CD36 (cluster of differentiation 36) antigen; once thought to be a plasma membrane fatty acid transporter of 472 aas and 2 TMSs, N- and C-terminal (Schwenk et al. 2010). Also called the scavenger receptor protein (SR-B2) as it binds many ligands including both Gram-positive and Gram-negative bacteria; it plays a role in immune development (Liu et al. 2016). Direct interaction of CD36 with glycerol phospholipids has been demonstrated (Tsuzuki et al. 2017). CD36 plays a role in the perception of specific odour-active volatile compounds including oleic aldehyde (cis-9-octadecenal), in the nasal cavity (Lee et al. 2017). Jay et al. 2020 have concluded that LCFAs diffuse rapidly across biological membranes and do not require an active protein transporter such as CD36 for their transmembrane movement. CD36 (SR-B2) may be a target to treat lipid overload-induced  cardiac dysfunction (Glatz et al. 2020). CD36 is released into the circulation (cCD36) of WT mice in response to tail-vein injection of oxPCCD36. The presence of cCD36 in hyperlipidemia revealed  a link between cCD36 and oxidized phospholipids generated under oxidative stress and low-grade inflammation associated with hyperlipidemia (Biswas et al. 2021). Inhibition of fatty acid translocase (FAT/CD36) palmitoylation enhances hepatic fatty acid beta-oxidation by increasing its localization to mitochondria and interaction with long-chain acyl-CoA synthetase 1 (Zeng et al. 2022). CD36 expression is related to human epidermal growth factor receptor 2 (HER2)-positive breast cancer (Ligorio et al. 2022).  A CD36 transmembrane domain peptide interrupts CD36 interactions with membrane partners on macrophages and inhibits atherogenic functions (Huang et al. 2023). CD36 is a transmembrane glycoprotein receptor for oxidized low density lipoprotein (LDL) and other endogenous danger signals and promotes athero-thrombotic processes. CD36 associates physically with other transmembrane proteins, including integrins, tetraspanins, and toll-like receptors, which modulate CD36-mediated cell signaling. The CD36 N-terminal TMS contains a GXXXG sequence motif that mediates protein-protein interactions with many membrane proteins. Huang et al. 2023 thus hypothesized that the nTMS is involved in CD36 interactions with other membrane proteins. CD36 interactions with partner cell surface proteins on murine peritoneal macrophages were detected with an immunofluorescence-based proximity ligation cross linking assay (PLA) and confirmed by immunoprecipitation/immunoblot. Prior to performing these assays, cells were incubated with a synthetic 29 amino acid peptide containing the 22 amino acids of CD36 nTMD or a control peptide in which the glycine residues in GXXXG motif were replaced by valines. Macrophages were preincubated with peptides and then treated with oxLDL to assess LDL uptake and other properties. CD36 nTMD peptide treated cells compared to untreated or control peptide treated cells showed decreased CD36 surface associations with tetraspanin CD9 (TC# 8.A.40.1.9) and ameliorated pathologically important CD36 mediated responses to oxLDL, including uptake of DiI-labeled oxLDL, foam cell formation, ROS generation, and inhibition of migration (Huang et al. 2023). CD36 may play a role in transmembrane transport and tissue partition of per- and polyfluoroalkyl substances (PFASs) in mice (Jia et al. 2023). CD36 preferentially mediates intestinal absorption of dietary Z-astaxanthin and especially the 9- Z-isomer due to higher binding affinity (Zhang et al. 2024).

Animals and slime molds

CD36 of Mus musculus (Q08857)

Lysosome membrane protein II or scavenger receptor class B type 2a, Scarb2a, of 531 aas and 2 TMSs, N- and C-terminal. In the rare minnow, Gobiocypris rarus, it is the grass carp reovirus receptor, GCRV (Ou et al. 2019).

Scarb2a of Danio rerio

Sensory neuron membrane protein 1, SNMP1, of 523 aas and 2 TMSs, N- and C-terminal, and possibly one more TMS internally. The expression patterns of SNMP1 and SNMP2 have been determined, indicating distinct functions for these two CD36-related proteins in the olfactory system (Blankenburg et al. 2019).

SNMP1 of Heliothis virescens (Tobacco budworm moth)

Sensory neuron membrane protein 2, SNMP2, of 520 aas and 2 TMSs, N- and C-terminal, and possibly one more TMS internally. The expression patterns of SNMP1 and SNMP2 have been determined, and they differ greatly, indicating distinct functions for these two CD36-related proteins in the olfactory system (Blankenburg et al. 2019).

ANMP2 of Heliothis virescens (Tobacco budworm moth)

Lysosomal integral membrane homodimeric protein 2, LIMP2. SCARB2, CD36L2, or LIMPII, of 478 aas and two TMSs at the N- and C-termini. It acts as a lysosomal receptor for glucosylceramidase (GBA) targeting (Reczek et al. 2007) as well as a receptor for enterovirus 71 (Yamayoshi et al. 2009; Zhou et al. 2019). It plays a role in the activation of autophagy (Sakane et al. 2020). It also functions in aminophospholipid transport and is part of lysosome-endoplasmic reticulum STARD3-VAPB-dependent contact sites (Rudnik et al. 2024). LIMP-2 functions as a virus receptor (see above), a chaperone for lysosomal enzyme targeting, and a lipid transporter. The large luminal domain of LIMP-2 contains a hydrophobic tunnel that enables transport of phospholipids, sphingosine and cholesterol from the lysosomal lumen to the membrane (Rudnik et al. 2024). It interacts with the endosomal protein STARD3 and the ER-resident protein VAPB. Colocalization and physical interaction between LIMP-2 and these proteins has been demonstrated. Moreover, interaction of LIMP-2 with VAPB required the presence of STARD3. Thus, LIMP-2 is part of ER-lysosome contact sites, possibly facilitating cholesterol transport from the lysosomal to the ER membrane, possibly a novel mechanism for inter-organelle communication and lipid trafficking mediated by LIMP-2.

LIMP2 or SCARB2 of Homo sapiens

Two component Carotenoid transporter CBP/Cameo2 (Sakudoh et al., 2010). Transports lutein, a carotenoid (Sakudoh et al. 2013). Since SCRB15 (9.B.39.1.5) transports β-carotene, CD30 family paralogues discriminate between different carotenoids (Sakudoh et al. 2013).

Soluble

Carotenoid transporter of Bombyx mori
Carotenoid-binding protein (CBP or yellow blood) (A4UVY6)
Membrane receptor and transporter, Cameo2 (D2KXB3)

Scavenger receptor class B, member 1 (SR-B1; SCARB1; CD36L1; CLA1) of 552 aas and 2 very hydrophobic TMSs, one at the N-terminus and one near the C-terminus, possibly with as many as 3 other less hydrophobic TMSs. It comprises the hepatits C receptor together with its co-receptor, CD81 tetraspanin (Bartosch et al., 2003). When defective, it leads to antibody deficiency. SR-B1 is a receptor for different ligands such as phospholipids, cholesterol esters, lipoproteins, phosphatidylserine and apoptotic cells (Proudfoot and Sahoo 2019). It facilitates the flux of free and esterified cholesterol between the cell surface and extracellular donors and acceptors, such as high density lipoproteins (HDL) and to a lesser extent, apoB-containing lipoproteins and modified lipoproteins (Orlowski et al. 2007). It is necessary for selective HDL-cholesterol uptake (Zanoni et al. 2016). It is probably involved in the phagocytosis of apoptotic cells, via its phosphatidylserine binding activity.  Several proteins have been implicated in fatty acid transport by enterocytes including the scavenger receptor CD36 (SR-B2), the scavenger receptor B1 (SR-B1), and the FA transport protein 4 (FATP4) (Cifarelli and Abumrad 2018). Fatty acetates are volatile compounds that bind specifically to amino acid region 149-168 of CD36 (Tsuzuki et al. 2022). SR-BI is highly expressed in liver and steroidogenic tissues (Yu 2022). It regulates selective uptake of cholesterol esters (CEs) from HDL, revealing its role in mediating reverse cholesterol transport (RCT) and steroid hormone synthesis. In addition, SR-BI is involved in cholesterol transport, cellular inflammatory responses, platelet reactivity, and HDL-initiated signaling in the vascular system in several mouse models. Mutations in the human SR-BI gene (SCARB1) have been found to be associated with abnormally high plasma HDL-C levels and an increased risk of atherosclerotic cardiovascular disease. The key regions of SR-BI transmembrane structure and the regulatory mechanisms of SR-BI expression have been reviewed (Yu 2022). A short amphipathic alpha helix in scavenger receptor BI facilitates bidirectional HDL-cholesterol transport through a hydrophobic tunnel within SR-BI (May and Sahoo 2022).  A deficiency of SR-B1 reduced the tumor load of colitis-induced or APC^{min /+} -induced colorectal cancer (Chen et al. 2023).

Animals

SR-B1 of Homo sapiens (Q8WTV0)

Putative fatty acid translocase, CD36 glycoprotein (FA translocase; FAT/CD36/SR-B2; Collagen type I receptor; thrombospondin receptor) (Glatz and Luiken 2017; Zhang et al. 2017).  It is a leukocyte differentiation antigen and adhesin of 472 aas protein with 2 TMSs, one N-terminal and one C-terminal (Schwenk et al. 2010). Studies have shown that TMS 1 plays a role in formation of a homodimeric structure which may be involved in regulating signal transduction (Wei et al. 2017). Uptake of long chain unsaturated fatty acids, eicosapentaenoic acid and docosahexaenoic acid, is facilitated by CD36/SR-B2 (Glatz and Luiken 2017). Glycosylation, ubiquitination and palmitoylation are involved in regulating CD36 stability, while phosphorylation at extracellular sites affects the rate of fatty acid uptake (Luiken et al. 2016). CD36 may facilitate fatty acid uptake by an indirect mechanism (Jay and Hamilton 2016), but fatty acid uptake studies in breast cancer cells are consistent with its role in transport (Zhao et al. 2017). CD36 is also a co-receptor that enhances the response to MICs of Toxoplasma gondii (Costa Mendonça-Natividade et al. 2019). CD36 is expressed in multiple cell types, mediates lipid uptake, immunological recognition, inflammation, molecular adhesion, and apoptosis. CD36 is a transmembrane glycoprotein that contains several posttranslational modification sites and binds to diverse ligands, including apoptotic cells, thrombospondin-1 (TSP-1), and fatty acids (FAs) (Wang and Li 2019). CD36 is responsible for several metabolic disorders. It is a multifunctional scavenger receptor mediating uptake of long-chain fatty acids. Akachar et al. 2021 determined whether Lys164, exposed to the protein surface, played roles in fatty acid uptake. Conformational changes involved Lys164 which influenced the folding, utility, solubility, and stability of the protein. It also provided the structural basis for forming an opening near the principal portal for the dissociation of palmitic acid (Akachar et al. 2021). How CD36 regulates the tumor microenvironment has been reviewed (Liao et al. 2022). CD36 mediates SARS-CoV-2-envelope-protein-induced platelet activation and thrombosis by direct binding (Tang et al. 2023). It is a skeletal muscle protein, involved in fatty acid transport, that influences fatty acid oxidation rates (Maunder et al. 2023). CD36 preferentially mediates intestinal absorption of dietary Z-astaxanthin (Zhang et al. 2024).  Downregulation of CD36 alleviates IgA nephropathy by promoting autophagy and inhibiting extracellular matrix accumulation in mesangial cells (Zhang et al. 2025).

Animals

CD36 of Homo sapiens (P16671)

Scavenger receptor class B member 1 protein 15, SCRB15 of 504 aas and 2 TMSs.  Transports β-carotene to the silk gland. Encoded by the Flesh (F) gene. 26% identical to the yellow cocoon gene product Cameo2, the lutein transporter (9.B.39.1.2; Sakudoh et al. 2013). Distinct pathways exist for the absorption and metabolism of β-carotene and zeaxanthin in the mouse intestine (Bandara et al. 2025).

Insects

SCRB15 of Bombyx mori (K7ZLU1)

Sensory neuron membrane protein 1, SNMP1 of 551 aas and 2 TMSs (N- and C-terminal). Plays an olfactory role that is not restricted to pheromone sensitivity. Has a role in detection and signal transduction of the fatty-acid-derived male pheromone 11-cis vaccenyl acetate (cVA). Not required for sensitivity to general odorants. Acts in concert with Or67d and lush to capture cVA molecules on the surface of Or67d expressing olfactory dendrites and facilitate their transfer to the odorant-receptor Orco complex. Essential for the electrophysiological responses of these olfactory sensory neurons (Benton et al. 2007; Jin et al. 2008; Gomez-Diaz et al. 2016).

SNMP1 of Drosophila melanogaster (Fruit fly)

Croquemort isoform 1 (CD36) of 259 aas and 2 TMSs, a homologue of human CD36, is a member of class B scavenger receptors, which are involved in phagocytosis of bacteria and cytokine release. Croquemort from Pacific white shrimp  (LvCroquemort) and its truncated form (LvCroquemort-S1) cDNA sequences have been identified (Hou et al. 2017). LvCroquemort transcripts are highly expressed in gills, hemocytes and testis.  Knock-down of LvCroquemort reduces bacterial clearance (Hou et al. 2017).

Croquemort isoform 1 (CD36) of Litopenaeus vannamei

Debris buster, Dsb of 615 aas and 2 TMSs, one near the N-terminus, and one near the C-terminus. Drosophila has 14 SR-B members whose functions are not well known. It is one of the scavenger receptors class B (SR-B) which are multifunctional transmembrane proteins which in vertebrates participate in lipid transport, pathogen clearance, lysosomal delivery and intracellular sorting. Dsb sorts components of the apical extracellular matrix which are essential for airway physiology. Since SR-B LIMP2-deficient mice show reduced expression of several apical plasma membrane proteins, sorting of proteins to the apical membrane is likely an evolutionarily conserved function of Dsb and LIMP2 (Wingen et al. 2017).

The debris buster of Drosophila melanogaster

Lysosomal membrane protein 2, LIMP2, LIMP-2, LIMPII, LGP85 or Scarb2, of 478 aas and 2 TMSs, N- and C-terminal.  LIMP2 plays a role in the regulation of membrane transport processes in the endocytic pathway. Knipper et al. 2006 showed that LIMP2-deficient mice display a progressive high-frequency hearing loss and decreased otoacoustic emissions as early as 4 weeks of age. The decline of functional KCNQ1/KCNE1 is likely to be the primary cause of the hearing loss because LIMP2 controls the localization and the level of apically expressed membrane proteins such as KCNQ1, KCNE1 in the stria vascularis (Knipper et al. 2006). LIMP2 deficiency also causes myoclonus epilepsy and glomerulosclerosis (Berkovic et al. 2008), and genetic variants are associated with Gaucher and Parkinson's diseases (Michelakakis et al. 2012). The pathologies associated with LIMP2 have been reviewed (Dibbens et al. 2016; Zigdon et al. 2017).  LIMP-2 is ubiquitinated in the N-terminal cytoplasmic domain (Fujimoto et al. 2020). It is involved in the activation of autophagy (Sakane et al. 2020).

LIMP2 of Mus musculus (Mouse)