policy.
You should take a few minutes to view the following pages:
How your contribution will be recorded
Anyone can edit a Wikipedia entry. You can do this either as a new user or you can register with Wikipedia and log on. When you click on the "Edit Wikipedia article" button, your browser will direct you to the edit page for this entry in Wikipedia. If you are a registered user and currently logged in, your changes will be recorded under your Wikipedia user name. However, if you are not a registered user or are not logged on, your changes will be logged under your computer's IP address. This has two main implications. Firstly, as a registered Wikipedia user your edits are more likely seen as valuable contribution (although all edits are open to community scrutiny regardless). Secondly, if you edit under an IP address you may be sharing this IP address with other users. If your IP address has previously been blocked (due to being flagged as a source of 'vandalism') your edits will also be blocked. You can find more information on this and creating a user account at Wikipedia.
If you have problems editing a particular page, contact us at firstname.lastname@example.org and we will try to help.
The community annotation is a new facility of the Pfam web site. If you have problems editing or experience problems with these pages please contact us.
|CD36 molecule (thrombospondin receptor)|
Predicted topology of CD36 in the plasma membrane
|Symbols||; BDPLT10; CHDS7; FAT; GP3B; GP4; GPIV; PASIV; SCARB3|
|External IDs||ChEMBL: GeneCards:|
|RNA expression pattern|
CD36 (cluster of differentiation 36), also known as FAT (fatty acid translocase), FAT/CD36, (FAT)/CD36, SCARB3, GP88, glycoprotein IV (gpIV), and glycoprotein IIIb (gpIIIb), is an integral membrane protein found on the surface of many cell types in vertebrate animals. CD36 is a member of the class B scavenger receptor family of cell surface proteins. CD36 binds many ligands including collagen, thrombospondin, erythrocytes parasitized with Plasmodium falciparum, oxidized low density lipoprotein, native lipoproteins, oxidized phospholipids, and long-chain fatty acids.
Recent work using genetically modified rodents have identified a clear role for CD36 in fatty acid metabolism, heart disease, taste, and dietary fat processing in the intestine. It may be involved in glucose intolerance, atherosclerosis, arterial hypertension, diabetes, cardiomyopathy and Alzheimer's disease.
- 1 Structure
- 2 Genetics
- 3 Tissue distribution
- 4 Function
- 5 Clinical significance
- 6 Interactions
- 7 Related proteins
- 8 See also
- 9 References
- 10 Further reading
- 11 External links
In humans, rats and mice, CD36 consists of 472 amino acids with a predicted molecular weight of approximately 53,000 Da. However, CD36 is extensively glycosylated and has an apparent molecular weight of 88,000 Da as determined by SDS polyacrylamide gel electrophoresis.
Using Kyte-Doolittle analysis, the amino acid sequence of CD36 predicts a hydrophobic region near each end of the protein large enough to span cellular membranes. Based on this notion and the observation that CD36 is found on the surface of cells, CD36 is thought to have a 'hairpin-like' structure with Î±-helices at the C- and N- termini projecting through the membrane and a larger extracellular loop (Fig. 1). This topology is supported by transfection experiments in cultured cells using deletion mutants of CD36.
Based on the crystal structure of the homologous SCARB2, a model of the extracellullar domain of CD36 has been produced. Like SCARB2, CD36 is proposed to contain an antiparallel Î²-barrel core with many short Î±-helices adorning it. The structure is predicted to contain a hydrophobic transport tunnel. Disulfide linkages between 4 of the 6 cysteine residues in the extracellular loop are required for efficient intracellular processing and transport of CD36 to the plasma membrane. It is not clear what role these linkages play on the function of the mature CD36 protein on the cell surface.
Besides glycosylation, additional posttranslational modifications have been reported for CD36. CD36 is modified with 4 palmitoyl chains, 2 on each of the two intracellular domains. The function of these lipid modifications is currently unknown but they likely promote the association of CD36 with the membrane and possibly lipid rafts which appear to be important for some CD36 functions. CD36 could be also phosphorylated at Y62, T92, T323, ubiquitinated at K56, K469, K472 and acetylated at K52, K56, K166, K231, K394, K398, K403.
In the absence of ligand, membrane bound CD36 exists primarily in a monomeric state. However exposure to the thrombospondin ligand causes CD36 to dimerize. This dimerization has been proposed to play an important role in CD36 signal transduction.
The gene is located on the long arm of chromosome 7 at band 11.2 (7q11.2) and is encoded by 15 exons that extend over more than 32 kilobases. Both the 5' and the 3' untranslated regions contain introns: the 5' with two and the 3' one. Exons 1, 2 and first 89 nucleotides of exon 3 and as well as exon 15 are non-coding. Exon 3 contains encodes the N-terminal cytoplasmic and transmembrane domains. The C-terminal cytoplasmic and transmembrane regions is encoded by exon 14. The extracellular domain is encoded by the central 11 exons. Alternative splicing of the untranslated regions gives rise to at least two mRNA species.
The transcription initiation site of the CD36 gene has been mapped to 289 nucleotides upstream from the translational start codon and a TATA box and several putative cis regulatory regions lie further 5'. A binding site for PEBP2/CBF factors has been identified between -158 and -90 and disruption of this site reduces expression. The gene is the transcriptional control of the nuclear receptor PPAR/RXR heterodimer (Peroxisome proliferator-activated receptor â€“ Retinoid X receptor) and gene expression can be up regulated using synthetic and natural ligands for PPAR and RXR, including the thiazolidinedione class of anti-diabetic drugs and the vitamin A metabolite 9-cis-retinoic acid respectively.
The protein itself belongs to the class B scavenger receptor family which includes receptor for selective cholesteryl ester uptake, scavenger receptor class B type I (SR-BI), and lysosomal integral membrane protein II (LIMP-II). CD36 interacts with a number of ligands, including collagen types I and IV, thrombospondin, erythrocytes parasitized with Plasmodium falciparum, platelet-agglutinating protein p37, oxidized low density lipoprotein and long-chain fatty acids. On macrophages CD36 forms part of a non opsonic receptor (the scavenger receptor CD36/alphaV beta3 complex) and is involved in phagocytosis. CD36 has also been implicated in hemostasis, thrombosis, malaria, inflammation, lipid metabolism and atherogenesis.
CD36 function in long-chain fatty acid uptake and signaling can be irreversibly inhibited by sulfo-N-succinimidyl oleate (SSO), which binds lysine 164 within a hydrophobic pocked shared by several CD36 ligands, e.g. fatty acid and oxLDL.
On binding a ligand the protein and ligand are internalized. This internalization is independent of macropinocytosis and occurs by an actin dependent mechanism requiring the activation Src-family kinases, JNK and Rho-family GTPases. Unlike macropinocytosis this process is not affected by inhibitors of phosphatidylinositol 3-kinase or Na+/H+ exchange.
Recently, CD36 was linked to store-operated calcium flux, phospholipase A2 activation, and production of prostaglandin E2
Infections with the human malaria parasite Plasmodium falciparum are characterized by sequestration of erythrocytes infected with mature forms of the parasite and CD36 has been shown to be a major sequestration receptor on microvascular endothelial cells. Parasitised erythrocytes adhere to endothelium at the trophozoite/schizonts stage simultaneous with the appearance of the var gene product (erythrocyte membrane protein 1) on the erythrocyte surface. The appearance of erythrocyte membrane protein 1 (PfEMP1) on the erythrocyte surface is a temperature dependent phenomenon which is due to increased protein trafficking to the erythrocyte surface at the raised temperature. PfEMP1 can bind other endothelial receptors - thrombospondin (TSP) and intercellular adhesion molecule 1 (ICAM-1) â€“ in addition to CD36 - and genes other than PfEMP1 also bind to CD36: cytoadherence linked protein (clag) and sequestrin. The PfEMP1 binding site on CD36 is known to be located on exon 5.
CD36 on the surface of the platelets has been shown to be involved in adherence but direct adherence to the endothelium by the infected erythrocytes also occurs. Autoaggregation of infected erythrocytes by platelets has been shown to correlate with severe malaria and cerebral malaria in particular and antiplatelet antibodies may offer some protection.
Several lines of evidence suggest that mutations in CD36 are protective against malaria: mutations in the promoters and within introns and in exon 5 reduce the risk of severe malaria. Gene diversity studies suggest there has been positive selection on this gene presumably due to malarial selection pressure. Dissenting reports are also known suggesting that CD36 is not the sole determinant of severe malaria. In addition a role for CD36 has been found in the clearance of gametocytes (stages I and II).
CD36 has been shown to have a role in the innate immune response to malaria in mouse models. Compared with wild type mice CD36 (-/-) mice the cytokine induction response and parasite clearance were impaired. Earlier peak parasitemias, higher parasite densities and higher mortality were noted. It is thought that CD36 is involved in the Plasmodium falciparum glycophosphatidylinositol (PfGPI) induced MAPK activation and proinflammatory cytokine secretion. When macrophages were exposed to PfGPI the proteins ERK1/2, JNK, p38, and c-Jun became phosphorylated. All these proteins are involved as secondary messengers in the immune response. These responses were blunted in the CD36 (-/-) mice. Also in the CD36 (-/-) macrophages secreted significantly less TNF-alpha on exposure to PfGPI. Work is ongoing to determine how these exactly how these responses provide protection against malaria.
CD36 deficiency and alloimmune thrombocytopenia
CD36 is also known as glycoprotein IV (gpIV) or glycoprotein IIIb (gpIIIb) in platelets and gives rise to the Naka[disambiguation needed] antigen. The Naka null phenotype is found in 0.3% of Caucasians and appears to be asymptomatic. The null phenotype is more common in African (2.5%), Japanese, and other Asian populations (5-11%).
Mutations in the human CD36 gene were first identified in a patient who, despite multiple platelet transfusions, continued to exhibit low platelet levels. This condition is known as refractoriness to platelet transfusion. Subsequent studies have shown that CD36 found on the surface of platelets. This antigen is recognized by the monoclonal antibodies (MAbs) OKM5 and OKM8. It is bound by the Plasmodium falciparum protein sequestrin.
Depending on the nature of the mutation in codon 90 CD36 may be absent either on both platelets and monocytes (type 1) or platelets alone (type 2). Type 2 has been divided into two subtypes - a and b. Deficiency restricted to the platelets alone is known as type 2a; if CD36 is also absent from the erythoblasts the phenotype is classified as type 2b. The molecular basis is known for some cases: T1264G in both Kenyans and Gambians; C478T (50%), 539 deletion of AC and 1159 insertion of an A, 1438-1449 deletion and a combined 839-841 deletion GAG and insertion of AAAAC in Japanese.
In a study of 827 apparently healthy Japanese volunteers, type I and II deficiencies were found in 8 (1.0%) and 48 (5.8%) respectively. In 1127 healthy French blood donors (almost all of whom were white Europeans) no CD36 deficiency was found. In a second group only 1 of 301 white test subjects was found to be CD36 deficient. 16 of the 206 sub-Saharan black Africans and 1 of 148 black Caribbeans were found to be CD36 -ve. Three of 13 CD36 -ve persons examined had anti CD36 antibodies. In a group of 250 black American blood donors 6 (2.4%) were found to be Naka antigen negative.
Fatty acid uptake
CD36's association with the ability to taste fats has made it a target for various studies regarding obesity and alteration of lipid tasting. CD36 mRNA expression was found to be reduced in taste bud cells (TBC) of obese sand rats (P. obesus) compared to lean controls, implicating an association between CD36 and obesity. Although actual levels of CD36 protein were not different between the obese and control rat cells, Abdoul-Azize et al. hypothesize that the physical distribution of CD36 could differ in obese rat cells. Changes in calcium mediation have been associated with CD36 and obesity as well. Taste bud cells (more specifically, cells from the circumvallate papillae) containing CD36 that were isolated from obese mice exhibited a significantly smaller increase in calcium after fatty acid stimulation when compared to control mice: CD36 associated calcium regulation is impaired when mice are made to be obese (but not in normal weight mice), and this could be a mechanism contributing to behavior changes in the obese mice, such as decreased lipid taste sensitivity and decreased attraction to fats.
There has been some investigation into human CD36 as well. A study examined oral detection of fat in obese subjects with genetic bases for high, medium, and low expression of the CD36 receptor. Those subjects with high CD36 expression were eight times more sensitive to certain fats (oleic acid and triolein) than the subjects with low CD36 expression. Those subjects with an intermediate amount of CD36 expression were sensitive to fat at a level between the high and low groups. This study demonstrates that there is a significant relationship between oral fat sensitivity and the amount of CD36 receptor expression, but further investigation into CD36 could be useful for learning more about lipid tasting in the context of obesity, as CD36 may be a target for therapies in the future.
A study conducted with mice determined that reducing inflammation via the CD36 pathway reduced brain injury in transient focal ischemic stroke; however, no injury alleviating affect was observed in the permanent focal ischemic stroke condition.
Structure of Limp-II. PDB entry
- Tandon NN, Kralisz U, Jamieson GA (5 May 1989). "Identification of glycoprotein IV (CD36) as a primary receptor for platelet-collagen adhesion". J. Biol. Chem. 264 (13): 7576â€“83. PMID 2468670.
- Silverstein RL, Baird M, Lo SK, Yesner LM (15 August 1992). "Sense and antisense cDNA transfection of CD36 (glycoprotein IV) in melanoma cells. Role of CD36 as a thrombospondin receptor". J. Biol. Chem. 267 (23): 16607â€“12. PMID 1379600.
- Oquendo P, Hundt E, Lawler J, Seed B (July 1989). "CD36 directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes". Cell 58 (1): 95â€“101. doi:10.1016/0092-8674(89)90406-6. PMID 2473841.
- Endemann G, Stanton LW, Madden KS, Bryant CM, White RT, Protter AA (5 June 1993). "CD36 is a receptor for oxidized-low-density lipoprotein". J. Biol. Chem. 268 (16): 11811â€“16. PMID 7685021.
- Nicholson AC, Frieda S, Pearce A, Silverstein RL (1 February 1995). "Oxidized LDL binds to CD36 on human monocyte-derived macrophages and transfected cell lines. Evidence implicating the lipid moiety of the lipoprotein as the binding site". Arterioscler. Thromb. Vasc. Biol. 15 (2): 269â€“75. doi:10.1161/01.ATV.15.2.269. PMID 7538425.
- Calvo D, GÃ³mez-Coronado D, SuÃ¡rez Y, LasunciÃ³n MA, Vega MA (1 April 1998). "Human CD36 is a high affinity receptor for the native lipoproteins HDL, LDL, and VLDL". J. Lipid Res. 39 (4): 777â€“88. PMID 9555943.
- Podrez EA, Poliakov E, Shen Z, Zhang R, Deng Y, Sun M, Finton PJ, Shan L, Gugiu B, Fox PL, Hoff HF, Salomon RG, Hazen SL (October 2002). "Identification of a novel family of oxidized phospholipids that serve as ligands for the macrophage scavenger receptor CD36". J. Biol. Chem. 277 (41): 38503â€“16. doi:10.1074/jbc.M203318200. PMID 12105195.
- Baillie AG, Coburn CT, Abumrad NA (September 1996). "Reversible binding of long-chain fatty acids to purified FAT, the adipose CD36 homolog". J. Membr. Biol. 153 (1): 75â€“81. doi:10.1007/s002329900111. PMID 8694909.
- Hajri T, Han XX, Bonen A, Abumrad NA (May 2002). "Defective fatty acid uptake modulates insulin responsiveness and metabolic responses to diet in CD36-null mice". J. Clin. Invest. 109 (10): 1381â€“9. doi:10.1172/JCI14596. PMC 150975. PMID 12021254.
- Pravenec M, Landa V, ZÃdek V, MusilovÃ¡ A, KazdovÃ¡ L, Qi N, Wang J, St Lezin E, Kurtz TW (2003). "Transgenic expression of CD36 in the spontaneously hypertensive rat is associated with amelioration of metabolic disturbances but has no effect on hypertension" (PDF). Physiol Res 52 (6): 681â€“8. PMID 14640889.
- Febbraio M, Podrez EA, Smith JD, Hajjar DP, Hazen SL, Hoff HF, Sharma K, Silverstein RL (April 2000). "Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in mice". J. Clin. Invest. 105 (8): 1049â€“56. doi:10.1172/JCI9259. PMC 300837. PMID 10772649.
- Laugerette F, Passilly-Degrace P, Patris B, Niot I, Febbraio M, Montmayeur JP, Besnard P (November 2005). "CD36 involvement in orosensory detection of dietary lipids, spontaneous fat preference, and digestive secretions". J. Clin. Invest. 115 (11): 3177â€“84. doi:10.1172/JCI25299. PMC 1265871. PMID 16276419.
- Drover VA, Ajmal M, Nassir F, Davidson NO, Nauli AM, Sahoo D, Tso P, Abumrad NA (May 2005). "CD36 deficiency impairs intestinal lipid secretion and clearance of chylomicrons from the blood". J. Clin. Invest. 115 (5): 1290â€“7. doi:10.1172/JCI21514. PMC 1074677. PMID 15841205.
- RaÄ‡ ME, Safranow K, Poncyljusz W (2007). "Molecular basis of human CD36 gene mutations". Mol. Med. 13 (5-6): 288â€“96. doi:10.2119/2006-00088.Rac. PMC 1936231. PMID 17673938.
- Greenwalt DE, Watt KW, So OY, Jiwani N (July 1990). "PAS IV, an integral membrane protein of mammary epithelial cells, is related to platelet and endothelial cell CD36 (GP IV)". Biochemistry 29 (30): 7054â€“9. doi:10.1021/bi00482a015. PMID 1699598.
- Kyte J, Doolittle RF (May 1982). "A simple method for displaying the hydropathic character of a protein". J. Mol. Biol. 157 (1): 105â€“32. doi:10.1016/0022-2836(82)90515-0. PMID 7108955.
- Gruarin P, Thorne RF, Dorahy DJ, Burns GF, Sitia R, Alessio M (August 2000). "CD36 is a ditopic glycoprotein with the N-terminal domain implicated in intracellular transport". Biochem. Biophys. Res. Commun. 275 (2): 446â€“54. doi:10.1006/bbrc.2000.3333. PMID 10964685.
- Tao N, Wagner SJ, Lublin DM (September 1996). "CD36 is palmitoylated on both N- and C-terminal cytoplasmic tails". J. Biol. Chem. 271 (37): 22315â€“20. doi:10.1074/jbc.271.37.22315. PMID 8798390.
- Neculai D, Schwake M, Ravichandran M, Zunke F, Collins RF, Peters J, Neculai M, Plumb J, Loppnau P, Pizarro JC, Seitova A, Trimble WS, Saftig P, Grinstein S, Dhe-Paganon S (2013). "Structure of LIMP-2 provides functional insights with implications for SR-BI and CD36". Nature 504 (7478): 172â€“176. doi:10.1038/nature12684. PMID 24162852.
- Gruarin P, Sitia R, Alessio M (December 1997). "Formation of one or more intrachain disulphide bonds is required for the intracellular processing and transport of CD36". Biochem. J. 328 (2): 635â€“42. PMC 1218965. PMID 9371725.
- Zeng Y, Tao N, Chung KN, Heuser JE, Lublin DM (November 2003). "Endocytosis of oxidized low density lipoprotein through scavenger receptor CD36 utilizes a lipid raft pathway that does not require caveolin-1". J. Biol. Chem. 278 (46): 45931â€“6. doi:10.1074/jbc.M307722200. PMID 12947091.
- Pohl J, Ring A, Korkmaz U, Ehehalt R, Stremmel W (January 2005). "FAT/CD36-mediated long-chain fatty acid uptake in adipocytes requires plasma membrane rafts". Mol. Biol. Cell 16 (1): 24â€“31. doi:10.1091/mbc.E04-07-0616. PMC 539148. PMID 15496455.
- Hornbeck PV, Kornhauser JM, Tkachev S, Zhang B, Skrzypek E, Murray B, Latham V, Sullivan M. "CD36 (human) protein page". PhosphoSitePlus. Cell Signaling Technology, Inc.
- Smith J, Su X, El-Maghrabi R, Stahl PD, Abumrad NA (May 2008). "Opposite regulation of CD36 ubiquitination by fatty acids and insulin: effects on fatty acid uptake.". J. Biol. Chem. 283 (20): 13578â€“85. doi:10.1074/jbc.M800008200. PMID 18353783.
- Kuda O, Pietka TA, Demianova Z, Kudova E, Cvacka J, Kopecky J, Abumrad NA (May 2013). "Sulfo-N-succinimidyl Oleate (SSO) Inhibits Fatty Acid Uptake and Signaling for Intracellular Calcium via Binding CD36 Lysine 164: SSO ALSO INHIBITS OXIDIZED LOW DENSITY LIPOPROTEIN UPTAKE BY MACROPHAGES.". J. Biol. Chem. 288 (22): 15547â€“55. doi:10.1074/jbc.M113.473298. PMID 23603908.
- Lundby A, Lage K, Weinert BT, Bekker-Jensen DB, Secher A, Skovgaard T, Kelstrup CD, Dmytriyev A, Choudhary C, Lundby C, Olsen JV (Aug 2012). "Proteomic analysis of lysine acetylation sites in rat tissues reveals organ specificity and subcellular patterns.". Cell Rep. 2 (2): 419â€“31. doi:10.1016/j.celrep.2012.07.006. PMID 22902405.
- Daviet L, Malvoisin E, Wild TF, McGregor JL (August 1997). "Thrombospondin induces dimerization of membrane-bound, but not soluble CD36". Thromb. Haemost. 78 (2): 897â€“901. PMID 9268192.
- FernÃ¡ndez-Ruiz E, Armesilla AL, SÃ¡nchez-Madrid F, Vega MA (September 1993). "Gene encoding the collagen type I and thrombospondin receptor CD36 is located on chromosome 7q11.2". Genomics 17 (3): 759â€“61. doi:10.1006/geno.1993.1401. PMID 7503937.
- Collins RF, Touret N, Kuwata H, Tandon NN, Grinstein S, Trimble WS (September 2009). "Uptake of oxLDL by CD36 occurs by an actin-dependent pathway distinct from macropinocytosis". J. Biol. Chem. 284 (44): 30288â€“97. doi:10.1074/jbc.M109.045104. PMC 2781584. PMID 19740737.
- Stewart CR, Stuart LM, Wilkinson K, van Gils JM, Deng J, Halle A, Rayner KJ, Boyer L, Zhong R, Frazier WA, Lacy-Hulbert A, El Khoury J, Golenbock DT, Moore KJ (February 2010). "CD36 ligands promote sterile inflammation through assembly of a Toll-like receptor 4 and 6 heterodimer". Nat. Immunol. 11 (2): 155â€“61. doi:10.1038/ni.1836. PMC 2809046. PMID 20037584.
- Kuda O, Jenkins CM, Skinner JR, Moon SH, Su X, Gross RW, Abumrad NA (May 2011). "CD36 Protein Is Involved in Store-operated Calcium Flux, Phospholipase A2 Activation, and Production of Prostaglandin E2". J Biol Chem. 286 (20): 17785â€“17795. doi:10.1074/jbc.M111.232975. PMC 3093854. PMID 21454644.
- Patel SN, Lu Z, Ayi K, Serghides L, Gowda DC, Kain KC (15 March 2007). "Disruption of CD36 impairs cytokine response to Plasmodium falciparum glycosylphosphatidylinositol and confers susceptibility to severe and fatal malaria in vivo". J. Immunol. 178 (6): 3954â€“61. doi:10.4049/jimmunol.178.6.3954. PMID 17339496.
- Ikeda H, Mitani T, Ohnuma M, Haga H, Ohtzuka S, Kato T, Nakase T, Sekiguchi S (1989). "A new platelet-specific antigen, Naka, involved in the refractoriness of HLA-matched platelet transfusion". Vox Sang. 57 (3): 213â€“7. doi:10.1111/j.1423-0410.1989.tb00826.x. PMID 2617957.
- Yamamoto N, Ikeda H, Tandon NN, Herman J, Tomiyama Y, Mitani T, Sekiguchi S, Lipsky R, Kralisz U, Jamieson GA (November 1990). "A platelet membrane glycoprotein (GP) deficiency in healthy blood donors: Naka- platelets lack detectable GPIV (CD36)". Blood 76 (9): 1698â€“703. PMID 1699620.
- Ockenhouse CF, Klotz FW, Tandon NN, Jamieson GA (April 1991). "Sequestrin, a CD36 recognition protein on Plasmodium falciparum malaria-infected erythrocytes identified by anti-idiotype antibodies". Proc. Natl. Acad. Sci. U.S.A. 88 (8): 3175â€“9. doi:10.1073/pnas.88.8.3175. PMC 51408. PMID 1707534.
- Toba K, Hanawa H, Watanabe K, Fuse I, Masuko M, Miyajima S, Takahashi M, Sakaue M, Abo T, Aizawa Y (October 2001). "Erythroid involvement in CD36 deficiency". Exp. Hematol. 29 (10): 1194â€“200. doi:10.1016/S0301-472X(01)00691-9. PMID 11602321.
- Yanai H, Chiba H, Fujiwara H, Morimoto M, Abe K, Yoshida S, Takahashi Y, Fuda H, Hui SP, Akita H, Kobayashi K, Matsuno K (September 2000). "Phenotype-genotype correlation in CD36 deficiency types I and II". Thromb. Haemost. 84 (3): 436â€“41. PMID 11019968.
- Lee K, Godeau B, Fromont P, Plonquet A, Debili N, Bachir D, Reviron D, Gourin J, Fernandez E, GalactÃ©ros F, Bierling P (August 1999). "CD36 deficiency is frequent and can cause platelet immunization in Africans". Transfusion 39 (8): 873â€“9. doi:10.1046/j.1537-2995.1999.39080873.x. PMID 10504124.
- Curtis BR, Aster RH (April 1996). "Incidence of the Nak(a)-negative platelet phenotype in African Americans is similar to that of Asians". Transfusion 36 (4): 331â€“4. doi:10.1046/j.1537-2995.1996.36496226147.x. PMID 8623134.
- Bierling P, Godeau B, Fromont P, Bettaieb A, Debili N, el-Kassar N, Rouby JJ, Vainchenker W, Duedari N (September 1995). "Posttransfusion purpura-like syndrome associated with CD36 (Naka) isoimmunization". Transfusion 35 (9): 777â€“82. doi:10.1046/j.1537-2995.1995.35996029165.x. PMID 7570941.
- Pravenec M, Churchill PC, Churchill MC, Viklicky O, Kazdova L, Aitman TJ, Petretto E, Hubner N, Wallace CA, Zimdahl H, Zidek V, Landa V, Dunbar J, Bidani A, Griffin K, Qi N, Maxova M, Kren V, Mlejnek P, Wang J, Kurtz TW (August 2008). "Identification of renal Cd36 as a determinant of blood pressure and risk for hypertension". Nat. Genet. 40 (8): 952â€“4. doi:10.1038/ng.164. PMID 18587397.
- Okamoto F, Tanaka T, Sohmiya K, Kawamura K (July 1998). "CD36 abnormality and impaired myocardial long-chain fatty acid uptake in patients with hypertrophic cardiomyopathy". Jpn. Circ. J. 62 (7): 499â€“504. doi:10.1253/jcj.62.499. PMID 9707006.
- Philips JA, Rubin EJ, Perrimon N (August 2005). "Drosophila RNAi screen reveals CD36 family member required for mycobacterial infection". Science 309 (5738): 1251â€“3. doi:10.1126/science.1116006. PMID 16020694.
- Abdoul-Azize S, Atek-Mebarki F, Bitam A, Sadou H, KoceÃ¯r EA, Khan NA (2013). "Oro-gustatory perception of dietary lipids and calcium signaling in taste bud cells are altered in nutritionally obesity-prone Psammomys obesus". PLoS ONE 8 (8): e68532. doi:10.1371/journal.pone.0068532. PMC 3731325. PMID 23936306.
- Chevrot M, Bernard A, Ancel D, Buttet M, Martin C, Abdoul-Azize S, Merlin JF, Poirier H, Niot I, Khan NA, Passilly-Degrace P, Besnard P (2013). "Obesity alters the gustatory perception of lipids in the mouse: Plausible involvement of lingual CD36". The Journal of Lipid Research 54 (9): 2485â€“94. doi:10.1194/jlr.M039446. PMC 3735945. PMID 23840049.
- Pepino MY, Love-Gregory L, Klein S, Abumrad NA (2012). "The fatty acid translocase gene CD36 and lingual lipase influence oral sensitivity to fat in obese subjects". The Journal of Lipid Research 53 (3): 561â€“6. doi:10.1194/jlr.M021873. PMC 3276480. PMID 22210925.
- Kim E, Tolhurst AT, Szeto HH, Cho S (2014). "Targeting CD36-Mediated Inflammation Reduces Acute Brain Injury in Transient, but not Permanent, Ischemic Stroke". CNS Neuroscience & Therapeutics: n/a. doi:10.1111/cns.12326. PMID 25216018.
- Huang MM, Bolen JB, Barnwell JW, Shattil SJ, Brugge JS (September 1991). "Membrane glycoprotein IV (CD36) is physically associated with the Fyn, Lyn, and Yes protein-tyrosine kinases in human platelets". Proc. Natl. Acad. Sci. U.S.A. 88 (17): 7844â€“8. doi:10.1073/pnas.88.17.7844. PMC 52400. PMID 1715582.
- Bull HA, Brickell PM, Dowd PM (August 1994). "Src-related protein tyrosine kinases are physically associated with the surface antigen CD36 in human dermal microvascular endothelial cells". FEBS Lett. 351 (1): 41â€“4. doi:10.1016/0014-5793(94)00814-0. PMID 7521304.
- Febbraio M, Silverstein RL (2007). "CD36: implications in cardiovascular disease". Int. J. Biochem. Cell Biol. 39 (11): 2012â€“30. doi:10.1016/j.biocel.2007.03.012. PMC 2034445. PMID 17466567.
- Abumrad NA, Ajmal M, Pothakos K, Robinson JK (September 2005). "CD36 expression and brain function: does CD36 deficiency impact learning ability?". Prostaglandins Other Lipid Mediat. 77 (1-4): 77â€“83. doi:10.1016/j.prostaglandins.2004.09.012. PMID 16099393.
- Biello D (2005-11-02). "Potential Taste Receptor for Fat Identified". Scientific American. Retrieved 2008-08-05.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
CD36 family Provide feedback
The CD36 family is thought to be a novel class of scavenger receptors. There is also evidence suggesting a possible role in signal transduction. CD36 is involved in cell adhesion.
Crombie R, Silverstein R; , J Biol Chem 1998;273:4855-4863.: Lysosomal integral membrane protein II binds thrombospondin-1. Structure-function homology with the cell adhesion molecule CD36 defines a conserved recognition motif. PUBMED:9478926 EPMC:9478926
Internal database links
External database links
This tab holds annotation information from the InterPro database.
InterPro entry IPR002159
CD36 is a transmembrane, highly glycosylated, 88kDa glycoprotein expressed by monocytes, macrophages, platelets, microvascular endothelial cells and adipose tissues. Platelet glycoprotein IV (GP IV)(GPIIIb) (CD36 antigen) is also called GPIV, OKM5-antigen or PASIV. CD36 recognises oxidized low density lipoprotein, long chain fatty acids, anionic phospholipids, collagen types I, IV and V, thrombospondin (TSP) and Plasmodium falciparum infected erythrocytes. The recognition of apoptotic neutrophils is in co-operation with TSP and avb3. Other ligands may still be unknown.
CD36 is a scavenger receptor for oxidized LDL and shed photoreceptor outer segments and in recognition and phagocytosis of apoptotic cells and is the cell adhesion molecule in platelet adhesion and aggregation, platelet-monocyte and platelet-tumor cell interaction [PUBMED:9478926].
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
|Cellular component||membrane (GO:0016020)|
|Biological process||cell adhesion (GO:0007155)|
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
The graphic that is shown by default represents the longest sequence with a given architecture. Each row contains the following information:
- the number of sequences which exhibit this architecture
a textual description of the architecture, e.g. Gla, EGF x 2, Trypsin.
This example describes an architecture with one
Gladomain, followed by two consecutive
EGFdomains, and finally a single
- a link to the page in the Pfam site showing information about the sequence that the graphic describes
- the UniProt description of the protein sequence
- the number of residues in the sequence
- the Pfam graphic itself.
Note that you can see the family page for a particular domain by clicking on the graphic. You can also choose to see all sequences which have a given architecture by clicking on the Show link in each row.
Finally, because some families can be found in a very large number of architectures, we load only the first fifty architectures by default. If you want to see more architectures, click the button at the bottom of the page to load the next set.
Loading domain graphics...
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...
There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.
We make a range of alignments for each Pfam-A family:
- the curated alignment from which the HMM for the family is built
- the alignment generated by searching the sequence database using the HMM
- Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
- alignment generated by searching the NCBI sequence database using the family HMM
- alignment generated by searching the metagenomics sequence database using the family HMM
You can see the alignments as HTML or in three different sequence viewers:
- a Java applet developed at the University of Dundee. You will need Java installed before running jalview
- an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
- an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.
- Pfam viewer
- an HTML-based viewer that uses DAS to retrieve alignment fragments on request
You can download (or view in your browser) a text representation of a Pfam alignment in various formats:
You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.
You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.
We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key: available, not generated, — not available.
Format an alignment
We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
If you find these logos useful in your own work, please consider citing the following article:
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
|Seed source:||Pfam-B_1229 (release 3.0)|
|Author:||Finn RD, Bateman A|
|Number in seed:||256|
|Number in full:||1604|
|Average length of the domain:||360.70 aa|
|Average identity of full alignment:||22 %|
|Average coverage of the sequence by the domain:||80.34 %|
|HMM build commands:||
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 80369284 -E 1000 --cpu 4 HMM pfamseq
|Family (HMM) version:||17|
|Download:||download the raw HMM for this family|
Weight segments by...
Change the size of the sunburst
selected sequences to HMM
a FASTA-format file
- 0 sequences
- 0 species
This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the More....
This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.
How the sunburst is generated
The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.
In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:
Colouring and labels
Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.
As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.
Anomalies in the taxonomy tree
There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.
Missing taxonomic levels
Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.
Unmapped species names
The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.
So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".
Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.
Too many species/sequences
For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.
The tree shows the occurrence of this domain across different species. More...
We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.
Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.
If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.
For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.
We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.
Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.
We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.
You can use the tree controls to manipulate how the interactive tree is displayed:
- show/hide the summary boxes
- highlight species that are represented in the seed alignment
- expand/collapse the tree or expand it to a given depth
- select a sub-tree or a set of species within the tree and view them graphically or as an alignment
- save a plain text representation of the tree
Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the CD36 domain has been found. There are 8 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.
Loading structure mapping...