BioPAX pathway converted from "Engulfment of particulate antigen into phagocytic vesicle" in the Reactome database.LEFT-TO-RIGHTEngulfment of particulate antigen into phagocytic vesicleThis event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a>Particulate Ag:DC receptorsReactome DB_ID: 9755323plasma membraneGENE ONTOLOGYGO:0005886Converted from EntitySet in ReactomeDC receptors recognizing apoptotic cellsReactome DB_ID: 9755321Cd364xPalmC-CD36Q08857Reactome DB_ID: 9742316UniProt:Q08857 Cd36Cd36FUNCTION 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 (PubMed:7685021). 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) (PubMed:19847289, PubMed:20037584, PubMed:23395392). 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). 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:17507371, PubMed:18753675, PubMed:21610069). Involved in oral fat perception and preferences (PubMed:16276419). 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 similarity) (PubMed:16276419). In taste receptor cells, mediates the induction of an increase in intracellular calcium levels by long-chain fatty acids, leading to the activation of the gustatory neurons in the nucleus of the solitary tract (PubMed:18162488). Important factor in both ventromedial hypothalamus neuronal sensing of long-chain fatty acid and the regulation of energy and glucose homeostasis (By similarity) (PubMed:23557700). Receptor for thombospondins, THBS1 and THBS2, mediating their antiangiogenic effects (PubMed:15748999). As a coreceptor for TLR4:TLR6 heterodimer, promotes inflammation in monocytes/macrophages. Upon ligand binding, such as oxLDL or amyloid-beta 42, interacts with the heterodimer TLR4:TLR6, the complex is internalized and triggers inflammatory response, leading to NF-kappa-B-dependent production of CXCL1, CXCL2 and CCL9 cytokines, via MYD88 signaling pathway, and CCL5 cytokine, via TICAM1 signaling pathway, as well as IL1B secretion, through the priming and activation of the NLRP3 inflammasome (PubMed:20037584, PubMed:23812099). Selective and nonredundant sensor of microbial diacylated lipopeptide that signal via TLR2:TLR6 heterodimer, this cluster triggers signaling from the cell surface, leading to the NF-kappa-B-dependent production of TNF, via MYD88 signaling pathway and subsequently is targeted to the Golgi in a lipid-raft dependent pathway (By similarity) (PubMed:15690042, PubMed:19847289).FUNCTION (Microbial infection) Acts as an accessory receptor for M.tuberculosis lipoprotein LprA, in conjunction with coreceptors TLR2 and TLR1; the lipoprotein acts as an agonist to modulate antigen presenting cell functions in response to the pathogen (PubMed:19362712). Directly mediates cytoadherence of Plasmodium falciparum parasitized erythrocytes and the internalization of particles independently of TLR signaling (PubMed:19864601, PubMed:23395392). Mediates uptake of E.coli and S.aureus but has no effect on uptake of M.fortuitum (PubMed:16020694).SUBUNIT Interacts with THBS1 and THBS2; the interactions mediate the THBS antiangiogenic activity (By similarity) (PubMed:15748999). Upon interaction with a ligand, such as oxidized low-density lipoprotein (oxLDL) or amyloid-beta 42, rapidly forms a complex with TLR4 and TLR6; the complex is internalized and triggers an inflammatory signal. Through its C-terminus, interacts with PTK2, PXN and LYN, but not with SRC. LYN kinase activity is required for facilitating TLR4-TLR6 heterodimerization and signal initiation (By similarity). Interacts with CD9, CD81, FCER1G, ITGB2 and/or ITGB2; forming a membrane heteromeric complex required for the internalization of CD36 and its ligands (PubMed:23395392).TISSUE SPECIFICITY Expressed in the apical side of lingual taste bud cells of the circumvallate papillae (PubMed:16276419, PubMed:21901153). Highly expressed in the intestine on the luminal surface of enterocytes. In small intestines expression levels follow a steep decreasing gradient from proximal to distal segments (PubMed:17507371). Expressed in macrophages (PubMed:23395392, PubMed:23812099). Cell surface expression detected in lung alveolar macrophages, dendritic macrophages and lung macrophages (at protein level) (PubMed:19362712).INDUCTION Expressed in a circadian manner in the circumvallate papillae, levels being lower during the dark period. Protein levels decrease in presence of lipids.PTM Ubiquitinated at Lys-469 and Lys-472. Ubiquitination is induced by fatty acids such as oleic acid and leads to degradation by the proteasome (PubMed:21610069, PubMed:18353783). Ubiquitination and degradation are inhibited by insulin which blocks the effect of fatty acids (PubMed:18353783).DISRUPTION PHENOTYPE The preference to lipids such linoleic acid is fully abolished in mutant mice as well as the induction of both flux and protein content of pancreatobiliary secretions (PubMed:21901153, PubMed:16276419). Animals with a double knockout of APOE and CD36, fed a Western diet for 12 weeks, exhibit much lower levels of CXCL1, CXCL2 and CCL5 cytokine mRNA expression in the descending aorta and a corresponding decrease in atherosclerotic lesion formation, compared to APOE single knockout mice. Enterocytes from proximal small intestine exhibit reduced uptake of fatty acid and cholesterol. They also show reduced fatty acid incorporation into triglycerides and triglyceride secretion (PubMed:17507371). After oral fat loading, animals have lipoproteins smaller than chylomicron in size in plasma and intestinal lymph (PubMed:18753675).SIMILARITY Belongs to the CD36 family.Mus musculusNCBI Taxonomy10090UniProtQ088573EQUALS-palmitoyl-L-cysteineMODMOD:00115464EQUAL466EQUAL7EQUAL2EQUAL472EQUALReactome Database ID Release 759742316Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9742316ReactomeR-MMU-516451Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-51645.1Reactomehttp://www.reactome.orgIntegrin alphaVbeta5Reactome DB_ID: 9730744Itgb5ITGB5O70309Reactome DB_ID: 9730742UniProt:O70309 Itgb5Itgb5FUNCTION Integrin alpha-V/beta-5 (ITGAV:ITGB5) is a receptor for fibronectin. It recognizes the sequence R-G-D in its ligand.SUBUNIT Heterodimer of an alpha and a beta subunit. Beta-5 (ITGB5) associates with alpha-V (ITGAV) (Probable). Interacts with MYO10 (By similarity). Interacts with DAB2. Integrin ITGAV:ITGB5 interacts with FBLN5 (via N-terminus) (PubMed:11805835). ITGAV:ITGB5 interacts with CCN3 (By similarity).SIMILARITY Belongs to the integrin beta chain family.UniProtO7030924EQUAL799EQUALReactome Database ID Release 759730742Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9730742ReactomeR-MMU-2159481Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-215948.11ItgavITGAV(31-1048)P43406Reactome DB_ID: 9729763UniProt:P43406 ItgavItgavFUNCTION The alpha-V (ITGAV) integrins are receptors for vitronectin, cytotactin, fibronectin, fibrinogen, laminin, matrix metalloproteinase-2, osteopontin, osteomodulin, prothrombin, thrombospondin, TGFB1 and vWF (PubMed:9827803, PubMed:10025398). They recognize the sequence R-G-D in a wide array of ligands. Alpha-V integrins may play a role in embryo implantation, angiogenesis and wound healing (PubMed:9827803). ITGAV:ITGB3 binds to fractalkine (CX3CL1) and may act as its coreceptor in CX3CR1-dependent fractalkine signaling (By similarity). ITGAV:ITGB3 binds to NRG1 (via EGF domain) and this binding is essential for NRG1-ERBB signaling. ITGAV:ITGB3 binds to FGF1 and this binding is essential for FGF1 signaling (By similarity). ITGAV:ITGB3 binds to FGF2 and this binding is essential for FGF2 signaling (By similarity). ITGAV:ITGB3 binds to IGF1 and this binding is essential for IGF1 signaling (By similarity). ITGAV:ITGB3 binds to IGF2 and this binding is essential for IGF2 signaling (By similarity). ITGAV:ITGB3 binds to IL1B and this binding is essential for IL1B signaling (By similarity). ITGAV:ITGB3 binds to PLA2G2A via a site (site 2) which is distinct from the classical ligand-binding site (site 1) and this induces integrin conformational changes and enhanced ligand binding to site 1 (By similarity). ITGAV:ITGB3 and ITGAV:ITGB6 act as a receptor for fibrillin-1 (FBN1) and mediate R-G-D-dependent cell adhesion to FBN1 (By similarity). Integrin alpha-V/beta-6 or alpha-V/beta-8 (ITGAV:ITGB6 or ITGAV:ITGB8) mediates R-G-D-dependent release of transforming growth factor beta-1 (TGF-beta-1) from regulatory Latency-associated peptide (LAP), thereby playing a key role in TGF-beta-1 activation (PubMed:10025398, PubMed:25127859). ITGAV:ITGB3 act as a receptor for CD40LG (By similarity).SUBUNIT Heterodimer of an alpha and a beta subunit. The alpha subunit is composed of a heavy and a light chain linked by a disulfide bond. Alpha-V (ITGAV) associates with either beta-1 (ITGB1), beta-3 (ITGB3), beta-5 (ITGB5), beta-6 (ITGB6) or beta-8 (ITGB8) (Probable). Interacts with RAB25. Interacts with CIB1 (By similarity). Integrins ITGAV:ITGB3 and ITGAV:ITGB5 interact with FBLN5 (via N-terminus) (PubMed:11805835). ITGAV:ITGB3 and ITGAV:ITGB5 interact with CCN3 (By similarity). ITGAV:ITGB3 interacts with ADGRA2 (By similarity). ITGAV:ITGB3 interacts with FGF2; it is likely that FGF2 can simultaneously bind ITGAV:ITGB3 and FGF receptors (By similarity). ITGAV:ITGB3 is found in a ternary complex with CX3CR1 and CX3CL1. ITGAV:ITGB3 is found in a ternary complex with NRG1 and ERBB3. ITGAV:ITGB3 is found in a ternary complex with FGF1 and FGFR1. ITGAV:ITGB3 is found in a ternary complex with IGF1 and IGF1R (By similarity). ITGAV:ITGB3 interacts with IGF2 (By similarity). ITGAV:ITGB3 and ITGAV:ITGB6 interact with FBN1 (By similarity). ITGAV:ITGB3 interacts with CD9, CD81 and CD151 (via second extracellular domain) (By similarity). ITGAV:ITGB6 interacts with TGFB1 (PubMed:10025398). ITGAV:ITGB3 interacts with PTN. Forms a complex with PTPRZ1 and PTN that stimulates endothelial cell migration through ITGB3 'Tyr-773' phosphorylation (By similarity).DISRUPTION PHENOTYPE Mice expressing a null mutation of the alpha-V subunit gene survive until late in embryonic development and occasionally even to birth. They demonstrate cleft palate, and defective development of CNS and gastrointestinal blood vessels.SIMILARITY Belongs to the integrin alpha chain family.UniProtP4340631EQUAL1048EQUALReactome Database ID Release 759729763Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9729763ReactomeR-MMU-2100131Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-210013.11Reactome Database ID Release 759730744Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9730744ReactomeR-MMU-12994971Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1299497.1Reactome Database ID Release 759755321Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9755321ReactomeR-MMU-12369041Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1236904.11Exogenous Particulate antigen (Ag)Reactome DB_ID: 1236726extracellular regionGENE ONTOLOGYGO:0005576Reactome Database ID Release 751236726Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1236726ReactomeR-ALL-12367262Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-1236726.2ChEBI23367additional informationMIMI:03611Reactome Database ID Release 759755323Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9755323ReactomeR-MMU-12369201Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1236920.1Exogenous Particulate antigen (Ag)Reactome DB_ID: 1236714phagocytic vesicleGENE ONTOLOGYGO:0045335Reactome Database ID Release 751236714Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=1236714ReactomeR-ALL-12367142Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-1236714.2ChEBI23367Converted from EntitySet in ReactomeDC receptors recognizing apoptotic cellsReactome DB_ID: 9755333Cd36CD36Q08857Reactome DB_ID: 97553252EQUAL472EQUALReactome Database ID Release 759755325Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9755325ReactomeR-MMU-12368351Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1236835.1alphaVbeta5Reactome DB_ID: 9755331ItgavITGAV(31-1048)P43406Reactome DB_ID: 975532731EQUAL1048EQUALReactome Database ID Release 759755327Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9755327ReactomeR-MMU-12367731Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1236773.11Itgb5ITGB5O70309Reactome DB_ID: 975532924EQUAL799EQUALReactome Database ID Release 759755329Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9755329ReactomeR-MMU-12367491Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1236749.11Reactome Database ID Release 759755331Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9755331ReactomeR-MMU-12369061Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1236906.1Reactome Database ID Release 759755333Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9755333ReactomeR-MMU-12368991Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1236899.1Reactome Database ID Release 759755335Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9755335ReactomeR-MMU-12369561Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1236956.1After internalization, F-actin is depolymerized from the phagosome, and the newly denuded vacuole membrane becomes accessible to early endosomes (Aderem & Underhill. 1999). 18331591Pubmed2008Contributions of proteomics to understanding phagosome maturationRogers, LDFoster, LJCell Microbiol 10:1405-1210358769Pubmed1999Mechanisms of phagocytosis in macrophagesAderem, AUnderhill, DMAnnu Rev Immunol 17:593-623inferred from electronic annotationEVIDENCE CODEECO:0000203