BioPAX pathway converted from "MHC class II antigen presentation" in the Reactome database. MHC class II antigen presentation MHC class II antigen presentation 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> Formation of MHC II alpha beta heterodimer Formation of MHC II alpha beta heterodimer 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 Reactome DB_ID: 10047544 1 integral component of lumenal side of endoplasmic reticulum membrane GO 0071556 HLA II beta chain [integral component of lumenal side of endoplasmic reticulum membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity HLA class II histocompatibility antigen, DP [integral component of lumenal side of endoplasmic reticulum membrane] HLA-DQB1 [integral component of lumenal side of endoplasmic reticulum membrane] HLA-DQB2 [integral component of lumenal side of endoplasmic reticulum membrane] HLA-DQB2 [integral component of lumenal side of endoplasmic reticulum membrane] Reactome http://www.reactome.org Canis familiaris NCBI Taxonomy 9615 UniProt F1PSQ5 UniProt F6V690 UniProt F1PTQ6 Converted from EntitySet in Reactome Reactome DB_ID: 10047532 1 HLA II alpha chain [integral component of lumenal side of endoplasmic reticulum membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity DLA-DQA1 [integral component of lumenal side of endoplasmic reticulum membrane] DLA-DRA [integral component of lumenal side of endoplasmic reticulum membrane] UniProt F1PTR6 UniProt A0A5F4BUG1 Reactome DB_ID: 10047546 1 MHC II alpha beta heterodimer [integral component of lumenal side of endoplasmic reticulum membrane] MHC II alpha beta heterodimer Converted from EntitySet in Reactome Reactome DB_ID: 10047544 1 Converted from EntitySet in Reactome Reactome DB_ID: 10047532 1 Reactome Database ID Release 81 10047546 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=10047546 Reactome R-CFA-2213186 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-CFA-2213186.1 Reactome Database ID Release 81 10048886 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=10048886 Reactome R-CFA-2213239 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-CFA-2213239.1 MHC II alpha and beta chains translocate to the ER and associate noncovalently to form an alpha beta heterodimer (Roche et al. 1991). This heterodimer then associates with a preformed invariant (Ii) chain trimer. 8415765 Pubmed 1993 The segment of invariant chain that is critical for association with major histocompatibility complex class II molecules contains the sequence of a peptide eluted from class II polypeptides Freisewinkel, IM Schenck, K Koch, N Proc Natl Acad Sci U S A 90:9703-6 1956401 Pubmed 1991 Formation of a nine-subunit complex by HLA class II glycoproteins and the invariant chain Roche, PA Marks, MS Cresswell, P Nature 354:392-4 9312039 Pubmed 1997 Interaction of MHC class II molecules with the invariant chain: role of the invariant chain (81-90) region Stumptner, P Benaroch, P EMBO J 16:5807-18 16242130 Pubmed 2005 Assembly of major histocompatibility complex class II subunits with invariant chain Neumann, J Koch, N FEBS Lett 579:6055-9 inferred by electronic annotation IEA GO IEA Interaction of invariant chain trimer and MHC II alpha beta dimer Interaction of invariant chain trimer and MHC II alpha beta dimer 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> Reactome DB_ID: 10047546 1 Reactome DB_ID: 10030095 1 endoplasmic reticulum lumen GO 0005788 UniProt:F1P8B4 CANX UniProt F1P8B4 Chain Coordinates 21 EQUAL 592 EQUAL Reactome DB_ID: 10047524 1 Invariant chain trimer [integral component of lumenal side of endoplasmic reticulum membrane] Invariant chain trimer Reactome DB_ID: 10047522 3 UniProt:A0A5F4BY04 CD74 UniProt A0A5F4BY04 1 EQUAL 296 EQUAL Reactome Database ID Release 81 10047524 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=10047524 Reactome R-CFA-2130599 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-CFA-2130599.1 Reactome DB_ID: 10047548 1 alpha beta dimer:Ii trimer:calnexin [integral component of lumenal side of endoplasmic reticulum membrane] alpha beta dimer:Ii trimer:calnexin Reactome DB_ID: 10047546 1 Reactome DB_ID: 10030095 1 21 EQUAL 592 EQUAL Reactome DB_ID: 10047524 1 Reactome Database ID Release 81 10047548 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=10047548 Reactome R-CFA-2213212 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-CFA-2213212.1 Reactome Database ID Release 81 10047550 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=10047550 Reactome R-CFA-2130478 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-CFA-2130478.1 MHC II alpha beta dimers associate with a third polypeptide, the invariant chain (Ii), required for class II molecules to reach the endocytic pathway (Roche et al. 1991). The interaction of Ii with the MHC II alpha beta dimer serves multiple functions. It plays a role in assembly, folding, egress from the ER and transport through the Golgi. Ii exists as a trimer; residues 163-183 of the Ii lumenal domain are involved in covalent cross-linking. Residues 96-104 are critical for association with class II alpha beta dimers (Bijlmakers et al. 1994, Freisewinkel et al. 1993). Residues 89-104 known as CLIP (Class II-associated invariant chain peptide) are the part of the Ii chain that binds antigen binding MHC class II groove, remaining bound until the MHC receptor is completely assembled. This CLIP domain prevents the premature binding of self-peptide fragments present in ER prior to MHC II localization within the endosomal compartment. The ER-resident chaperone protein calnexin rapidly associates with newly synthesized alpha, beta and invariant chains, and remains associated until the final nonamer assembly. The stoichiometry of calnexin in this interaction and the dynamics of association-dissociation are not known. Calnexin may stabilize the free class II chains and regulate their intracellular transport by facilitating the production of transport competent molecules out of the ER (Anderson & Cresswell 1994, Schreiber et al. 1995). 2190094 Pubmed 1990 Invariant chain association with HLA-DR molecules inhibits immunogenic peptide binding Roche, PA Cresswell, P Nature 345:615-8 8689559 Pubmed 1995 How MHC class II molecules acquire peptide cargo: biosynthesis and trafficking through the endocytic pathway Wolf, PR Ploegh, HL Annu Rev Cell Dev Biol 11:267-306 21116285 Pubmed 2011 Invariant chain increases the half-life of MHC II by delaying endosomal maturation Landsverk, OJ Barois, N Gregers, TF Bakke, O Immunol Cell Biol 89:619-29 16618111 Pubmed 2006 Invariant chain transmembrane domain trimerization: a step in MHC class II assembly Dixon, AM Stanley, BJ Matthews, EE Dawson, JP Engelman, DM Biochemistry 45:5228-34 1656276 Pubmed 1991 Sequence analysis of peptides bound to MHC class II molecules Rudensky, AYu Preston-Hurlburt, P Hong, SC Barlow, A Janeway CA, Jr Nature 353:622-7 8313912 Pubmed 1994 A role for calnexin (IP90) in the assembly of class II MHC molecules Anderson, KS Cresswell, P EMBO J 13:675-82 8148318 Pubmed 1994 Class II histocompatibility molecules associate with calnexin during assembly in the endoplasmic reticulum Schreiber, KL Bell, MP Huntoon, CJ Rajagopalan, S Brenner, MB McKean, DJ Int Immunol 6:101-11 19703008 Pubmed 2009 MHC II and the endocytic pathway: regulation by invariant chain Landsverk, OJ Bakke, O Gregers, TF Scand J Immunol 70:184-93 7519244 Pubmed 1994 Mapping functional regions in the lumenal domain of the class II-associated invariant chain Bijlmakers, MJ Benaroch, P Ploegh, HL J Exp Med 180:623-9 inferred by electronic annotation IEA GO IEA Formation of nonameric complex Formation of nonameric complex 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> Reactome DB_ID: 10047546 2 Reactome DB_ID: 10047548 1 Reactome DB_ID: 10048895 1 2xMHC II alpha beta heterodimer:alpha beta dimer:Ii trimer:calnexin [integral component of lumenal side of endoplasmic reticulum membrane] 2xMHC II alpha beta heterodimer:alpha beta dimer:Ii trimer:calnexin Reactome DB_ID: 10047546 2 Reactome DB_ID: 10047548 1 Reactome Database ID Release 81 10048895 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=10048895 Reactome R-CFA-8951502 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-CFA-8951502.1 Reactome Database ID Release 81 10048897 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=10048897 Reactome R-CFA-2213241 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-CFA-2213241.1 Progressive addition of two more preformed alpha beta dimers to the invariant chain trimer and alpha beta complex ((alpha beta)1:(Ii)3) forms the complete nonameric structure ((alpha beta:Ii)3). Calnexin then disassociates on egress of the nonameric complex from the ER. inferred by electronic annotation IEA GO IEA Dissociation of CANX from nonameric complex Dissociation of CANX from nonameric complex 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> Reactome DB_ID: 10048895 1 Reactome DB_ID: 10030095 1 21 EQUAL 592 EQUAL Reactome DB_ID: 10085012 1 2xMHC II alpha beta heterodimer:alpha beta dimer:Ii trimer [integral component of lumenal side of endoplasmic reticulum membrane] 2xMHC II alpha beta heterodimer:alpha beta dimer:Ii trimer Reactome DB_ID: 10047546 2 Reactome DB_ID: 10085010 1 alpha beta dimer:Ii trimer [integral component of lumenal side of endoplasmic reticulum membrane] alpha beta dimer:Ii trimer Reactome DB_ID: 10047546 1 Reactome DB_ID: 10047524 1 Reactome Database ID Release 81 10085010 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=10085010 Reactome R-CFA-8980063 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-CFA-8980063.1 Reactome Database ID Release 81 10085012 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=10085012 Reactome R-CFA-8980062 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-CFA-8980062.1 Reactome Database ID Release 81 10085014 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=10085014 Reactome R-CFA-8951500 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-CFA-8951500.1 Calnexin disassociates on egress of the nonameric complex from the ER. inferred by electronic annotation IEA GO IEA Formation of COPII vesicle Formation of COPII vesicle 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> Reactome DB_ID: 10047700 1 endoplasmic reticulum membrane GO 0005789 COPII [endoplasmic reticulum membrane] COPII Reactome DB_ID: 10016328 1 SAR1B:GTP:SEC23:SEC24 [endoplasmic reticulum membrane] SAR1B:GTP:SEC23:SEC24 Reactome DB_ID: 10016046 1 SEC23:SEC24 [endoplasmic reticulum membrane] SEC23:SEC24 Reactome DB_ID: 10016044 1 UniProt:J9P1Q5 SEC23A UniProt J9P1Q5 1 EQUAL 765 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 10016040 1 SEC24 [endoplasmic reticulum membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity SEC24D [endoplasmic reticulum membrane] SEC24C [endoplasmic reticulum membrane] SEC24A [endoplasmic reticulum membrane] SEC24B [endoplasmic reticulum membrane] UniProt E2RSG8 UniProt E2RE90 UniProt E2RRN0 UniProt F1Q043 Reactome Database ID Release 81 10016046 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=10016046 Reactome R-CFA-204007 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-CFA-204007.1 Reactome DB_ID: 10016050 1 SAR1B:GTP [endoplasmic reticulum membrane] SAR1B:GTP Reactome DB_ID: 10016048 1 UniProt:E2RRQ3 SAR1B UniProt E2RRQ3 1 EQUAL 198 EQUAL Reactome DB_ID: 29438 1 cytosol GO 0005829 GTP(4-) [ChEBI:37565] GTP(4-) GTP gtp guanosine 5'-triphosphate(4-) ChEBI 37565 Reactome Database ID Release 81 10016050 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=10016050 Reactome R-CFA-204003 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-CFA-204003.1 Reactome Database ID Release 81 10016328 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=10016328 Reactome R-CFA-203997 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-CFA-203997.1 Reactome DB_ID: 10035077 1 Sec13p:Sec31p Complex [endoplasmic reticulum membrane] Sec13p:Sec31p Complex Reactome DB_ID: 10035073 1 UniProt:A0A5F4CH65 SEC31A UniProt A0A5F4CH65 1 EQUAL 1220 EQUAL Reactome DB_ID: 10035075 1 UniProt:A0A5F4CM74 SEC13 UniProt A0A5F4CM74 2 EQUAL 322 EQUAL Reactome Database ID Release 81 10035077 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=10035077 Reactome R-CFA-203993 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-CFA-203993.1 Reactome Database ID Release 81 10047700 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=10047700 Reactome R-CFA-203999 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-CFA-203999.1 Reactome DB_ID: 10047698 1 Nonameric complex [integral component of lumenal side of endoplasmic reticulum membrane] Nonameric complex Reactome DB_ID: 10047546 3 Reactome DB_ID: 10047524 1 Reactome Database ID Release 81 10047698 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=10047698 Reactome R-CFA-2130477 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-CFA-2130477.1 Reactome DB_ID: 10047730 1 ER to Golgi transport vesicle membrane GO 0012507 Nonameric complex in COPII vesicle [ER to Golgi transport vesicle membrane] Nonameric complex in COPII vesicle Reactome DB_ID: 10047700 1 Reactome DB_ID: 10047728 1 Nonameric complex [ER to Golgi transport vesicle membrane] Nonameric complex Reactome DB_ID: 10047726 3 MHC II alpha/beta dimer [ER to Golgi transport vesicle membrane] MHC II alpha/beta dimer Converted from EntitySet in Reactome Reactome DB_ID: 10047712 1 HLA II alpha chain [ER to Golgi transport vesicle membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity DLA-DRA [ER to Golgi transport vesicle membrane] DLA-DQA1 [ER to Golgi transport vesicle membrane] Converted from EntitySet in Reactome Reactome DB_ID: 10047724 1 HLA II beta chain [ER to Golgi transport vesicle membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity HLA class II histocompatibility antigen, DP [ER to Golgi transport vesicle membrane] HLA-DQB1 [ER to Golgi transport vesicle membrane] HLA-DQB2 [ER to Golgi transport vesicle membrane] HLA-DQB2 [ER to Golgi transport vesicle membrane] Reactome Database ID Release 81 10047726 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=10047726 Reactome R-CFA-2213181 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-CFA-2213181.1 Reactome DB_ID: 10047704 1 Invariant chain trimer [ER to Golgi transport vesicle membrane] Invariant chain trimer Reactome DB_ID: 10047702 3 1 EQUAL 296 EQUAL Reactome Database ID Release 81 10047704 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=10047704 Reactome R-CFA-2130697 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-CFA-2130697.1 Reactome Database ID Release 81 10047728 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=10047728 Reactome R-CFA-2130379 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-CFA-2130379.1 Reactome Database ID Release 81 10047730 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=10047730 Reactome R-CFA-2213211 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-CFA-2213211.1 Reactome Database ID Release 81 10047732 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=10047732 Reactome R-CFA-2130731 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-CFA-2130731.1 Immediately after assembly in the ER nonameric (alpha beta:Ii)3 complexes egress from ER, facilitated by the presence of Ii, and enter the Golgi complex (Wolf & Ploegh 1995, Geuze 1998). Incorrectly folded or oligomerized alpha, beta and Ii chains are retained in the ER and degraded. The Sec23/24-Sar1 pre-budding complex binds to the nonameric complex and then recruits Sec13/31 outer shell, which buds off from the membrane as a coat protein complex II (COPII) vesicle to be transported to the Golgi complex (Bickford et al. 2004). 2391366 Pubmed 1990 Invariant chain trimers are sequestered in the rough endoplasmic reticulum in the absence of association with HLA class II antigens Marks, MS Blum, JS Cresswell, P J Cell Biol 111:839-55 11790530 Pubmed 2002 Trafficking of MHC class II molecules in the late secretory pathway Hiltbold, EM Roche, PA Curr Opin Immunol 14:30-5 15093828 Pubmed 2004 A structural view of the COPII vesicle coat Bickford, LC Mossessova, E Goldberg, J Curr Opin Struct Biol 14:147-53 9639994 Pubmed 1998 The role of endosomes and lysosomes in MHC class II functioning Geuze, HJ Immunol Today 19:282-7 inferred by electronic annotation IEA GO IEA Fusion of COPII vesicle with Golgi complex Fusion of COPII vesicle with Golgi complex 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> Reactome DB_ID: 10047730 1 Reactome DB_ID: 10047700 1 Reactome DB_ID: 10047518 1 Golgi membrane GO 0000139 Nonameric complex [Golgi membrane] Nonameric complex Reactome DB_ID: 10047494 1 Invariant chain trimer [Golgi membrane] Invariant chain trimer Reactome DB_ID: 10047492 3 1 EQUAL 296 EQUAL Reactome Database ID Release 81 10047494 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=10047494 Reactome R-CFA-2214377 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-CFA-2214377.1 Reactome DB_ID: 10047516 3 MHC II alpha/beta dimer [Golgi membrane] MHC II alpha/beta dimer Converted from EntitySet in Reactome Reactome DB_ID: 10047514 1 HLA II beta chain [Golgi membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity HLA-DQB2 [Golgi membrane] HLA class II histocompatibility antigen, DP [Golgi membrane] HLA-DQB1 [Golgi membrane] HLA-DQB2 [Golgi membrane] Converted from EntitySet in Reactome Reactome DB_ID: 10047502 1 HLA II alpha chain [Golgi membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity DLA-DRA [Golgi membrane] DLA-DQA1 [Golgi membrane] Reactome Database ID Release 81 10047516 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=10047516 Reactome R-CFA-2214375 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-CFA-2214375.1 Reactome Database ID Release 81 10047518 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=10047518 Reactome R-CFA-2214394 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-CFA-2214394.1 Reactome Database ID Release 81 10048899 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=10048899 Reactome R-CFA-2213243 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-CFA-2213243.1 The COPII vesicle uncoats and fuses with the cis-Golgi, releasing the MHC II:Ii complex into the Golgi. 10480952 Pubmed 1999 Direct transport of newly synthesized HLA-DR from the trans-Golgi network to major histocompatibility complex class II containing compartments (MIICS) demonstrated using a novel tyrosine-sulfated chimera Davidson, HW J Biol Chem 274:27315-22 inferred by electronic annotation IEA GO IEA Transport of MHC II:Ii complex along Golgi to TGN Transport of MHC II:Ii complex along Golgi to TGN Translocation of MHC II:Ii complex to TGN 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> Reactome DB_ID: 10047518 1 Reactome DB_ID: 10047462 1 trans-Golgi network membrane GO 0032588 Nonameric complex [trans-Golgi network membrane] Nonameric complex Reactome DB_ID: 10047438 1 Invariant chain trimer [trans-Golgi network membrane] Invariant chain trimer Reactome DB_ID: 10047436 3 1 EQUAL 296 EQUAL Reactome Database ID Release 81 10047438 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=10047438 Reactome R-CFA-2130720 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-CFA-2130720.1 Reactome DB_ID: 10047460 3 MHC II alpha/beta dimer [trans-Golgi network membrane] MHC II alpha/beta dimer Converted from EntitySet in Reactome Reactome DB_ID: 10047458 1 HLA II beta chain [trans-Golgi network membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity HLA class II histocompatibility antigen, DP [trans-Golgi network membrane] HLA-DQB2 [trans-Golgi network membrane] HLA-DQB2 [trans-Golgi network membrane] HLA-DQB1 [trans-Golgi network membrane] Converted from EntitySet in Reactome Reactome DB_ID: 10047446 1 HLA II alpha chain [trans-Golgi network membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity DLA-DQA1 [trans-Golgi network membrane] DLA-DRA [trans-Golgi network membrane] Reactome Database ID Release 81 10047460 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=10047460 Reactome R-CFA-2213184 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-CFA-2213184.1 Reactome Database ID Release 81 10047462 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=10047462 Reactome R-CFA-2130491 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-CFA-2130491.1 Reactome Database ID Release 81 10047520 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=10047520 Reactome R-CFA-2130393 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-CFA-2130393.1 Nonameric MHC II:Ii complex move through the various cisternae to reach the trans-golgi network (TGN), a tubulo-vesicular organelle located at the trans-face of Golgi stacks. From the TGN, MHC II:Ii complexes are targeted to the endocytic pathway for peptide loading. 11529500 Pubmed 2001 Trans-Golgi network sorting Gu, F Crump, CM Thomas, G Cell Mol Life Sci 58:1067-84 inferred by electronic annotation IEA GO IEA TGN-lysosomal vesicle coat assembly TGN-lysosomal vesicle coat assembly 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> Reactome DB_ID: 10025191 1 AP-1 Complex [cytosol] AP-1 Complex Reactome DB_ID: 10025175 1 Ghost homologue of AP1G1 [cytosol] Ghost homologue of AP1G1 Reactome DB_ID: 10025189 1 UniProt:E2RRJ6 AP1B1 UniProt E2RRJ6 1 EQUAL 949 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 10025181 1 AP-1 mu [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity AP1M1 [cytosol] AP1M2 [cytosol] UniProt F1PYG5 UniProt F1PFJ0 Converted from EntitySet in Reactome Reactome DB_ID: 10025187 1 AP-1 sigma [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity AP1S2 [cytosol] AP1S1 [cytosol] UniProt A0A5F4CQU4 UniProt E2RLN5 Reactome Database ID Release 81 10025191 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=10025191 Reactome R-CFA-167717 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-CFA-167717.1 Reactome DB_ID: 10047462 1 Reactome DB_ID: 10025161 1 Clathrin Triskelion [cytosol] Clathrin Triskelion Reactome DB_ID: 10025157 3 UniProt:F1PHQ0 CLTC UniProt F1PHQ0 2 EQUAL 1675 EQUAL Reactome DB_ID: 10025159 3 UniProt:A0A5F4D392 CLTA UniProt A0A5F4D392 1 EQUAL 248 EQUAL Reactome Database ID Release 81 10025161 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=10025161 Reactome R-CFA-350827 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-CFA-350827.1 Reactome DB_ID: 10018637 1 Arf1-GTP [Golgi membrane] Arf1-GTP Reactome DB_ID: 29438 1 Reactome DB_ID: 10018635 1 UniProt:E2RNQ7 ARF1 UniProt E2RNQ7 2 EQUAL 181 EQUAL Reactome Database ID Release 81 10018637 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=10018637 Reactome R-CFA-199981 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-CFA-199981.1 Converted from EntitySet in Reactome Reactome DB_ID: 10047653 1 Dynamin [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity DNM2 [cytosol] UniProt E2RNC3 Reactome DB_ID: 10047655 1 AP-1 Complex:Arf1-GTP:Clathrin Triskelion:Nonameric complex [trans-Golgi network membrane] AP-1 Complex:Arf1-GTP:Clathrin Triskelion:Nonameric complex Reactome DB_ID: 10025191 1 Reactome DB_ID: 10047462 1 Reactome DB_ID: 10025161 1 Reactome DB_ID: 10018637 1 Converted from EntitySet in Reactome Reactome DB_ID: 10047653 1 Reactome Database ID Release 81 10047655 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=10047655 Reactome R-CFA-8951497 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-CFA-8951497.1 Reactome Database ID Release 81 10047657 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=10047657 Reactome R-CFA-2130619 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-CFA-2130619.1 The trans-Golgi network (TGN) is the sorting and package centre for trafficking cargo to the endoplasmic reticulum, plasma membrane and endosomes. Signal peptides determine the sorting and trafficking of proteins to the endosomal-lysosomal pathway or to the cell surface. The main signals that mediate targeting of MHC-II molecules to the endocytic pathway are two dileucine-based motifs, Leu23-Ile24 and Pro31-Leu33 present in the short cytoplasmic tail of Ii (Odorizzi et al. 1994). These motifs bind both the adaptor proteins AP-1 and AP-2, which are components of clathrin coats associated with the TGN/endosomes and the plasma membrane, respectively (McCormick et al. 2005). The precise pathway of class II:Ii complex trafficking from TGN to endocytic pathway is not well understood. In one view MHC II:Ii complexes directly traffic from the TGN to lysosomes, possibly using AP-1 dependent endocytic vesicles (Peters et al. 1991, Amigorena et al. 1994). Alternatively trafficking occurs via transient expression on the cell surface followed by rapid internalization and delivery to endocytic compartments. Early immunoelectron microscopy data has shown the presence of MHC class II:Ii complex molecules primarily in TGN and lysosomes (Peters et al. 1991, Hiltbold & Roche 2002). This theory was further supported by a study examining the trafficking of sulphate-tagged class II molecules, which concluded that the rapid appearance of these molecules in lysosomes was consistent with their direct transport from the TGN to lysosomes (Hiltbold & Roche 2002, Davidson 1999). The transport of cargo MHC II:Ii complexes from the TGN to lysosomes may be mediated by small TGN vesicles coated with AP-1 and clathrin. The di-leucine-based sorting signal in the Ii cytoplasmic chain recruits AP-1 and clathrin from cytosol to TGN to form AP-1 clathrin-coated TGN-derived vesicles. This process is regulated by the small GTPase ARF-1 (Salamero et al. 1996). 15911768 Pubmed 2005 Involvement of clathrin and AP-2 in the trafficking of MHC class II molecules to antigen-processing compartments McCormick, PJ Martina, JA Bonifacino, JS Proc Natl Acad Sci U S A 102:7910-5 7650016 Pubmed 1995 A role for acidic residues in di-leucine motif-based targeting to the endocytic pathway Pond, L Kuhn, LA Teyton, L Schutze, MP Tainer, JA Jackson, MR Peterson, PA J Biol Chem 270:19989-97 7592972 Pubmed 1995 Structure-activity relationship of the leucine-based sorting motifs in the cytosolic tail of the major histocompatibility complex-associated invariant chain Motta, A Bremnes, B Morelli, MA Frank, RW Saviano, G Bakke, O J Biol Chem 270:27165-71 8034737 Pubmed 1994 Sorting signals in the MHC class II invariant chain cytoplasmic tail and transmembrane region determine trafficking to an endocytic processing compartment Odorizzi, CG Trowbridge, IS Xue, L Hopkins, Colin R Davis, CD Collawn, JF J Cell Biol 126:317-30 10593899 Pubmed 1999 The leucine-based sorting motifs in the cytoplasmic domain of the invariant chain are recognized by the clathrin adaptors AP1 and AP2 and their medium chains Hofmann, MW Höning, S Rodionov, D Dobberstein, B von Figura, K Bakke, O J Biol Chem 274:36153-8 9497313 Pubmed 1998 Medium chains of adaptor complexes AP-1 and AP-2 recognize leucine-based sorting signals from the invariant chain Rodionov, DG Bakke, O J Biol Chem 273:6005-8 11520080 Pubmed 2001 Intracellular transport of MHC class II and associated invariant chain in antigen presenting cells from AP-3-deficient mocha mice Sevilla, LM Richter, SS Miller, J Cell Immunol 210:143-53 8177316 Pubmed 1994 Transient accumulation of new class II MHC molecules in a novel endocytic compartment in B lymphocytes Amigorena, S Drake, JR Webster, P Mellman, I Nature 369:113-20 14731593 Pubmed 1994 Targeting of membrane proteins to endosomes and lysosomes Sandoval, IV Bakke, O Trends Cell Biol 4:292-7 2121367 Pubmed 1990 MHC class II-associated invariant chain contains a sorting signal for endosomal compartments Bakke, O Dobberstein, B Cell 63:707-16 8939989 Pubmed 1996 Expression of major histocompatibility complex class II molecules in HeLa cells promotes the recruitment of AP-1 Golgi-specific assembly proteins on Golgi membranes Salamero, J Le Borgne, R Saudrais, C Goud, B Hoflack, B J Biol Chem 271:30318-21 inferred by electronic annotation IEA GO IEA Dissociation of Arf1:GDP, AP-1 Clathrin coated nonameric complex Dissociation of Arf1:GDP, AP-1 Clathrin coated nonameric complex 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> Reactome DB_ID: 10047655 1 Reactome DB_ID: 29372 1 hydrogenphosphate [ChEBI:43474] hydrogenphosphate [PO3(OH)](2-) HYDROGENPHOSPHATE ION hydrogen phosphate [P(OH)O3](2-) HPO4(2-) phosphate INORGANIC PHOSPHATE GROUP ChEBI 43474 Reactome DB_ID: 10047687 1 AP-1 Clathrin coated nonameric complex [trans-Golgi network membrane] AP-1 Clathrin coated nonameric complex Reactome DB_ID: 10047462 1 Reactome DB_ID: 10047679 1 AP-1 Complex [trans-Golgi network membrane] AP-1 Complex Reactome DB_ID: 10047663 1 Ghost homologue of AP1G1 [trans-Golgi network membrane] Ghost homologue of AP1G1 Converted from EntitySet in Reactome Reactome DB_ID: 10047669 1 AP1M1,2 [trans-Golgi network membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity AP1M2 [trans-Golgi network membrane] AP1M1 [trans-Golgi network membrane] Converted from EntitySet in Reactome Reactome DB_ID: 10047675 1 AP1S1,2,3 [trans-Golgi network membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity AP1S2 [trans-Golgi network membrane] AP1S1 [trans-Golgi network membrane] Reactome DB_ID: 10047677 1 1 EQUAL 949 EQUAL Reactome Database ID Release 81 10047679 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=10047679 Reactome R-CFA-2130687 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-CFA-2130687.1 Reactome DB_ID: 10047685 1 Clathrin [trans-Golgi network membrane] Clathrin Reactome DB_ID: 10047681 3 2 EQUAL 1675 EQUAL Reactome DB_ID: 10047683 3 1 EQUAL 248 EQUAL Reactome Database ID Release 81 10047685 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=10047685 Reactome R-CFA-2130469 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-CFA-2130469.1 Converted from EntitySet in Reactome Reactome DB_ID: 10047653 1 Reactome Database ID Release 81 10047687 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=10047687 Reactome R-CFA-2130552 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-CFA-2130552.1 Reactome DB_ID: 10018633 1 Arf1-GDP [cytosol] Arf1-GDP Reactome DB_ID: 10018631 1 2 EQUAL 181 EQUAL Reactome DB_ID: 29420 1 GDP(3-) [ChEBI:58189] GDP(3-) guanosine 5'-diphosphate(3-) 5'-O-[(phosphonatooxy)phosphinato]guanosine guanosine 5'-diphosphate trianion GDP GDP trianion guanosine 5'-diphosphate ChEBI 58189 Reactome Database ID Release 81 10018633 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=10018633 Reactome R-CFA-201340 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-CFA-201340.1 Reactome Database ID Release 81 10085006 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=10085006 Reactome R-CFA-8951498 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-CFA-8951498.1 The trans-Golgi network (TGN) is the sorting and package centre for trafficking cargo to the endoplasmic reticulum, plasma membrane and endosomes. Signal peptides determine the sorting and trafficking of proteins to the endosomal-lysosomal pathway or to the cell surface. The main signals that mediate targeting of MHC-II molecules to the endocytic pathway are two dileucine-based motifs, Leu23-Ile24 and Pro31-Leu33 present in the short cytoplasmic tail of Ii (Odorizzi et al. 1994). These motifs bind both the adaptor proteins AP-1 and AP-2, which are components of clathrin coats associated with the TGN/endosomes and the plasma membrane, respectively (McCormick et al. 2005). The precise pathway of class II:Ii complex trafficking from TGN to endocytic pathway is not well understood. In one view MHC II:Ii complexes directly traffic from the TGN to lysosomes, possibly using AP-1 dependent endocytic vesicles (Peters et al. 1991, Amigorena et al. 1994). Alternatively trafficking occurs via transient expression on the cell surface followed by rapid internalization and delivery to endocytic compartments. Early immunoelectron microscopy data has shown the presence of MHC class II:Ii complex molecules primarily in TGN and lysosomes (Peters et al. 1991, Hiltbold & Roche 2002). This theory was further supported by a study examining the trafficking of sulphate-tagged class II molecules, which concluded that the rapid appearance of these molecules in lysosomes was consistent with their direct transport from the TGN to lysosomes (Hiltbold & Roche 2002, Davidson 1999). The transport of cargo MHC II:Ii complexes from the TGN to lysosomes may be mediated by small TGN vesicles coated with AP-1 and clathrin. The di-leucine-based sorting signal in the Ii cytoplasmic chain recruits AP-1 and clathrin from cytosol to TGN to form AP-1 clathrin-coated TGN-derived vesicles. This process is regulated by the small GTPase ARF-1 (Salamero et al. 1996). inferred by electronic annotation IEA GO IEA 3.6.5.4 3.6.5.3 3.6.5.2 3.6.5.1 Translocation of TGN-lysosome vesicle to lysosome Translocation of TGN-lysosome vesicle to lysosome 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> Reactome DB_ID: 10047687 1 Reactome DB_ID: 29438 1 Reactome DB_ID: 29372 1 Reactome DB_ID: 29420 1 Reactome DB_ID: 10047689 1 TGN-lysosome vesicle with nonameric complex [trans-Golgi network membrane] TGN-lysosome vesicle with nonameric complex Reactome DB_ID: 10047462 1 Reactome DB_ID: 10047679 1 Reactome DB_ID: 10047685 1 Reactome Database ID Release 81 10047689 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=10047689 Reactome R-CFA-2213234 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-CFA-2213234.1 Converted from EntitySet in Reactome Reactome DB_ID: 10047653 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10047653 GO 0003924 GO molecular function Reactome Database ID Release 81 10047690 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=10047690 Reactome Database ID Release 81 10047692 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=10047692 Reactome R-CFA-2130641 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-CFA-2130641.1 Budding vesicles loaded with the nonameric complex bud off from the TGN to reach the late-endosome/lysosome membrane. inferred by electronic annotation IEA GO IEA TGN-lysosome vesicle uncoating and release of nonameric complex to lysosome TGN-lysosome vesicle uncoating and release of nonameric complex to lysosome 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> Reactome DB_ID: 10047689 1 Reactome DB_ID: 10025191 1 Reactome DB_ID: 10047372 1 lysosomal membrane GO 0005765 Nonameric complex [lysosomal membrane] Nonameric complex Reactome DB_ID: 10047348 1 Invariant chain trimer [lysosomal membrane] Invariant chain trimer Reactome DB_ID: 10047346 3 1 EQUAL 296 EQUAL Reactome Database ID Release 81 10047348 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=10047348 Reactome R-CFA-2130584 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-CFA-2130584.1 Reactome DB_ID: 10047370 3 MHC II alpha/beta dimer [lysosomal membrane] MHC II alpha/beta dimer Converted from EntitySet in Reactome Reactome DB_ID: 10047356 1 HLA II alpha chain [lysosomal membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity DLA-DRA [lysosomal membrane] DLA-DQA1 [lysosomal membrane] Converted from EntitySet in Reactome Reactome DB_ID: 10047368 1 HLA II beta chain [lysosomal membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity HLA-DQB2 [lysosomal membrane] HLA-DQB2 [lysosomal membrane] HLA-DQB1 [lysosomal membrane] HLA class II histocompatibility antigen, DP [lysosomal membrane] Reactome Database ID Release 81 10047370 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=10047370 Reactome R-CFA-2213179 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-CFA-2213179.1 Reactome Database ID Release 81 10047372 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=10047372 Reactome R-CFA-2130532 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-CFA-2130532.1 Reactome DB_ID: 10025161 1 Reactome Database ID Release 81 10048884 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=10048884 Reactome R-CFA-2213236 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-CFA-2213236.1 On reaching the late endosomes/lysosomes the TGN-lysosome vesicle uncoats and fuses with the lysosome to releases the MHC II nonameric complex. inferred by electronic annotation IEA GO IEA Transport of MHC II:Ii complex to plasma membrane Transport of MHC II:Ii complex to plasma membrane 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> Reactome DB_ID: 10047462 1 Reactome DB_ID: 10047488 1 transport vesicle membrane GO 0030658 MHC class II alpha/beta/Ii nonamer [transport vesicle membrane] MHC class II alpha/beta/Ii nonamer Converted from EntitySet in Reactome Reactome DB_ID: 10047482 3 HLA II beta chain [transport vesicle membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity HLA class II histocompatibility antigen, DP [transport vesicle membrane] HLA-DQB1 [transport vesicle membrane] HLA-DQB2 [transport vesicle membrane] HLA-DQB2 [transport vesicle membrane] Reactome DB_ID: 10047486 1 Invariant chain trimer [transport vesicle membrane] Invariant chain trimer Reactome DB_ID: 10047484 3 1 EQUAL 296 EQUAL Reactome Database ID Release 81 10047486 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=10047486 Reactome R-CFA-2130656 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-CFA-2130656.1 Converted from EntitySet in Reactome Reactome DB_ID: 10047470 3 HLA II alpha chain [transport vesicle membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity DLA-DQA1 [transport vesicle membrane] DLA-DRA [transport vesicle membrane] Reactome Database ID Release 81 10047488 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=10047488 Reactome R-CFA-2130431 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-CFA-2130431.1 Reactome Database ID Release 81 10047490 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=10047490 Reactome R-CFA-2130378 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-CFA-2130378.1 The newly formed MHC II-Ii complex exits the TGN and ultimately is delivered to late-endosome/lysosome compartments. A proportion of the nonameric complex traffics directly from the TGN to these compartments, while a substantial population follow the indirect pathway involving transport from the TGN to the plasma membrane, followed by endocytic delivery to early endosomes, late endosomes, and finally lysosomes (McCormick et al. 2005). Transport carrier vesicles may traffic the cargo MHC II-Ii complex from the TGN to the plasma membrane. 16824007 Pubmed 2006 The formation of TGN-to-plasma-membrane transport carriers Bard, F Malhotra, V Annu Rev Cell Dev Biol 22:439-55 10540230 Pubmed 1999 Cell surface expression and metabolism of major histocompatibility complex class II invariant chain (CD74) by diverse cell lines Ong, GL Goldenberg, DM Hansen, HJ Mattes, MJ Immunology 98:296-302 8397411 Pubmed 1993 Cell surface HLA-DR-invariant chain complexes are targeted to endosomes by rapid internalization Roche, PA Teletski, CL Stang, E Bakke, O Long, EO Proc Natl Acad Sci U S A 90:8581-5 inferred by electronic annotation IEA GO IEA Insertion of MHC II:Ii complex in to the plasma membrane Insertion of MHC II:Ii complex in to the plasma membrane 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> Reactome DB_ID: 10047488 1 Reactome DB_ID: 10047640 1 plasma membrane GO 0005886 MHC class II alpha/beta/Ii nonamer [plasma membrane] MHC class II alpha/beta/Ii nonamer Reactome DB_ID: 10015161 3 MHC class II alpha/beta dimer [plasma membrane] MHC class II alpha/beta dimer Converted from EntitySet in Reactome Reactome DB_ID: 10015141 1 HLA II alpha chain [plasma membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity DLA-DRA [plasma membrane] DLA-DQA1 [plasma membrane] Converted from EntitySet in Reactome Reactome DB_ID: 10015159 1 HLA II beta chain [plasma membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity HLA class II histocompatibility antigen, DP [plasma membrane] HLA-DQB1 [plasma membrane] HLA-DQB2 [plasma membrane] HLA-DQB2 [plasma membrane] Reactome Database ID Release 81 10015161 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=10015161 Reactome R-CFA-2213189 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-CFA-2213189.1 Reactome DB_ID: 10047638 1 CD74 trimer [plasma membrane] CD74 trimer Reactome DB_ID: 10047636 3 1 EQUAL 296 EQUAL Reactome Database ID Release 81 10047638 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=10047638 Reactome R-CFA-2130505 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-CFA-2130505.1 Reactome Database ID Release 81 10047640 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=10047640 Reactome R-CFA-2130467 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-CFA-2130467.1 Reactome Database ID Release 81 10047642 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=10047642 Reactome R-CFA-2130500 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-CFA-2130500.1 On reaching the cell surface, transport carrier vesicles insert the cargo MHC II:Ii complex into the plasma membrane. inferred by electronic annotation IEA GO IEA Recruitment of clathrin coated vesicle by Ii Recruitment of clathrin coated vesicle by Ii 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> Reactome DB_ID: 10047640 1 Reactome DB_ID: 10010586 1 Clathrin:AP-2 complex [plasma membrane] Clathrin:AP-2 complex Reactome DB_ID: 10010574 1 AP-2 complex [plasma membrane] AP-2 complex Converted from EntitySet in Reactome Reactome DB_ID: 10010572 1 Adaptor protein complex 2 (AP-2) large adaptins [plasma membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity AP2A1 [plasma membrane] AP2A2 [plasma membrane] UniProt A0A5F4BU88 UniProt A0A5F4BTD6 Reactome DB_ID: 10010554 1 UniProt:A0A5F4CPQ9 AP2B1 UniProt A0A5F4CPQ9 1 EQUAL 937 EQUAL Reactome DB_ID: 10010558 1 UniProt:A0A5F4BQ86 AP2M1 UniProt A0A5F4BQ86 1 EQUAL 435 EQUAL Reactome DB_ID: 10010562 1 UniProt:A0A5F4CSI6 AP2S1 UniProt A0A5F4CSI6 1 EQUAL 142 EQUAL Reactome Database ID Release 81 10010574 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=10010574 Reactome R-CFA-177480 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-CFA-177480.1 Reactome DB_ID: 10010584 1 Clathrin [plasma membrane] Clathrin Reactome DB_ID: 10010582 3 2 EQUAL 1675 EQUAL Reactome DB_ID: 10010578 3 1 EQUAL 248 EQUAL Reactome Database ID Release 81 10010584 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=10010584 Reactome R-CFA-177482 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-CFA-177482.1 Reactome Database ID Release 81 10010586 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=10010586 Reactome R-CFA-177505 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-CFA-177505.1 Reactome DB_ID: 10047659 1 Clathrin coated MHC class II alpha/beta/Ii nonamer [plasma membrane] Clathrin coated MHC class II alpha/beta/Ii nonamer Reactome DB_ID: 10047640 1 Reactome DB_ID: 10010586 1 Reactome Database ID Release 81 10047659 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=10047659 Reactome R-CFA-2130309 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-CFA-2130309.1 Reactome Database ID Release 81 10047661 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=10047661 Reactome R-CFA-2130640 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-CFA-2130640.1 Plasma membrane-associated nonameric complexes (MHC II alpha/beta/Ii complex) are rapidly internalized and delivered to late endosomes (LEs) and lysosomes. The dileucine-based signal present in the cytoplasmic tail of Ii is required for sorting of the nonameric MHC II-Ii complex from the plasma membrane to peptide loading compartments. These signals promote rapid internalization by recognising and binding to clathrin adaptor AP-2, a scaffolding-protein complex that brings together components of the vesicle-formation machinery. AP-2 is an essential component of an endocytic clathrin coat and participates in initiation of coat assembly. The critical role of AP2 in delivering MHC II:Ii complex to antigen processing compartments came from RNA interference studies targeting clathrin and AP2. The knockout of AP2 profoundly inhibited MHC II:Ii complex internalization and resulted in the accumulation of Ii at the surface (Dugast et al. 2005, McCormick et al. 2005). 15749704 Pubmed 2005 AP2 clathrin adaptor complex, but not AP1, controls the access of the major histocompatibility complex (MHC) class II to endosomes Dugast, M Toussaint, H Dousset, C Benaroch, P J Biol Chem 280:19656-64 inferred by electronic annotation IEA GO IEA 3.6.5.4 3.6.5.3 3.6.5.2 3.6.5.1 Internalization of MHC II:Ii clathrin coated vesicle Internalization of MHC II:Ii clathrin coated vesicle 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> Reactome DB_ID: 29356 1 water [ChEBI:15377] water ChEBI 15377 Reactome DB_ID: 10047659 1 Reactome DB_ID: 10010590 1 UniProt:F1PDT4 SH3GL2 UniProt F1PDT4 1 EQUAL 352 EQUAL Reactome DB_ID: 29438 1 Reactome DB_ID: 29372 1 Reactome DB_ID: 10047604 1 clathrin-coated endocytic vesicle membrane GO 0030669 Clathrin coated MHC class II alpha/beta/Ii nonamer [clathrin-coated endocytic vesicle membrane] Clathrin coated MHC class II alpha/beta/Ii nonamer Reactome DB_ID: 10047602 1 Clathrin:AP2 complex [clathrin-coated endocytic vesicle membrane] Clathrin:AP2 complex Reactome DB_ID: 10047600 1 Clathrin [clathrin-coated endocytic vesicle membrane] Clathrin Reactome DB_ID: 10047596 3 endolysosome membrane GO 0036020 2 EQUAL 1675 EQUAL Reactome DB_ID: 10047598 3 1 EQUAL 248 EQUAL Reactome Database ID Release 81 10047600 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=10047600 Reactome R-CFA-2130407 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-CFA-2130407.1 Reactome DB_ID: 10047594 1 Adaptor protein 2 complex [endolysosome membrane] Adaptor protein 2 complex Converted from EntitySet in Reactome Reactome DB_ID: 10047592 1 Adaptor protein complex 2 (AP-2) large adaptins [endolysosome membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity AP2A1 [endolysosome membrane] AP2A2 [endolysosome membrane] Reactome DB_ID: 10047584 1 1 EQUAL 435 EQUAL Reactome DB_ID: 10047586 1 1 EQUAL 142 EQUAL Reactome DB_ID: 10047582 1 1 EQUAL 937 EQUAL Reactome Database ID Release 81 10047594 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=10047594 Reactome R-CFA-2130637 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-CFA-2130637.1 Reactome Database ID Release 81 10047602 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=10047602 Reactome R-CFA-2130671 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-CFA-2130671.1 Reactome DB_ID: 10047580 1 1 EQUAL 352 EQUAL Reactome DB_ID: 10047578 1 MHC class II alpha/beta/Ii nonamer [clathrin-coated endocytic vesicle membrane] MHC class II alpha/beta/Ii nonamer Reactome DB_ID: 10047576 3 MHC class II alpha/beta dimer [clathrin-coated endocytic vesicle membrane] MHC class II alpha/beta dimer Converted from EntitySet in Reactome Reactome DB_ID: 10047562 1 HLA II alpha chain [clathrin-coated endocytic vesicle membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity DLA-DRA [clathrin-coated endocytic vesicle membrane] DLA-DQA1 [clathrin-coated endocytic vesicle membrane] Converted from EntitySet in Reactome Reactome DB_ID: 10047574 1 HLA II beta chain [clathrin-coated endocytic vesicle membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity HLA-DQB2 [clathrin-coated endocytic vesicle membrane] HLA class II histocompatibility antigen, DP [clathrin-coated endocytic vesicle membrane] HLA-DQB1 [clathrin-coated endocytic vesicle membrane] HLA-DQB2 [clathrin-coated endocytic vesicle membrane] Reactome Database ID Release 81 10047576 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=10047576 Reactome R-CFA-2213178 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-CFA-2213178.1 Reactome DB_ID: 10047554 1 Invariant chain trimer [clathrin-coated endocytic vesicle membrane] Invariant chain trimer Reactome DB_ID: 10047552 3 1 EQUAL 296 EQUAL Reactome Database ID Release 81 10047554 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=10047554 Reactome R-CFA-2130372 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-CFA-2130372.1 Reactome Database ID Release 81 10047578 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=10047578 Reactome R-CFA-2130425 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-CFA-2130425.1 Reactome Database ID Release 81 10047604 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=10047604 Reactome R-CFA-2130331 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-CFA-2130331.1 Reactome DB_ID: 29420 1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10030207 Dynamin-1/2/3 [plasma membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Reactome Database ID Release 81 10030208 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=10030208 Reactome Database ID Release 81 10047696 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=10047696 Reactome R-CFA-2130725 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-CFA-2130725.1 MHC II:Ii complexes are internalized in to the endocytic clathrin coated-pit. Dynamin, the GTPase involved in the scission of clathrin-coated vesicles from plasma membrane is observed to be involved in the effective endocytosis of MHC II:Ii complexes. Wang et al, demonstrated that overexpression of a dominant-negative mutant of the GTPase dynamin resulted in the cell surface accumulation of MHC II:Ii complex, supporting that endocytosis is required for delivery to antigen processing compartments (Wang et al, 1997). However, another study using the same dynamin mutant generated opposite conclusions (Davidson, 1999). This discrepancy may be caused by differences in experimental set-up and in the levels of expression of the dynamin mutant and MHC II chains (Dugast et al, 2005). 9202021 Pubmed 1997 Decreased endosomal delivery of major histocompatibility complex class II-invariant chain complexes in dynamin-deficient cells Wang, K Peterson, PA Karlsson, L J Biol Chem 272:17055-60 inferred by electronic annotation IEA GO IEA Uncoating of clathrin-coated vesicles and fusion with endosomes Uncoating of clathrin-coated vesicles and fusion with endosomes 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> Reactome DB_ID: 10047604 1 Reactome DB_ID: 10047602 1 Reactome DB_ID: 10047580 1 1 EQUAL 352 EQUAL Reactome DB_ID: 10047632 1 endocytic vesicle membrane GO 0030666 Nonameric complex [endocytic vesicle membrane] Nonameric complex Reactome DB_ID: 10047630 3 MHC class II alpha/beta dimer [endocytic vesicle membrane] MHC class II alpha/beta dimer Converted from EntitySet in Reactome Reactome DB_ID: 10047616 1 HLA II alpha chain [endocytic vesicle membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity DLA-DRA [endocytic vesicle membrane] DLA-DQA1 [endocytic vesicle membrane] Converted from EntitySet in Reactome Reactome DB_ID: 10047628 1 HLA II beta chain [endocytic vesicle membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity HLA-DQB2 [endocytic vesicle membrane] HLA class II histocompatibility antigen, DP [endocytic vesicle membrane] HLA-DQB1 [endocytic vesicle membrane] HLA-DQB2 [endocytic vesicle membrane] Reactome Database ID Release 81 10047630 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=10047630 Reactome R-CFA-2213187 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-CFA-2213187.1 Reactome DB_ID: 10047608 1 Invariant chain trimer [endocytic vesicle membrane] Invariant chain trimer Reactome DB_ID: 10047606 3 1 EQUAL 296 EQUAL Reactome Database ID Release 81 10047608 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=10047608 Reactome R-CFA-2130371 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-CFA-2130371.1 Reactome Database ID Release 81 10047632 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=10047632 Reactome R-CFA-2130531 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-CFA-2130531.1 Reactome Database ID Release 81 10047634 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=10047634 Reactome R-CFA-2130486 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-CFA-2130486.1 MHC II:Ii complexes bound to clathrin-coated vesicles rapidly fuse with endosomes. inferred by electronic annotation IEA GO IEA Trafficking of nonameric complex in the endocytic pathway Trafficking of nonameric complex in the endocytic pathway 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> Reactome DB_ID: 10047632 1 Reactome DB_ID: 10047372 1 Reactome Database ID Release 81 10048882 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=10048882 Reactome R-CFA-2213235 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-CFA-2213235.1 The internalized nonameric complex passes through the endocytic pathway and finally reach the acidic late endosomal/lysosomal compartments, where the Ii component is progressively degraded by proteases. Proteolysis of Ii occurs through sequential cleavages from the lumenal (C-terminal) side, generating cleavage products of approximately 22 kDa (lip22) and 10 kDa (lip10), finally leaving only CLIP bound within the peptide binding groove of MHC II (Landsverk et al. 2009). inferred by electronic annotation IEA GO IEA 3.4.22.41 3.4.22.40 3.4.22.34 3.4.22.8 3.4.22.28 3.4.22.16 3.4.22.27 3.4.22.38 3.4.22.1 3.4.22.15 3.4.22.14 Initial proteolyis of Ii by aspartic proteases to lip22 Initial proteolyis of Ii by aspartic proteases to lip22 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> Reactome DB_ID: 10047372 1 Reactome DB_ID: 10047378 1 MHC II:lip22 nonamer [lysosomal membrane] MHC II:lip22 nonamer Reactome DB_ID: 10047370 3 Reactome DB_ID: 10047376 1 lip22 trimer [lysosomal membrane] lip22 trimer Reactome DB_ID: 10047374 3 1 EQUAL 176 EQUAL Reactome Database ID Release 81 10047376 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=10047376 Reactome R-CFA-2213190 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-CFA-2213190.1 Reactome Database ID Release 81 10047378 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=10047378 Reactome R-CFA-2130680 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-CFA-2130680.1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10047380 lysosomal lumen GO 0043202 UniProt:E2QXF2 LGMN UniProt E2QXF2 18 EQUAL 323 EQUAL GO 0004197 GO molecular function Reactome Database ID Release 81 10047381 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=10047381 Reactome Database ID Release 81 10047383 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=10047383 Reactome R-CFA-2130336 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-CFA-2130336.1 Within acidic endocytic compartments Ii is proteolytically cleaved, ultimately freeing the class II peptide-binding groove for loading of antigenic peptides. Ii is degraded in a stepwise manner by a combination of aspartyl and cysteine proteases, following a well defined path with intermediates lip22, lip10 and finally CLIP. The initial Ii cleavage has been ascribed to leupeptin-insensitive cysteine or aspartic proteases, which include aspartyl protease and asparagine endopeptidase (AEP) (Maric et al. 1994, Manoury et al. 2003, Costantino et al. 2008). These proteases generate 22 kDa fragments of Ii (lip22). The trimerization domain of human Ii (residues 134-208) has three possible AEP cleavage sites, Asn148, 165 and 171. Asn171, located at the C-terminal end of helix B, is the demonstrated cleavage site for AEP (Manoury et al. 2003, Jasanoff et al. 1998). This cleavage eliminates the C-terminal trimerization domain of Ii, which causes disassociation of the (MHC II:Ii)3 nonamer and exposes new cleavage sites in the MHC II:lip22 trimers (Villadangos et al. 1999, Guillaume et al. 2008). The residue numbering of Ii given above is based on Uniprot isoform 1. 9843486 Pubmed 1998 Structure of a trimeric domain of the MHC class II-associated chaperonin and targeting protein Ii Jasanoff, A Wagner, G Wiley, DC EMBO J 17:6812-8 18582577 Pubmed 2008 Endosomal sorting of MHC class II determines antigen presentation by dendritic cells van Niel, G Wubbolts, R Stoorvogel, W Curr Opin Cell Biol 20:437-44 18292509 Pubmed 2008 Lysosomal cysteine and aspartic proteases are heterogeneously expressed and act redundantly to initiate human invariant chain degradation Costantino, CM Hang, HC Kent, SC Hafler, DA Ploegh, HL J Immunol 180:2876-85 8134367 Pubmed 1994 Endosomal aspartic proteinases are required for invariant-chain processing Mari?, MA Taylor, MD Blum, JS Proc Natl Acad Sci U S A 91:2171-5 10631941 Pubmed 1999 Proteases involved in MHC class II antigen presentation Villadangos, JA Bryant, RA Deussing, J Driessen, C Lennon-Duménil, AM Riese, RJ Roth, W Saftig, P Shi, GP Chapman, HA Peters, C Ploegh, HL Immunol Rev 172:109-20 inferred by electronic annotation IEA GO IEA 3.4.22.41 3.4.22.40 3.4.22.34 3.4.22.8 3.4.22.28 3.4.22.16 3.4.22.27 3.4.22.38 3.4.22.1 3.4.22.15 3.4.22.14 Cleavage of lip22 to lip10 Cleavage of lip22 to lip10 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> Reactome DB_ID: 10047378 1 Reactome DB_ID: 10047389 1 MHC II:lip10 nonamer [lysosomal membrane] MHC II:lip10 nonamer Reactome DB_ID: 10047387 1 lip10 trimer [lysosomal membrane] lip10 trimer Reactome DB_ID: 10047385 3 1 EQUAL 117 EQUAL Reactome Database ID Release 81 10047387 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=10047387 Reactome R-CFA-2213183 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-CFA-2213183.1 Reactome DB_ID: 10047370 3 Reactome Database ID Release 81 10047389 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=10047389 Reactome R-CFA-2130723 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-CFA-2130723.1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10047644 Cathepsin [lysosomal lumen] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity CTSS [lysosomal lumen] UniProt F1PAK0 Reactome Database ID Release 81 10047645 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=10047645 Reactome Database ID Release 81 10047647 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=10047647 Reactome R-CFA-2130504 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-CFA-2130504.1 The cleavage of lip22 occurs in residues 115-125, closer to the C-terminus than CLIP (residues 81-105). The resulting lip10 fragment is approximately 100 residues long and extends just through the C-terminus of the Ii CLIP. The proteases responsible for generating lip10 in vivo are not determined. Cysteine proteases like cathepsin S (CatS) are capable of degrading lip22 to lip10 (Bania et al. 2003) but in the presence of LHVS, an inhibitor of CatS, lip22 degradation is still observed, suggesting that other proteases are involved (Villadangos et al. 1997), possibly aspartic proteinases such as cathepsins D and E (Kageyama et al. 1996). The degradation of lip22 may depend on cell type (Bania et al. 2003). The lip22 and lip10 intermediate forms are still maintained as a nonameric complex due to the existence of the last trimerisation domain in the transmembrane region. 11684289 Pubmed 2001 Presentation of antigens by MHC class II molecules: getting the most out of them Villadangos, JA Mol Immunol 38:329-46 12078484 Pubmed 2002 Proteolysis and antigen presentation by MHC class II molecules Bryant, PW Lennon-Duménil, AM Fiebiger, E Lagaudrière-Gesbert, C Ploegh, HL Adv Immunol 80:71-114 12748383 Pubmed 2003 Human cathepsin S, but not cathepsin L, degrades efficiently MHC class II-associated invariant chain in nonprofessional APCs Bania, J Gatti, E Lelouard, H David, A Cappello, F Weber, E Camosseto, V Pierre, P Proc Natl Acad Sci U S A 100:6664-9 8687433 Pubmed 1996 Potential sites for processing of the human invariant chain by cathepsins D and E Kageyama, T Yonezawa, S Ichinose, M Miki, K Moriyama, A Biochem Biophys Res Commun 223:549-53 9254653 Pubmed 1997 Degradation of mouse invariant chain: roles of cathepsins S and D and the influence of major histocompatibility complex polymorphism Villadangos, JA Riese, RJ Peters, C Chapman, HA Ploegh, HL J Exp Med 186:549-60 inferred by electronic annotation IEA GO IEA 3.4.22.41 3.4.22.40 3.4.22.34 3.4.22.8 3.4.22.28 3.4.22.16 3.4.22.27 3.4.22.38 3.4.22.1 3.4.22.15 3.4.22.14 Generation of CLIP from lip10 Generation of CLIP from lip10 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> Reactome DB_ID: 10047389 1 Reactome DB_ID: 10047393 3 MHC II:CLIP [lysosomal membrane] MHC II:CLIP Reactome DB_ID: 10047370 1 Reactome DB_ID: 10047391 1 81 EQUAL 104 EQUAL Reactome Database ID Release 81 10047393 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=10047393 Reactome R-CFA-2130574 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-CFA-2130574.1 PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10047431 Cathepsin [lysosomal lumen] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity CTSD [lysosomal lumen] CTSL3 [lysosomal lumen] CTSL [lysosomal lumen] CTSF [lysosomal lumen] CTSS [lysosomal lumen] UniProt Q4LAL9 UniProt F1PMM9 UniProt Q9GL24 UniProt E2RR02 Reactome Database ID Release 81 10047432 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=10047432 Reactome Database ID Release 81 10047434 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=10047434 Reactome R-CFA-2130349 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-CFA-2130349.1 The lip10 fragments bound in the nonameric complex are processed leaving only the CLIP fragment (81-105) bound to the MHC II peptide binding groove. Three cysteine proteases have been shown to be capable of digesting lip10, each with a different expression pattern among different APC. Cathepsin (Cat) S digests Ii in B cells and dendritic cells, thymic epithelial cells use Cat L and Cat L, while Cat S and F are active in macrophages (Villadangos, 2001; Bryant et al, 2002). Cat S appears to be the major enzyme involved as demonstrated by the use of specific inhibitors and of knockout experiments (Stumptner-Cuvelette et al. 2002). Following lip10 digestion, the MHC-like molecule HLA-DM induces the exchange of CLIP fragment for a highly diverse array of antigens (Denzin & Cresswell. 1995). 10748235 Pubmed 2000 Role for cathepsin F in invariant chain processing and major histocompatibility complex class II peptide loading by macrophages Shi, GP Bryant, RA Riese, R Verhelst, S Driessen, C Li, Z Bromme, D Ploegh, HL Chapman, HA J Exp Med 191:1177-86 11853874 Pubmed 2002 Multiple roles of the invariant chain in MHC class II function Stumptner-Cuvelette, P Benaroch, P Biochim Biophys Acta 1542:1-13 7606781 Pubmed 1995 HLA-DM induces CLIP dissociation from MHC class II alpha beta dimers and facilitates peptide loading Denzin, LK Cresswell, P Cell 82:155-65 10072072 Pubmed 1999 Cathepsin S required for normal MHC class II peptide loading and germinal center development Shi, GP Villadangos, JA Dranoff, G Small, C Gu, L Haley, KJ Riese, R Ploegh, HL Chapman, HA Immunity 10:197-206 9545226 Pubmed 1998 Cathepsin L: critical role in Ii degradation and CD4 T cell selection in the thymus Nakagawa, T Roth, W Wong, P Nelson, A Farr, A Deussing, J Villadangos, JA Ploegh, H Peters, C Rudensky, AY Science 280:450-3 inferred by electronic annotation IEA GO IEA 1.8 Reduction of disulphide bonds in MHC II antigens Reduction of disulphide bonds in MHC II antigens 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> Reactome DB_ID: 2213221 1 Antigen [lysosomal lumen] Antigen Reactome DB_ID: 2213225 1 unfolded antigen [lysosomal lumen] unfolded antigen PHYSIOL-LEFT-TO-RIGHT ACTIVATION Reactome DB_ID: 10048890 UniProt:F1PK63 IFI30 UniProt F1PK63 58 EQUAL 232 EQUAL GO 0016667 GO molecular function Reactome Database ID Release 81 10048891 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=10048891 Reactome Database ID Release 81 10048893 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=10048893 Reactome R-CFA-2213240 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-CFA-2213240.1 MHC class II epitopes require protein denaturation and removal of intra- and inter-chain disulphide bonds prior to proteolysis. The lysosomal thiol reductase gamma-IFN-inducible lysosomal thiol reductase (GILT) has been shown to facilitate MHC class II-restricted antigen (Ag) processing by breaking disulphide bonds. GILT is constitutively expressed in APCs. The reduction of disulphide bonds by mature GILT is optimal at acidic pH (Hastings et al. 2006, Arunachalam et al. 2000). 10639150 Pubmed 2000 Enzymatic reduction of disulfide bonds in lysosomes: characterization of a gamma-interferon-inducible lysosomal thiol reductase (GILT) Arunachalam, B Phan, UT Geuze, HJ Cresswell, P Proc Natl Acad Sci U S A 97:745-50 17142755 Pubmed 2006 Functional requirements for the lysosomal thiol reductase GILT in MHC class II-restricted antigen processing Hastings, KT Lackman, RL Cresswell, P J Immunol 177:8569-77 inferred by electronic annotation IEA GO IEA 3.4.22.41 3.4.22.40 3.4.22.34 3.4.22.8 3.4.22.28 3.4.22.16 3.4.22.27 3.4.22.38 3.4.22.1 3.4.22.15 3.4.22.14 MHC class II antigen processing MHC class II antigen processing 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> Reactome DB_ID: 2213225 1 Reactome DB_ID: 2213226 3 MHC class II epitopes [lysosomal lumen] MHC class II epitopes PHYSIOL-LEFT-TO-RIGHT ACTIVATION Converted from EntitySet in Reactome Reactome DB_ID: 10047431 Reactome Database ID Release 81 10047694 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=10047694 Reactome R-CFA-2130706 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-CFA-2130706.1 Antigen processing and loading on to MHC class II molecules occurs in late endocytic/lysosomal vesicles, where epitopes which require extensive proteolytic processing are generated (Bryant & Ploegh 2003). These late endosome/lysosomal-like compartments are enriched in MHC II and are referred to as MIICs (MHC class II compartments) (Peters et al. 1991). A variety of lysosomal proteases like cathepsins S, D, B etc. and Asparaginyl endopeptidase (AEP) are suggested to be involved in the processing of antigens to generate CD4+ T cell epitopes (Deusing et al. 1998, Shi et al. 1999, Pluger et al. 2002, Watts et al. 2005). An initial cleavage by endopeptidases (AEP) would be necessary to unlock the antigen and allow further trimming of the ends by exopeptidases (Cathepsins). In the acidic environment of the lysosome, cathepsins are generally activated by autocatalytic cleavage of a propeptide which otherwise blocks the active site. 16181339 Pubmed 2005 Asparaginyl endopeptidase: case history of a class II MHC compartment protease Watts, C Matthews, SP Mazzeo, D Manoury, B Moss, CX Immunol Rev 207:218-28 11813165 Pubmed 2002 Specific role for cathepsin S in the generation of antigenic peptides in vivo Plüger, EB Boes, M Alfonso, C Schröter, CJ Kalbacher, H Ploegh, HL Driessen, C Eur J Immunol 32:467-76 14734116 Pubmed 2004 Class II MHC peptide loading by the professionals Bryant, P Ploegh, H Curr Opin Immunol 16:96-102 10809954 Pubmed 2000 Lysosomal cathepsin B plays an important role in antigen processing, while cathepsin D is involved in degradation of the invariant chain inovalbumin-immunized mice Zhang, T Maekawa, Y Hanba, J Dainichi, T Nashed, BF Hisaeda, H Sakai, T Asao, T Himeno, K Good, RA Katunuma, Nobuhiko Immunology 100:13-20 1847504 Pubmed 1991 Segregation of MHC class II molecules from MHC class I molecules in the Golgi complex for transport to lysosomal compartments Peters, PJ Neefjes, JJ Oorschot, V Ploegh, HL Geuze, HJ Nature 349:669-76 12742663 Pubmed 2003 Antigen processing and presentation in human muscle: cathepsin S is critical for MHC class II expression and upregulated in inflammatory myopathies Wiendl, H Lautwein, A Mitsdörffer, M Krause, S Erfurth, S Wienhold, W Morgalla, M Weber, E Overkleeft, HS Lochmüller, H Melms, A Tolosa, E Driessen, C J Neuroimmunol 138:132-43 9539769 Pubmed 1998 Cathepsins B and D are dispensable for major histocompatibility complex class II-mediated antigen presentation Deussing, J Roth, W Saftig, P Peters, C Ploegh, HL Villadangos, JA Proc Natl Acad Sci U S A 95:4516-21 inferred by electronic annotation IEA GO IEA Transport of antigen loaded MHC II molecules to surface Transport of antigen loaded MHC II molecules to surface 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> Reactome DB_ID: 10048901 1 peptide loaded MHC class II [lysosomal membrane] peptide loaded MHC class II Reactome DB_ID: 2213226 1 Reactome DB_ID: 10047370 1 Reactome Database ID Release 81 10048901 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=10048901 Reactome R-CFA-2213223 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-CFA-2213223.1 Reactome DB_ID: 10048975 1 Dynein:Dynactin:microtubule [cytosol] Dynein:Dynactin:microtubule Reactome DB_ID: 10027577 1 Microtubule [cytosol] Microtubule Reactome DB_ID: 10027575 13 Microtubule protofilament [cytosol] Microtubule protofilament Reactome Database ID Release 81 10027577 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=10027577 Reactome R-CFA-190599 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-CFA-190599.1 Reactome DB_ID: 10005955 1 Dynein complex [cytosol] Dynein complex Reactome DB_ID: 10005927 1 DHC dimer [cytosol] DHC dimer Reactome DB_ID: 10005925 2 UniProt:F1PGY9 DYNC1H1 UniProt F1PGY9 1 EQUAL 4646 EQUAL Reactome Database ID Release 81 10005927 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=10005927 Reactome R-CFA-2029144 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-CFA-2029144.1 Converted from EntitySet in Reactome Reactome DB_ID: 10005937 2 DICs [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity DYNC1I1 [cytosol] DYNC1I2 [cytosol] UniProt F1PSE8 UniProt A0A5F4CZW1 Converted from EntitySet in Reactome Reactome DB_ID: 10005953 2 DLIs [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity DYNC1LI1 [cytosol] DYNC1LI2 [cytosol] UniProt A0A5F4D394 UniProt F1P6V8 Converted from EntitySet in Reactome Reactome DB_ID: 10005943 2 DLCs [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity DYNLL2 [cytosol] DYNLL1 [cytosol] UniProt E2RFR5 UniProt A0A5F4CQ75 Reactome Database ID Release 81 10005955 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=10005955 Reactome R-CFA-2029145 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-CFA-2029145.1 Reactome DB_ID: 10048973 1 Dynactin [cytosol] Dynactin Reactome DB_ID: 10048971 1 Dynactin arm [cytosol] Dynactin arm Reactome DB_ID: 10048969 1 Dynactin shoulder [cytosol] Dynactin shoulder Reactome DB_ID: 10048965 1 DCTN3 dimer [cytosol] DCTN3 dimer Reactome DB_ID: 10021928 2 UniProt:E2RBC1 DCTN3 UniProt E2RBC1 1 EQUAL 186 EQUAL Reactome Database ID Release 81 10048965 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=10048965 Reactome R-CFA-8982337 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-CFA-8982337.1 Reactome DB_ID: 10048967 1 Dynamitin tetramer [cytosol] Dynamitin tetramer Reactome DB_ID: 10021936 4 UniProt:A0A5F4C6E4 DCTN2 UniProt A0A5F4C6E4 2 EQUAL 401 EQUAL Reactome Database ID Release 81 10048967 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=10048967 Reactome R-CFA-8982328 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-CFA-8982328.1 Reactome Database ID Release 81 10048969 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=10048969 Reactome R-CFA-8982344 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-CFA-8982344.1 Reactome DB_ID: 10048963 1 DCTN1 dimer [cytosol] DCTN1 dimer Reactome DB_ID: 10021912 2 UniProt:F6UMF1 DCTN1 UniProt F6UMF1 1 EQUAL 1278 EQUAL Reactome Database ID Release 81 10048963 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=10048963 Reactome R-CFA-8982336 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-CFA-8982336.1 Reactome Database ID Release 81 10048971 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=10048971 Reactome R-CFA-8982311 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-CFA-8982311.1 Reactome DB_ID: 10048961 1 Dynactin rod [cytosol] Dynactin rod Reactome DB_ID: 10048927 1 Arp1 octameric polymer [cytosol] Arp1 octameric polymer Reactome DB_ID: 10021932 8 UniProt:P61162 ACTR1A UniProt P61162 1 EQUAL 376 EQUAL Reactome Database ID Release 81 10048927 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=10048927 Reactome R-CFA-8982309 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-CFA-8982309.1 Reactome DB_ID: 10048959 1 ACTR10:DCTN4:DCTN5:DCTN6 [cytosol] ACTR10:DCTN4:DCTN5:DCTN6 Reactome DB_ID: 10048943 1 UniProt:E2RLP1 ACTR10 UniProt E2RLP1 1 EQUAL 417 EQUAL Reactome DB_ID: 10048957 1 Pointed end complex [cytosol] Pointed end complex Reactome DB_ID: 10048955 1 UniProt:F1PXZ8 DCTN6 UniProt F1PXZ8 1 EQUAL 190 EQUAL Reactome DB_ID: 10048947 1 UniProt:E2RG82 DCTN4 UniProt E2RG82 2 EQUAL 460 EQUAL Reactome DB_ID: 10048951 1 UniProt:E2RNC1 DCTN5 UniProt E2RNC1 1 EQUAL 182 EQUAL Reactome Database ID Release 81 10048957 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=10048957 Reactome R-CFA-8982345 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-CFA-8982345.1 Reactome Database ID Release 81 10048959 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=10048959 Reactome R-CFA-8982321 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-CFA-8982321.1 Converted from EntitySet in Reactome Reactome DB_ID: 10048939 1 CAPZ [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Reactome Database ID Release 81 10048961 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=10048961 Reactome R-CFA-8982312 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-CFA-8982312.1 Reactome Database ID Release 81 10048973 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=10048973 Reactome R-CFA-2029120 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-CFA-2029120.1 Reactome Database ID Release 81 10048975 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=10048975 Reactome R-CFA-2029135 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-CFA-2029135.1 Reactome DB_ID: 10023571 1 UniProt:E2RSI4 SPTBN2 UniProt E2RSI4 2 EQUAL 2390 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 10048985 1 ARP-1 [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity ACTR1B [cytosol] ACTR1A [cytosol] UniProt A0A5F4BXQ1 Reactome DB_ID: 10048925 1 RAB7:RILP:ORP1L complex [lysosomal membrane] RAB7:RILP:ORP1L complex Reactome DB_ID: 10048919 2 RAB7A:GTP [lysosomal membrane] RAB7A:GTP Reactome DB_ID: 2213216 1 GTP [ChEBI:15996] GTP Guanosine 5'-triphosphate ChEBI 15996 Converted from EntitySet in Reactome Reactome DB_ID: 10048917 1 Homologues of RAB7A [lysosomal membrane] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity RAB7A [lysosomal membrane] RAB7A [lysosomal membrane] UniProt A0A5F4BPT0 UniProt P18067 Reactome Database ID Release 81 10048919 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=10048919 Reactome R-CFA-2213222 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-CFA-2213222.1 Reactome DB_ID: 10048907 1 RILP dimer [lysosomal membrane] RILP dimer Reactome DB_ID: 10048905 2 UniProt:E2R525 RILP UniProt E2R525 1 EQUAL 401 EQUAL Reactome Database ID Release 81 10048907 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=10048907 Reactome R-CFA-2213233 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-CFA-2213233.1 Reactome DB_ID: 10048923 2 UniProt:E2RMD4 OSBPL1A UniProt E2RMD4 1 EQUAL 950 EQUAL Reactome Database ID Release 81 10048925 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=10048925 Reactome R-CFA-2213215 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-CFA-2213215.1 Reactome DB_ID: 10048979 1 Kinesins:Dynactin:microtubule [cytosol] Kinesins:Dynactin:microtubule Reactome DB_ID: 10027577 1 Reactome DB_ID: 10048973 1 Converted from EntitySet in Reactome Reactome DB_ID: 10048977 1 Kinesins [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity KIF26A [cytosol] UniProt F1PU35 Reactome Database ID Release 81 10048979 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=10048979 Reactome R-CFA-2213219 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-CFA-2213219.1 Reactome DB_ID: 113592 1 ATP(4-) [ChEBI:30616] ATP(4-) Adenosine 5'-triphosphate atp ATP ChEBI 30616 Reactome DB_ID: 10048987 1 peptide loaded MHC class II [plasma membrane] peptide loaded MHC class II Reactome DB_ID: 10015161 1 Reactome DB_ID: 2213228 1 MHC class II epitopes [plasma membrane] MHC class II epitopes Reactome Database ID Release 81 10048987 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=10048987 Reactome R-CFA-2213232 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-CFA-2213232.1 Reactome DB_ID: 10048975 1 Reactome DB_ID: 10023571 1 2 EQUAL 2390 EQUAL Reactome DB_ID: 29370 1 ADP(3-) [ChEBI:456216] ADP(3-) ADP trianion 5&apos;-O-[(phosphonatooxy)phosphinato]adenosine ADP ChEBI 456216 Converted from EntitySet in Reactome Reactome DB_ID: 10048985 1 Reactome DB_ID: 10048925 1 Reactome DB_ID: 10048979 1 Reactome Database ID Release 81 10048989 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=10048989 Reactome R-CFA-2213248 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-CFA-2213248.1 Once MHC class II-peptide complexes are formed, they must be transported back to the cell surface. It is unclear how this occurs. LEs/lysosomes with peptide loaded MHC II molecules may move in a bidirectional manner in a stop-and-go fashion along microtubules to the plasma membrane, driven by the activities of the oppositely-directed motor proteins dynein and kinesin (Wubbolts et al. 1996, 1999, Chow et al. 2002, Rocha & Neefjes 2007). Ultimately, LEs/lysosomes fuse to the plasma membrane delivering the MHC II-peptide complexes to the surface (Raposo et al. 1996, Rocha & Neefjes 2007). RAB7-GTP present on LEs/lysosome membrane interacts with Rab7-interacting lysosomal protein (RILP) and oxysterol-binding protein-related protein 1L (ORP1L) to form a tripartite RILP-Rab7-ORP1L complex. RILP binds to the p150 dynactin subunit to recruit the dynein or kinesin motor proteins. ORP1L recruits this complex to betaIII spectrin domains, which appears to be critical for dynein motor activation and transport of LEs/lysosome vesicles to the cell periphery (Johansson et al. 2007, Rocha & Neefjes 2008). 8642258 Pubmed 1996 B lymphocytes secrete antigen-presenting vesicles Raposo, G Nijman, HW Stoorvogel, W Liejendekker, R Harding, CV Melief, CJ Geuze, HJ J Exp Med 183:1161-72 12198549 Pubmed 2002 Dendritic cell maturation triggers retrograde MHC class II transport from lysosomes to the plasma membrane Chow, A Toomre, D Garrett, W Mellman, I Nature 418:988-94 17283181 Pubmed 2007 Activation of endosomal dynein motors by stepwise assembly of Rab7-RILP-p150Glued, ORP1L, and the receptor betalll spectrin Johansson, M Rocha, N Zwart, W Jordens, I Janssen, L Kuijl, C Olkkonen, VM Neefjes, J J Cell Biol 176:459-71 19564404 Pubmed 2009 Cholesterol sensor ORP1L contacts the ER protein VAP to control Rab7-RILP-p150 Glued and late endosome positioning Rocha, Nuno Kuijl, Coenraad van der Kant, Rik Janssen, Lennert Houben, Diane Janssen, Hans Zwart, Wilbert Neefjes, Jacques J. Cell Biol. 185:1209-25 18046453 Pubmed 2008 MHC class II molecules on the move for successful antigen presentation Rocha, N Neefjes, J EMBO J 27:1-5 8909537 Pubmed 1996 Direct vesicular transport of MHC class II molecules from lysosomal structures to the cell surface Wubbolts, R Fernandez-Borja, M Oomen, L Verwoerd, D Janssen, H Calafat, J Tulp, A Dusseljee, S Neefjes, J J Cell Biol 135:611-22 10036229 Pubmed 1999 Opposing motor activities of dynein and kinesin determine retention and transport of MHC class II-containing compartments Wubbolts, R Fernandez-Borja, M Jordens, I Reits, E Dusseljee, S Echeverri, C Vallee, RB Neefjes, J J Cell Sci 112:785-95 inferred by electronic annotation IEA GO IEA Reactome Database ID Release 81 10095767 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=10095767 Reactome R-CFA-2132295 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-CFA-2132295.1 GO 0019886 GO biological process Antigen presenting cells (APCs) such as B cells, dendritic cells (DCs) and monocytes/macrophages express major histocompatibility complex class II molecules (MHC II) at their surface and present exogenous antigenic peptides to CD4+ T helper cells. CD4+ T cells play a central role in immune protection. On their activation they stimulate differentiation of B cells into antibody-producing B-cell blasts and initiate adaptive immune responses. MHC class II molecules are transmembrane glycoprotein heterodimers of alpha and beta subunits. Newly synthesized MHC II molecules present in the endoplasmic reticulum bind to a chaperone protein called invariant (Ii) chain. The binding of Ii prevents the premature binding of self antigens to the nascent MHC molecules in the ER and also guides MHC molecules to endocytic compartments. In the acidic endosomal environment, Ii is degraded in a stepwise manner, ultimately to free the class II peptide-binding groove for loading of antigenic peptides. Exogenous antigens are internalized by the APC by receptor mediated endocytosis, phagocytosis or pinocytosis into endocytic compartments of MHC class II positive cells, where engulfed antigens are degraded in a low pH environment by multiple acidic proteases, generating MHC class II epitopes. Antigenic peptides are then loaded into the class II ligand-binding groove. The resulting class II peptide complexes then move to the cell surface, where they are scanned by CD4+ T cells for specific recognition (Berger & Roche 2009, Zhou & Blum 2004, Watts 2004, Landsverk et al. 2009). 9316394 Pubmed 1997 Peptide binding and antigen presentation by class II histocompatibility glycoproteins Jensen, PE Biopolymers 43:303-22 19217269 Pubmed 2009 MHC molecules and microbial antigen processing in phagosomes Ramachandra, L Simmons, D Harding, CV Curr Opin Immunol 21:98-104 15531770 Pubmed 2004 Presentation of cytosolic antigens via MHC class II molecules Zhou, D Blum, JS Immunol Res 30:279-90 19092054 Pubmed 2009 MHC class II transport at a glance Berger, AC Roche, PA J Cell Sci 122:1-4 15224094 Pubmed 2004 The exogenous pathway for antigen presentation on major histocompatibility complex class II and CD1 molecules Watts, C Nat Immunol 5:685-92 inferred by electronic annotation IEA GO IEA