BioPAX pathway converted from "NICD3 binds to TACC3" in the Reactome database. LEFT-TO-RIGHT NICD3 binds to TACC3 Based on studies in mice, the intracellular domain of NOTCH3, NICD3, binds to transforming acidic coiled-coil protein-3 (TACC3). The interaction involves the ankyrin repeats of NOTCH3. The two proteins co-localize in the cytosol and possibly in the nucleus. TACC3 is implicated as a negative regulator of NOTCH signaling and may compete with NOTCH binding to RPBJ (Bargo et al. 2010). Authored: Orlic-Milacic, Marija, 2017-09-20 Reviewed: Haw, Robin, 2017-10-30 Edited: Orlic-Milacic, Marija, 2017-11-02 NICD3 NOTCH3(1662-2321) NICD 3 fragment N3ICD Reactome DB_ID: 157647 cytosol GENE ONTOLOGY GO:0005829 UniProt:Q9UM47 NOTCH3 NOTCH3 FUNCTION Functions as a receptor for membrane-bound ligands Jagged1, Jagged2 and Delta1 to regulate cell-fate determination (PubMed:15350543). Upon ligand activation through the released notch intracellular domain (NICD) it forms a transcriptional activator complex with RBPJ/RBPSUH and activates genes of the enhancer of split locus. Affects the implementation of differentiation, proliferation and apoptotic programs (By similarity).SUBUNIT Heterodimer of a C-terminal fragment N(TM) and a N-terminal fragment N(EC) which are probably linked by disulfide bonds (By similarity). Interacts with MAML1, MAML2 and MAML3 which act as transcriptional coactivators for NOTCH3. Interacts with PSMA1. Interacts with HIF1AN.TISSUE SPECIFICITY Ubiquitously expressed in fetal and adult tissues.DOMAIN The EGF-like domains 10 and 11 are required for binding the ligands JAG1 and DLL1.PTM Synthesized in the endoplasmic reticulum as an inactive form which is proteolytically cleaved by a furin-like convertase in the trans-Golgi network before it reaches the plasma membrane to yield an active, ligand-accessible form. Cleavage results in a C-terminal fragment N(TM) and a N-terminal fragment N(EC). Following ligand binding, it is cleaved by TNF-alpha converting enzyme (TACE) to yield a membrane-associated intermediate fragment called notch extracellular truncation (NEXT). This fragment is then cleaved by presenilin dependent gamma-secretase to release a notch-derived peptide containing the intracellular domain (NICD) from the membrane.PTM Phosphorylated.PTM Hydroxylated by HIF1AN.SIMILARITY Belongs to the NOTCH family. Homo sapiens NCBI Taxonomy 9606 UniProt Q9UM47 1662 EQUAL 2321 EQUAL Reactome Database ID Release 83 157647 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=157647 Reactome R-HSA-157647 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-157647.1 Reactome http://www.reactome.org TACC3 Transforming acidic coiled-coil-containing protein 3 ERIC1 Reactome DB_ID: 2160956 UniProt:Q9Y6A5 TACC3 TACC3 ERIC1 FUNCTION Plays a role in the microtubule-dependent coupling of the nucleus and the centrosome. Involved in the processes that regulate centrosome-mediated interkinetic nuclear migration (INM) of neural progenitors (By similarity). Acts as component of the TACC3/ch-TOG/clathrin complex proposed to contribute to stabilization of kinetochore fibers of the mitotic spindle by acting as inter-microtubule bridge. The TACC3/ch-TOG/clathrin complex is required for the maintenance of kinetochore fiber tension (PubMed:21297582, PubMed:23532825). May be involved in the control of cell growth and differentiation. May contribute to cancer (PubMed:14767476).SUBUNIT Interacts with microtubules. Interacts with CKAP5 independently of clathrin. Interacts with CKAP5 and clathrin forming the TACC3/ch-TOG/clathrin complex located at spindle inter-microtubules bridges; TACC3 (phosphorylated at Ser-558 by AURKA) and CLTC are proposed to form a composite microtubule interaction surface (PubMed:21297582, PubMed:23918938, PubMed:25596274). Interacts with CCDC100/CEP120. The coiled coil C-terminal region interacts with AH receptor nuclear translocator protein (ARNT) and ARNT2 (By similarity). Interacts with GCN5L2 and PCAF (PubMed:14767476).INDUCTION Up-regulated in various cancer cell lines.SIMILARITY Belongs to the TACC family. UniProt Q9Y6A5 1 EQUAL 838 EQUAL Reactome Database ID Release 83 2160956 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=2160956 Reactome R-HSA-2160956 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-2160956.1 NICD3:TACC3 Reactome DB_ID: 9017852 1 1 Reactome Database ID Release 83 9017852 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9017852 Reactome R-HSA-9017852 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9017852.1 Reactome Database ID Release 83 9017855 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9017855 Reactome R-HSA-9017855 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-9017855.1 20804727 Pubmed 2010 Transforming acidic coiled-coil protein-3 (Tacc3) acts as a negative regulator of Notch signaling through binding to CDC10/Ankyrin repeats Bargo, Sharon Raafat, Ahmed McCurdy, David Amirjazil, Idean Shu, Youmin Traicoff, June Plant, Joshua Vonderhaar, Barbara K Callahan, Robert Biochem. Biophys. Res. Commun. 400:606-12 GENE ONTOLOGY GO:0045746 gene ontology term for cellular process MI MI:0359