BioPAX pathway converted from "NUMB binds ITCH" in the Reactome database. LEFT-TO-RIGHT NUMB binds ITCH 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> NUMB NUMB A0A1D5NU12 Reactome DB_ID: 10452750 plasma membrane GENE ONTOLOGY GO:0005886 UniProt:A0A1D5NU12 NUMB Gallus gallus NCBI Taxonomy 9031 UniProt A0A1D5NU12 1 EQUAL 651 EQUAL Reactome Database ID Release 78 10452750 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10452750 Reactome R-GGA-443595 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-443595.1 Reactome http://www.reactome.org ITCH ITCH A0A1D5PQP3 Reactome DB_ID: 10458555 cytosol GENE ONTOLOGY GO:0005829 UniProt:A0A1D5PQP3 ITCH ITCH CATALYTIC ACTIVITY: S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin- conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. {ECO:0000256|PIRNR:PIRNR001569, ECO:0000256|SAAS:SAAS00628607}. UniProt A0A1D5PQP3 1 EQUAL 903 EQUAL Reactome Database ID Release 78 10458555 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10458555 Reactome R-GGA-975995 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-975995.1 NUMB:ITCH Reactome DB_ID: 10481488 1 1 Reactome Database ID Release 78 10481488 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10481488 Reactome R-GGA-5610562 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5610562.1 Reactome Database ID Release 78 10481490 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10481490 Reactome R-GGA-5610735 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-GGA-5610735.1 NUMB is a negative regulator of Hh signaling that acts by promoting the ITCH-dependent ubiquitination of GLI1. ITCH is an E3 ligase that is kept in an inactive conformation by an intramolecular interaction between the HECT domain and a WW motif. Binding of the adaptor protein NUMB to the WW region of ITCH displaces the HECT domain and promotes the catalytic activity of the E3 ligase (di Marcotullio et al, 2006; 2011). 20818436 Pubmed 2011 Numb activates the E3 ligase Itch to control Gli1 function through a novel degradation signal Di Marcotullio, L Greco, A MazzĂ , D Canettieri, G Pietrosanti, L Infante, P Coni, S Moretti, M De Smaele, E Ferretti, E Screpanti, I Gulino, A Oncogene 30:65-76 17115028 Pubmed 2006 Numb is a suppressor of Hedgehog signalling and targets Gli1 for Itch-dependent ubiquitination Di Marcotullio, L Ferretti, Elisabetta Greco, Azzura De Smaele, Enrico Po, Agnese Sico, Maria Anna Alimandi, M Giannini, Giuseppe Maroder, Marella Screpanti, I Gulino, Alberto Nat. Cell Biol. 8:1415-23 inferred from electronic annotation EVIDENCE CODE ECO:0000203