BioPAX pathway converted from "Fcgamma receptor (FCGR) dependent phagocytosis" in the Reactome database. Fcgamma receptor (FCGR) dependent phagocytosis 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> FCGR activation This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> LEFT-TO-RIGHT Cross-linking of FCGRIA with IgG-coated Ag 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> Antigen:IgG Reactome DB_ID: 9763688 plasma membrane GENE ONTOLOGY GO:0005886 Antigen Reactome DB_ID: 173548 Reactome Database ID Release 78 173548 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=173548 Reactome R-ALL-173548 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-173548.2 Reactome http://www.reactome.org ChEBI 36080 additional information MI MI:0361 1 IgG Reactome DB_ID: 9763686 extracellular region GENE ONTOLOGY GO:0005576 IgG Heavy Chain Reactome DB_ID: 9763684 Converted from EntitySet in Reactome IgG C region Ig gamma C region Reactome DB_ID: 9763682 Converted from EntitySet in Reactome Homologues of IGHG1 Reactome DB_ID: 9763658 Ighg3 IGHG1 A0A1Y7VJN6 Reactome DB_ID: 9763645 UniProt:A0A1Y7VJN6 Ighg3 Mus musculus NCBI Taxonomy 10090 UniProt A0A1Y7VJN6 1 EQUAL 330 EQUAL Reactome Database ID Release 78 9763645 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=9763645 Reactome R-MMU-1478805 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1478805.1 IGHG1 Ighg2c F6TQW2 Reactome DB_ID: 9763649 UniProt:F6TQW2 Ighg2c UniProt F6TQW2 1 EQUAL 330 EQUAL Reactome Database ID Release 78 9763649 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=9763649 Reactome R-MMU-1478805-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1478805-2.1 Igh-3 IGHG1 P01867 Reactome DB_ID: 9763652 UniProt:P01867 Igh-3 Igh-3 PTM O-linked glycan consists of Gal-GalNAc disaccharide which is modified with 2 sialic acid residues. UniProt P01867 1 EQUAL 330 EQUAL Reactome Database ID Release 78 9763652 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=9763652 Reactome R-MMU-1478805-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1478805-3.1 Ighg1 IGHG1 P01869 Reactome DB_ID: 9763656 UniProt:P01869 Ighg1 UniProt P01869 1 EQUAL 330 EQUAL Reactome Database ID Release 78 9763656 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=9763656 Reactome R-MMU-1478805-4 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1478805-4.1 Reactome Database ID Release 78 9763658 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=9763658 Reactome R-MMU-1478805-5 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1478805-5.1 Converted from EntitySet in Reactome Homologues of IGHG2 Reactome DB_ID: 9763668 Ighg3 IGHG2 A0A1Y7VJN6 Reactome DB_ID: 9763660 1 EQUAL 326 EQUAL Reactome Database ID Release 78 9763660 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=9763660 Reactome R-MMU-1478808 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1478808.1 IGHG2 Ighg2c F6TQW2 Reactome DB_ID: 9763662 1 EQUAL 326 EQUAL Reactome Database ID Release 78 9763662 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=9763662 Reactome R-MMU-1478808-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1478808-2.1 Igh-3 IGHG2 P01867 Reactome DB_ID: 9763664 1 EQUAL 326 EQUAL Reactome Database ID Release 78 9763664 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=9763664 Reactome R-MMU-1478808-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1478808-3.1 Ighg1 IGHG2 P01869 Reactome DB_ID: 9763666 1 EQUAL 326 EQUAL Reactome Database ID Release 78 9763666 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=9763666 Reactome R-MMU-1478808-4 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1478808-4.1 Reactome Database ID Release 78 9763668 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=9763668 Reactome R-MMU-1478808-5 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1478808-5.1 Ighg3 IGHG3 A0A1Y7VJN6 Reactome DB_ID: 9763670 1 EQUAL 377 EQUAL Reactome Database ID Release 78 9763670 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=9763670 Reactome R-MMU-1478810 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1478810.1 Converted from EntitySet in Reactome Homologues of IGHG4 Reactome DB_ID: 9763680 Ighg3 IGHG4 A0A1Y7VJN6 Reactome DB_ID: 9763672 1 EQUAL 327 EQUAL Reactome Database ID Release 78 9763672 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=9763672 Reactome R-MMU-1478807 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1478807.1 IGHG4 Ighg2c F6TQW2 Reactome DB_ID: 9763674 1 EQUAL 327 EQUAL Reactome Database ID Release 78 9763674 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=9763674 Reactome R-MMU-1478807-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1478807-2.1 Igh-3 IGHG4 P01867 Reactome DB_ID: 9763676 1 EQUAL 327 EQUAL Reactome Database ID Release 78 9763676 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=9763676 Reactome R-MMU-1478807-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1478807-3.1 Ighg1 IGHG4 P01869 Reactome DB_ID: 9763678 1 EQUAL 327 EQUAL Reactome Database ID Release 78 9763678 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=9763678 Reactome R-MMU-1478807-4 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1478807-4.1 Reactome Database ID Release 78 9763680 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=9763680 Reactome R-MMU-1478807-5 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1478807-5.1 Reactome Database ID Release 78 9763682 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=9763682 Reactome R-MMU-1584646 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1584646.1 1 Converted from EntitySet in Reactome Ig Heavy Chain V Region Reactome DB_ID: 9763641 Ighv5-12 IgH heavy chain V-III region VH26 precursor A0A075B5Q4 Reactome DB_ID: 9763281 UniProt:A0A075B5Q4 Ighv5-12 UniProt A0A075B5Q4 20 EQUAL 117 EQUAL Reactome Database ID Release 78 9763281 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=9763281 Reactome R-MMU-197044 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-197044.1 Converted from EntitySet in Reactome Homologues of Ig heavy chain V-I region EU Reactome DB_ID: 9763502 Ighv14-1 A0A075B5R4 Reactome DB_ID: 9763285 UniProt:A0A075B5R4 Ighv14-1 UniProt A0A075B5R4 Reactome Database ID Release 78 9763285 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=9763285 Reactome R-MMU-983534 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534.1 Ighv14-2 A0A075B5R7 Reactome DB_ID: 9763289 UniProt:A0A075B5R7 Ighv14-2 UniProt A0A075B5R7 Reactome Database ID Release 78 9763289 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=9763289 Reactome R-MMU-983534-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-2.1 Ighv14-3 A0A075B5R9 Reactome DB_ID: 9763293 UniProt:A0A075B5R9 Ighv14-3 UniProt A0A075B5R9 Reactome Database ID Release 78 9763293 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=9763293 Reactome R-MMU-983534-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-3.1 Ighv14-4 A0A075B5S3 Reactome DB_ID: 9763297 UniProt:A0A075B5S3 Ighv14-4 UniProt A0A075B5S3 Reactome Database ID Release 78 9763297 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=9763297 Reactome R-MMU-983534-4 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-4.1 Ighv1-4 A0A075B5T4 Reactome DB_ID: 9763299 UniProt:A0A075B5T4 Ighv1-4 UniProt A0A075B5T4 Reactome Database ID Release 78 9763299 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=9763299 Reactome R-MMU-983534-5 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-5.1 Ighv1-5 A0A075B5T5 Reactome DB_ID: 9763303 UniProt:A0A075B5T5 Ighv1-5 UniProt A0A075B5T5 Reactome Database ID Release 78 9763303 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=9763303 Reactome R-MMU-983534-6 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-6.1 Ighv1-7 A0A075B5T7 Reactome DB_ID: 9763307 UniProt:A0A075B5T7 Ighv1-7 UniProt A0A075B5T7 Reactome Database ID Release 78 9763307 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=9763307 Reactome R-MMU-983534-7 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-7.1 Ighv15-2 A0A075B5T8 Reactome DB_ID: 9763311 UniProt:A0A075B5T8 Ighv15-2 UniProt A0A075B5T8 Reactome Database ID Release 78 9763311 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=9763311 Reactome R-MMU-983534-8 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-8.1 Ighv1-9 A0A075B5T9 Reactome DB_ID: 9763315 UniProt:A0A075B5T9 Ighv1-9 UniProt A0A075B5T9 Reactome Database ID Release 78 9763315 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=9763315 Reactome R-MMU-983534-9 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-9.1 Ighv1-12 A0A075B5U0 Reactome DB_ID: 9763319 UniProt:A0A075B5U0 Ighv1-12 UniProt A0A075B5U0 Reactome Database ID Release 78 9763319 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=9763319 Reactome R-MMU-983534-10 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-10.1 Ighv1-16 A0A075B5U1 Reactome DB_ID: 9763323 UniProt:A0A075B5U1 Ighv1-16 UniProt A0A075B5U1 Reactome Database ID Release 78 9763323 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=9763323 Reactome R-MMU-983534-11 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-11.1 Ighv1-18 A0A075B5U4 Reactome DB_ID: 9763327 UniProt:A0A075B5U4 Ighv1-18 UniProt A0A075B5U4 Reactome Database ID Release 78 9763327 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=9763327 Reactome R-MMU-983534-12 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-12.1 Ighv1-19 A0A075B5U5 Reactome DB_ID: 9763331 UniProt:A0A075B5U5 Ighv1-19 UniProt A0A075B5U5 Reactome Database ID Release 78 9763331 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=9763331 Reactome R-MMU-983534-13 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-13.1 Ighv1-20 A0A075B5U6 Reactome DB_ID: 9763335 UniProt:A0A075B5U6 Ighv1-20 UniProt A0A075B5U6 Reactome Database ID Release 78 9763335 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=9763335 Reactome R-MMU-983534-14 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-14.1 Ighv1-22 A0A075B5U7 Reactome DB_ID: 9763339 UniProt:A0A075B5U7 Ighv1-22 UniProt A0A075B5U7 Reactome Database ID Release 78 9763339 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=9763339 Reactome R-MMU-983534-15 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-15.1 Ighv1-24 A0A075B5U9 Reactome DB_ID: 9763343 UniProt:A0A075B5U9 Ighv1-24 UniProt A0A075B5U9 Reactome Database ID Release 78 9763343 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=9763343 Reactome R-MMU-983534-16 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-16.1 Ighv1-26 A0A075B5V0 Reactome DB_ID: 9763347 UniProt:A0A075B5V0 Ighv1-26 UniProt A0A075B5V0 Reactome Database ID Release 78 9763347 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=9763347 Reactome R-MMU-983534-17 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-17.1 Ighv1-31 A0A075B5V1 Reactome DB_ID: 9763351 UniProt:A0A075B5V1 Ighv1-31 UniProt A0A075B5V1 Reactome Database ID Release 78 9763351 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=9763351 Reactome R-MMU-983534-18 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-18.1 Ighv1-34 A0A075B5V2 Reactome DB_ID: 9763355 UniProt:A0A075B5V2 Ighv1-34 UniProt A0A075B5V2 Reactome Database ID Release 78 9763355 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=9763355 Reactome R-MMU-983534-19 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-19.1 Ighv1-36 A0A075B5V3 Reactome DB_ID: 9763359 UniProt:A0A075B5V3 Ighv1-36 UniProt A0A075B5V3 Reactome Database ID Release 78 9763359 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=9763359 Reactome R-MMU-983534-20 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-20.1 Ighv1-37 A0A075B5V4 Reactome DB_ID: 9763363 UniProt:A0A075B5V4 Ighv1-37 UniProt A0A075B5V4 Reactome Database ID Release 78 9763363 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=9763363 Reactome R-MMU-983534-21 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-21.1 Ighv1-39 A0A075B5V5 Reactome DB_ID: 9763367 UniProt:A0A075B5V5 Ighv1-39 UniProt A0A075B5V5 Reactome Database ID Release 78 9763367 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=9763367 Reactome R-MMU-983534-22 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-22.1 Ighv1-42 A0A075B5V6 Reactome DB_ID: 9763371 UniProt:A0A075B5V6 Ighv1-42 UniProt A0A075B5V6 Reactome Database ID Release 78 9763371 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=9763371 Reactome R-MMU-983534-23 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-23.1 Ighv1-43 A0A075B5V7 Reactome DB_ID: 9763375 UniProt:A0A075B5V7 Ighv1-43 UniProt A0A075B5V7 Reactome Database ID Release 78 9763375 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=9763375 Reactome R-MMU-983534-24 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-24.1 Ighv1-47 A0A075B5V8 Reactome DB_ID: 9763379 UniProt:A0A075B5V8 Ighv1-47 UniProt A0A075B5V8 Reactome Database ID Release 78 9763379 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=9763379 Reactome R-MMU-983534-25 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-25.1 Ighv1-49 A0A075B5V9 Reactome DB_ID: 9763383 UniProt:A0A075B5V9 Ighv1-49 UniProt A0A075B5V9 Reactome Database ID Release 78 9763383 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=9763383 Reactome R-MMU-983534-26 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-26.1 Ighv1-50 A0A075B5W1 Reactome DB_ID: 9763387 UniProt:A0A075B5W1 Ighv1-50 UniProt A0A075B5W1 Reactome Database ID Release 78 9763387 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=9763387 Reactome R-MMU-983534-27 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-27.1 Ighv1-52 A0A075B5W2 Reactome DB_ID: 9763391 UniProt:A0A075B5W2 Ighv1-52 UniProt A0A075B5W2 Reactome Database ID Release 78 9763391 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=9763391 Reactome R-MMU-983534-28 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-28.1 Ighv1-53 A0A075B5W3 Reactome DB_ID: 9763395 UniProt:A0A075B5W3 Ighv1-53 UniProt A0A075B5W3 Reactome Database ID Release 78 9763395 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=9763395 Reactome R-MMU-983534-29 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-29.1 Ighv1-54 A0A075B5W5 Reactome DB_ID: 9763399 UniProt:A0A075B5W5 Ighv1-54 UniProt A0A075B5W5 Reactome Database ID Release 78 9763399 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=9763399 Reactome R-MMU-983534-30 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-30.1 Ighv1-55 A0A075B5W6 Reactome DB_ID: 9763403 UniProt:A0A075B5W6 Ighv1-55 UniProt A0A075B5W6 Reactome Database ID Release 78 9763403 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=9763403 Reactome R-MMU-983534-31 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-31.1 Ighv1-56 A0A075B5W7 Reactome DB_ID: 9763407 UniProt:A0A075B5W7 Ighv1-56 UniProt A0A075B5W7 Reactome Database ID Release 78 9763407 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=9763407 Reactome R-MMU-983534-32 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-32.1 Ighv1-58 A0A075B5W9 Reactome DB_ID: 9763411 UniProt:A0A075B5W9 Ighv1-58 UniProt A0A075B5W9 Reactome Database ID Release 78 9763411 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=9763411 Reactome R-MMU-983534-33 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-33.1 Ighv1-59 A0A075B5X0 Reactome DB_ID: 9763415 UniProt:A0A075B5X0 Ighv1-59 UniProt A0A075B5X0 Reactome Database ID Release 78 9763415 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=9763415 Reactome R-MMU-983534-34 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-34.1 Ighv1-63 A0A075B5X2 Reactome DB_ID: 9763419 UniProt:A0A075B5X2 Ighv1-63 UniProt A0A075B5X2 Reactome Database ID Release 78 9763419 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=9763419 Reactome R-MMU-983534-35 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-35.1 Ighv1-64 A0A075B5X3 Reactome DB_ID: 9763423 UniProt:A0A075B5X3 Ighv1-64 UniProt A0A075B5X3 Reactome Database ID Release 78 9763423 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=9763423 Reactome R-MMU-983534-36 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-36.1 Ighv1-66 A0A075B5X5 Reactome DB_ID: 9763427 UniProt:A0A075B5X5 Ighv1-66 UniProt A0A075B5X5 Reactome Database ID Release 78 9763427 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=9763427 Reactome R-MMU-983534-37 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-37.1 Ighv1-67 A0A075B5X6 Reactome DB_ID: 9763431 UniProt:A0A075B5X6 Ighv1-67 UniProt A0A075B5X6 Reactome Database ID Release 78 9763431 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=9763431 Reactome R-MMU-983534-38 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-38.1 Ighv1-69 A0A075B5X7 Reactome DB_ID: 9763435 UniProt:A0A075B5X7 Ighv1-69 UniProt A0A075B5X7 Reactome Database ID Release 78 9763435 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=9763435 Reactome R-MMU-983534-39 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-39.1 Ighv1-74 A0A075B5Y1 Reactome DB_ID: 9763439 UniProt:A0A075B5Y1 Ighv1-74 UniProt A0A075B5Y1 Reactome Database ID Release 78 9763439 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=9763439 Reactome R-MMU-983534-40 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-40.1 Ighv1-75 A0A075B5Y2 Reactome DB_ID: 9763443 UniProt:A0A075B5Y2 Ighv1-75 UniProt A0A075B5Y2 Reactome Database ID Release 78 9763443 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=9763443 Reactome R-MMU-983534-41 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-41.1 Ighv1-80 A0A075B5Y3 Reactome DB_ID: 9763445 UniProt:A0A075B5Y3 Ighv1-80 UniProt A0A075B5Y3 Reactome Database ID Release 78 9763445 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=9763445 Reactome R-MMU-983534-42 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-42.1 Ighv1-81 A0A075B5Y4 Reactome DB_ID: 9763449 UniProt:A0A075B5Y4 Ighv1-81 UniProt A0A075B5Y4 Reactome Database ID Release 78 9763449 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=9763449 Reactome R-MMU-983534-43 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-43.1 Ighv1-85 A0A075B5Y6 Reactome DB_ID: 9763453 UniProt:A0A075B5Y6 Ighv1-85 UniProt A0A075B5Y6 Reactome Database ID Release 78 9763453 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=9763453 Reactome R-MMU-983534-44 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-44.1 Ighv1-78 A0A075B674 Reactome DB_ID: 9763457 UniProt:A0A075B674 Ighv1-78 UniProt A0A075B674 Reactome Database ID Release 78 9763457 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=9763457 Reactome R-MMU-983534-45 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-45.1 Ighv1-62-2 A0A075B680 Reactome DB_ID: 9763461 UniProt:A0A075B680 Ighv1-62-2 UniProt A0A075B680 Reactome Database ID Release 78 9763461 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=9763461 Reactome R-MMU-983534-46 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-46.1 Ighv1-23 A0A0A6YVW3 Reactome DB_ID: 9763465 UniProt:A0A0A6YVW3 Ighv1-23 UniProt A0A0A6YVW3 Reactome Database ID Release 78 9763465 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=9763465 Reactome R-MMU-983534-47 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-47.1 Ighv1-11 A0A0A6YWI9 Reactome DB_ID: 9763469 UniProt:A0A0A6YWI9 Ighv1-11 UniProt A0A0A6YWI9 Reactome Database ID Release 78 9763469 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=9763469 Reactome R-MMU-983534-48 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-48.1 Ighv1-15 A0A0A6YXA5 Reactome DB_ID: 9763473 UniProt:A0A0A6YXA5 Ighv1-15 UniProt A0A0A6YXA5 Reactome Database ID Release 78 9763473 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=9763473 Reactome R-MMU-983534-49 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-49.1 Ighv1-82 A0A0B4J1J7 Reactome DB_ID: 9763477 UniProt:A0A0B4J1J7 Ighv1-82 UniProt A0A0B4J1J7 Reactome Database ID Release 78 9763477 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=9763477 Reactome R-MMU-983534-50 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-50.1 Ighv1-77 A0A0B4J1M0 Reactome DB_ID: 9763481 UniProt:A0A0B4J1M0 Ighv1-77 UniProt A0A0B4J1M0 Reactome Database ID Release 78 9763481 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=9763481 Reactome R-MMU-983534-51 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-51.1 Ighv1-76 A0A0B4J1N0 Reactome DB_ID: 9763485 UniProt:A0A0B4J1N0 Ighv1-76 UniProt A0A0B4J1N0 Reactome Database ID Release 78 9763485 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=9763485 Reactome R-MMU-983534-52 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-52.1 P01749 Ighv1-61 Reactome DB_ID: 9763489 UniProt:P01749 Ighv1-61 UniProt P01749 Reactome Database ID Release 78 9763489 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=9763489 Reactome R-MMU-983534-53 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-53.1 P01754 Ighv1-62-3 Reactome DB_ID: 9763493 UniProt:P01754 Ighv1-62-3 UniProt P01754 Reactome Database ID Release 78 9763493 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=9763493 Reactome R-MMU-983534-54 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-54.1 Gm5629 P06327 Reactome DB_ID: 9763497 UniProt:P06327 Gm5629 UniProt P06327 Reactome Database ID Release 78 9763497 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=9763497 Reactome R-MMU-983534-55 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-55.1 P06328 Ighv1-72 Reactome DB_ID: 9763500 UniProt:P06328 Ighv1-72 Ighv1-72 recommendedName: fullName evidence="3"Ig heavy chain V region 1-72 alternativeName: fullName evidence="2"Ig heavy chain V region VH558 B4 UniProt P06328 Reactome Database ID Release 78 9763500 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=9763500 Reactome R-MMU-983534-56 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-56.1 Reactome Database ID Release 78 9763502 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=9763502 Reactome R-MMU-983534-57 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983534-57.1 Converted from EntitySet in Reactome Homologues of IGHV1-2 Reactome DB_ID: 9763243 Ighv1-4 IGHV1-2 A0A075B5T4 Reactome DB_ID: 9763237 20 EQUAL 117 EQUAL Reactome Database ID Release 78 9763237 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=9763237 Reactome R-MMU-8948191 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-8948191.1 IGHV1-2 Ighv1-80 A0A075B5Y3 Reactome DB_ID: 9763241 20 EQUAL 117 EQUAL Reactome Database ID Release 78 9763241 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=9763241 Reactome R-MMU-8948191-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-8948191-2.1 Reactome Database ID Release 78 9763243 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=9763243 Reactome R-MMU-8948191-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-8948191-3.1 Converted from EntitySet in Reactome Homologues of Ig heavy chain V-II region MCE Reactome DB_ID: 9763540 Ighv8-6 A0A075B5W4 Reactome DB_ID: 9763506 UniProt:A0A075B5W4 Ighv8-6 UniProt A0A075B5W4 Reactome Database ID Release 78 9763506 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=9763506 Reactome R-MMU-983592 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983592.1 Ighv8-9 A0A075B5X1 Reactome DB_ID: 9763510 UniProt:A0A075B5X1 Ighv8-9 UniProt A0A075B5X1 Reactome Database ID Release 78 9763510 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=9763510 Reactome R-MMU-983592-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983592-2.1 Ighv8-11 A0A075B5X4 Reactome DB_ID: 9763514 UniProt:A0A075B5X4 Ighv8-11 UniProt A0A075B5X4 Reactome Database ID Release 78 9763514 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=9763514 Reactome R-MMU-983592-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983592-3.1 Ighv8-12 A0A075B5X8 Reactome DB_ID: 9763518 UniProt:A0A075B5X8 Ighv8-12 UniProt A0A075B5X8 Reactome Database ID Release 78 9763518 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=9763518 Reactome R-MMU-983592-4 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983592-4.1 Ighv8-13 A0A075B5Y0 Reactome DB_ID: 9763522 UniProt:A0A075B5Y0 Ighv8-13 UniProt A0A075B5Y0 Reactome Database ID Release 78 9763522 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=9763522 Reactome R-MMU-983592-5 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983592-5.1 Ighv8-4 A0A075B693 Reactome DB_ID: 9763526 UniProt:A0A075B693 Ighv8-4 UniProt A0A075B693 Reactome Database ID Release 78 9763526 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=9763526 Reactome R-MMU-983592-6 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983592-6.1 Ighv8-2 A0A0A6YW58 Reactome DB_ID: 9763530 UniProt:A0A0A6YW58 Ighv8-2 UniProt A0A0A6YW58 Reactome Database ID Release 78 9763530 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=9763530 Reactome R-MMU-983592-7 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983592-7.1 Ighv8-8 A0A0A6YXQ0 Reactome DB_ID: 9763534 UniProt:A0A0A6YXQ0 Ighv8-8 UniProt A0A0A6YXQ0 Reactome Database ID Release 78 9763534 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=9763534 Reactome R-MMU-983592-8 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983592-8.1 Ighv8-5 A0A0A6YY60 Reactome DB_ID: 9763538 UniProt:A0A0A6YY60 Ighv8-5 UniProt A0A0A6YY60 Reactome Database ID Release 78 9763538 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=9763538 Reactome R-MMU-983592-9 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983592-9.1 Reactome Database ID Release 78 9763540 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=9763540 Reactome R-MMU-983592-10 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983592-10.1 Converted from EntitySet in Reactome Homologues of Ig heavy chain V-II region NEWM Reactome DB_ID: 9763569 Ighv3-3 A0A075B5S4 Reactome DB_ID: 9763544 UniProt:A0A075B5S4 Ighv3-3 UniProt A0A075B5S4 Reactome Database ID Release 78 9763544 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=9763544 Reactome R-MMU-983653 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983653.1 Ighv3-1 A0A075B5S6 Reactome DB_ID: 9763548 UniProt:A0A075B5S6 Ighv3-1 UniProt A0A075B5S6 Reactome Database ID Release 78 9763548 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=9763548 Reactome R-MMU-983653-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983653-2.1 Ighv3-8 A0A075B5T0 Reactome DB_ID: 9763552 UniProt:A0A075B5T0 Ighv3-8 UniProt A0A075B5T0 Reactome Database ID Release 78 9763552 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=9763552 Reactome R-MMU-983653-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983653-3.1 Ighv12-3 A0A075B5T1 Reactome DB_ID: 9763556 UniProt:A0A075B5T1 Ighv12-3 UniProt A0A075B5T1 Reactome Database ID Release 78 9763556 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=9763556 Reactome R-MMU-983653-4 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983653-4.1 Ighv3-4 A0A0A6YXF1 Reactome DB_ID: 9763560 UniProt:A0A0A6YXF1 Ighv3-4 UniProt A0A0A6YXF1 Reactome Database ID Release 78 9763560 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=9763560 Reactome R-MMU-983653-5 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983653-5.1 P18531 Ighv3-6 Reactome DB_ID: 9763563 UniProt:P18531 Ighv3-6 Ighv3-6 Gm16932 recommendedName: Ig heavy chain V region 3-6 alternativeName: Ig heavy chain V region M315 UniProt P18531 Reactome Database ID Release 78 9763563 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=9763563 Reactome R-MMU-983653-6 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983653-6.1 P18533 Reactome DB_ID: 9763567 UniProt:P18533 UniProt P18533 Reactome Database ID Release 78 9763567 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=9763567 Reactome R-MMU-983653-7 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983653-7.1 Reactome Database ID Release 78 9763569 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=9763569 Reactome R-MMU-983653-8 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983653-8.1 Converted from EntitySet in Reactome Homologues of Ig heavy chain V-III region BUT Reactome DB_ID: 9763609 Ighv5-2 A0A075B5P7 Reactome DB_ID: 9763573 UniProt:A0A075B5P7 Ighv5-2 UniProt A0A075B5P7 Reactome Database ID Release 78 9763573 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=9763573 Reactome R-MMU-983622 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983622.1 Ighv5-4 A0A075B5P9 Reactome DB_ID: 9763577 UniProt:A0A075B5P9 Ighv5-4 UniProt A0A075B5P9 Reactome Database ID Release 78 9763577 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=9763577 Reactome R-MMU-983622-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983622-2.1 Ighv5-6 A0A075B5Q0 Reactome DB_ID: 9763581 UniProt:A0A075B5Q0 Ighv5-6 UniProt A0A075B5Q0 Reactome Database ID Release 78 9763581 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=9763581 Reactome R-MMU-983622-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983622-3.1 Ighv5-9 A0A075B5Q2 Reactome DB_ID: 9763585 UniProt:A0A075B5Q2 Ighv5-9 UniProt A0A075B5Q2 Reactome Database ID Release 78 9763585 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=9763585 Reactome R-MMU-983622-4 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983622-4.1 Ighv5-12 A0A075B5Q4 Reactome DB_ID: 9763587 Reactome Database ID Release 78 9763587 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=9763587 Reactome R-MMU-983622-5 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983622-5.1 Ighv5-9-1 A0A075B5Q6 Reactome DB_ID: 9763591 UniProt:A0A075B5Q6 Ighv5-9-1 UniProt A0A075B5Q6 Reactome Database ID Release 78 9763591 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=9763591 Reactome R-MMU-983622-6 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983622-6.1 Ighv5-16 A0A075B5R0 Reactome DB_ID: 9763595 UniProt:A0A075B5R0 Ighv5-16 UniProt A0A075B5R0 Reactome Database ID Release 78 9763595 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=9763595 Reactome R-MMU-983622-7 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983622-7.1 Ighv11-1 A0A075B5R6 Reactome DB_ID: 9763599 UniProt:A0A075B5R6 Ighv11-1 UniProt A0A075B5R6 Reactome Database ID Release 78 9763599 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=9763599 Reactome R-MMU-983622-8 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983622-8.1 Ighv11-2 A0A075B5R8 Reactome DB_ID: 9763603 UniProt:A0A075B5R8 Ighv11-2 UniProt A0A075B5R8 Reactome Database ID Release 78 9763603 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=9763603 Reactome R-MMU-983622-9 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983622-9.1 Ighv5-12-4 A0A0A6YWG4 Reactome DB_ID: 9763607 UniProt:A0A0A6YWG4 Ighv5-12-4 UniProt A0A0A6YWG4 Reactome Database ID Release 78 9763607 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=9763607 Reactome R-MMU-983622-10 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983622-10.1 Reactome Database ID Release 78 9763609 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=9763609 Reactome R-MMU-983622-11 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983622-11.1 Ighv4-1 A0A075B5R5 Reactome DB_ID: 9763613 UniProt:A0A075B5R5 Ighv4-1 UniProt A0A075B5R5 Reactome Database ID Release 78 9763613 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=9763613 Reactome R-MMU-983571 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983571.1 Ighv5-17 A0A075B5R1 Reactome DB_ID: 9763617 UniProt:A0A075B5R1 Ighv5-17 UniProt A0A075B5R1 Reactome Database ID Release 78 9763617 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=9763617 Reactome R-MMU-983614 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983614.1 Converted from EntitySet in Reactome Homologues of Ig heavy chain V-III region TRO Reactome DB_ID: 9763623 Ighv5-15 A0A075B5Q9 Reactome DB_ID: 9763621 UniProt:A0A075B5Q9 Ighv5-15 UniProt A0A075B5Q9 Reactome Database ID Release 78 9763621 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=9763621 Reactome R-MMU-983550 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983550.1 Reactome Database ID Release 78 9763623 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=9763623 Reactome R-MMU-983550-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983550-2.1 Converted from EntitySet in Reactome Homologues of Ig heavy chain V-II region ARH-77 Reactome DB_ID: 9763639 Ighv3-3 Ig heavy chain V-II region ARH-77 A0A075B5S4 Reactome DB_ID: 9763625 20 EQUAL 146 EQUAL Reactome Database ID Release 78 9763625 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=9763625 Reactome R-MMU-1591202 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1591202.1 Ighv3-1 Ig heavy chain V-II region ARH-77 A0A075B5S6 Reactome DB_ID: 9763627 20 EQUAL 146 EQUAL Reactome Database ID Release 78 9763627 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=9763627 Reactome R-MMU-1591202-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1591202-2.1 Ighv3-8 Ig heavy chain V-II region ARH-77 A0A075B5T0 Reactome DB_ID: 9763629 20 EQUAL 146 EQUAL Reactome Database ID Release 78 9763629 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=9763629 Reactome R-MMU-1591202-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1591202-3.1 Ighv12-3 Ig heavy chain V-II region ARH-77 A0A075B5T1 Reactome DB_ID: 9763631 20 EQUAL 146 EQUAL Reactome Database ID Release 78 9763631 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=9763631 Reactome R-MMU-1591202-4 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1591202-4.1 Ighv3-4 Ig heavy chain V-II region ARH-77 A0A0A6YXF1 Reactome DB_ID: 9763633 20 EQUAL 146 EQUAL Reactome Database ID Release 78 9763633 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=9763633 Reactome R-MMU-1591202-5 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1591202-5.1 P18531 Ighv3-6 Ig heavy chain V-II region ARH-77 Reactome DB_ID: 9763635 20 EQUAL 146 EQUAL Reactome Database ID Release 78 9763635 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=9763635 Reactome R-MMU-1591202-6 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1591202-6.1 P18533 Ig heavy chain V-II region ARH-77 Reactome DB_ID: 9763637 20 EQUAL 146 EQUAL Reactome Database ID Release 78 9763637 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=9763637 Reactome R-MMU-1591202-7 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1591202-7.1 Reactome Database ID Release 78 9763639 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=9763639 Reactome R-MMU-1591202-8 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1591202-8.1 Reactome Database ID Release 78 9763641 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=9763641 Reactome R-MMU-197042 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-197042.1 1 Reactome Database ID Release 78 9763684 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=9763684 Reactome R-MMU-1591203 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1591203.1 2 Immunoglobulin Kappa Light Chain Reactome DB_ID: 9763277 Igkc IGKC P01837 Reactome DB_ID: 9763141 UniProt:P01837 Igkc Igkc SIMILARITY Contains 1 Ig-like (immunoglobulin-like) domain. UniProt P01837 1 EQUAL 106 EQUAL Reactome Database ID Release 78 9763141 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=9763141 Reactome R-MMU-197041 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-197041.1 1 Converted from EntitySet in Reactome Ig Kappa Light Chain V Region Reactome DB_ID: 9763275 Igkv8-21 IGKV4-1(21-?) A0A140T8P7 Reactome DB_ID: 9763145 UniProt:A0A140T8P7 Igkv8-21 UniProt A0A140T8P7 21 EQUAL -1 EQUAL Reactome Database ID Release 78 9763145 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=9763145 Reactome R-MMU-197024 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-197024.1 Converted from EntitySet in Reactome Homologues of IGKV1-5(23-?) Reactome DB_ID: 9763171 Igkv9-124 IGKV1-5(23-?) A0A075B5K2 Reactome DB_ID: 9763149 UniProt:A0A075B5K2 Igkv9-124 UniProt A0A075B5K2 23 EQUAL -1 EQUAL Reactome Database ID Release 78 9763149 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=9763149 Reactome R-MMU-197018 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-197018.1 Igkv10-95 IGKV1-5(23-?) A0A075B5L0 Reactome DB_ID: 9763153 UniProt:A0A075B5L0 Igkv10-95 UniProt A0A075B5L0 23 EQUAL -1 EQUAL Reactome Database ID Release 78 9763153 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=9763153 Reactome R-MMU-197018-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-197018-2.1 Igkv10-94 IGKV1-5(23-?) A0A075B5L1 Reactome DB_ID: 9763157 UniProt:A0A075B5L1 Igkv10-94 UniProt A0A075B5L1 23 EQUAL -1 EQUAL Reactome Database ID Release 78 9763157 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=9763157 Reactome R-MMU-197018-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-197018-3.1 Igkv10-96 IGKV1-5(23-?) A0A140T8M1 Reactome DB_ID: 9763161 UniProt:A0A140T8M1 Igkv10-96 UniProt A0A140T8M1 23 EQUAL -1 EQUAL Reactome Database ID Release 78 9763161 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=9763161 Reactome R-MMU-197018-4 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-197018-4.1 Igkv9-123 IGKV1-5(23-?) A0A140T8N8 Reactome DB_ID: 9763165 UniProt:A0A140T8N8 Igkv9-123 UniProt A0A140T8N8 23 EQUAL -1 EQUAL Reactome Database ID Release 78 9763165 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=9763165 Reactome R-MMU-197018-5 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-197018-5.1 Gm5571 IGKV1-5(23-?) P01639 Reactome DB_ID: 9763169 UniProt:P01639 Gm5571 UniProt P01639 23 EQUAL -1 EQUAL Reactome Database ID Release 78 9763169 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=9763169 Reactome R-MMU-197018-6 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-197018-6.1 Reactome Database ID Release 78 9763171 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=9763171 Reactome R-MMU-197018-7 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-197018-7.1 Igkv2-137 IGKVA18(21-?) A0A0B4J1H6 Reactome DB_ID: 9763175 UniProt:A0A0B4J1H6 Igkv2-137 UniProt A0A0B4J1H6 21 EQUAL -1 EQUAL Reactome Database ID Release 78 9763175 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=9763175 Reactome R-MMU-197052 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-197052.1 Converted from EntitySet in Reactome Homologues of Ig kappa chain V region EV15 Reactome DB_ID: 9763185 Igkv17-127 Ig kappa chain V region EV15 A0A075B5J9 Reactome DB_ID: 9763179 UniProt:A0A075B5J9 Igkv17-127 UniProt A0A075B5J9 21 EQUAL 115 EQUAL Reactome Database ID Release 78 9763179 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=9763179 Reactome R-MMU-983573 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983573.1 Igkv17-121 Ig kappa chain V region EV15 A0A075B5K3 Reactome DB_ID: 9763183 UniProt:A0A075B5K3 Igkv17-121 UniProt A0A075B5K3 21 EQUAL 115 EQUAL Reactome Database ID Release 78 9763183 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=9763183 Reactome R-MMU-983573-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983573-2.1 Reactome Database ID Release 78 9763185 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=9763185 Reactome R-MMU-983573-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983573-3.1 Igkv13-84 A0A140T8N3 Reactome DB_ID: 9763189 UniProt:A0A140T8N3 Igkv13-84 UniProt A0A140T8N3 Reactome Database ID Release 78 9763189 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=9763189 Reactome R-MMU-983553 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983553.1 Converted from EntitySet in Reactome Homologues of Ig kappa chain V-I region BAN Reactome DB_ID: 9763203 Igkv9-124 A0A075B5K2 Reactome DB_ID: 9763191 Reactome Database ID Release 78 9763191 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=9763191 Reactome R-MMU-983608 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983608.1 Igkv10-95 A0A075B5L0 Reactome DB_ID: 9763193 Reactome Database ID Release 78 9763193 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=9763193 Reactome R-MMU-983608-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983608-2.1 Igkv10-94 A0A075B5L1 Reactome DB_ID: 9763195 Reactome Database ID Release 78 9763195 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=9763195 Reactome R-MMU-983608-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983608-3.1 Igkv10-96 A0A140T8M1 Reactome DB_ID: 9763197 Reactome Database ID Release 78 9763197 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=9763197 Reactome R-MMU-983608-4 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983608-4.1 Igkv9-123 A0A140T8N8 Reactome DB_ID: 9763199 Reactome Database ID Release 78 9763199 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=9763199 Reactome R-MMU-983608-5 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983608-5.1 Gm5571 P01639 Reactome DB_ID: 9763201 Reactome Database ID Release 78 9763201 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=9763201 Reactome R-MMU-983608-6 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983608-6.1 Reactome Database ID Release 78 9763203 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=9763203 Reactome R-MMU-983608-7 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983608-7.1 A0A0G2JDU3 Igkv20-101-2 Reactome DB_ID: 9763207 UniProt:A0A0G2JDU3 Igkv20-101-2 UniProt A0A0G2JDU3 Reactome Database ID Release 78 9763207 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=9763207 Reactome R-MMU-983643 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983643.1 Converted from EntitySet in Reactome Homologues of Ig kappa chain V-I region HK101 Reactome DB_ID: 9763217 A0A0G2JDU3 Igkv20-101-2 Ig kappa chain V-I region HK101 Reactome DB_ID: 9763211 23 EQUAL -1 EQUAL Reactome Database ID Release 78 9763211 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=9763211 Reactome R-MMU-983562 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983562.1 Gm42543 Ig kappa chain V-I region HK101 A0A0G2JET4 Reactome DB_ID: 9763215 UniProt:A0A0G2JET4 Gm42543 UniProt A0A0G2JET4 23 EQUAL -1 EQUAL Reactome Database ID Release 78 9763215 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=9763215 Reactome R-MMU-983562-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983562-2.1 Reactome Database ID Release 78 9763217 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=9763217 Reactome R-MMU-983562-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983562-3.1 Converted from EntitySet in Reactome Homologues of Ig kappa chain V-I region Wes Reactome DB_ID: 9763221 Gm42543 A0A0G2JET4 Reactome DB_ID: 9763219 Reactome Database ID Release 78 9763219 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=9763219 Reactome R-MMU-983523 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983523.1 Reactome Database ID Release 78 9763221 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=9763221 Reactome R-MMU-983523-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983523-2.1 Gm5153 P01627 Reactome DB_ID: 9763225 UniProt:P01627 Gm5153 UniProt P01627 Reactome Database ID Release 78 9763225 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=9763225 Reactome R-MMU-983657 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983657.1 Igkv1-35 Ig kappa chain V-II region RPMI 6410 A0A075B5N0 Reactome DB_ID: 9763229 UniProt:A0A075B5N0 Igkv1-35 UniProt A0A075B5N0 21 EQUAL 133 EQUAL Reactome Database ID Release 78 9763229 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=9763229 Reactome R-MMU-983584 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983584.1 Igkv18-36 A0A075B5M9 Reactome DB_ID: 9763233 UniProt:A0A075B5M9 Igkv18-36 UniProt A0A075B5M9 Reactome Database ID Release 78 9763233 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=9763233 Reactome R-MMU-983596 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983596.1 Converted from EntitySet in Reactome Homologues of IGKV1-12 Reactome DB_ID: 9763249 IGKV1-12 Igkv20-101-2 A0A0G2JDU3 Reactome DB_ID: 9763245 23 EQUAL 117 EQUAL Reactome Database ID Release 78 9763245 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=9763245 Reactome R-MMU-8948185 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-8948185.1 Gm42543 IGKV1-12 A0A0G2JET4 Reactome DB_ID: 9763247 23 EQUAL 117 EQUAL Reactome Database ID Release 78 9763247 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=9763247 Reactome R-MMU-8948185-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-8948185-2.1 Reactome Database ID Release 78 9763249 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=9763249 Reactome R-MMU-8948185-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-8948185-3.1 Converted from EntitySet in Reactome Homologues of IGKV2D-30 Reactome DB_ID: 9763271 Igkv1-35 IGKV2D-30 A0A075B5N0 Reactome DB_ID: 9763253 21 EQUAL 120 EQUAL Reactome Database ID Release 78 9763253 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=9763253 Reactome R-MMU-8948186 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-8948186.1 Igkv1-135 IGKV2D-30 A0A0B4J1H7 Reactome DB_ID: 9763257 UniProt:A0A0B4J1H7 Igkv1-135 UniProt A0A0B4J1H7 21 EQUAL 120 EQUAL Reactome Database ID Release 78 9763257 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=9763257 Reactome R-MMU-8948186-2 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-8948186-2.1 Igkv1-133 IGKV2D-30 A0A0B4J1H8 Reactome DB_ID: 9763261 UniProt:A0A0B4J1H8 Igkv1-133 UniProt A0A0B4J1H8 21 EQUAL 120 EQUAL Reactome Database ID Release 78 9763261 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=9763261 Reactome R-MMU-8948186-3 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-8948186-3.1 Igkv1-132 IGKV2D-30 A0A0B4J1H9 Reactome DB_ID: 9763265 UniProt:A0A0B4J1H9 Igkv1-132 UniProt A0A0B4J1H9 21 EQUAL 120 EQUAL Reactome Database ID Release 78 9763265 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=9763265 Reactome R-MMU-8948186-4 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-8948186-4.1 Igkv1-131 IGKV2D-30 A0A140T8M8 Reactome DB_ID: 9763269 UniProt:A0A140T8M8 Igkv1-131 UniProt A0A140T8M8 21 EQUAL 120 EQUAL Reactome Database ID Release 78 9763269 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=9763269 Reactome R-MMU-8948186-5 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-8948186-5.1 Reactome Database ID Release 78 9763271 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=9763271 Reactome R-MMU-8948186-6 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-8948186-6.1 Reactome Database ID Release 78 9763275 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=9763275 Reactome R-MMU-197037 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-197037.1 1 Reactome Database ID Release 78 9763277 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=9763277 Reactome R-MMU-983670 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983670.1 2 Reactome Database ID Release 78 9763686 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=9763686 Reactome R-MMU-182629 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-182629.1 1 Reactome Database ID Release 78 9763688 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=9763688 Reactome R-MMU-173552 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-173552.1 FCGRIA:CD3G homodimer Reactome DB_ID: 9808255 CD3G homodimer Reactome DB_ID: 9808253 Cd3g CD3G P11942 Reactome DB_ID: 9769582 UniProt:P11942 Cd3g UniProt P11942 23 EQUAL 182 EQUAL Reactome Database ID Release 78 9769582 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=9769582 Reactome R-MMU-197917 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-197917.1 2 Reactome Database ID Release 78 9808253 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=9808253 Reactome R-MMU-1861690 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1861690.1 1 Fcgr1 FCGR1A P26151 Reactome DB_ID: 9795768 UniProt:P26151 Fcgr1 UniProt P26151 16 EQUAL 374 EQUAL Reactome Database ID Release 78 9795768 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=9795768 Reactome R-MMU-197835 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-197835.1 1 Reactome Database ID Release 78 9808255 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=9808255 Reactome R-MMU-2029093 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029093.1 IgG-Ag:FCGRIA:CD3G homodimer Reactome DB_ID: 9808257 1 1 Reactome Database ID Release 78 9808257 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=9808257 Reactome R-MMU-2029132 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029132.1 Reactome Database ID Release 78 9808259 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=9808259 Reactome R-MMU-2029455 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029455.1 FCGRI is coded by three different genes (A, B, and C) and is expressed on most myeloid cells including monocytes, macrophages and dendritic cells (Allen & Seed 1988). FCGRI is a high affinity IgG receptor capable of binding monomeric IgG. FCGRI exists as a complex containing ligand (IgG) binding extracellular alpha-chain and homodimer of signal transducing FcR gamma (CD3G) chains, or a heterodimer of signal transducing FcR gamma and zeta chains (Ernst et al. 1993, Scholl & Geha 1993, van Vugt et al. 1996). The cytoplasmic domain of FCGRI does not have signaling motifs, however it is suggested that the gamma-subunit might be required for generating the phagocytic signal (Duchemin et al. 1994, Indik et al. 1995).<br>The first step in Fc-gamma receptor (FCGR) phagocytosis is binding and clustering of FCGRs by IgG-coated foreign particles. FCGR are clustered at the cell surface by multivalent antigen-antibody complexes and recruited to lipid raft micro domains; monovalent ligand binding is insufficient to generate a signal. This cross-linking results in the localization of FCGRs into lipid rafts and this may aid in recruiting and complexing with additional signalling proteins associated with lipid rafts (Bournazos et al. 2009, Kwiatkowska & Sobota 2001, Kono et al. 2002). This is followed by phosphorylation of the tyrosine residues with in the immuno tyrosine activation motif (ITAM) located on the cytoplasmic portion of accessory gamma/zeta chains by membrane-associated tyrosine kinases of the Src family (Duchemin et al. 1994, van Vugt et al. 1996). 8611682 Pubmed 1996 FcR gamma-chain is essential for both surface expression and function of human Fc gamma RI (CD64) in vivo van Vugt, MJ Heijnen, AF Capel, PJ Park, SY Ra, C Saito, T Verbeek, JS van de Winkel, JG Blood 87:3593-9 8327478 Pubmed 1993 Association of the high-affinity receptor for IgG (Fc gamma RI) with the gamma subunit of the IgE receptor Ernst, LK Duchemin, AM Anderson, CL Proc Natl Acad Sci U S A 90:6023-7 7512959 Pubmed 1994 Clustering of the high affinity Fc receptor for immunoglobulin G (Fc gamma RI) results in phosphorylation of its associated gamma-chain Duchemin, AM Ernst, LK Anderson, CL J Biol Chem 269:12111-7 8541526 Pubmed 1995 The molecular dissection of Fc gamma receptor mediated phagocytosis Indik, ZK Park, JG Hunter, S Schreiber, AD Blood 86:4389-99 12077245 Pubmed 2002 Spatial raft coalescence represents an initial step in Fc gamma R signaling Kono, H Suzuki, T Yamamoto, K Okada, M Yamamoto, T Honda, Z J Immunol 169:193-203 7516890 Pubmed 1994 The high affinity Fc gamma receptor (CD64) induces phagocytosis in the absence of its cytoplasmic domain: the gamma subunit of Fc gamma RIIIA imparts phagocytic function to Fc gamma RI Indik, ZK Hunter, S Huang, MM Pan, XQ Chien, P Kelly, C Levinson, AI Kimberly, RP Schreiber, AD Exp Hematol 22:599-606 2974947 Pubmed 1988 Nucleotide sequence of three cDNAs for the human high affinity Fc receptor (FcRI) Allen, JM Seed, B Nucleic Acids Res 16:11824 8415618 Pubmed 1993 Physical association between the high-affinity IgG receptor (Fc gamma RI) and the gamma subunit of the high-affinity IgE receptor (Fc epsilon RI gamma) Scholl, PR Geha, RS Proc Natl Acad Sci U S A 90:8847-50 inferred from electronic annotation EVIDENCE CODE ECO:0000203 LEFT-TO-RIGHT Cross-linking of FCGRIIA with IgG-coated Ag 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> Fcgr2 FCGR2A P08101 Reactome DB_ID: 9804228 UniProt:P08101 Fcgr2 UniProt P08101 34 EQUAL 317 EQUAL Reactome Database ID Release 78 9804228 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=9804228 Reactome R-MMU-197838 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-197838.1 IgG-Ag:FCGRIIA Reactome DB_ID: 9804230 1 1 Reactome Database ID Release 78 9804230 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=9804230 Reactome R-MMU-1861689 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1861689.1 Reactome Database ID Release 78 9804232 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=9804232 Reactome R-MMU-1861621 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1861621.1 FCGRII (CD32) is a low-affinity receptor encoded by three different genes (A, B and C) (Brooks et al. 1989). FCGRIIA functions as a single-chain transmembrane receptor containing both the ligand-binding extracellular domain and a signal transducing cytoplasmic domain that contains distinct immunoreceptor tyrosine-based activation motif (ITAM). This ITAM-like domain in FCGRIIA contains two YXXL motifs with a spacer sequence of 12 amino acids instead of the usual 7. Isoform FCGRIIB is expressed in various leukocytes, including human monocytes and, as opposed to the activating Fc receptors it has an immunoreceptor tyrosine-based inhibitory motif (ITIM) and negatively regulates phagocytosis (Van den Herik-Oudijk IE et al. 1995, Mitchell et al. 1994, Tridandapani et al. 2002). <br>The first step in Fc-gamma receptor (FCGR) phagocytosis is binding and clustering of FCGRs by IgG-coated foreign particles. FCGR are clustered at the cell surface by multivalent antigen-antibody complexes and recruited to lipid raft micro domains; monovalent ligand binding is insufficient to generate a signal. This cross-linking results in the localization of FCGRs into lipid rafts and this may aid in recruiting and complexing with additional signalling proteins associated with lipid rafts (Bournazos et al. 2009, Kwiatkowska & Sobota 2001, Kono et al. 2002). This is followed by phosphorylation of the tyrosine residues within the ITAM located on the cytoplasmic portion of FCGRIIA by membrane-associated tyrosine kinases of the Src family (Mitchell et al. 1994). 7521687 Pubmed 1994 Substitutions and deletions in the cytoplasmic domain of the phagocytic receptor Fc gamma RIIA: effect on receptor tyrosine phosphorylation and phagocytosis Mitchell, MA Huang, MM Chien, P Indik, ZK Pan, XQ Schreiber, AD Blood 84:1753-9 19494328 Pubmed 2009 Association of FcgammaRIIa (CD32a) with lipid rafts regulates ligand binding activity Bournazos, S Hart, SP Chamberlain, LH Glennie, MJ Dransfield, I J Immunol 182:8026-36 11298323 Pubmed 2001 The clustered Fcgamma receptor II is recruited to Lyn-containing membrane domains and undergoes phosphorylation in a cholesterol-dependent manner Kwiatkowska, K Sobota, A Eur J Immunol 31:989-98 11741917 Pubmed 2002 Regulated expression and inhibitory function of Fcgamma RIIb in human monocytic cells Tridandapani, S Siefker, K Teillaud, JL Carter, JE Wewers, MD Anderson, CL J Biol Chem 277:5082-9 7718892 Pubmed 1995 Identification of signaling motifs within human Fc gamma RIIa and Fc gamma RIIb isoforms Van den Herik-Oudijk, IE Capel, PJ van der Bruggen, T van de Winkel, JG Blood 85:2202-11 2529342 Pubmed 1989 Structure and expression of human IgG FcRII(CD32). Functional heterogeneity is encoded by the alternatively spliced products of multiple genes Brooks, DG Qiu, WQ Luster, AD Ravetch, JV J Exp Med 170:1369-85 LEFT-TO-RIGHT Cross-linking of FCGRIIIA with IgG-coated Ag 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> FCGRIIIA:CD3G/CD3Z dimers Reactome DB_ID: 9808274 Fcgr4 FCGR3A A0A0B4J1G0 Reactome DB_ID: 9769855 UniProt:A0A0B4J1G0 Fcgr4 UniProt A0A0B4J1G0 17 EQUAL 254 EQUAL Reactome Database ID Release 78 9769855 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=9769855 Reactome R-MMU-197836 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-197836.1 1 Converted from EntitySet in Reactome CD3G/CD3Z dimers Reactome DB_ID: 9808272 CD3G:CD3Z heterodimer Reactome DB_ID: 9808268 1 Cd247 CD247-1 P24161 Reactome DB_ID: 9769588 UniProt:P24161 Cd247 UniProt P24161 22 EQUAL 164 EQUAL Reactome Database ID Release 78 9769588 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=9769588 Reactome R-MMU-198166 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-198166.1 1 Reactome Database ID Release 78 9808268 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=9808268 Reactome R-MMU-1861602 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1861602.1 CD3Z homodimer Reactome DB_ID: 9808270 2 Reactome Database ID Release 78 9808270 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=9808270 Reactome R-MMU-1861695 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1861695.1 Reactome Database ID Release 78 9808272 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=9808272 Reactome R-MMU-2029116 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029116.1 1 Reactome Database ID Release 78 9808274 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=9808274 Reactome R-MMU-2029097 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029097.1 IgG-Ag:FCGRIIIA:CD3G/CD3Z dimers Reactome DB_ID: 9808276 1 1 Reactome Database ID Release 78 9808276 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=9808276 Reactome R-MMU-2029163 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029163.1 Reactome Database ID Release 78 9808278 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=9808278 Reactome R-MMU-2029457 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029457.1 FCGRIII (CD16) is a low affinity Fc gamma receptor and is encoded by two genes (A and B), the transmembrane form FCGRIIIA and the GPI anchored FCGRIIIB (Edberg et al. 1989). FCGRIIIA is involved in phagocytosis and is expressed in macrophages and natural killer cells as a multi chain complex consisting of a single alpha chain containing IgG binding domains and a signal transducing gamma and/or zeta dimer (Wirthmuller et al. 1992, Lanier et al. 1989, Garcia Garcia & Rosales 2002). Both gamma and zeta chains contain a conserved immunoreceptor tyrosine based activation motif (ITAM), which has 2 copies of the YXXL sequence (Isakov 1997). However, the gamma chain of FCGRIIIA is approximately sixfold more efficient in mediating phagocytosis than the zeta subunit (Park & Schreiber 1995). Phosphorylation of the conserved tyrosine residues of the ITAM in these accessory proteins is required for the phagocytic signal mediated by FCRGIIIA. <br>The first step in Fc-gamma receptor (FCGR) phagocytosis is binding and clustering of FCGRs by IgG-coated foreign particles (For this particular pathway the coated foreing particle is the Leishmania parasite). FCGR are clustered at the cell surface by multivalent antigen-antibody complexes and recruited to lipid raft micro domains; monovalent ligand binding is insufficient to generate a signal. <br>This cross linking results in the localisation of FCGRs into lipid rafts and this may aid in their recruiting and complexing with additional signalling proteins associated with lipid rafts (Kono et al. 2002). This is followed by phosphorylation of the tyrosine residues within the ITAM located on the cytoplasmic portion of accessory gamma/zeta chains by membrane associated tyrosine kinases of the Src family (Park et al. 1993). 8408649 Pubmed 1993 In the absence of other Fc receptors, Fc gamma RIIIA transmits a phagocytic signal that requires the cytoplasmic domain of its gamma subunit Park, JG Isaacs, RE Chien, P Schreiber, AD J Clin Invest 92:1967-73 8408660 Pubmed 1993 Conserved cytoplasmic tyrosine residues of the gamma subunit are required for a phagocytic signal mediated by Fc gamma RIIIA Park, JG Murray, RK Chien, P Darby, C Schreiber, AD J Clin Invest 92:2073-9 12488490 Pubmed 2002 Signal transduction during Fc receptor-mediated phagocytosis García-García, E Rosales, Carlos J Leukoc Biol 72:1092-108 2474607 Pubmed 1989 Human Fc gamma RIII (CD16). Isoforms with distinct allelic expression, extracellular domains, and membrane linkages on polymorphonuclear and natural killer cells Edberg, JC Redecha, PB Salmon, JE Kimberly, RP J Immunol 143:1642-9 9000531 Pubmed 1997 Immunoreceptor tyrosine-based activation motif (ITAM), a unique module linking antigen and Fc receptors to their signaling cascades Isakov, N J Leukoc Biol 61:6-16 2532305 Pubmed 1989 Co-association of CD3 zeta with a receptor (CD16) for IgG Fc on human natural killer cells Lanier, LL Yu, G Phillips, JH Nature 342:803-5 1314888 Pubmed 1992 Signal transduction by Fc gamma RIII (CD16) is mediated through the gamma chain Wirthmueller, U Kurosaki, T Murakami, MS Ravetch, JV J Exp Med 175:1381-90 LEFT-TO-RIGHT 2.7.10 Sequestering and phosphorylation Fc gamma receptors in the lipid rafts 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> ATP Adenosine 5'-triphosphate ATP(4-) Reactome DB_ID: 113592 cytosol GENE ONTOLOGY GO:0005829 ATP(4-) [ChEBI:30616] ATP(4-) ATP atp Adenosine 5'-triphosphate ChEBI CHEBI:30616 Reactome Database ID Release 78 113592 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=113592 Reactome R-ALL-113592 5 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-113592.5 COMPOUND C00002 2 clustered IgG-Ag:FCGRs Reactome DB_ID: 9808284 Converted from EntitySet in Reactome FCGRs Reactome DB_ID: 9808282 Reactome Database ID Release 78 9808282 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=9808282 Reactome R-MMU-2029103 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029103.1 1 1 Reactome Database ID Release 78 9808284 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=9808284 Reactome R-MMU-2029146 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029146.1 clustered IgG-Ag:p-FCGRs Reactome DB_ID: 9808209 1 Converted from EntitySet in Reactome p-FCGRs Reactome DB_ID: 9808207 FCGRIA:p-Y160,Y171-CD3G dimer Reactome DB_ID: 9808195 p-Y160,Y171-CD3G dimer Reactome DB_ID: 9808193 P11942 phospho-Cd3g p-Y160,Y171-CD3G Reactome DB_ID: 9771114 160 EQUAL O4'-phospho-L-tyrosine MOD MOD:00048 171 EQUAL 23 EQUAL 182 EQUAL Reactome Database ID Release 78 9771114 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=9771114 Reactome R-MMU-202362 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-202362.1 2 Reactome Database ID Release 78 9808193 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=9808193 Reactome R-MMU-1861560 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1861560.1 1 1 Reactome Database ID Release 78 9808195 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=9808195 Reactome R-MMU-2029117 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029117.1 FCGRIIIA:p-2Y-CD3G/p-6Y-CD3Z dimers Reactome DB_ID: 9808201 1 Converted from EntitySet in Reactome p-CD3 dimers Reactome DB_ID: 9808199 p-Y160,Y171-CD3G:p-6Y-CD3Z Reactome DB_ID: 9808197 1 P24161 phospho-Cd247 p-6Y-CD247 Reactome DB_ID: 9771124 72 EQUAL 83 EQUAL 111 EQUAL 123 EQUAL 142 EQUAL 153 EQUAL 22 EQUAL 164 EQUAL Reactome Database ID Release 78 9771124 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=9771124 Reactome R-MMU-202166 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-202166.1 1 Reactome Database ID Release 78 9808197 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=9808197 Reactome R-MMU-1861710 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1861710.1 p-6Y-CD247 dimer Reactome DB_ID: 9771126 2 Reactome Database ID Release 78 9771126 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=9771126 Reactome R-MMU-202303 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-202303.1 Reactome Database ID Release 78 9808199 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=9808199 Reactome R-MMU-2029108 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029108.1 1 Reactome Database ID Release 78 9808201 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=9808201 Reactome R-MMU-2029118 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029118.1 P08101 phospho-Fcgr2 p-Y288,Y304-FCGR2A Reactome DB_ID: 9808205 288 EQUAL 304 EQUAL 34 EQUAL 317 EQUAL Reactome Database ID Release 78 9808205 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=9808205 Reactome R-MMU-2029069 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029069.1 Reactome Database ID Release 78 9808207 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=9808207 Reactome R-MMU-2029104 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029104.1 1 Reactome Database ID Release 78 9808209 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=9808209 Reactome R-MMU-2029128 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029128.1 ADP Adenosine 5'-diphosphate ADP(3-) Reactome DB_ID: 29370 ADP(3-) [ChEBI:456216] ADP(3-) ADP 5&apos;-O-[(phosphonatooxy)phosphinato]adenosine ADP trianion ChEBI CHEBI:456216 Reactome Database ID Release 78 29370 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=29370 Reactome R-ALL-29370 5 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29370.5 COMPOUND C00008 2 ACTIVATION Converted from EntitySet in Reactome Src family kinases (SFKs) Reactome DB_ID: 9808286 Src SRC-2 P05480 Reactome DB_ID: 9767647 UniProt:P05480 Src Src FUNCTION Non-receptor protein tyrosine kinase which is activated following engagement of many different classes of cellular receptors including immune response receptors, integrins and other adhesion receptors, receptor protein tyrosine kinases, G protein-coupled receptors as well as cytokine receptors. Participates in signaling pathways that control a diverse spectrum of biological activities including gene transcription, immune response, cell adhesion, cell cycle progression, apoptosis, migration, and transformation. Due to functional redundancy between members of the SRC kinase family, identification of the specific role of each SRC kinase is very difficult. SRC appears to be one of the primary kinases activated following engagement of receptors and plays a role in the activation of other protein tyrosine kinase (PTK) families. Receptor clustering or dimerization leads to recruitment of SRC to the receptor complexes where it phosphorylates the tyrosine residues within the receptor cytoplasmic domains. Plays an important role in the regulation of cytoskeletal organization through phosphorylation of specific substrates such as AFAP1. Phosphorylation of AFAP1 allows the SRC SH2 domain to bind AFAP1 and to localize to actin filaments. Cytoskeletal reorganization is also controlled through the phosphorylation of cortactin (CTTN) (Probable). When cells adhere via focal adhesions to the extracellular matrix, signals are transmitted by integrins into the cell resulting in tyrosine phosphorylation of a number of focal adhesion proteins, including PTK2/FAK1 and paxillin (PXN) (By similarity). In addition to phosphorylating focal adhesion proteins, SRC is also active at the sites of cell-cell contact adherens junctions and phosphorylates substrates such as beta-catenin (CTNNB1), delta-catenin (CTNND1), and plakoglobin (JUP). Another type of cell-cell junction, the gap junction, is also a target for SRC, which phosphorylates connexin-43 (GJA1). SRC is implicated in regulation of pre-mRNA-processing and phosphorylates RNA-binding proteins such as KHDRBS1 (Probable). Also plays a role in PDGF-mediated tyrosine phosphorylation of both STAT1 and STAT3, leading to increased DNA binding activity of these transcription factors (PubMed:9344858). Involved in the RAS pathway through phosphorylation of RASA1 and RASGRF1. Plays a role in EGF-mediated calcium-activated chloride channel activation (By similarity). Required for epidermal growth factor receptor (EGFR) internalization through phosphorylation of clathrin heavy chain (CLTC and CLTCL1) at 'Tyr-1477'. Involved in beta-arrestin (ARRB1 and ARRB2) desensitization through phosphorylation and activation of GRK2, leading to beta-arrestin phosphorylation and internalization. Has a critical role in the stimulation of the CDK20/MAPK3 mitogen-activated protein kinase cascade by epidermal growth factor (Probable). Might be involved not only in mediating the transduction of mitogenic signals at the level of the plasma membrane but also in controlling progression through the cell cycle via interaction with regulatory proteins in the nucleus (By similarity). Plays an important role in osteoclastic bone resorption in conjunction with PTK2B/PYK2. Both the formation of a SRC-PTK2B/PYK2 complex and SRC kinase activity are necessary for this function. Recruited to activated integrins by PTK2B/PYK2, thereby phosphorylating CBL, which in turn induces the activation and recruitment of phosphatidylinositol 3-kinase to the cell membrane in a signaling pathway that is critical for osteoclast function (PubMed:14739300). Promotes energy production in osteoclasts by activating mitochondrial cytochrome C oxidase (PubMed:12615910). Phosphorylates DDR2 on tyrosine residues, thereby promoting its subsequent autophosphorylation. Phosphorylates RUNX3 and COX2 on tyrosine residues, TNK2 on 'Tyr-284' and CBL on 'Tyr-738'. Enhances DDX58/RIG-I-elicited antiviral signaling. Phosphorylates PDPK1 at 'Tyr-9', 'Tyr-373' and 'Tyr-376'. Phosphorylates BCAR1 at 'Tyr-226'. Phosphorylates CBLC at multiple tyrosine residues, phosphorylation at 'Tyr-341' activates CBLC E3 activity. Involved in anchorage-independent cell growth (By similarity). Required for podosome formation (PubMed:21525037). Mediates IL6 signaling by activating YAP1-NOTCH pathway to induce inflammation-induced epithelial regeneration (PubMed:25731159).ACTIVITY REGULATION Phosphorylation by CSK at Tyr-529 inhibits kinase activity. Inhibitory phosphorylation at Tyr-529 is enhanced by heme. Further phosphorylation by CDK1 partially reactivates CSK-inactivated SRC and facilitates complete reactivation by protein tyrosine phosphatase PTPRC. Integrin engagement stimulates kinase activity. Phosphorylation by PTK2/FAK1 enhances kinase activity. Butein and pseudosubstrate-based peptide inhibitors like CIYKYYF act as inhibitors. Phosphorylation at Tyr-418 increases kinase activity.SUBUNIT Part of a complex comprised of PTPRA, BCAR1, BCAR3 (via SH2 domain) and SRC; the formation of the complex is dependent on integrin mediated-tyrosine phosphorylation of PTPRA (PubMed:22801373). Interacts with CDCP1, TGFB1I1 and TOM1L2 (By similarity). Interacts with DDEF1/ASAP1 via its SH3 domain (PubMed:9819391). Interacts with CCPG1 (PubMed:17000758). Interacts with the cytoplasmic domain of MUC1, phosphorylates it and increases binding of MUC1 with beta-catenin (By similarity). Interacts with RALGPS1 via its SH3 domain (By similarity). Interacts with CAV2 (tyrosine phosphorylated form) (By similarity). Interacts (via the SH3 domain and the protein kinase domain) with ARRB1; the interaction is independent of the phosphorylation state of SRC C-terminus (By similarity). Interacts with FCAMR and PXN (By similarity). Interacts with ARRB2 (PubMed:19122674). Interacts with ARRB1 (By similarity). Interacts with SRCIN1 (By similarity). Interacts with NDFIP2 and more weakly with NDFIP1 (By similarity). Interacts with PIK3CA and/or PIK3C2B, PTK2/FAK1, ESR1 (dimethylated on arginine) and FAK (PubMed:14739300). Interacts (via SH2 and SH3 domain) with TNK2 (By similarity). Interacts (via protein kinase domain) with the tyrosine phosphorylated form of RUNX3 (via runt domain) (By similarity). Interacts with TRAF3 (via RING-type zinc finger domain) (By similarity). Interacts with DDX58, MAVS and TBK1 (By similarity). Interacts (via SH2 domain) with RACK1; the interaction is enhanced by tyrosine phosphorylation of RACK1 and inhibits SRC activity (By similarity). Interacts (via SH2 domain) with the 'Tyr-402' phosphorylated form of PTK2B/PYK2 (PubMed:14739300). Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated) (PubMed:16684964). Identified in a complex containing FGFR4, NCAM1, CDH2, PLCG1, FRS2, SRC, SHC1, GAP43 and CTTN (PubMed:11433297). Interacts with EPHB1; activates the MAPK/ERK cascade to regulate cell migration (PubMed:12925710). Interacts with ERBB2 and STAT1 (PubMed:7542762, PubMed:9344858). Interacts with PDGFRA (tyrosine phosphorylated) (PubMed:14644164). Interacts with CSF1R (PubMed:7681396). Interacts (via SH2 domain) with the 'Tyr-9' phosphorylated form of PDPK1 (By similarity). Interacts with DDR2 (By similarity). Interacts with AMOTL2; this interaction regulates the translocation of phosphorylated SRC to peripheral cell-matrix adhesion sites (By similarity). Interacts with DDR1 and DAB2 (PubMed:20093046). Interacts with TRAP1 (By similarity). Interacts with CBLC; the interaction is enhanced when SRC is phosphorylated at 'Tyr-424' (By similarity). Interacts with ARHGEF5 (PubMed:21525037). Interacts (via cytoplasmic domain) with CEACAM1 (via SH2 domain); this interaction is regulated by trans-homophilic cell adhesion (By similarity). Interacts with MPP2 (By similarity). Interacts with PRR7 (By similarity). Interacts (via kinase domain and to a lesser extent the SH2 domain) directly with PDLIM4; this interaction results in PTPN13-mediated dephosphorylation of this protein leading to its inactivation (By similarity). Interacts with P85 (PIK3R1 or PIK3R2) (By similarity). Interacts with HNRNPA2B1 (PubMed:31320558). Interacts with IL6ST/gp130 (By similarity). Interacts (via SH3 domain) with PELP1 in the presence of 17-beta-estradiol (By similarity).PTM Myristoylated at Gly-2, and this is essential for targeting to membranes.PTM Dephosphorylated at Tyr-529 by PTPRJ (By similarity). Phosphorylated on Tyr-529 by c-Src kinase (CSK). The phosphorylated form is termed pp60c-src. Dephosphorylated by PTPRJ at Tyr-418. Normally maintained in an inactive conformation with the SH2 domain engaged with Tyr-529, the SH3 domain engaged with the SH2-kinase linker, and Tyr-418 dephosphorylated. Dephosphorylation of Tyr-529 as a result of protein tyrosine phosphatase (PTP) action disrupts the intramolecular interaction between the SH2 domain and Tyr-529, Tyr-418 can then become autophosphorylated, resulting in SRC activation. Phosphorylation of Tyr-529 by CSK allows this interaction to reform, resulting in SRC inactivation. CDK5-mediated phosphorylation at Ser-74 targets SRC to ubiquitin-dependent degradation and thus leads to cytoskeletal reorganization. Phosphorylated by PTK2/FAK1; this enhances kinase activity. Phosphorylated by PTK2B/PYK2; this enhances kinase activity (By similarity). Upon activation of IL6ST by IL6, Tyr-418 is phosphorylated and Tyr-529 dephosphorylated (PubMed:25731159).PTM S-nitrosylation is important for activation of its kinase activity.PTM Ubiquitinated in response to CDK5-mediated phosphorylation. Ubiquitination mediated by CBLC requires SRC autophosphorylation at Tyr-418 and may lead to lysosomal degradation (By similarity).SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. UniProt P05480 2 EQUAL 536 EQUAL Reactome Database ID Release 78 9767647 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=9767647 Reactome R-MMU-191648 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-191648.1 Lyn Tyrosine-protein kinase Lyn LYN_MOUSE Lyn Reactome DB_ID: 1112642 UniProt:P25911 Lyn Lyn FUNCTION Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integrin signaling, but also responses to DNA damage and genotoxic agents. Functions primarily as negative regulator, but can also function as activator, depending on the context. Required for the initiation of the B-cell response, but also for its down-regulation and termination. Plays an important role in the regulation of B-cell differentiation, proliferation, survival and apoptosis, and is important for immune self-tolerance. Acts downstream of several immune receptors, including the B-cell receptor, CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A, TLR2 and TLR4. Plays a role in the inflammatory response to bacterial lipopolysaccharide. Mediates the responses to cytokines and growth factors in hematopoietic progenitors, platelets, erythrocytes, and in mature myeloid cells, such as dendritic cells, neutrophils and eosinophils. Acts downstream of EPOR, KIT, MPL, the chemokine receptor CXCR4, as well as the receptors for IL3, IL5 and CSF2. Plays an important role in integrin signaling. Regulates cell proliferation, survival, differentiation, migration, adhesion, degranulation, and cytokine release. Down-regulates signaling pathways by phosphorylation of immunoreceptor tyrosine-based inhibitory motifs (ITIM), that then serve as binding sites for phosphatases, such as PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1, that modulate signaling by dephosphorylation of kinases and their substrates. Phosphorylates LIME1 in response to CD22 activation. Phosphorylates BTK, CBL, CD5, CD19, CD72, CD79A, CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B, SYK and TEC. Promotes phosphorylation of SIRPA, PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. Required for rapid phosphorylation of FER in response to FCER1 activation. Mediates KIT phosphorylation. Acts as an effector of EPOR (erythropoietin receptor) in controlling KIT expression and may play a role in erythroid differentiation during the switch between proliferation and maturation. Depending on the context, activates or inhibits several signaling cascades. Regulates phosphatidylinositol 3-kinase activity and AKT1 activation. Regulates activation of the MAP kinase signaling cascade, including activation of MAP2K1/MEK1, MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1 and MAPK9/JNK2. Mediates activation of STAT5A and/or STAT5B. Phosphorylates LPXN on 'Tyr-72'. Kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation. Phosphorylates SCIMP on 'Tyr-96'; this enhances binding of SCIMP to TLR4, promoting the phosphorylation of TLR4, and a selective cytokine response to lipopolysaccharide in macrophages (PubMed:28098138). Phosphorylates CLNK (PubMed:12681493).ACTIVITY REGULATION Subject to autoinhibition, mediated by intramolecular interactions between the SH2 domain and the C-terminal phosphotyrosine. Phosphorylation at Tyr-397 is required for optimal activity. Phosphorylated by CSK at Tyr-508; phosphorylation at Tyr-508 inhibits kinase activity. Kinase activity is modulated by dephosphorylation by PTPRC/CD45. Inhibited by dasatinib, PP2, and SU6656.SUBUNIT Interacts with TEC. Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with LIME1 and with CD79A upon activation of the B-cell antigen receptor. Interacts with the B-cell receptor complex. Interacts with phosphorylated THEMIS2. Interacts with EPOR. Interacts with MS4A2/FCER1B. Interaction (via the SH2 and SH3 domains) with MUC1 is stimulated by IL7 and the subsequent phosphorylation increases the binding between MUC1 and CTNNB1/beta-catenin. Interacts with ADAM15. Interacts with NDFIP2 and more weakly with NDFIP1. Interacts with FASLG. Interacts with KIT. Interacts with HCLS1. Interacts with FCGR2B. Interacts with FCGR1A; the interaction may be indirect. Interacts with CD19, CD22, CD79A and CD79B. Interacts (via SH3 domain) with CBLC, PPP1R15A and PDE4A. Interacts with TGFB1I1. Interacts (via SH3 domain) with PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase; this interaction enhances phosphatidylinositol 3-kinase activity. Interacts with CSF2RB, the common subunit of the IL3, IL5 and CSF2 receptors. Interacts with PAG1; identified in a complex with PAG1 and STAT3. Interacts with ABL1. Interacts with PTPN6/SHP-1. Interacts (via SH3 domain) with SCIMP (via proline-rich region) (PubMed:28098138). This interaction facilitates the phosphorylation of SCIMP on 'Tyr-96', which enhances binding of SCIMP to TLR4, and consequently the phosphorylation of TLR4 in response to stimulation by lipopolysaccharide in macrophages (PubMed:28098138). Interacts with LPXN (via LD motif 3) and the interaction is induced upon B-cell antigen receptor (BCR) activation. Interacts (via SH3-domain) with ANKRD54 (via ankyrin repeat region) in an activation-independent status of LYN. Forms a multiprotein complex with ANKRD54 and HCLS1. Interacts (via SH2 and SH3 domains) with UNC119; leading to LYN activation (By similarity). Interacts with CD36. Interacts with LYN (PubMed:22496641). Interacts with SKAP1 and FYB1; this interaction promotes the phosphorylation of CLNK (PubMed:12681493).TISSUE SPECIFICITY Detected in bone marrow-derived monocytes and macrophages (at protein level) (PubMed:28098138, PubMed:2017160). Expressed predominantly in B-lymphoid and myeloid cells (PubMed:2017160).DOMAIN The protein kinase domain plays an important role in its localization in the cell membrane.PTM Ubiquitinated by CBL, leading to its degradation.PTM Phosphorylated on tyrosine residues in response to KIT signaling (By similarity). Autophosphorylated. Phosphorylation at Tyr-397 is required for optimal activity. Phosphorylation at Tyr-508 inhibits kinase activity. Phosphorylated at Tyr-508 by CSK. Dephosphorylated by PTPRC/CD45. Becomes rapidly phosphorylated upon activation of the B-cell receptor and the immunoglobulin receptor FCGR1A.DISRUPTION PHENOTYPE No visible phenotype at birth. B-cell development in the bone marrow proceeds normally, but mice have reduced numbers of peripheral B-cells, with a greater proportion of immature cells and an increased turnover rate. Dendritic cells also have a more immature phenotype. Mice develop severe asthma upon exposure to airborne antigen. Mice display elevated levels of serum IgM. Aging mice display strongly increased levels of myeloid cells, severe extramedullary hematoipoiesis and tend to develop monocyte/macrophage tumors. After about 16 weeks, mice begin to develop splenomegaly and glomerulonephritis, and display autoimmune antibodies. Their B-cells are hypersensitive to stimulation of the B-cell receptor, and display enhanced activation of the MAP kinase signaling pathway. Mice do not display an allergic response upon IgE receptor engagement.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. UniProt P25911 2 EQUAL 512 EQUAL Reactome Database ID Release 78 1112642 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=1112642 Reactome R-MMU-1112642 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1112642.2 Fgr FGR P14234 Reactome DB_ID: 9783552 UniProt:P14234 Fgr UniProt P14234 1 EQUAL 529 EQUAL Reactome Database ID Release 78 9783552 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=9783552 Reactome R-MMU-432116 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-432116.1 Hck HCK P08103 Reactome DB_ID: 9787919 UniProt:P08103 Hck Hck FUNCTION Non-receptor tyrosine-protein kinase found in hematopoietic cells that transmits signals from cell surface receptors and plays an important role in the regulation of innate immune responses, including neutrophil, monocyte, macrophage and mast cell functions, phagocytosis, cell survival and proliferation, cell adhesion and migration. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as FCGR1A and FCGR2A, but also CSF3R, PLAUR, the receptors for IFNG, IL2, IL6 and IL8, and integrins, such as ITGB1 and ITGB2. During the phagocytic process, mediates mobilization of secretory lysosomes, degranulation, and activation of NADPH oxidase to bring about the respiratory burst. Plays a role in the release of inflammatory molecules. Promotes reorganization of the actin cytoskeleton and actin polymerization, formation of podosomes and cell protrusions. Inhibits TP73-mediated transcription activation and TP73-mediated apoptosis. Phosphorylates CBL in response to activation of immunoglobulin gamma Fc region receptors. Phosphorylates ADAM15, BCR, ELMO1, FCGR2A, GAB1, GAB2, RAPGEF1, STAT5B, TP73, VAV1 and WAS (By similarity).ACTIVITY REGULATION Subject to autoinhibition, mediated by intramolecular interactions involving the SH2 and SH3 domains. Kinase activity is also regulated by phosphorylation at regulatory tyrosine residues. Phosphorylation at Tyr-409 is required for optimal activity. Phosphorylation at Tyr-520 inhibits kinase activity. Inhibited by PP1.SUBUNIT Interacts with ADAM15. Interacts with FASLG. Interacts with ARRB1 and ARRB2. Interacts with FCGR1A; the interaction may be indirect. Interacts with IL6ST. Interacts (via SH3 domain) with ELMO1. Interacts (via SH3 domain) with TP73. Interacts with YAP1. Interacts with ABL1 and ITGB1, and thereby recruits ABL1 to activated ITGB1 (By similarity). Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with CBL. Interacts with VAV1, WAS and RAPGEF1. Interacts (via SH3 domain) with WDCP (By similarity).TISSUE SPECIFICITY Expressed predominantly in cells of the myeloid and B-lymphoid lineages.PTM Phosphorylated on several tyrosine residues. Autophosphorylated. Becomes rapidly phosphorylated upon activation of the immunoglobulin receptors FCGR1A and FCGR2A. Phosphorylation at Tyr-409 increases kinase activity. Phosphorylation at Tyr-520 inhibits kinase activity. Kinase activity is not required for phosphorylation at Tyr-520, suggesting that this site may be a target of other kinases.PTM Ubiquitinated by CBL, leading to its degradation via the proteasome.PTM Isoform 2 palmitoylation at position 2 requires prior myristoylation. Palmitoylation at position 3 is required for caveolar localization of isoform 2.DISRUPTION PHENOTYPE No visible phenotype, but macrophages have impaired phagocytosis. Mice lacking both HCK and FGR are extremely sensitive to infections by L.monocytogenes.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. UniProt P08103 2 EQUAL 526 EQUAL Reactome Database ID Release 78 9787919 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=9787919 Reactome R-MMU-167708 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-167708.1 Fyn FYN_MOUSE Reactome DB_ID: 420333 UniProt:P39688 Fyn Fyn FUNCTION Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remodeling, cell motility, immune response and axon guidance. Inactive FYN is phosphorylated on its C-terminal tail within the catalytic domain. Following activation by PKA, the protein subsequently associates with PTK2/FAK1, allowing PTK2/FAK1 phosphorylation, activation and targeting to focal adhesions. Involved in the regulation of cell adhesion and motility through phosphorylation of CTNNB1 (beta-catenin) and CTNND1 (delta-catenin). Regulates cytoskeletal remodeling by phosphorylating several proteins including the actin regulator WAS and the microtubule-associated proteins MAP2 and MAPT. Promotes cell survival by phosphorylating AGAP2/PIKE-A and preventing its apoptotic cleavage. Participates in signal transduction pathways that regulate the integrity of the glomerular slit diaphragm (an essential part of the glomerular filter of the kidney) by phosphorylating several slit diaphragm components including NPHS1, KIRREL1 and TRPC6. Plays a role in neural processes by phosphorylating DPYSL2, a multifunctional adapter protein within the central nervous system, ARHGAP32, a regulator for Rho family GTPases implicated in various neural functions, and SNCA, a small pre-synaptic protein. Participates in the downstream signaling pathways that lead to T-cell differentiation and proliferation following T-cell receptor (TCR) stimulation. Phosphorylates PTK2B/PYK2 in response to T-cell receptor activation. Also participates in negative feedback regulation of TCR signaling through phosphorylation of PAG1, thereby promoting interaction between PAG1 and CSK and recruitment of CSK to lipid rafts. CSK maintains LCK and FYN in an inactive form. Promotes CD28-induced phosphorylation of VAV1. In mast cells, phosphorylates CLNK after activation of immunoglobulin epsilon receptor signaling (PubMed:12681493).ACTIVITY REGULATION Inhibited by phosphorylation of Tyr-531 by leukocyte common antigen and activated by dephosphorylation of this site.SUBUNIT Interacts (via its SH3 domain) with PIK3R1 and PRMT8 (By similarity). Interacts with FYB1, PAG1, and SH2D1A (By similarity). Interacts with CD79A (tyrosine-phosphorylated form); the interaction increases FYN activity (PubMed:8168489). Interacts with TOM1L1 (phosphorylated form) (PubMed:11711534). Interacts with SH2D1A and SLAMF1 (By similarity). Interacts with and phosphorylates ITCH, down-regulating its activity (By similarity). Interacts with FASLG (By similarity). Interacts with RUNX3 (By similarity). Interacts with KIT (By similarity). Interacts with EPHA8; possible downstream effector of EPHA8 in regulation of cell adhesion (By similarity). Interacts with PTK2/FAK1; this interaction leads to PTK2/FAK1 phosphorylation and activation (By similarity). Interacts with CAV1; this interaction couples integrins to the Ras-ERK pathway (By similarity). Interacts (via SH3 domain) with KLHL2 (via N-terminus) (By similarity). Interacts with KDR (tyrosine phosphorylated) (PubMed:16966330). Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated) (PubMed:7681396, PubMed:9312046). Interacts with UNC119 (By similarity). Interacts (via SH2 domain) with PTPRH (phosphorylated form) (PubMed:20398064). Interacts with PTPRO (phosphorylated form) (PubMed:20398064). Interacts with PTPRB (phosphorylated form) (PubMed:20398064). Interacts with FYB2 (By similarity). Interacts with DSCAM (PubMed:22685302). Interacts with SKAP1 and FYB1; this interaction promotes the phosphorylation of CLNK (PubMed:12681493).TISSUE SPECIFICITY Isoform 1 is highly expressed in the brain, isoform 2 is expressed in cells of hemopoietic lineages, especially T-lymphocytes.PTM Autophosphorylated at Tyr-420 (PubMed:8441403). Phosphorylation on the C-terminal tail at Tyr-531 by CSK maintains the enzyme in an inactive state (PubMed:8441403). PTPRC/CD45 dephosphorylates Tyr-531 leading to activation. Ultraviolet B (UVB) strongly increase phosphorylation at Thr-15 and kinase activity, and promotes translocation from the cytoplasm to the nucleus. Dephosphorylation at Tyr-420 by PTPN2 negatively regulates T-cell receptor signaling (By similarity). Phosphorylated at tyrosine residues, which can be enhanced by NTN1 (PubMed:22685302).PTM Palmitoylated (PubMed:19956733, PubMed:7980442, PubMed:8413237, PubMed:9201723). Palmitoylation at Cys-3 and Cys-6, probably by ZDHHC21, regulates subcellular location (PubMed:7980442, PubMed:8413237, PubMed:9201723, PubMed:19956733).PTM Myristoylation is required prior to palmitoylation.DISRUPTION PHENOTYPE Mice have various neural defects, including defective long term potentiation, impaired spatial memory, hypomyelination, abnormal dendrite orientation and uncoordinated hippocampal structure.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily. UniProt P39688 2 EQUAL 537 EQUAL Reactome Database ID Release 78 420333 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=420333 Reactome R-MMU-420333 2 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-420333.2 Yes1 YES1 Q04736 Reactome DB_ID: 9772794 UniProt:Q04736 Yes1 UniProt Q04736 2 EQUAL 543 EQUAL Reactome Database ID Release 78 9772794 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=9772794 Reactome R-MMU-373640 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-373640.1 Reactome Database ID Release 78 9808286 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=9808286 Reactome R-MMU-1861597 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1861597.1 GENE ONTOLOGY GO:0004713 gene ontology term for cellular function MI MI:0355 Same Catalyst Activity Reactome Database ID Release 78 9808287 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=9808287 Reactome Database ID Release 78 9808289 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=9808289 Reactome R-MMU-2029459 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029459.1 After cross linking, Fc gamma receptors are sequestered to lipid rafts where they are complexed with some of the tyrosine kinases of Src family and undergo phosphorylation on the tyrosine residues contained in conserved ITAM sequences. At least six out of nine members of the Src family kinases (SRC, FYN, FGR, HCK, YES and LYN ) have been identified in the phagocytic cells and are implicated in the initiation of Fc gamma mediated signaling. (Suzuki et al. 2000, Majeed et al. 2001, Kwiatkowska et al. 2003). Some of these kinases have been found associated with specific receptors. In monocytes HCK and LYN have been found associated with FCGRI (Durden et al. 1995), whereas only HCK with FCGRIIA (Ghazizadeh et al. 1994) while FGR in neutrophils (Hamada et al. 1993) and LCK in NK cells with FCGRIIIA (Pignata et al. 1993) <br>The implication of Src kinases in phosphorylation was first supported by pharmacological findings that herbimycin A, a tyrosine kinase inhibitor relatively specific for Src-family kinases, potently suppressed Fc receptor mediated functions (Greenberg et al. 1993, Suzuki et al. 2000). However, their particular involvement in phagocytosis remains unclear, as targeted disruption of single or multiple Src family genes did not result in significant alterations in phagocytosis (Hunter et al. 1993, Fitzer Attas et al. 2000, Suzuki et al. 2000). HCK, FGR and LYN triple-deficient (-/-) macrophages have shown significant delays in FCGR mediated phagocytosis, but these deficiencies do not completly disrupt the process (Fitzer Attas et al. 2000). <br>Tyrosine residues Y288 and Y304 (Y282 and Y298 according to the literature reference, it is 6 residues shorter compared to uniprot entry due to an alternate initiation codon usage), within ITAM sequence in the cytoplasmic domain of FCGRIIA are the key target sites that are phosphorylated by Src family kinases (Mitchell et al, 1994). In case of FCGRIA and FCGRIIIA the specific tyrosine residues within ITAMs of the associated gamma/zeta chains are phosphorylated by activated Src family kinases (SFKs) (Park et al. 1993). 8327512 Pubmed 1993 Association of immunoglobulin G Fc receptor II with Src-like protein-tyrosine kinase Fgr in neutrophils Hamada, F Aoki, M Akiyama, T Toyoshima, K Proc Natl Acad Sci U S A 90:6305-9 9000504 Pubmed 1997 Tyrosine phosphorylation and Fcgamma receptor-mediated phagocytosis Strzelecka, A Kwiatkowska, K Sobota, A FEBS Lett 400:11-4 11698501 Pubmed 2001 Role of Src kinases and Syk in Fcgamma receptor-mediated phagocytosis and phagosome-lysosome fusion Majeed, M Caveggion, E Lowell, CA Berton, G J Leukoc Biol 70:801-11 10684859 Pubmed 2000 Fcgamma receptor-mediated phagocytosis in macrophages lacking the Src family tyrosine kinases Hck, Fgr, and Lyn Fitzer-Attas, CJ Lowry, M Crowley, MT Finn, AJ Meng, F DeFranco, AL Lowell, CA J Exp Med 191:669-82 8132624 Pubmed 1994 Physical and functional association of Src-related protein tyrosine kinases with Fc gamma RII in monocytic THP-1 cells Ghazizadeh, S Bolen, JB Fleit, HB J Biol Chem 269:8878-84 8405229 Pubmed 1993 Fc gamma RIIA-mediated phagocytosis and receptor phosphorylation in cells deficient in the protein tyrosine kinase Src Hunter, S Huang, MM Indik, ZK Schreiber, AD Exp Hematol 21:1492-7 16921024 Pubmed 2006 Differential kinase requirements in human and mouse Fc-gamma receptor phagocytosis and endocytosis Huang, ZY Barreda, DR Worth, RG Indik, ZK Kim, MK Chien, P Schreiber, AD J Leukoc Biol 80:1553-62 12508114 Pubmed 2003 Phosphorylation of FcgammaRIIA is required for the receptor-induced actin rearrangement and capping: the role of membrane rafts Kwiatkowska, K Frey, J Sobota, A J Cell Sci 116:537-50 10861086 Pubmed 2000 Differential involvement of Src family kinases in Fc gamma receptor-mediated phagocytosis Suzuki, T Kono, H Hirose, N Okada, M Yamamoto, T Yamamoto, K Honda, Z J Immunol 165:473-82 1372004 Pubmed 1992 Activation of Fc gamma RII induces tyrosine phosphorylation of multiple proteins including Fc gamma RII Huang, MM Indik, Z Brass, LF Hoxie, JA Schreiber, AD Brugge, JS J Biol Chem 267:5467-73 7535819 Pubmed 1995 The Fc gamma RI receptor signals through the activation of hck and MAP kinase Durden, DL Kim, HM Calore, B Liu, Y J Immunol 154:4039-47 8258691 Pubmed 1993 Fc gamma RIIIA-mediated signaling involves src-family lck in human natural killer cells Pignata, C Prasad, KV Robertson, MJ Levine, H Rudd, CE Ritz, J J Immunol 151:6794-800 LEFT-TO-RIGHT Recruitment of SYK to phosphorylated ITAMs 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> Syk SYK P48025 Reactome DB_ID: 9759903 UniProt:P48025 Syk Syk ptk72 Sykb FUNCTION Non-receptor tyrosine kinase which mediates signal transduction downstream of a variety of transmembrane receptors including classical immunoreceptors like the B-cell receptor (BCR). Regulates several biological processes including innate and adaptive immunity, cell adhesion, osteoclast maturation, platelet activation and vascular development. Assembles into signaling complexes with activated receptors at the plasma membrane via interaction between its SH2 domains and the receptor tyrosine-phosphorylated ITAM domains. The association with the receptor can also be indirect and mediated by adapter proteins containing ITAM or partial hemITAM domains. The phosphorylation of the ITAM domains is generally mediated by SRC subfamily kinases upon engagement of the receptor. More rarely signal transduction via SYK could be ITAM-independent. Direct downstream effectors phosphorylated by SYK include VAV1, PLCG1, PI-3-kinase, LCP2 and BLNK. Initially identified as essential in B-cell receptor (BCR) signaling, it is necessary for the maturation of B-cells most probably at the pro-B to pre-B transition. Activated upon BCR engagement, it phosphorylates and activates BLNK an adapter linking the activated BCR to downstream signaling adapters and effectors. It also phosphorylates and activates PLCG1 and the PKC signaling pathway. It also phosphorylates BTK and regulates its activity in B-cell antigen receptor (BCR)-coupled signaling. In addition to its function downstream of BCR plays also a role in T-cell receptor signaling. Plays also a crucial role in the innate immune response to fungal, bacterial and viral pathogens. It is for instance activated by the membrane lectin CLEC7A. Upon stimulation by fungal proteins, CLEC7A together with SYK activates immune cells inducing the production of ROS. Also activates the inflammasome and NF-kappa-B-mediated transcription of chemokines and cytokines in presence of pathogens. Regulates neutrophil degranulation and phagocytosis through activation of the MAPK signaling cascade. Required for the stimulation of neutrophil phagocytosis by IL15 (By similarity). Also mediates the activation of dendritic cells by cell necrosis stimuli. Also involved in mast cells activation. Involved in interleukin-3/IL3-mediated signaling pathway in basophils (PubMed:19098920). Also functions downstream of receptors mediating cell adhesion. Relays for instance, integrin-mediated neutrophils and macrophages activation and P-selectin receptor/SELPG-mediated recruitment of leukocytes to inflammatory loci. Plays also a role in non-immune processes. It is for instance involved in vascular development where it may regulate blood and lymphatic vascular separation. It is also required for osteoclast development and function. Functions in the activation of platelets by collagen, mediating PLCG2 phosphorylation and activation. May be coupled to the collagen receptor by the ITAM domain-containing FCER1G. Also activated by the membrane lectin CLEC1B that is required for activation of platelets by PDPN/podoplanin. Involved in platelet adhesion being activated by ITGB3 engaged by fibrinogen. Together with CEACAM20, enhances production of the cytokine CXCL8/IL-8 via the NFKB pathway and may thus have a role in the intestinal immune response (PubMed:26195794).ACTIVITY REGULATION Autoinhibited. Intramolecular binding of the interdomains A and B (also called linker region) to parts of the catalytic domain keep the catalytic center in an inactive conformation. The phosphorylation of the interdomains or the binding of the SH2 domains with dually phosphorylated ITAM domains on transmembrane proteins disrupt those intramolecular interactions allowing the kinase domain to adopt an active conformation. The phosphorylation of SYK and of the ITAM domains which is responsible for SYK activation is essentially mediated by SRC subfamily kinases, like LYN, upon transmembrane receptors engagement. May also be negatively regulated by PTPN6 through dephosphorylation (By similarity). Downstream signaling adapters and intermediates like BLNK or RHOH may mediate positive and/or negative feedback regulation. Negatively regulated by CBL and CBLB through ubiquitination and probable degradation. Phosphorylates SH3BP2 which in turn may regulate SYK through LYN (By similarity).SUBUNIT Interacts with LYN; phosphorylates SYK. Interacts with RHOH (phosphorylated); regulates mast cells activation. Interacts with NFAM1 (phosphorylated); probably involved in BCR signaling. Interacts with VAV1 (via SH2 domain); phosphorylates VAV1 upon BCR activation (By similarity). Interacts with GAB2 (phosphorylated); probably involved in IgE Fc receptor signaling. Interacts (via its SH2 domains) with CD79A (via its phosphorylated ITAM domain); the interaction stimulates SYK autophosphorylation and activation. Interacts (via SH2 domains) with FCER1G (via ITAM domain); activates SYK and mediates neutrophils and macrophages integrin-mediated activation. Interaction with FCER1G in basophils triggers IL3-induced IL4 production (PubMed:19098920). Interacts with ITGB2 and FGR; involved in ITGB2 downstream signaling. Interacts with ITGB3; upon activation by ITGB3 promotes platelet adhesion (By similarity). Interacts (via SH2 domains) with TYROBP (via ITAM domain); involved in neutrophils and macrophages integrin-mediated activation. Interacts with MSN and SELPLG; mediates the selectin-dependent activation of SYK by SELPLG (By similarity). Interacts with BLNK (via SH2 domain). Interacts (via the second SH2 domain) with USP25 (via C-terminus); phosphorylates USP25 and regulates USP25 intracellular levels (By similarity). Interacts (via SH2 domains) with CLEC1B (dimer) (By similarity). Interacts with CLEC7A; participates in leukocyte activation in presence of fungal pathogens. Interacts (phosphorylated) with SLA; may regulate SYK through CBL recruitment (By similarity). Interacts with YWHAG; attenuates BCR-induced membrane translocation and activation of SYK (By similarity). Interacts (via SH2 domains) with GCSAM; the interaction increases after B-cell receptor stimulation, resulting in enhanced SYK autophosphorylation and activity (By similarity). Interacts with TNS2; leading to the phosphorylation of SYK (By similarity). Interacts with FLNA (via filamin repeat 5); docks SYK to the plasma membrane (By similarity). Interacts with CEACAM1; lipopolysaccharide activated neutrophils induce phosphorylation of SYK resulting in the formation of a complex including TLR4 and the phosphorylated form of SYK and CEACAM1, which in turn, recruits PTPN6 that dephosphorylates SYK, reducing the production of reactive oxygen species (ROS) and lysosome disruption, leading to a reduction of the inflammasome activity (PubMed:22496641). Interacts (via SH2 domains) with CEACAM20 (phosphorylated form); the interaction further enhances CEACAM20 phosphorylation (PubMed:26195794). Interacts with IL15RA (By similarity).DOMAIN The SH2 domains mediate the interaction of SYK with the phosphorylated ITAM domains of transmembrane proteins. Some proteins like CLEC1B have a partial ITAM domain (also called hemITAM) containing a single YxxL motif. The interaction with SYK requires CLEC1B homodimerization (By similarity).PTM Autophosphorylated. Phosphorylated on tyrosine residues by LYN following receptors engagement. Phosphorylation on Tyr-317 creates a binding site for CBL, an adapter protein that serves as a negative regulator of BCR-stimulated calcium ion signaling. Phosphorylation at Tyr-342 creates a binding site for VAV1 (By similarity). Phosphorylation on Tyr-342 and Tyr-346 enhances the phosphorylation and activation of phospholipase C-gamma and the early phase of calcium ion mobilization via a phosphoinositide 3-kinase-independent pathway (By similarity). Phosphorylated on tyrosine residues in response to IL15 (By similarity). Phosphorylation on Ser-291 is very common, it peaks 5 minutes after BCR stimulation, and creates a binding site for YWHAG (By similarity). Phosphorylation at Tyr-624 creates a binding site for BLNK (By similarity). Dephosphorylated by PTPN6 (By similarity).PTM Ubiquitinated by CBLB after BCR activation; which promotes proteasomal degradation.DISRUPTION PHENOTYPE Embryos display severe systemic hemorrhage and mice are not viable dying perinatally. While T-cells development is not affected, the development of B-cells is impaired most probably at the pro-B to pre-B transition and mice lack mature B-cells.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. SYK/ZAP-70 subfamily. UniProt P48025 1 EQUAL 635 EQUAL Reactome Database ID Release 78 9759903 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=9759903 Reactome R-MMU-58268 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-58268.1 clustered IgG-Ag:p-FCGRs:SYK Reactome DB_ID: 9808240 1 1 Reactome Database ID Release 78 9808240 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=9808240 Reactome R-MMU-2029129 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029129.1 Reactome Database ID Release 78 9808242 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=9808242 Reactome R-MMU-2029452 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029452.1 SYK is a tyrosine kinase related to ZAP70 that is expressed in all hematopoietic cells and coimmunoprecipitates with the gamma chain associated with FCGRIIIA in macrophages and with FCERI in mast cells. SYK is very important for FCGR phagocytosis and is recruited to these phosphorylated ITAM residues through its two SRC homology 2 (SH2) domains (Agarwal et al. 1993). When SYK kinase expression is inhibited with antisense oligonucleotides both in vitro and in vivo, phagocytosis and inflammation are abolished (Matsuda et al. 1997). The domain structure of SYK comprises a regulatory region at the N-terminus consisting of a pair of SH2 domains separated by an inter-SH2 linker called interdomain A, an SH2-domain-kinase linker termed interdomain B, and a C-terminal kinase domain (Arias-Palomo et al. 2009). In resting state SYK exists in an auto-inhibited conformation by the interactions between the SH2-SH2 regulatory region and the inter-SH2 linker and the catalytic domain. This interdomain interaction reduces the conformational flexibility required by the kinase domain for catalysis (Arias-Palomo et al. 2007). Changes in the orientation of the SH2 domains could control the disruption of the auto inhibitory interactions and the activation of SYK. These movements could be totally or partially induced by the binding to phosphorylated ITAMs and/or phosphorylation of tyrosine residues in interdomain A or B (Arias-Palomo et al. 2009). Tsang et al. suggested that SYK functions as an OR-gate switch with respect to phosphorylation and ITAM binding, as either one stimulus OR the other is sufficient to cause full activation (Tsang et al. 2008). 18818202 Pubmed 2008 Molecular mechanism of the Syk activation switch Tsang, E Giannetti, AM Shaw, D Dinh, M Tse, JK Gandhi, S Ho, H Wang, S Papp, E Bradshaw, JM J Biol Chem 283:32650-9 9314552 Pubmed 1997 A critical role for Syk in signal transduction and phagocytosis mediated by Fcgamma receptors on macrophages Crowley, MT Costello, PS Fitzer-Attas, CJ Turner, M Meng, F Lowell, C Tybulewicz, VL DeFranco, AL J Exp Med 186:1027-39 7522622 Pubmed 1994 Protein-tyrosine kinase p72syk in Fc gamma RI receptor signaling Durden, DL Liu, YB Blood 84:2102-8 8340414 Pubmed 1993 Involvement of p72syk, a protein-tyrosine kinase, in Fc gamma receptor signaling Agarwal, A Salem, P Robbins, KC J Biol Chem 268:15900-5 18021750 Pubmed 2007 3D structure of Syk kinase determined by single-particle electron microscopy Arias-Palomo, E Recuero-Checa, MA Bustelo, XR Llorca, O Biochim Biophys Acta 1774:1493-9 7530449 Pubmed 1995 Tyrosine phosphorylation and association of Syk with Fc gamma RII in monocytic THP-1 cells Ghazizadeh, S Bolen, JB Fleit, HB Biochem J 305:669-74 8226994 Pubmed 1993 Cross-linking of Fc gamma receptor I (Fc gamma RI) and receptor II (Fc gamma RII) on monocytic cells activates a signal transduction pathway common to both Fc receptors that involves the stimulation of p72 Syk protein tyrosine kinase Kiener, PA Rankin, BM Burkhardt, AL Schieven, GL Gilliland, LK Rowley, RB Bolen, JB Ledbetter, JA J Biol Chem 268:24442-8 8862523 Pubmed 1996 Abrogation of the Fc gamma receptor IIA-mediated phagocytic signal by stem-loop Syk antisense oligonucleotides Matsuda, M Park, JG Wang, DC Hunter, S Chien, P Schreiber, AD Mol Biol Cell 7:1095-106 Reactome Database ID Release 78 9862302 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=9862302 Reactome R-MMU-2029481 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029481.1 Cross-linking of FCGRs with IgG coated immune complexes results in tyrosine phosphorylation of the immuno tyrosine activation motif (ITAMs) of the rececptor by membrane-bound tyrosine kinases of the SRC family. The phosphorylated ITAM tyrosines serve as docking sites for Src homology 2 (SH2) domain-containing SYK kinase. Recruitment and activation of SYK is critical for FCGR-mediated signaling in phagocytosis, but the exact role of SYK in this process is unclear. Activated SYK then transmits downstream signals leading to actin polymerization and particle internalization. 18322649 Pubmed 2008 Molecular mechanisms of phagocytic uptake in mammalian cells Groves, E Dart, AE Covarelli, V Caron, E Cell Mol Life Sci 65:1957-76 17050193 Pubmed 2006 Fcgamma receptor signaling in phagocytes Joshi, T Butchar, JP Tridandapani, S Int J Hematol 84:210-6 Regulation of actin dynamics for phagocytic cup formation This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> LEFT-TO-RIGHT Recruitment of VAV1 to p-6Y-SYK 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> clustered IgG-Ag:p-FCGRs:p-6Y-SYK Reactome DB_ID: 9808211 1 P48025 phospho-Syk p-6Y-SYK Reactome DB_ID: 9794521 348 EQUAL 352 EQUAL 525 EQUAL 526 EQUAL 131 EQUAL 323 EQUAL 1 EQUAL 635 EQUAL Reactome Database ID Release 78 9794521 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=9794521 Reactome R-MMU-983586 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-983586.1 1 Reactome Database ID Release 78 9808211 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=9808211 Reactome R-MMU-2029158 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029158.1 PIP3 PI(3,4,5)P3 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate Phosphatidylinositol-3,4,5-trisphosphate Reactome DB_ID: 179838 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate [ChEBI:16618] 1-phosphatidyl-1D-myo-inositol 3,4,5-trisphosphate PIP3 ChEBI CHEBI:16618 Reactome Database ID Release 78 179838 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=179838 Reactome R-ALL-179838 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-179838.3 COMPOUND C05981 Converted from EntitySet in Reactome VAV1,2,3 VAV1,VAV2,VAV3 Reactome DB_ID: 9783413 Vav1 Proto-oncogene vav VAV_MOUSE Vav1 Reactome DB_ID: 434625 UniProt:P27870 Vav1 Vav1 Vav FUNCTION Couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation.SUBUNIT Interacts with SHB (By similarity). Interacts with APS, DOCK2, GRB2, GRB3, DOCK2, SLA, TEC and ZNF655/VIK. Interacts with SIAH2; without leading to its degradation. Associates with BLNK, PLCG1, GRB2 and NCK1 in a B-cell antigen receptor-dependent fashion. Interacts with CBLB; which inhibits tyrosine phosphorylation and down-regulates activity (PubMed:10646609, PubMed:10646608). May interact with CCPG1 (PubMed:17000758). Interacts with CLNK (PubMed:11463797). Interacts with THEMIS2 (PubMed:20644716). Interacts with NEK3 and this interaction is prolactin-dependent. Interacts with ITK. Interacts with PTK2B/PYK2 (By similarity). Interacts with HCK. Interacts with PTK2B/PYK2. Interacts (via SH2 domain) with SYK (By similarity). Interacts with ANKRD54 (PubMed:19064729). Interacts with CD6 (PubMed:24584089). Interacts with isoform 2 of CRACR2A (By similarity).TISSUE SPECIFICITY Widely expressed in hematopoietic cells but not in other cell types. Found in the spleen and lung.DOMAIN The DH domain is involved in interaction with CCPG1.PTM Phosphorylated by FYN (By similarity). Phosphorylated on tyrosine residues by HCK in response to IFNG and bacterial lipopolysaccharide (LPS). UniProt P27870 1 EQUAL 845 EQUAL Reactome Database ID Release 78 434625 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=434625 Reactome R-MMU-434625 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-434625.1 Vav2 VAV2 Q60992 Reactome DB_ID: 9772585 UniProt:Q60992 Vav2 Vav2 FUNCTION Guanine nucleotide exchange factor for the Rho family of Ras-related GTPases. Plays an important role in angiogenesis. Its recruitment by phosphorylated EPHA2 is critical for EFNA1-induced RAC1 GTPase activation and vascular endothelial cell migration and assembly.SUBUNIT Interacts (via SH2 domains) with the phosphorylated form of EPHA2. Interacts with NEK3 and PRLR and this interaction is prolactin-dependent (By similarity). Interacts with SSX2IP.PTM Phosphorylated on tyrosine residues in response to FGR activation. UniProt Q60992 1 EQUAL 878 EQUAL Reactome Database ID Release 78 9772585 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=9772585 Reactome R-MMU-195012 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-195012.1 Vav3 VAV3 Q9R0C8 Reactome DB_ID: 9772589 UniProt:Q9R0C8 Vav3 UniProt Q9R0C8 1 EQUAL 847 EQUAL Reactome Database ID Release 78 9772589 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=9772589 Reactome R-MMU-430152 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-430152.1 Reactome Database ID Release 78 9783413 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=9783413 Reactome R-MMU-430172 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-430172.1 clustered IgG-Ag:p-FCGRs:p-6Y-SYK:VAV Reactome DB_ID: 9808244 1 1 1 Reactome Database ID Release 78 9808244 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=9808244 Reactome R-MMU-2029133 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029133.1 Reactome Database ID Release 78 9808280 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=9808280 Reactome R-MMU-2029458 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029458.1 VAV family members are cytoplasmic guanine nucleotide exchange factors (GEFs) for Rho-family GTPases (RAC, RHO and CDC42). VAV1 is found predominantly in hematopoietic cells, whereas VAV2 and VAV3 are more broadly expressed. VAV proteins link the cell surface receptors like FCGR to the intracellular Rho GTPases and the actin cytoskeleton during phagocytosis (Hall et al 2006). Experiments using two-hybrid system suggest that VAV1 with its SH2 domain directly binds to the phosphorylated Y342 of SYK (Deckert et al. 1996). VAV proteins are also recruited to membrane through their PH domain by binding PI(3,4,5)P3 produced by PI3K. 8986718 Pubmed 1996 Functional and physical interactions of Syk family kinases with the Vav proto-oncogene product Deckert, M Tartare-Deckert, S Couture, C Mustelin, T Altman, A Immunity 5:591-604 16546099 Pubmed 2006 Requirements for Vav guanine nucleotide exchange factors and Rho GTPases in FcgammaR- and complement-mediated phagocytosis Hall, AB Gakidis, MA Glogauer, M Wilsbacher, JL Gao, S Swat, W Brugge, JS Immunity 24:305-16 LEFT-TO-RIGHT 2.7.10 Phosphorylation of VAV 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> clustered IgG-Ag:p-FCGRs:p-6Y-SYK:p-VAV Reactome DB_ID: 9808235 1 Converted from EntitySet in Reactome p-VAV family Reactome DB_ID: 9808233 P27870 phospho-Vav1 p-Y174-VAV1 Reactome DB_ID: 9784044 174 EQUAL 1 EQUAL 845 EQUAL Reactome Database ID Release 78 9784044 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=9784044 Reactome R-MMU-437946 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-437946.1 Q60992 phospho-Vav2 p-Y172-VAV2 Reactome DB_ID: 9784066 172 EQUAL 1 EQUAL 878 EQUAL Reactome Database ID Release 78 9784066 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=9784066 Reactome R-MMU-442307 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-442307.1 Q9R0C8 phospho-Vav3 p-Y173-VAV3 Reactome DB_ID: 9784078 173 EQUAL 1 EQUAL 847 EQUAL Reactome Database ID Release 78 9784078 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=9784078 Reactome R-MMU-442287 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-442287.1 Reactome Database ID Release 78 9808233 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=9808233 Reactome R-MMU-2029115 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029115.1 1 Reactome Database ID Release 78 9808235 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=9808235 Reactome R-MMU-2029131 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029131.1 ACTIVATION activeUnit: #Protein174 Reactome Database ID Release 78 9808245 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=9808245 Reactome Database ID Release 78 9808247 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=9808247 Reactome R-MMU-2029453 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029453.1 VAV proteins exist in an auto-inhibitory state folded in such a way as to inhibit the GEF activity of its DH domain. This folding is mediated through binding of tyrosines in the acidic domain to the DH domain and through binding of the CH domain to the C1 region. Activation of VAV may involve at least three different events to relieve this auto-inhibition. Phosphorylation of the tyrosines in the acidic domain causes them to be displaced from the DH domain, binding of a ligand to the CH domain may cause it to release the C1 domain and binding of PIP3 to PH domain may alter its conformation. VAV1 is phosphorylated on Y174 in the acidic domain, and this is mediated by Syk and Src-family tyrosine kinases. Once activated, VAV1 is then involved in the activation of RAC and CDC42 downstream of FCGR. 8809042 Pubmed 1996 Vav in natural killer cells is tyrosine phosphorylated upon cross-linking of Fc gamma RIIIA and is constitutively associated with a serine/threonine kinase Xu, X Chong, AS Biochem J 318:527-32 12670394 Pubmed 2003 Vav1: a key signal transducer downstream of the TCR Tybulewicz, VL Ardouin, L Prisco, A Reynolds, LF Immunol Rev 192:42-52 LEFT-TO-RIGHT Activation of RAC1 by VAV 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> GTP Guanosine 5'-triphosphate GTP)(4-) Reactome DB_ID: 29438 GTP(4-) [ChEBI:37565] GTP(4-) GTP gtp guanosine 5'-triphosphate(4-) ChEBI CHEBI:37565 Reactome Database ID Release 78 29438 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=29438 Reactome R-ALL-29438 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29438.4 COMPOUND C00044 RAC1:GDP Reactome DB_ID: 9808231 GDP Guanosine 5'-diphosphate Guanosine diphosphate GDP(3-) Reactome DB_ID: 29420 GDP(3-) [ChEBI:58189] GDP(3-) 5'-O-[(phosphonatooxy)phosphinato]guanosine guanosine 5'-diphosphate(3-) GDP guanosine 5'-diphosphate trianion guanosine 5'-diphosphate GDP trianion ChEBI CHEBI:58189 Reactome Database ID Release 78 29420 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=29420 Reactome R-ALL-29420 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-29420.3 COMPOUND C00035 1 Rac1 Ras-related C3 botulinum toxin substrate 1 RAC1_MOUSE Rac1 Reactome DB_ID: 2316449 UniProt:P63001 Rac1 Rac1 FUNCTION Plasma membrane-associated small GTPase which cycles between active GTP-bound and inactive GDP-bound states (PubMed:24352656). In its active state, binds to a variety of effector proteins to regulate cellular responses such as secretory processes, phagocytosis of apoptotic cells, epithelial cell polarization, neurons adhesion, migration and differentiation, and growth-factor induced formation of membrane ruffles. Rac1 p21/rho GDI heterodimer is the active component of the cytosolic factor sigma 1, which is involved in stimulation of the NADPH oxidase activity in macrophages. Essential for the SPATA13-mediated regulation of cell migration and adhesion assembly and disassembly. Stimulates PKN2 kinase activity. In concert with RAB7A, plays a role in regulating the formation of RBs (ruffled borders) in osteoclasts. In glioma cells, promotes cell migration and invasion. Required for atypical chemokine receptor ACKR2-induced LIMK1-PAK1-dependent phosphorylation of cofilin (CFL1) and for up-regulation of ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation. In podocytes, promotes nuclear shuttling of NR3C2; this modulation is required for a proper kidney functioning. In neurons, is involved in dendritic spine formation and synaptic plasticity (PubMed:24352656, PubMed:26969129). In hippocampal neurons, involved in spine morphogenesis and synapse formation, through local activation at synapses by guanine nucleotide exchange factors (GEFs), such as ARHGEF6/ARHGEF7/PIX (PubMed:12695502). In synapses, seems to mediate the regulation of F-actin cluster formation performed by SHANK3. In neurons, plays a crucial role in regulating GABA(A) receptor synaptic stability and hence GABAergic inhibitory synaptic transmission through its role in PAK1 activation and eventually F-actin stabilization (By similarity).ACTIVITY REGULATION Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. GTP hydrolysis is stimulated by ARHGAP30 and ARHGAP44.SUBUNIT Interacts with the GEF proteins PREX1, FARP1, FARP2, DOCK1, DOCK2 and DOCK7, which promote the exchange between GDP and GTP, and therefore activate it. Part of a quaternary complex containing PARD3, some PARD6 protein (PARD6A, PARD6B or PARD6G) and some atypical PKC protein (PRKCI or PRKCZ), which plays a central role in epithelial cell polarization. Found in a trimeric complex composed of DOCK1 and ELMO1, which plays a central role in phagocytosis of apoptotic cells. Interacts with RALBP1 via its effector domain. Interacts with BAIAP2, BAIAP2L1, PLXNB1, CYFIP1/SRA-1 and DEF6. Probably found in a ternary complex composed of DSCAM, PAK1 and RAC1. Interacts with DSCAM; the interaction requires PAK1. Interacts with TBC1D2. Interacts with UNKL. Interacts with USP6. Interacts with SPATA13. Interacts with ITGB4. Interacts with the GTP-bound form of RAB7A. Interacts with ARHGEF2. Interacts with ARHGEF16; mediates activation of RAC1 by EPHA2. Interacts with NOXA1. Interacts with S100A8 and calprotectin (S100A8/9). Interacts with ARHGDIA; the interaction is induced by SEMA5A, mediated through PLXNB3 and inactivates and stabilizes RAC1. Interacts with PACSIN2. Interacts with ITGB1BP1 (By similarity). Interacts with the GEF protein RASGRF2, which promotes the exchange between GDP and GTP, and therefore activates it. Interacts with PARD6A, PARD6B and PARD6G in a GTP-dependent manner. Part of a complex with MAP2K3, MAP3K3 and CCM2. Interacts with NISCH. Interacts with PIP5K1A. Interacts (GTP-bound form preferentially) with PKN2 (via the REM repeats); the interaction stimulates autophosphorylation and phosphorylation of PKN2. Interacts with SRGAP2. Interacts with PLXNB3. Interacts (when active) with PPP5C (via TPR repeats); activates PPP5C phosphatase activity and translocates PPP5C to the cell membrane. Interacts with RAPH1 (via Ras associating and PH domains) (By similarity). Interacts with MTSS2 (via IMD domain); this interaction may be important to potentiate PDGF-induced RAC1 activation. Interacts (GTP-bound form) with SH3RF3. Interacts with PAK2 (By similarity). Interacts (GTP-bound form) with SH3RF1 (PubMed:22959435). Found in a complex with SH3RF1, MAPK8IP1/JIP1, MAP3K11/MLK3, MAP2K7/MKK7 and MAPK8/JNK1 (PubMed:23963642). Interacts (both active GTP- or inactive GDP-bound forms) with SH3RF2 (By similarity). Interacts (GTP-bound form preferentially) with CYRIB (By similarity). Interacts with DOCK4 (via DOCKER domain); functions as a guanine nucleotide exchange factor (GEF) for RAC1 (By similarity). Interacts with GARRE1 (By similarity).TISSUE SPECIFICITY Widely expressed.DEVELOPMENTAL STAGE Expressed in the neocortical neurons in the developing brain.DOMAIN The effector region mediates interaction with DEF6.PTM GTP-bound active form is ubiquitinated by HACE1, leading to its degradation by the proteasome.DISRUPTION PHENOTYPE Conditional knockout of Rac1 in the telencephalic ventricular zone of embryos leads to primary microcephaly. Self-renewal, survival, and differentiation of telencephalic neural progenitor cells is affected.SIMILARITY Belongs to the small GTPase superfamily. Rho family. UniProt P63001 1 EQUAL 189 EQUAL Reactome Database ID Release 78 2316449 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=2316449 Reactome R-MMU-2316449 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2316449.1 1 Reactome Database ID Release 78 9808231 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=9808231 Reactome R-MMU-5674631 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-5674631.1 Rac1:GTP Reactome DB_ID: 2316458 1 1 Reactome Database ID Release 78 2316458 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=2316458 Reactome R-MMU-2316458 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2316458.1 ACTIVATION activeUnit: #Protein179 GENE ONTOLOGY GO:0005085 Reactome Database ID Release 78 9808236 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=9808236 Reactome Database ID Release 78 9808238 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=9808238 Reactome R-MMU-2029451 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029451.1 The organized movements of membranes and the actin cytoskeleton are coordinated in phagocytosis by small GTPases of the Rho family. Specifically, RAC1 and CDC42 are known to be stimulated upon engagement of FCGR and are essential for the extension of the pseudopods that surround and engulf the phagocytic particle (Scott et al 2005). RAC1 is known to regulate actin dynamics. It is active throughout the phagocytic cup and activated RAC1 is necessary to assemble F actin. However, closing the phagocytic cup requires RAC1 to be deactivated (Naakaya et al 2007). Deletion of RAC1 prevents FCGR mediated phagocytosis (Hall et al 2006). RAC1 activation involves transition from an inactive GDP bound to an active GTP bound state catalysed by guanine exchanges factors (GEFs). VAV has been implicated in the activation of RAC1 (Patel et al 2002). 15169870 Pubmed 2004 Cdc42, Rac1, and Rac2 display distinct patterns of activation during phagocytosis Hoppe, AD Swanson, JA Mol Biol Cell 15:3509-19 18591655 Pubmed 2008 Spatiotemporal activation of Rac1 for engulfment of apoptotic cells Nakaya, M Kitano, M Matsuda, M Nagata, S Proc Natl Acad Sci U S A 105:9198-203 15809313 Pubmed 2005 Phosphatidylinositol-4,5-bisphosphate hydrolysis directs actin remodeling during phagocytosis Scott, CC Dobson, W Botelho, RJ Coady-Osberg, N Chavrier, P Knecht, DA Heath, C Stahl, P Grinstein, S J Cell Biol 169:139-49 8990121 Pubmed 1997 Phosphotyrosine-dependent activation of Rac-1 GDP/GTP exchange by the vav proto-oncogene product Crespo, P Schuebel, KE Ostrom, AA Gutkind, JS Bustelo, XR Nature 385:169-72 11950933 Pubmed 2002 Vav regulates activation of Rac but not Cdc42 during FcgammaR-mediated phagocytosis Patel, JC Hall, A Caron, E Mol Biol Cell 13:1215-26 LEFT-TO-RIGHT Recruitment of CRKII:DOCK180:ELMO complex to FCGR 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> CRK:DOCK180:ELMO1,ELMO2 Reactome DB_ID: 9808446 Crk CRK Q64010 Reactome DB_ID: 9764305 UniProt:Q64010 Crk UniProt Q64010 1 EQUAL 304 EQUAL Reactome Database ID Release 78 9764305 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=9764305 Reactome R-MMU-2980677 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2980677.1 1 Dock1 DOCK1 Q8BUR4 Reactome DB_ID: 9781306 UniProt:Q8BUR4 Dock1 UniProt Q8BUR4 1 EQUAL 1865 EQUAL Reactome Database ID Release 78 9781306 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=9781306 Reactome R-MMU-372654 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-372654.1 1 Converted from EntitySet in Reactome ELMO1,ELMO2 Reactome DB_ID: 9808444 Elmo1 ELMO1 Q8BPU7 Reactome DB_ID: 9808438 UniProt:Q8BPU7 Elmo1 UniProt Q8BPU7 1 EQUAL 727 EQUAL Reactome Database ID Release 78 9808438 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=9808438 Reactome R-MMU-200932 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-200932.1 Elmo2 ELMO2 Q8BHL5 Reactome DB_ID: 9808442 UniProt:Q8BHL5 Elmo2 UniProt Q8BHL5 1 EQUAL 720 EQUAL Reactome Database ID Release 78 9808442 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=9808442 Reactome R-MMU-372642 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-372642.1 Reactome Database ID Release 78 9808444 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=9808444 Reactome R-MMU-372640 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-372640.1 1 Reactome Database ID Release 78 9808446 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=9808446 Reactome R-MMU-2029141 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029141.1 CRKII:DOCK180:ELMO complex recruited to phagocytic cup Reactome DB_ID: 9808448 1 1 Reactome Database ID Release 78 9808448 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=9808448 Reactome R-MMU-2029130 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029130.1 Reactome Database ID Release 78 9811049 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=9811049 Reactome R-MMU-2197697 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2197697.1 Macrophages lacking all the three isoforms of VAV did not affect FCGR-mediated phagocytosis suggesting that RAC1 is regulated by GEFs other than VAV downstream of the FCGR (Hall et al 2006). DOCK180, a member of GEFs, is found to be involved in the activation of RAC1. DOCK180 associates with the adaptor protein CRKII and the complex is found to accumulate at the phagocytic cup. DOCK180 is recruited to the sites of phagocytosis by binding to SH3 domain of CRKII through its proline-rich motif (Hasegawa et al 1996). CRKII is likely recruited to the activated FCGR complex by binding phosphorylated ITAM tyrosines on the receptor or through other phosphotyrosines on ancillary proteins that are recruited to the receptor complex (Lee et al 2007). Unlike the usual GEFs, DOCK180 does not contain the conserved Dbl homology (DH) domain. Instead, it has a DHR-2 or DOCKER domain capable of loading RAC with GTP (Brugnera et al 2002). Binding of DOCK180 to RAC alone is insufficient for GTP loading, and a DOCK180-ELMO interaction is required. ELMO1, as well as ELMO2, form a complex with DOCK180 and they function together as a bipartite GEF to optimally activate RAC (Gumienny et al 2001, Brugnera et al 2002). 16472672 Pubmed 2006 Dock180-ELMO cooperation in Rac activation Lu, M Ravichandran, KS Methods Enzymol 406:388-402 8657152 Pubmed 1996 DOCK180, a major CRK-binding protein, alters cell morphology upon translocation to the cell membrane Hasegawa, H Kiyokawa, E Tanaka, S Nagashima, K Gotoh, N Shibuya, M Kurata, T Matsuda, M Mol Cell Biol 16:1770-6 12134158 Pubmed 2002 Unconventional Rac-GEF activity is mediated through the Dock180-ELMO complex Brugnera, E Haney, L Grimsley, C Lu, M Walk, SF Tosello-Trampont, AC Macara, IG Madhani, H Fink, GR Ravichandran, KS Nat Cell Biol 4:574-82 11595183 Pubmed 2001 CED-12/ELMO, a novel member of the CrkII/Dock180/Rac pathway, is required for phagocytosis and cell migration Gumienny, TL Brugnera, E Tosello-Trampont, AC Kinchen, JM Haney, LB Nishiwaki, K Walk, SF Nemergut, ME Macara, IG Francis, R Schedl, T Qin, Y Van Aelst, L Hengartner, MO Ravichandran, KS Cell 107:27-41 17308335 Pubmed 2007 Role of CrkII in Fcgamma receptor-mediated phagocytosis Lee, WL Cosio, G Ireton, K Grinstein, S J Biol Chem 282:11135-43 LEFT-TO-RIGHT Activation of RAC1 by CRKII:DOCK180:ELMO 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> ACTIVATION activeUnit: #Complex28 Reactome Database ID Release 78 9808449 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=9808449 Reactome Database ID Release 78 9808451 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=9808451 Reactome R-MMU-2029467 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029467.1 RAC1 is activated from inactive GDP-bound state to active GTP-bound form by the GEF activity of DOCK180:ELMO complex. LEFT-TO-RIGHT RAC1:GTP and PIP3 bind WAVE Regulatory Complex (WRC) 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> WAVE Regulatory Complex Reactome DB_ID: 9808344 Nckap1 NCKAP1 P28660 Reactome DB_ID: 9808300 UniProt:P28660 Nckap1 UniProt P28660 1 EQUAL 1128 EQUAL Reactome Database ID Release 78 9808300 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=9808300 Reactome R-MMU-200979 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-200979.1 1 Q8K1X4 Nckap1l NCKAP1L Reactome DB_ID: 9808342 UniProt:Q8K1X4 Nckap1l UniProt Q8K1X4 1 EQUAL 1127 EQUAL Reactome Database ID Release 78 9808342 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=9808342 Reactome R-MMU-5694031 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-5694031.1 1 Brk1 BRK1 Q91VR8 Reactome DB_ID: 9808304 UniProt:Q91VR8 Brk1 UniProt Q91VR8 2 EQUAL 75 EQUAL Reactome Database ID Release 78 9808304 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=9808304 Reactome R-MMU-1671645 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1671645.1 1 Converted from EntitySet in Reactome ABI Reactome DB_ID: 9808314 Abi1 ABI1 Q8CBW3 Reactome DB_ID: 9808308 UniProt:Q8CBW3 Abi1 UniProt Q8CBW3 2 EQUAL 508 EQUAL Reactome Database ID Release 78 9808308 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=9808308 Reactome R-MMU-1671643 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1671643.1 Abi2 ABI2 P62484 Reactome DB_ID: 9808312 UniProt:P62484 Abi2 UniProt P62484 1 EQUAL 513 EQUAL Reactome Database ID Release 78 9808312 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=9808312 Reactome R-MMU-1671647 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1671647.1 Reactome Database ID Release 78 9808314 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=9808314 Reactome R-MMU-1671649 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1671649.1 1 Converted from EntitySet in Reactome WAVEs Reactome DB_ID: 9808328 Wasf2 WASF2 Q8BH43 Reactome DB_ID: 9808318 UniProt:Q8BH43 Wasf2 UniProt Q8BH43 1 EQUAL 498 EQUAL Reactome Database ID Release 78 9808318 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=9808318 Reactome R-MMU-200972 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-200972.1 Wasf1 WASF1 Q8R5H6 Reactome DB_ID: 9808322 UniProt:Q8R5H6 Wasf1 UniProt Q8R5H6 1 EQUAL 559 EQUAL Reactome Database ID Release 78 9808322 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=9808322 Reactome R-MMU-200965 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-200965.1 Wasf3 WASF3 Q8VHI6 Reactome DB_ID: 9808326 UniProt:Q8VHI6 Wasf3 UniProt Q8VHI6 1 EQUAL 502 EQUAL Reactome Database ID Release 78 9808326 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=9808326 Reactome R-MMU-200975 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-200975.1 Reactome Database ID Release 78 9808328 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=9808328 Reactome R-MMU-2029114 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029114.1 1 Converted from EntitySet in Reactome CYFIP1,CYFIP2 Reactome DB_ID: 9808338 Cyfip1 CYFIP1 Q7TMB8 Reactome DB_ID: 9808332 UniProt:Q7TMB8 Cyfip1 UniProt Q7TMB8 1 EQUAL 1253 EQUAL Reactome Database ID Release 78 9808332 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=9808332 Reactome R-MMU-5672575 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-5672575.1 Cyfip2 CYFIP2 Q5SQX6 Reactome DB_ID: 9808336 UniProt:Q5SQX6 Cyfip2 UniProt Q5SQX6 1 EQUAL 1278 EQUAL Reactome Database ID Release 78 9808336 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=9808336 Reactome R-MMU-1671642 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1671642.1 Reactome Database ID Release 78 9808338 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=9808338 Reactome R-MMU-5672576 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-5672576.1 1 Reactome Database ID Release 78 9808344 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=9808344 Reactome R-MMU-2029154 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029154.1 Baiap2 BAIAP2 Q8BKX1 Reactome DB_ID: 9808296 UniProt:Q8BKX1 Baiap2 UniProt Q8BKX1 1 EQUAL 552 EQUAL Reactome Database ID Release 78 9808296 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=9808296 Reactome R-MMU-442574 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-442574.1 WRC:IRSp53/58:RAC1:GTP:PIP3 Reactome DB_ID: 9808346 1 1 1 1 Reactome Database ID Release 78 9808346 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=9808346 Reactome R-MMU-2029147 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029147.1 Reactome Database ID Release 78 9808348 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=9808348 Reactome R-MMU-2029465 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029465.1 WASP family verprolin-homologous proteins (WAVEs) function downstream of RAC1 and are involved in activation of the ARP2/3 complex. The resulting actin polymerization mediates the projection of the plasma membrane in lamellipodia and membrane ruffles. WAVEs exist as a pentameric hetero-complex called WAVE Regulatory Complex (WRC). The WRC consists of a WAVE family protein (WASF1, WASF2 or WASF3 - commonly known as WAVE1, WAVE2 or WAVE3), ABI (Abelson-interacting protein), NCKAP1 (NAP1, p125NAP1), CYFIP1 (SRA1) or the closely related CYFIP2 (PIR121), and BRK1 (HSPC300, BRICK). Of the three structurally conserved WAVEs in mammals, the importance of WAVE2 in activation of the ARP2/3 complex and the consequent formation of branched actin filaments is best established. WAVEs in the WRC are intrinsically inactive and are stimulated by RAC1 GTPase and phosphatidylinositols (PIP3). The C-terminal VCA domain of WAVE2 (and likely WAVE1 and WAVE3) which can bind both the ARP2/3 complex and actin monomers (G-actin) is masked in the inactive state. After PIP3 binds to the polybasic region of WAVE2 (and likely WAVE1 and WAVE3) and RAC1:GTP binds to the CYFIP1 (or CYFIP2) subunit of the WRC, allosteric changes most likely occur which allow WAVEs to interact with the ARP2/3 complex. The interactions between WAVEs and RAC1 are indirect. BAIAP2/IRSp53, an insulin receptor substrate, acts as a linker, binding both activated RAC1 and the proline-rich region of WAVE2 (and likely WAVE1 and WAVE3) and forming a trimolecular complex. CYFIP1 (or CYFIP2) in the WAVE regulatory complex binds directly to RAC1:GTP and links it to WAVE2 (and likely WAVE1 and WAVE3) (Derivery et al. 2009, Yamazaki et al. 2006, Takenawa & Suetsugu 2007, Chen et al. 2010, Pollard 2007, Lebensohn & Kirschner 2009). 16702231 Pubmed 2006 Optimization of WAVE2 complex-induced actin polymerization by membrane-bound IRSp53, PIP(3), and Rac Suetsugu, S Kurisu, S Oikawa, T Yamazaki, D Oda, A Takenawa, T J Cell Biol 173:571-85 19917258 Pubmed 2009 Activation of the WAVE complex by coincident signals controls actin assembly Lebensohn, AM Kirschner, Marc W Mol Cell 36:512-24 19206172 Pubmed 2009 The Wave complex is intrinsically inactive Derivery, E Lombard, B Loew, D Gautreau, A Cell Motil Cytoskeleton 66:777-90 17164293 Pubmed 2007 Rac-WAVE-mediated actin reorganization is required for organization and maintenance of cell-cell adhesion Yamazaki, D Oikawa, T Takenawa, T J Cell Sci 120:86-100 17183359 Pubmed 2007 The WASP-WAVE protein network: connecting the membrane to the cytoskeleton Takenawa, T Suetsugu, S Nat Rev Mol Cell Biol 8:37-48 17477841 Pubmed 2007 Regulation of actin filament assembly by Arp2/3 complex and formins Pollard, TD Annu Rev Biophys Biomol Struct 36:451-77 21107423 Pubmed 2010 Structure and control of the actin regulatory WAVE complex Chen, Z Borek, D Padrick, SB Gomez, TS Metlagel, Z Ismail, AM Umetani, J Billadeau, DD Otwinowski, Z Rosen, MK Nature 468:533-8 9843499 Pubmed 1998 WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac Miki, H Suetsugu, S Takenawa, T EMBO J 17:6932-41 LEFT-TO-RIGHT 2.7.11 p-ERK phosphorylates WAVEs and ABI 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> 8 p-Y-WRC:IRSp53/58:RAC1:GTP:PIP3 Reactome DB_ID: 9808426 1 1 1 p-Y-WRC Reactome DB_ID: 9808424 1 Converted from EntitySet in Reactome p-Y-WAVE Reactome DB_ID: 9808422 Q8BH43 phospho-Wasf2 p-Y150-WASF2 Reactome DB_ID: 9808416 150 EQUAL 1 EQUAL 498 EQUAL Reactome Database ID Release 78 9808416 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=9808416 Reactome R-MMU-2130193 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2130193.1 Q8R5H6 phospho-Wasf1 p-Y151-WASF1 Reactome DB_ID: 9808418 151 EQUAL 1 EQUAL 559 EQUAL Reactome Database ID Release 78 9808418 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=9808418 Reactome R-MMU-2029058 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029058.1 Q8VHI6 phospho-Wasf3 p-Y151-WASF3 Reactome DB_ID: 9808420 151 EQUAL 1 EQUAL 502 EQUAL Reactome Database ID Release 78 9808420 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=9808420 Reactome R-MMU-2029006 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029006.1 Reactome Database ID Release 78 9808422 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=9808422 Reactome R-MMU-2029107 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029107.1 1 1 1 1 1 Reactome Database ID Release 78 9808424 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=9808424 Reactome R-MMU-2130185 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2130185.1 1 Reactome Database ID Release 78 9808426 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=9808426 Reactome R-MMU-2130182 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2130182.1 8 p-Y,S,T-WRC:IRSp53/58:RAC1:GTP:PIP3 Reactome DB_ID: 9808414 p-Y,S,T-WRC Reactome DB_ID: 9808412 1 1 1 Converted from EntitySet in Reactome p-ABI Reactome DB_ID: 9808393 Q8CBW3 phospho-Abi1 p-5S-ABI1 Reactome DB_ID: 9808385 183 EQUAL O-phospho-L-serine MOD MOD:00046 216 EQUAL 225 EQUAL 392 EQUAL 410 EQUAL 2 EQUAL 508 EQUAL Reactome Database ID Release 78 9808385 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=9808385 Reactome R-MMU-2029034 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029034.1 P62484 phospho-Abi2 p-4S-ABI2 Reactome DB_ID: 9808391 183 EQUAL 216 EQUAL 225 EQUAL 410 EQUAL 1 EQUAL 513 EQUAL Reactome Database ID Release 78 9808391 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=9808391 Reactome R-MMU-2029003 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029003.1 Reactome Database ID Release 78 9808393 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=9808393 Reactome R-MMU-2029100 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029100.1 1 Converted from EntitySet in Reactome p-Y,S,T-WAVE Reactome DB_ID: 9808410 Q8BH43 phospho-Wasf2 p-Y150,S343,T346-WASF2 Reactome DB_ID: 9808398 343 EQUAL 346 EQUAL O-phospho-L-threonine MOD MOD:00047 1 EQUAL 498 EQUAL Reactome Database ID Release 78 9808398 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=9808398 Reactome R-MMU-2130179 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2130179.1 Q8R5H6 phospho-Wasf1 p-Y151,S,T-WASF1 Reactome DB_ID: 9808403 1 EQUAL 559 EQUAL Reactome Database ID Release 78 9808403 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=9808403 Reactome R-MMU-5672390 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-5672390.1 Q8VHI6 phospho-Wasf3 p-Y151,S,T-WASF3 Reactome DB_ID: 9808408 1 EQUAL 502 EQUAL Reactome Database ID Release 78 9808408 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=9808408 Reactome R-MMU-5672385 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-5672385.1 Reactome Database ID Release 78 9808410 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=9808410 Reactome R-MMU-2263504 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2263504.1 1 1 Reactome Database ID Release 78 9808412 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=9808412 Reactome R-MMU-2029134 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029134.1 1 1 1 1 Reactome Database ID Release 78 9808414 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=9808414 Reactome R-MMU-2029148 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029148.1 ACTIVATION Converted from EntitySet in Reactome p-ERK dimer p-T,Y MAPK dimers Reactome DB_ID: 9764810 p-T202, Y204 MAPK3 dimer Reactome DB_ID: 9764806 Q63844 phospho-Mapk3 p-T202,Y204-MAPK3 Reactome DB_ID: 9758324 UniProt:Q63844 Mapk3 Mapk3 Erk1 Prkm3 FUNCTION Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade.ACTIVITY REGULATION Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-203 and Tyr-205 in response to external stimuli like insulin or NGF. Both phosphorylations are required for activity. This phosphorylation causes dramatic conformational changes, which enable full activation and interaction of MAPK1/ERK2 with its substrates. Dephosphorylated and inactivated by DUSP3, DUSP6 and DUSP9.SUBUNIT Binds both upstream activators and downstream substrates in multimolecular complexes. Found in a complex with at least BRAF, HRAS, MAP2K1/MEK1, MAPK3 and RGS14. Interacts with TPR. Interacts with ADAM15, ARRB2, CANX, DAPK1 (via death domain), HSF4, IER3, MAP2K1/MEK1, NISCH, and SGK1 (By similarity). Interacts with MORG1 (PubMed:15118098). Interacts with PEA15 (PubMed:11702783). Interacts with isoform 1 of MKNK2 and this binding prevents from dephosphorylation and inactivation (PubMed:16162500). Interacts with CDKN2AIP. Interacts with HSF1 (via D domain and preferentially with hyperphosphorylated form); this interaction occurs upon heat shock. Interacts with CAVIN4 (By similarity). Interacts with GIT1; this interaction is necessary for MAPK3 localization to focal adhesions (PubMed:15923189). Interacts with ZNF263 (By similarity).DOMAIN The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.PTM Dually phosphorylated on Thr-203 and Tyr-205, which activates the enzyme. Ligand-activated ALK induces tyrosine phosphorylation (By similarity). Dephosphorylated by PTPRJ at Tyr-205 (By similarity). Autophosphorylated on threonine and tyrosine residues in vitro. Phosphorylated upon FLT3 and KIT signaling (By similarity).SIMILARITY Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. UniProt Q63844 202 EQUAL 204 EQUAL 2 EQUAL 379 EQUAL Reactome Database ID Release 78 9758324 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=9758324 Reactome R-MMU-109842 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-109842.1 2 Reactome Database ID Release 78 9764806 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=9764806 Reactome R-MMU-109844 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-109844.1 p-T185,Y187 MAPK1 dimer Reactome DB_ID: 9764808 P63085 phospho-Mapk1 p-T185,Y187-MAPK1 Reactome DB_ID: 9758340 UniProt:P63085 Mapk1 Mapk1 Erk2 Mapk Prkm1 FUNCTION Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK cascade. They participate also in a signaling cascade initiated by activated KIT and KITLG/SCF. Depending on the cellular context, the MAPK/ERK cascade mediates diverse biological functions such as cell growth, adhesion, survival and differentiation through the regulation of transcription, translation, cytoskeletal rearrangements. The MAPK/ERK cascade plays also a role in initiation and regulation of meiosis, mitosis, and postmitotic functions in differentiated cells by phosphorylating a number of transcription factors. About 160 substrates have already been discovered for ERKs. Many of these substrates are localized in the nucleus, and seem to participate in the regulation of transcription upon stimulation. However, other substrates are found in the cytosol as well as in other cellular organelles, and those are responsible for processes such as translation, mitosis and apoptosis. Moreover, the MAPK/ERK cascade is also involved in the regulation of the endosomal dynamics, including lysosome processing and endosome cycling through the perinuclear recycling compartment (PNRC); as well as in the fragmentation of the Golgi apparatus during mitosis. The substrates include transcription factors (such as ATF2, BCL6, ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of translation (such as EIF4EBP1) and a variety of other signaling-related molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which enable the propagation the MAPK/ERK signal to additional cytosolic and nuclear targets, thereby extending the specificity of the cascade. Mediates phosphorylation of TPR in response to EGF stimulation. May play a role in the spindle assembly checkpoint. Phosphorylates PML and promotes its interaction with PIN1, leading to PML degradation. Phosphorylates CDK2AP2 (By similarity).FUNCTION Acts as a transcriptional repressor. Binds to a [GC]AAA[GC] consensus sequence. Repress the expression of interferon gamma-induced genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1, IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity is independent of kinase activity.ACTIVITY REGULATION Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on Thr-183 and Tyr-185 in response to external stimuli like insulin or NGF. Both phosphorylations are required for activity. This phosphorylation causes dramatic conformational changes, which enable full activation and interaction of MAPK1/ERK2 with its substrates. Phosphorylation on Ser-27 by SGK1 results in its activation by enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2. Dephosphorylated and inactivated by DUSP1, DUSP3, DUSP6 and DUSP9. Inactivated by pyrimidylpyrrole inhibitors.SUBUNIT Binds both upstream activators and downstream substrates in multimolecular complexes. This interaction inhibits its tyrosine-kinase activity. Interacts with ADAM15, ARHGEF2, ARRB2, DAPK1 (via death domain), HSF4, IER3, IPO7, DUSP6, NISCH, SGK1, and isoform 1 of NEK2. Interacts (via phosphorylated form) with TPR (via C-terminal region and phosphorylated form); the interaction requires dimerization of MAPK1/ERK2 and increases following EGF stimulation (By similarity). Interacts (phosphorylated form) with CAV2 ('Tyr-19'-phosphorylated form); the interaction, promoted by insulin, leads to nuclear location and MAPK1 activation. Interacts with DCC (By similarity). Interacts with MORG1 (PubMed:15118098). Interacts with PEA15 (PubMed:16162500). Interacts with MKNK2. MKNK2 isoform 1 binding prevents from dephosphorylation and inactivation (PubMed:11702783). The phosphorylated form interacts with PML. Interacts with STYX. Interacts with CDK2AP2. Interacts with CAVIN4 (By similarity). Interacts with DUSP7; the interaction enhances DUSP7 phosphatase activity (PubMed:27783954). Interacts with GIT1; this interaction is necessary for MAPK1 localization to focal adhesions (PubMed:15923189). Interacts with ZNF263 (By similarity).TISSUE SPECIFICITY Widely expressed.DOMAIN The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.PTM Dually phosphorylated on Thr-183 and Tyr-185, which activates the enzyme. Ligand-activated ALK induces tyrosine phosphorylation (By similarity). Dephosphorylated by PTPRJ at Tyr-185 (By similarity). Phosphorylated upon FLT3 and KIT signaling (By similarity). Dephosphorylated by DUSP1 at Thr-183 and Tyr-185 (PubMed:8221888).PTM ISGylated.SIMILARITY Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. UniProt P63085 185 EQUAL 187 EQUAL 2 EQUAL 360 EQUAL Reactome Database ID Release 78 9758340 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=9758340 Reactome R-MMU-109853 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-109853.1 2 Reactome Database ID Release 78 9764808 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=9764808 Reactome R-MMU-109855 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-109855.1 Reactome Database ID Release 78 9764810 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=9764810 Reactome R-MMU-1268261 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-1268261.1 GENE ONTOLOGY GO:0004674 Reactome Database ID Release 78 9808465 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=9808465 Reactome Database ID Release 78 9808467 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=9808467 Reactome R-MMU-2029469 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2029469.1 The ARP2/3 complex shows higher affinity for the phosphorylated VCA domain of WAVE2 than for the unphosphorylated VCA domain. WAVE proteins can be phosphorylated by various kinases. Active ERK (Mitogen activated protein kinase 3) phosphorylates the WAVE regulatory complex (WRC) on multiple serine/threonine sites within the proline-rich domains (PRDs) of WAVE2 and ABI1. Phosphorylation of the PRDs would disrupt their interaction with SH3 and PLP binding domains, potentially altering WRC activation. ERK phosphorylates both S343 and T346 in WAVE2 and S183, S216, S225, S392, and S410 in ABI1. Cumulatively, the phosphorylation of both WAVE2 and ABI in the WAVE regulatory complex (WRC) contributes to the RAC-induced WRC conformational change that exposes the VCA domain, leading to binding and activation of ARP2/3 (Mendoza et al. 2011, Nakanishi et al. 2007). ERK phosphorylation sites in WAVE2 are not strictly conserved in WAVE1 and WAVE3 but, based on the amino acid sequence, other potential ERK phosphorylation sites exist. 15657136 Pubmed 2005 Abelson-interactor-1 promotes WAVE2 membrane translocation and Abelson-mediated tyrosine phosphorylation required for WAVE2 activation Leng, Y Zhang, J Badour, K Arpaia, E Freeman, S Cheung, P Siu, M Siminovitch, K Proc Natl Acad Sci U S A 102:1098-103 21419341 Pubmed 2011 ERK-MAPK drives lamellipodia protrusion by activating the WAVE2 regulatory complex Mendoza, MC Er, EE Zhang, W Ballif, BA Elliott, HL Danuser, G Blenis, J Mol Cell 41:661-71 17202194 Pubmed 2007 Effect of WAVE2 phosphorylation on activation of the Arp2/3 complex Nakanishi, O Suetsugu, S Yamazaki, D Takenawa, T J Biochem 141:319-25 LEFT-TO-RIGHT 2.7.10 ABL phosphorylates WAVEs 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> 3 3 ACTIVATION Abl1 ABL1 P00520 Reactome DB_ID: 9776652 UniProt:P00520 Abl1 Abl1 Abl FUNCTION Non-receptor tyrosine-protein kinase that plays a role in many key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion, receptor endocytosis, autophagy, DNA damage response and apoptosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like WASF3 (involved in branch formation); ANXA1 (involved in membrane anchoring); DBN1, DBNL, CTTN, RAPH1 and ENAH (involved in signaling); or MAPT and PXN (microtubule-binding proteins). Phosphorylation of WASF3 is critical for the stimulation of lamellipodia formation and cell migration. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as BCAR1, CRK, CRKL, DOK1, EFS or NEDD9. Phosphorylates multiple receptor tyrosine kinases and more particularly promotes endocytosis of EGFR, facilitates the formation of neuromuscular synapses through MUSK, inhibits PDGFRB-mediated chemotaxis and modulates the endocytosis of activated B-cell receptor complexes. Other substrates which are involved in endocytosis regulation are the caveolin (CAV1) and RIN1. Moreover, ABL1 regulates the CBL family of ubiquitin ligases that drive receptor down-regulation and actin remodeling. Phosphorylation of CBL leads to increased EGFR stability. Involved in late-stage autophagy by regulating positively the trafficking and function of lysosomal components. ABL1 targets to mitochondria in response to oxidative stress and thereby mediates mitochondrial dysfunction and cell death. In response to oxidative stress, phosphorylates serine/threonine kinase PRKD2 at 'Tyr-717' (By similarity). ABL1 is also translocated in the nucleus where it has DNA-binding activity and is involved in DNA-damage response and apoptosis. Many substrates are known mediators of DNA repair: DDB1, DDB2, ERCC3, ERCC6, RAD9A, RAD51, RAD52 or WRN. Activates the proapoptotic pathway when the DNA damage is too severe to be repaired. Phosphorylates TP73, a primary regulator for this type of damage-induced apoptosis. Phosphorylates the caspase CASP9 on 'Tyr-191' and regulates its processing in the apoptotic response to DNA damage. Phosphorylates PSMA7 that leads to an inhibition of proteasomal activity and cell cycle transition blocks. Regulates T-cell differentiation in a TBX21-dependent manner (PubMed:21690296). Phosphorylates TBX21 on tyrosine residues leading to an enhancement of its transcriptional activator activity (PubMed:21690296).ACTIVITY REGULATION Stabilized in the inactive form by an association between the SH3 domain and the SH2-TK linker region, interactions of the N-terminal cap, and contributions from an N-terminal myristoyl group and phospholipids. Activated by autophosphorylation as well as by SRC-family kinase-mediated phosphorylation (By similarity). Activated by RIN1 binding to the SH2 and SH3 domains. Also stimulated by cell death inducers and DNA-damage (By similarity). Phosphatidylinositol 4,5-bisphosphate (PIP2), a highly abundant phosphoinositide known to regulate cytoskeletal and membrane proteins, inhibits also the tyrosine kinase activity. Inhibited by imatinib mesylate (Gleevec).SUBUNIT Interacts with INPPL1/SHIP2. Interacts with SORBS1 following insulin stimulation. Found in a trimolecular complex containing CDK5 and CABLES1. Interacts with CABLES1 and PSTPIP1. Interacts with ZDHHC16. Interacts with the 14-3-3 proteins, YWHAB, YWHAE, YWHAG, YWHAH, SFN AND YWHAZ; the interaction with 14-3-3 proteins requires phosphorylation on Thr-734 and sequesters ABL1 into the cytoplasm. Interacts (via SH3 domain) with CASP9; the interaction is direct and increases in the response of cells to genotoxic stress and ABL1/c-Abl activation (By similarity). Interacts with ABI1, ABI2, BCR, CRK, FYN, LYN, PSMA7 RAD9A, RAD51, RAD52, TP73 and WASF3. A complex made of ABL1, CTTN and MYLK regulates cortical actin-based cytoskeletal rearrangement critical to sphingosine 1-phosphate (S1P)-mediated endothelial cell (EC) barrier enhancement. Interacts with STX17; probably phosphorylates STX17 (By similarity). Interacts with ITGB1, HCK and FGR. Found in a complex with ABL1, ABL2, CRK and UNC119; leading to the inhibition of CRK phosphorylation by ABL kinases (By similarity). Interacts with TBX21 (PubMed:21690296).TISSUE SPECIFICITY Widely expressed.PTM Acetylated at Lys-710 by EP300 which promotes the cytoplasmic translocation.PTM Phosphorylation at Tyr-70 by members of the SRC family of kinases disrupts SH3 domain-based autoinhibitory interactions and intermolecular associations, such as that with ABI1, and also enhances kinase activity (By similarity). Phosphorylation at Tyr-226 and Tyr-393 correlate with increased activity (By similarity). DNA damage-induced activation of ABL1 requires the function of ATM and Ser-446 phosphorylation. Phosphorylation at Thr-547 and Ser-569 has been attributed to a CDC2-associated kinase and is coupled to cell division. Phosphorylation at Ser-618 and Ser-619 by PAK2 increases binding to CRK and reduces binding to ABI1 (By similarity). Phosphorylation on Thr-734 is required for binding 14-3-3 proteins for cytoplasmic translocation (By similarity). Phosphorylated by PDGFRB and PRKDC.PTM Polyubiquitinated. Polyubiquitination of ABL1 leads to degradation (By similarity).PTM Isoform IV is myristoylated on Gly-2.DISRUPTION PHENOTYPE Mutants are born with the expected Mendelian frequency, but fail to thrive and most die within three weeks after birth. Most mutants are runted, and have atrophied thymuses with severe thymocyte deficiency. Mutants that survive to weaning age are most often runted, and about half of them show lymphopenia. They display a major reduction in the number of pre-B and immature B-cell classes in bone marrow with a wide variation between individuals, but essentially normal mature B-cell levels. Mutants are highly susceptible to infections.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. ABL subfamily. UniProt P00520 1 EQUAL 1130 EQUAL Reactome Database ID Release 78 9776652 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=9776652 Reactome R-MMU-375987 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-375987.1 Reactome Database ID Release 78 9809441 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=9809441 Reactome Database ID Release 78 9809443 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=9809443 Reactome R-MMU-2130194 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2130194.1 Abelson interactor-1 (ABL) tyrosine kinase phosphorylates the strictly conserved tyrosine 150 in WAVE2 (Y151 in WAVE1 and WAVE3) (Leng et al. 2003, Chen et al. 2010). LEFT-TO-RIGHT WIP binds WASP,N-WASP, activating them 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 WIP family proteins Reactome DB_ID: 9808368 Wipf1 WIPF1 Q8K1I7 Reactome DB_ID: 9808358 UniProt:Q8K1I7 Wipf1 UniProt Q8K1I7 1 EQUAL 503 EQUAL Reactome Database ID Release 78 9808358 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=9808358 Reactome R-MMU-201874 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-201874.1 Wipf2 WIPF2 Q6PEV3 Reactome DB_ID: 9808362 UniProt:Q6PEV3 Wipf2 UniProt Q6PEV3 1 EQUAL 440 EQUAL Reactome Database ID Release 78 9808362 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=9808362 Reactome R-MMU-2197666 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2197666.1 Wipf3 WIPF3 P0C7L0 Reactome DB_ID: 9808366 UniProt:P0C7L0 Wipf3 UniProt P0C7L0 1 EQUAL 483 EQUAL Reactome Database ID Release 78 9808366 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=9808366 Reactome R-MMU-2197670 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2197670.1 Reactome Database ID Release 78 9808368 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=9808368 Reactome R-MMU-2197678 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2197678.1 Converted from EntitySet in Reactome SH3 domain proteins Reactome DB_ID: 9808354 Grb2 GRB2-1 Q60631 Reactome DB_ID: 9756223 UniProt:Q60631 Grb2 Grb2 FUNCTION Adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway.SUBUNIT Associates (via SH2 domain) with activated EGF and PDGF receptors (tyrosine phosphorylated) (By similarity). Interacts with PDGFRA (tyrosine phosphorylated); the interaction may be indirect (PubMed:8943348). Interacts with IRS4 (when Tyr-phosphorylated) (PubMed:11113178). Also associates to other cellular Tyr-phosphorylated proteins such as SIT1, IRS1, SHC and LNK; probably via the concerted action of both its SH2 and SH3 domains (By similarity). It also seems to interact with RAS in the signaling pathway leading to DNA synthesis. Interacts with SOS1 (By similarity). Forms a complex with MUC1 and SOS1, through interaction of the SH3 domains with SOS1 and the SH2 domain with phosphorylated MUC1 (By similarity). Interacts with phosphorylated MET (By similarity). Interacts with phosphorylated TOM1L1 (PubMed:11711534). Interacts with the phosphorylated C-terminus of SH2B2 (By similarity). Interacts with phosphorylated SIT1, LAX1, LAT, LAT2 and LIME1 upon TCR and/or BCR activation (By similarity) (PubMed:16249387, PubMed:14610044, PubMed:15477350, PubMed:15477348, PubMed:22561606). Interacts with NISCH, PTPNS1 and REPS2 (By similarity). Interacts with syntrophin SNTA1 (PubMed:11551227). Interacts (via SH3 domains) with REPS1 (PubMed:9395447). Interacts (via SH3 domains) with PIK3C2B (By similarity). Interacts with CBL and CBLB (By similarity). Interacts with AJUBA and CLNK (PubMed:10330178, PubMed:11463797). Interacts (via SH2 domain) with TEK/TIE2 (tyrosine phosphorylated) (PubMed:10521483). Interacts with SHB, INPP5D/SHIP1, SKAP1 and SKAP2 (By similarity). Interacts with PTPN11 (PubMed:8943348). Interacts with PRNP (PubMed:11571277). Interacts with RALGPS1 (By similarity). Interacts also with HCST (PubMed:16582911). Interacts with KDR (PubMed:16966330). Interacts with FLT1 (tyrosine-phosphorylated) (PubMed:9722576). Interacts with GAPT and PTPRE (By similarity). Interacts (via SH2 domain) with KIF26A (By similarity). Interacts (via SH3 2) with GAB2 (PubMed:10068651). Interacts with ADAM15 (By similarity). Interacts with THEMIS2 (PubMed:20644716). Interacts (via SH2 domain) with AXL (phosphorylated) (By similarity). Interacts (via SH2 domain) with KIT (phosphorylated) (PubMed:10377264). Interacts with PTPRJ and BCR (By similarity). Interacts with PTPN23 (By similarity). Interacts with FLT4 (tyrosine phosphorylated) (By similarity). Interacts with EPHB1 and SHC1; activates the MAPK/ERK cascade to regulate cell migration (PubMed:12925710). Part of a complex including TNK2, GRB2 and one receptor tyrosine kinase (RTK) such as AXL and PDGFRL, in which GRB2 promotes RTK recruitment by TNK2 (By similarity). Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated) (PubMed:9312046). Interacts with ERBB4 (By similarity). Interacts with NTRK1 (phosphorylated upon ligand-binding) (By similarity). Interacts with PTK2/FAK1 (tyrosine phosphorylated) (PubMed:7997267). Interacts with PTK2B/PYK2 (tyrosine phosphorylated) (By similarity). Interacts (via SH2-domain) with SCIMP; this interaction is dependent on phosphorylation of SCIMP 'Tyr-58' (PubMed:21930792, PubMed:28098138, PubMed:28290451). Interacts (via SH3 domains) with GAREM1 (via proline-rich domain and tyrosine phosphorylated); the interaction occurs upon EGF stimulation (By similarity). Interacts with DAB2 (PubMed:9569023). Interacts with TESPA1 (By similarity). Interacts with THEMIS (PubMed:19597498, PubMed:19597497, PubMed:19805304, PubMed:22561606). Interacts with PLCG1, LAT and THEMIS upon TCR activation in thymocytes; the association is weaker in the absence of TESPA1 (PubMed:22561606). Interacts with CD28 (By similarity). Interacts with RAB13; may recruit RAB13 to the leading edge of migrating endothelial cells where it can activate RHOA (PubMed:21543326). Interacts with ASAP3 (phosphorylated form) (By similarity). Interacts (via SH2 domain) with PTPRH (phosphorylated form) (PubMed:20398064). Interacts with PTPRO (phosphorylated form) (PubMed:20398064). Interacts with PTPRB (phosphorylated form) (PubMed:20398064). Interacts (via SH3 domain 2) with PRR14 (via proline-rich region) (By similarity). Interacts with DENND2B (By similarity). Interacts with SPRY2 (By similarity). Interacts with LRRC8A (PubMed:32930093).TISSUE SPECIFICITY Expressed in macrophages.DOMAIN The SH3 domains mediate interaction with RALGPS1 and SHB.SIMILARITY Belongs to the GRB2/sem-5/DRK family. UniProt Q60631 1 EQUAL 217 EQUAL Reactome Database ID Release 78 9756223 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=9756223 Reactome R-MMU-74686 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-74686.1 Nck1 NCK1 Q99M51 Reactome DB_ID: 9775538 UniProt:Q99M51 Nck1 UniProt Q99M51 1 EQUAL 377 EQUAL Reactome Database ID Release 78 9775538 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=9775538 Reactome R-MMU-197954 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-197954.1 Q9ESJ4 Nckipsd NCKIPSD Reactome DB_ID: 9808352 UniProt:Q9ESJ4 Nckipsd UniProt Q9ESJ4 1 EQUAL 722 EQUAL Reactome Database ID Release 78 9808352 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=9808352 Reactome R-MMU-2197671 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2197671.1 Reactome Database ID Release 78 9808354 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=9808354 Reactome R-MMU-2197679 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2197679.1 CDC42:GTP:WASP/N-WASP Reactome DB_ID: 9811043 Cdc42:GTP Reactome DB_ID: 448879 Cdc42 Cell division control protein 42 homolog Reactome DB_ID: 448841 UniProt:P60766 Cdc42 Cdc42 FUNCTION Plasma membrane-associated small GTPase which cycles between an active GTP-bound and an inactive GDP-bound state (PubMed:24352656). In its active state binds to a variety of effector proteins to regulate cellular responses. Involved in epithelial cell polarization processes. Regulates the bipolar attachment of spindle microtubules to kinetochores before chromosome congression in metaphase. Regulates cell migration (By similarity). In neurons, plays a role in the extension and maintenance of the formation of filopodia, thin and actin-rich surface projections. Required for DOCK10-mediated spine formation in Purkinje cells and hippocampal neurons (PubMed:25851601). Facilitates filopodia formation upon DOCK11-activation (PubMed:22494997). Upon activation by CaMKII, modulates dendritic spine structural plasticity by relaying CaMKII transient activation to synapse-specific, long-term signaling (By similarity). Also plays a role in phagocytosis through organization of the F-actin cytoskeleton associated with forming phagocytic cups (By similarity).ACTIVITY REGULATION Regulated by guanine nucleotide exchange factors (GEFs) which promote the exchange of bound GDP for free GTP, GTPase activating proteins (GAPs) which increase the GTP hydrolysis activity, and GDP dissociation inhibitors which inhibit the dissociation of the nucleotide from the GTPase. Inhibited by GAPs such as ARHGAP44 (PubMed:24352656, PubMed:26969129).SUBUNIT Interacts with CDC42EP1, CDC42EP2, CDC42EP3, CDC42EP4, CDC42EP5, CDC42SE1, CDC42SE2, PARD6A, PARD6B and PARD6G (in a GTP-dependent manner) (PubMed:10490598, PubMed:10934474). Interacts with activated CSPG4 and with BAIAP2 (By similarity). Interacts with DOCK11/Zizimin2; the interaction activates CDC42 by exchanging GDP for GTP (PubMed:15710388, PubMed:16968698). Interacts with DOCK9; the interaction activates CDC42 by exchanging GDP for GTP (By similarity). Interacts with DOCK8 (via DHR-2 domain); the interaction activates CDC42 by exchanging GDP for GTP (PubMed:22461490). Interacts with IQGAP1 (PubMed:16968698). Interacts with NET1 and ARHGAP33/TCGAP (PubMed:9535835, PubMed:12773384). Part of a complex with PARD3, PARD6A or PARD6B and PRKCI or PRKCZ (PubMed:10934474). The GTP-bound form interacts with CCPG1 (PubMed:17000758). Interacts with USP6 (By similarity). Interacts with NEK6 (By similarity). Part of a collagen stimulated complex involved in cell migration composed of CDC42, CRK, TNK2 and BCAR1/p130cas (By similarity). Interacts with ITGB1BP1 (By similarity). Interacts with ARHGDIA; this interaction inactivates and stabilizes CDC42. Interacts with ARHGDIB; this maintains CDC42 in the inactive, GDP-bound form (By similarity). Interacts in (GTP-bound form) with FNBP1L and ABI1, but only in the presence of FNBP1L (By similarity).PTM Phosphorylated by SRC in an EGF-dependent manner, this stimulates the binding of the Rho-GDP dissociation inhibitor RhoGDI.SIMILARITY Belongs to the small GTPase superfamily. Rho family. CDC42 subfamily. UniProt P60766 1 EQUAL 188 EQUAL Reactome Database ID Release 78 448841 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=448841 Reactome R-MMU-448841 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-448841.1 1 1 Reactome Database ID Release 78 448879 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=448879 Reactome R-MMU-448879 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-448879.1 1 PIP2 PI(4,5)P2 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate Phosphatidylinositol-4,5-bisphosphate 1-phosphatidyl-1D-myo-inositol 4,5- bisphosphate Reactome DB_ID: 179856 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate [ChEBI:18348] 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate PIP2 ChEBI CHEBI:18348 Reactome Database ID Release 78 179856 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=179856 Reactome R-ALL-179856 3 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-ALL-179856.3 COMPOUND C04637 1 Converted from EntitySet in Reactome WASP/N-WASP Reactome DB_ID: 9811041 Was WAS P70315 Reactome DB_ID: 9783422 UniProt:P70315 Was Was Wasp FUNCTION Effector protein for Rho-type GTPases that regulates actin filament reorganization via its interaction with the Arp2/3 complex. Important for efficient actin polymerization. Possible regulator of lymphocyte and platelet function. Mediates actin filament reorganization and the formation of actin pedestals upon infection by pathogenic bacteria. In addition to its role in the cytoplasmic cytoskeleton, also promotes actin polymerization in the nucleus, thereby regulating gene transcription and repair of damaged DNA. Promotes homologous recombination (HR) repair in response to DNA damage by promoting nuclear actin polymerization, leading to drive motility of double-strand breaks (DSBs).SUBUNIT Binds the Arp2/3 complex (By similarity). Interacts with CDC42, RAC, NCK, HCK, FYN, SRC kinase FGR, BTK, ABL1, PSTPIP1, WIP, and to the p85 subunit of PLC-gamma (PubMed:9488710). Interacts (via C-terminus) with ALDOA (By similarity). Interacts with NCK1 (via SH3 domains) (PubMed:8910519). Interacts with FCHSD2 (PubMed:23437151).DOMAIN The WH1 (Wasp homology 1) domain may bind a Pro-rich ligand.DOMAIN The CRIB (Cdc42/Rac-interactive-binding) region binds to the C-terminal WH2 domain in the autoinhibited state of the protein. Binding of Rho-type GTPases to the CRIB induces a conformation change and leads to activation.PTM Phosphorylated at Tyr-293 by FYN and HCK, inducing WAS effector activity after TCR engagement. Phosphorylation at Tyr-293 enhances WAS activity in promoting actin polymerization and filopodia formation. UniProt P70315 2 EQUAL 502 EQUAL Reactome Database ID Release 78 9783422 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=9783422 Reactome R-MMU-201879 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-201879.1 Wasl N-WASP Q91YD9 Reactome DB_ID: 9771715 UniProt:Q91YD9 Wasl Wasl FUNCTION Regulates actin polymerization by stimulating the actin-nucleating activity of the Arp2/3 complex. Involved in various processes, such as mitosis and cytokinesis, via its role in the regulation of actin polymerization. Together with CDC42, involved in the extension and maintenance of the formation of thin, actin-rich surface projections called filopodia. In addition to its role in the cytoplasm, also plays a role in the nucleus by regulating gene transcription, probably by promoting nuclear actin polymerization (By similarity). Binds to HSF1/HSTF1 and forms a complex on heat shock promoter elements (HSE) that negatively regulates HSP90 expression (PubMed:12871950). Plays a role in dendrite spine morphogenesis (PubMed:25851601).SUBUNIT Binds actin and the Arp2/3 complex. Interacts with CDC42 (By similarity). Interacts with FCHSD1 (PubMed:29887380). Interacts with FCHSD2 (PubMed:23437151, PubMed:29887380). Binds to SH3 domains of GRB2. Interacts with the C-terminal SH3 domain of DNMBP (PubMed:14506234). Interacts with SNX9 (By similarity). Interacts with the WW domains of PRPF40A/FBP11 (PubMed:14697212). Interacts with PTK2/FAK1 (PubMed:14676198). Interacts with PACSIN1, PACSIN2 and PACSIN3 (PubMed:11082044). Interacts with NOSTRIN. Binds to TNK2. Interacts with SNX33. Interacts with NONO (via second RRM domain); the interaction is direct. Component of a multiprotein complex with NONO and SFPQ; associates with the complex via direct interaction with NONO (By similarity).PTM Phosphorylation at Ser-239, Tyr-253, Ser-480 and Ser-481 enhances actin polymerization activity. UniProt Q91YD9 1 EQUAL 505 EQUAL Reactome Database ID Release 78 9771715 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=9771715 Reactome R-MMU-201873 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-201873.1 Reactome Database ID Release 78 9811041 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=9811041 Reactome R-MMU-201892 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-201892.1 1 Reactome Database ID Release 78 9811043 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=9811043 Reactome R-MMU-442584 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-442584.1 CDC42:GTP:WASP/N-WASP:WIP:SH3 proteins Reactome DB_ID: 9811045 1 1 1 1 1 Reactome Database ID Release 78 9811045 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=9811045 Reactome R-MMU-2197683 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2197683.1 Reactome Database ID Release 78 9811047 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=9811047 Reactome R-MMU-2197691 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2197691.1 WASP interacting proteins (WIP) family includes WIPF1 (WIP), WIPF2 (WIRE,WICH) and WIPF3 (CR16, corticosteroids and regional expression-16). WIPs share a specific proline rich sequence that interacts with the WH1 domain of WASP and N-WASP (WASL). WIPs form heterocomplexes with WASPs and may contribute to the WASP protein stability (Aspenstrom 2002, Kato et al. 2002, Ho et al. 2001, Moreau et al. 2000).<br>SH3 domain containing adaptor proteins like GRB2 (Carlier et al. 2000), NCK (Rohatgi et al. 2001) and WISH (DIP/SPIN90) (Fukuoka et al. 2001) bind to the proline rich domain in WASPs and activate the ARP2/3 complex. By binding simultaneously to N-WASP and the ARP2/3 complex, GRB2 works synergistically with CDC42 in the activation of ARP2/3 complex-mediated actin assembly (Carlier et al. 2000). 11553796 Pubmed 2001 CR16 forms a complex with N-WASP in brain and is a novel member of a conserved proline-rich actin-binding protein family Ho, HY Rohatgi, R Ma, L Kirschner, Marc W Proc Natl Acad Sci U S A 98:11306-11 11157975 Pubmed 2001 A novel neural Wiskott-Aldrich syndrome protein (N-WASP) binding protein, WISH, induces Arp2/3 complex activation independent of Cdc42 Fukuoka, M Suetsugu, S Miki, H Fukami, K Endo, T Takenawa, T J Cell Biol 152:471-82 10878810 Pubmed 2000 A complex of N-WASP and WIP integrates signalling cascades that lead to actin polymerization Moreau, Violaine Frischknecht, F Reckmann, I Vincentelli, R Rabut, G Stewart, D Way, M Nat Cell Biol 2:441-8 11340081 Pubmed 2001 Nck and phosphatidylinositol 4,5-bisphosphate synergistically activate actin polymerization through the N-WASP-Arp2/3 pathway Rohatgi, R Nollau, P Ho, HY Kirschner, Marc W Mayer, BJ J Biol Chem 276:26448-52 12213210 Pubmed 2002 The WASP-binding protein WIRE has a role in the regulation of the actin filament system downstream of the platelet-derived growth factor receptor Aspenström, P Exp Cell Res 279:21-33 11829459 Pubmed 2002 WICH, a novel verprolin homology domain-containing protein that functions cooperatively with N-WASP in actin-microspike formation Kato, M Miki, H Kurita, S Endo, T Nakagawa, H Miyamoto, S Takenawa, T Biochem Biophys Res Commun 291:41-7 10781580 Pubmed 2000 GRB2 links signaling to actin assembly by enhancing interaction of neural Wiskott-Aldrich syndrome protein (N-WASp) with actin-related protein (ARP2/3) complex Carlier, MF Nioche, P Broutin-L'Hermite, I Boujemaa, R Le Clainche, C Egile, C Garbay, C Ducruix, A Sansonetti, P Pantaloni, D J Biol Chem 275:21946-52 LEFT-TO-RIGHT 2.7.10 Src phosphorylate WASP,N-WASP 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> 2 2 CDC42:GTP:p-Y-WASP/p-Y-WASL:WIP:SH3 proteins Reactome DB_ID: 9808378 1 1 Converted from EntitySet in Reactome p-Y291-WASP/p-Y256-N-WASP Reactome DB_ID: 9808376 Q91YD9 phospho-Wasl p-Y256-WASL Reactome DB_ID: 9808371 256 EQUAL 1 EQUAL 505 EQUAL Reactome Database ID Release 78 9808371 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=9808371 Reactome R-MMU-2197672 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2197672.1 P70315 phospho-Was p-Y291-WAS Reactome DB_ID: 9808374 291 EQUAL 2 EQUAL 502 EQUAL Reactome Database ID Release 78 9808374 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=9808374 Reactome R-MMU-2197668 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2197668.1 Reactome Database ID Release 78 9808376 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=9808376 Reactome R-MMU-2197676 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2197676.1 1 1 1 Reactome Database ID Release 78 9808378 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=9808378 Reactome R-MMU-2197680 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2197680.1 ACTIVATION Converted from EntitySet in Reactome Src-kinases Reactome DB_ID: 9811051 Ptk2 PTK2 P34152 Reactome DB_ID: 9770718 UniProt:P34152 Ptk2 Ptk2 Fadk Fak Fak1 Kiaa4203 FUNCTION Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1.ACTIVITY REGULATION Subject to autoinhibition, mediated by interactions between the FERM domain and the kinase domain. Activated by autophosphorylation at Tyr-397. This promotes interaction with SRC and phosphorylation at Tyr-576 and Tyr-577 in the kinase activation loop by SRC. Phosphorylation at Tyr-397, Tyr-576 and Tyr-577 is required for maximal kinase activity.SUBUNIT Interacts with GIT1. Component of a complex that contains at least FER, CTTN and PTK2/FAK1. Interacts with BMX. Interacts with STEAP4. Interacts with ZFYVE21. Interacts with ESR1. Interacts with FGR, FLT4 and RET. Interacts with EPHA2 in resting cells; activation of EPHA2 recruits PTPN11, leading to dephosphorylation of PTK2/FAK1 and dissociation of the complex. Interacts with EPHA1 (kinase activity-dependent) (By similarity). Interacts with MISP (By similarity). Interacts with PIAS1. Interacts with ARHGAP26 and SHC1. Interacts with RB1CC1; this inhibits PTK2/FAK1 activity and activation of downstream signaling pathways. Interacts with P53/TP53. Interacts with STAT1. Interacts with WASL. Interacts with ARHGEF7. Interacts with DCC. Interacts (via first Pro-rich region) with CAS family members (via SH3 domain), including BCAR1, BCAR3, CASS4 and NEDD9. Interacts with SORBS1. Interacts with ARHGEF28. Interacts with SHB. Part of a complex composed of THSD1, PTK2/FAK1, TLN1 and VCL (By similarity). Interacts with PXN and TLN1. Interacts with TGFB1I1. Interacts with PIK3R1 or PIK3R2. Interacts with SRC, GRB2 and GRB7. Interacts with LPXN (via LD motif 3). Interacts with CD36. Interacts with EMP2; regulates PTK2 activation and localization (By similarity). Interacts with DSCAM (PubMed:22685302).DEVELOPMENTAL STAGE Isoform 9 is detected in neonate myocardium; levels are low directly after birth, high five to fifteen days after birth, and not detectable in adult (at protein level). Isoform 9 is detected in neonate myocardium; levels are high directly after birth, decrease during the first week of life and are low thereafter.DOMAIN The first Pro-rich domain interacts with the SH3 domain of CAS family members, such as BCAR1 and NEDD9.DOMAIN The C-terminal region is the site of focal adhesion targeting (FAT) sequence which mediates the localization of FAK1 to focal adhesions.PTM Phosphorylated on tyrosine residues upon activation, e.g. upon integrin signaling. Tyr-397 is the major autophosphorylation site, but other kinases can also phosphorylate this residue. Phosphorylation at Tyr-397 promotes interaction with SRC and SRC family members, leading to phosphorylation at Tyr-576, Tyr-577 and at additional tyrosine residues. FGR promotes phosphorylation at Tyr-397 and Tyr-576. FER promotes phosphorylation at Tyr-577, Tyr-861 and Tyr-925, even when cells are not adherent. Tyr-397, Tyr-576 and Ser-722 are phosphorylated only when cells are adherent. Phosphorylation at Tyr-397 is important for interaction with BMX, PIK3R1 and SHC1. Phosphorylation at Tyr-925 is important for interaction with GRB2. Dephosphorylated by PTPN11; PTPN11 is recruited to PTK2 via EPHA2 (tyrosine phosphorylated). Microtubule-induced dephosphorylation at Tyr-397 is crucial for the induction of focal adhesion disassembly; this dephosphorylation could be catalyzed by PTPN11 and regulated by ZFYVE21. Phosphorylation on tyrosine residues is enhanced by NTN1 (PubMed:22685302).PTM Sumoylated; this enhances autophosphorylation.DISRUPTION PHENOTYPE Embryonically lethal. Embryos die at about 8.5 dpc, despite normal implantation. Embryos do not develop a normal head fold, neural tube or heart tube. Endothelial-specific gene disruption is lethal at about 11 dpc, due to defects in embryonic angiogenesis.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. FAK subfamily. UniProt P34152 2 EQUAL 1052 EQUAL Reactome Database ID Release 78 9770718 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=9770718 Reactome R-MMU-201621 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-201621.1 Btk Tyrosine-protein kinase BTK ecNumber2.7.10.2/ecNumber BTK_MOUSE Btk Reactome DB_ID: 2685636 UniProt:P35991 Btk Btk Bpk FUNCTION Non-receptor tyrosine kinase indispensable for B lymphocyte development, differentiation and signaling. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. After BCR engagement and activation at the plasma membrane, phosphorylates PLCG2 at several sites, igniting the downstream signaling pathway through calcium mobilization, followed by activation of the protein kinase C (PKC) family members. PLCG2 phosphorylation is performed in close cooperation with the adapter protein B-cell linker protein BLNK. BTK acts as a platform to bring together a diverse array of signaling proteins and is implicated in cytokine receptor signaling pathways. Plays an important role in the function of immune cells of innate as well as adaptive immunity, as a component of the Toll-like receptors (TLR) pathway. The TLR pathway acts as a primary surveillance system for the detection of pathogens and are crucial to the activation of host defense. Especially, is a critical molecule in regulating TLR9 activation in splenic B-cells. Within the TLR pathway, induces tyrosine phosphorylation of TIRAP which leads to TIRAP degradation. BTK plays also a critical role in transcription regulation. Induces the activity of NF-kappa-B, which is involved in regulating the expression of hundreds of genes. BTK is involved on the signaling pathway linking TLR8 and TLR9 to NF-kappa-B. Transiently phosphorylates transcription factor GTF2I on tyrosine residues in response to BCR. GTF2I then translocates to the nucleus to bind regulatory enhancer elements to modulate gene expression. ARID3A and NFAT are other transcriptional target of BTK. BTK is required for the formation of functional ARID3A DNA-binding complexes. There is however no evidence that BTK itself binds directly to DNA. BTK has a dual role in the regulation of apoptosis.ACTIVITY REGULATION Activated by phosphorylation. In primary B lymphocytes, is almost always non-phosphorylated and is thus catalytically inactive. Stimulation of TLR8 and TLR9 causes BTK activation. As a negative feedback mechanism to fine-tune BCR signaling, activated PRKCB down-modulates BTK function via direct phosphorylation of BTK at Ser-180, resulting in translocation of BTK back to the cytoplasmic fraction. PIN1, SH3BP5, and IBTK were also identified as BTK activity inhibitors. Interaction with CAV1 leads to dramatic down-regulation of the kinase activity of BTK. LFM-13A is a specific inhibitor of BTK. Dasatinib, a cancer drug acting as a tyrosine kinase inhibitor, also blocks BTK activity.SUBUNIT Binds GTF2I through the PH domain. Interacts with SH3BP5 via the SH3 domain. Interacts with IBTK via its PH domain (By similarity). Interacts with ARID3A. Interacts with CAV1, FASLG, PIN1, TLR8 and TLR9 (By similarity).DOMAIN The PH domain mediates the binding to inositol polyphosphate and phosphoinositides, leading to its targeting to the plasma membrane. It is extended in the BTK kinase family by a region designated the TH (Tec homology) domain, which consists of about 80 residues preceding the SH3 domain.PTM Following B-cell receptor (BCR) engagement, translocates to the plasma membrane where it gets phosphorylated at Tyr-551 by LYN and SYK. Phosphorylation at Tyr-551 is followed by autophosphorylation of Tyr-223 which may create a docking site for a SH2 containing protein. Phosphorylation at Ser-180 by PRKCB, leads in translocation of BTK back to the cytoplasmic fraction. Phosphorylation at Ser-21 and Ser-115 creates a binding site for PIN1 at these Ser-Pro motifs, and promotes it's recruitment (By similarity).DISEASE Defects in Btk are the cause of murine X-linked immunodeficiency (XID).DISRUPTION PHENOTYPE Prevents BCR-induced activation of NF-kappa-B.SIMILARITY Belongs to the protein kinase superfamily. Tyr protein kinase family. TEC subfamily. UniProt P35991 2 EQUAL 659 EQUAL Reactome Database ID Release 78 2685636 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=2685636 Reactome R-MMU-2685636 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2685636.1 Reactome Database ID Release 78 9811051 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=9811051 Reactome R-MMU-2197681 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2197681.1 Reactome Database ID Release 78 9811052 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=9811052 Reactome Database ID Release 78 9811054 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=9811054 Reactome R-MMU-2197698 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2197698.1 WASP is phosphorylated on Tyr291 (Cory et al. 2002) and N-WASP (WASL) on Tyr256 (Wu et al. 2004) by Src family of tyrosine kinases and this phosphorylation may release the autoinhibitory intramolecular interactions. The phosphorylation seems to be enhanced by the activation of CDC42. WASP phosphorylation and binding of CDC42 have a synergistic effect on the activation of the ARP2/3 complex (Takenawa & Suetsugu 2007). In N-WASP, the phosphorylation may reduce its nuclear translocation and may sustain it in its functional site in the cytoplasm (Wu et al. 2004). 12235133 Pubmed 2002 Phosphorylation of tyrosine 291 enhances the ability of WASp to stimulate actin polymerization and filopodium formation. Wiskott-Aldrich Syndrome protein Cory, GO Garg, R Cramer, R Ridley, AJ J Biol Chem 277:45115-21 14676198 Pubmed 2004 Focal adhesion kinase regulation of N-WASP subcellular localization and function Wu, X Suetsugu, S Cooper, LA Takenawa, T Guan, JL J Biol Chem 279:9565-76 LEFT-TO-RIGHT (WASPs, WAVE):G-actin:ARP2/3 binds F-actin 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> WAVE2, WASP, N-WASP:ARP2/3 complex:G-actin Reactome DB_ID: 9808430 Converted from EntitySet in Reactome WAVE2, WASP, N-WASP Reactome DB_ID: 9808428 Reactome Database ID Release 78 9808428 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=9808428 Reactome R-MMU-2197675 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-MMU-2197675.1 1 G-actin Reactome DB_ID: 9771670 Converted from EntitySet in Reactome actin, cytoplasmic Reactome DB_ID: 2263466 Actb Actin, cytoplasmic 1 ACTB_MOUSE