BioPAX pathway converted from "Advanced glycosylation endproduct receptor signaling" in the Reactome database. Advanced glycosylation endproduct receptor signaling This 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> LEFT-TO-RIGHT The TRTK-12 fragment of F-actin capping protein alpha binds the AGER ligand S100B This 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> S100B homodimer Reactome DB_ID: 9764031 extracellular region GENE ONTOLOGY GO:0005576 S100b S100B P50114 Reactome DB_ID: 9764029 UniProt:P50114 S100b Mus musculus NCBI Taxonomy 10090 UniProt P50114 2 EQUAL 92 EQUAL Reactome Database ID Release 78 9764029 Database 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=9764029 Reactome R-MMU-879433 1 Reactome 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-879433.1 Reactome http://www.reactome.org 2 Reactome Database ID Release 78 9764031 Database 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=9764031 Reactome R-MMU-879449 1 Reactome 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-879449.1 Converted from EntitySet in Reactome F-actin capping protein alpha protein fragment TRTK-12 Reactome DB_ID: 9787782 Capza1 CAPZA1(265-276) P47753 Reactome DB_ID: 9787777 UniProt:P47753 Capza1 Capza1 Cappa1 FUNCTION F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends. Unlike other capping proteins (such as gelsolin and severin), these proteins do not sever actin filaments. May play a role in the formation of epithelial cell junctions.SUBUNIT Heterodimer of an alpha and a beta subunit. Component of the WASH complex, composed of F-actin-capping protein subunit alpha (CAPZA1, CAPZA2 or CAPZA3), F-actin-capping protein subunit beta (CAPZB), WASHC1, WASHC2, WASHC3, WASHC4 and WASHC5. Interacts with S100B and S100A. Interacts with SH3BP1; recruits CAPZA1 to forming cell junctions. Interacts with CD2AP. Directly interacts with CRACD; this interaction decreases binding to actin (By similarity).SIMILARITY Belongs to the F-actin-capping protein alpha subunit family. UniProt P47753 265 EQUAL 276 EQUAL Reactome Database ID Release 78 9787777 Database 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=9787777 Reactome R-MMU-879421 1 Reactome 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-879421.1 Capza2 CAPZA2(265-276) P47754 Reactome DB_ID: 9787780 UniProt:P47754 Capza2 Capza2 Cappa2 FUNCTION F-actin-capping proteins bind in a Ca(2+)-independent manner to the fast growing ends of actin filaments (barbed end) thereby blocking the exchange of subunits at these ends. Unlike other capping proteins (such as gelsolin and severin), these proteins do not sever actin filaments.SUBUNIT Heterodimer of an alpha and a beta subunit. Component of the WASH complex, composed of F-actin-capping protein subunit alpha (CAPZA1, CAPZA2 or CAPZA3), F-actin-capping protein subunit beta (CAPZB), WASHC1, WASHC2, WASHC3, WASHC4 and WASHC5. Interacts with RCSD1/CAPZIP (By similarity). Directly interacts with CRACD; this interaction decreases binding to actin (By similarity).SIMILARITY Belongs to the F-actin-capping protein alpha subunit family. UniProt P47754 265 EQUAL 276 EQUAL Reactome Database ID Release 78 9787780 Database 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=9787780 Reactome R-MMU-879417 1 Reactome 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-879417.1 Reactome Database ID Release 78 9787782 Database 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=9787782 Reactome R-MMU-879446 1 Reactome 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-879446.1 F-actin capping protein fragment TRTK12:S100B homodimer Reactome DB_ID: 9787784 1 1 Reactome Database ID Release 78 9787784 Database 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=9787784 Reactome R-MMU-879368 1 Reactome 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-879368.1 Reactome Database ID Release 78 9787786 Database 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=9787786 Reactome R-MMU-879377 1 Reactome 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-879377.1 The TRTK-12 fragment of the F-actin capping protein alpha subunit binds S100B in a calcium dependent manner. S100B undergoes a conformational change that is required for subsequent binding to effector proteins (Inman et al. 2002). S100B is a ligand for AGER (Hofmann et al. 1999). In addition this interaction between S100B andF-actin capping protein alpha could be important for regulating actin filament extension (Ivenkov et al. 1995). 10399917 Pubmed 1999 RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides Hofmann, MA Drury, S Fu, C Qu, W Taguchi, A Lu, Y Avila, C Kambham, N Bierhaus, A Nawroth, P Neurath, MF Slattery, T Beach, D McClary, J Nagashima, M Morser, J Stern, D Schmidt, AM Cell 97:889-901 7540176 Pubmed 1995 Characterization of S-100b binding epitopes. Identification of a novel target, the actin capping protein, CapZ Ivanenkov, VV Jamieson GA, Jr Gruenstein, E Dimlich, RV J Biol Chem 270:14651-8 12470955 Pubmed 2002 Solution NMR structure of S100B bound to the high-affinity target peptide TRTK-12 Inman, KG Yang, R Rustandi, RR Miller, KE Baldisseri, DM Weber, DJ J Mol Biol 324:1003-14 inferred from electronic annotation EVIDENCE CODE ECO:0000203 LEFT-TO-RIGHT Advanced glycosylation end product-specific receptor (AGER/RAGE) is a multiligand receptor This 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> Converted from EntitySet in Reactome AGER ligands Reactome DB_ID: 9764043 AGE adducts:Peptide Reactome DB_ID: 879479 Peptide Reactome DB_ID: 879484 peptide [ChEBI:16670] peptide peptido peptidos Peptid ChEBI CHEBI:16670 Reactome Database ID Release 78 879484 Database 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=879484 Reactome R-ALL-879484 2 Reactome 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-879484.2 1 Converted from EntitySet in Reactome AGE adducts Reactome DB_ID: 879487 NECML N(6)-carboxymethyl-lysine N(6)-carboxymethyl-L-lysine Reactome DB_ID: 879473 N(6)-carboxymethyl-L-lysine [ChEBI:53014] N(6)-carboxymethyl-L-lysine ChEBI CHEBI:53014 Reactome Database ID Release 78 879473 Database 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=879473 Reactome R-ALL-879473 3 Reactome 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-879473.3 N(6)-(1-carboxyethyl)-L-lysine N-epsilon-(1-(1-carboxy)ethyl)lysine Reactome DB_ID: 938699 N(6)-(1-carboxyethyl)-L-lysine [ChEBI:60125] N(6)-(1-carboxyethyl)-L-lysine ChEBI CHEBI:60125 Reactome Database ID Release 78 938699 Database 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=938699 Reactome R-ALL-938699 3 Reactome 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-938699.3 Reactome Database ID Release 78 879487 Database 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=879487 Reactome R-ALL-879487 1 Reactome 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-879487.1 1 Reactome Database ID Release 78 879479 Database 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=879479 Reactome R-ALL-879479 1 Reactome 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-879479.1 Hmgb1 HMGB1 P63158 Reactome DB_ID: 9764035 UniProt:P63158 Hmgb1 UniProt P63158 2 EQUAL 215 EQUAL Reactome Database ID Release 78 9764035 Database 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=9764035 Reactome R-MMU-879382 1 Reactome 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-879382.1 App APP(672-713) P12023 Reactome DB_ID: 9764039 UniProt:P12023 App UniProt P12023 672 EQUAL 713 EQUAL Reactome Database ID Release 78 9764039 Database 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=9764039 Reactome R-MMU-879340 1 Reactome 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-879340.1 Reactome Database ID Release 78 9764043 Database 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=9764043 Reactome R-MMU-879455 1 Reactome 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-879455.1 Ager AGER Q62151 Reactome DB_ID: 9764025 plasma membrane GENE ONTOLOGY GO:0005886 UniProt:Q62151 Ager UniProt Q62151 23 EQUAL 404 EQUAL Reactome Database ID Release 78 9764025 Database 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=9764025 Reactome R-MMU-197639 1 Reactome 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-197639.1 AGER ligands:AGER Reactome DB_ID: 9764045 1 1 Reactome Database ID Release 78 9764045 Database 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=9764045 Reactome R-MMU-879365 1 Reactome 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-879365.1 Reactome Database ID Release 78 9787788 Database 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=9787788 Reactome R-MMU-879411 1 Reactome 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-879411.1 Advanced glycosylation end product specific receptor (AGER) also known as Receptor for advanced glycation end products (RAGE) is a multi-ligand membrane receptor belonging to the immunoglobulin superfamily. It recognizes a large variety of modified proteins known as advanced glycation/glycosylation endproducts (AGEs) a heterogenous group of structures (Ikeda et al. 1996) that accumulate in patients with diabetes, atherosclerosis, renal failure or ageing (Schmidt et al. 1999). The most prevalent class of AGE in vivo are N(6)-carboxymethyllysine (NECML) adducts (Kislinger et al. 1991). AGER is a receptor for amyloid-beta peptide (Ab)(Yan et al. 1996), mediating Ab neurotoxicity and promoting Ab influx into the brain (Zhang et al. 2009). AGER also responds to the proinflammatory S100/calgranulins (Hofmann et al. 1999) and High mobility group protein B1 (HMGB1/Amphoterin/DEF) (Hori et al. 1995). The major pathway is NFkappaB activation, but AGER can also activate rho-GTPases and thereby MAPK and JNK cascades. (Bierhaus et al. 2005). 8672512 Pubmed 1996 N (epsilon)-(carboxymethyl)lysine protein adduct is a major immunological epitope in proteins modified with advanced glycation end products of the Maillard reaction Ikeda, K Higashi, T Sano, H Jinnouchi, Y Yoshida, M Araki, T Ueda, S Horiuchi, S Biochemistry 35:8075-83 7592757 Pubmed 1995 The receptor for advanced glycation end products (RAGE) is a cellular binding site for amphoterin. Mediation of neurite outgrowth and co-expression of rage and amphoterin in the developing nervous system Hori, O Brett, J Slattery, T Cao, R Zhang, J Chen, JX Nagashima, M Lundh, ER Vijay, S Nitecki, D J Biol Chem 270:25752-61 16133426 Pubmed 2005 Understanding RAGE, the receptor for advanced glycation end products Bierhaus, A Humpert, PM Morcos, M Wendt, T Chavakis, T Arnold, B Stern, DM Nawroth, PP J Mol Med 83:876-86 8751438 Pubmed 1996 RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease Yan, SD Chen, X Fu, J Chen, M Zhu, H Roher, A Slattery, T Zhao, L Nagashima, M Morser, J Migheli, A Nawroth, P Stern, D Schmidt, AM Nature 382:685-91 19672558 Pubmed 2009 Ectodomain shedding of the receptor for advanced glycation end products: a novel therapeutic target for Alzheimer's disease Zhang, L Postina, R Wang, Y Cell Mol Life Sci 66:3923-35 10531386 Pubmed 1999 N(epsilon)-(carboxymethyl)lysine adducts of proteins are ligands for receptor for advanced glycation end products that activate cell signaling pathways and modulate gene expression Kislinger, T Fu, C Huber, B Qu, W Taguchi, A Du Yan, S Hofmann, M Yan, SF Pischetsrieder, M Stern, D Schmidt, AM J Biol Chem 274:31740-9 Reactome Database ID Release 78 9861970 Database 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=9861970 Reactome R-MMU-879415 1 Reactome 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-879415.1 Advanced Glycosylation End- product-specific Receptor (AGER) also known as Receptor for Advanced Glycation End-products (RAGE) is a multi-ligand membrane receptor belonging to the immunoglobulin superfamily. It is considered to be a Pattern Recognition Receptor (Liliensiek et al. 2004). It recognizes a large variety of modified proteins known as advanced glycation/glycosylation endproducts (AGEs), a heterogenous group of structures that are generated by the Maillard reaction, a consequence of long-term incubation of proteins with glucose (Ikeda et al. 1996). Their accumulation is associated with diabetes, atherosclerosis, renal failure and ageing (Schmidt et al. 1999). The most prevalent class of AGE in vivo are N(6)-carboxymethyllysine (NECML) adducts (Kislinger et al. 1991). In addition to AGEs, AGER is a signal transduction receptor for amyloid-beta peptide (Ab) (Yan et al. 1996), mediating Ab neurotoxicity and promoting Ab influx into the brain. AGER also responds to the proinflammatory S100/calgranulins (Hofmann et al. 1999) and High mobility group protein B1 (HMGB1/Amphoterin/DEF), a protein linked to neurite outgrowth and cellular motility (Hori et al. 1995).<br><br>The major inflammatory pathway stimulated by AGER activation is NFkappaB. Though the signaling cascade is unclear, several pieces of experimental data suggest that activation of AGER leads to sustained activation and upregulation of NFkappaB, measured as NFkappaB translocation to the nucleus, and increased levels of de novo synthesized NFkappaB (Bierhaus et al. 2001). As this is clearly an indirect effect it is represented here as positive regulation of NFkappaB translocation to the nucleus. AGER can bind ERK1/2 and thereby activate the MAPK and JNK cascades (Bierhaus et al. 2005). 11723063 Pubmed 2001 Diabetes-associated sustained activation of the transcription factor nuclear factor-kappaB Bierhaus, A Schiekofer, S Schwaninger, M Andrassy, M Humpert, PM Chen, J Hong, M Luther, T Henle, T Klöting, I Morcos, M Hofmann, M Tritschler, H Weigle, B Kasper, M Smith, M Perry, George Schmidt, AM Stern, DM Häring, Hans-Ulrich Schleicher, E Nawroth, PP Diabetes 50:2792-808 15173891 Pubmed 2004 Receptor for advanced glycation end products (RAGE) regulates sepsis but not the adaptive immune response Liliensiek, B Weigand, MA Bierhaus, A Nicklas, W Kasper, M Hofer, S Plachky, J Gröne, HJ Kurschus, FC Schmidt, AM Yan, SD Martin, E Schleicher, E Stern, DM Hämmerling G, G Nawroth, PP Arnold, B J Clin Invest 113:1641-50