BioPAX pathway converted from "CSNK1A1 phosphorylates SMO dimer" in the Reactome database.LEFT-TO-RIGHT2.7.11CSNK1A1 phosphorylates SMO dimerInitial activation of SMO in response to HH occurs with the CSNK1A1-mediated phosphorylation of serine and threonine residues in the C-terminal tail. While many potential CSNK1A1 target residues have been identified in in vitro assays, residues S588, S590, T593 and S595 in the S0 region appear to be the most critical for function (Chen et al, 2011). Initial phosphorylation increases the affinity of the C-terminal tail for both CSNK1A1 and ADRBK1/GRK2, establishing a positive feedback mechanism that promotes further phosphorylation. CSNK1A1 and ADRBK1-mediated phosphorylation is thought to promote an open, activated conformation of the C-terminal tails, analogous to that in Drosophila Smo upon pathway activation (Chen et al, 2011; Chen et al, 2010; Zhao et al, 2007).Authored: Rothfels, Karen, 2014-10-24Reviewed: Liu, Yulu Cherry, 2014-11-09Edited: Gillespie, Marc E, 2014-10-30SMO dimer:CSNK1A1Reactome DB_ID: 5632602ciliary membraneGENE ONTOLOGYGO:0060170CSNK1A1CK1alphaCSNK1A1Reactome DB_ID: 5632507ciliumGENE ONTOLOGYGO:0005929UniProt:P48729 CSNK1A1CSNK1A1FUNCTION Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates CTNNB1 at 'Ser-45'. May phosphorylate PER1 and PER2. May play a role in segregating chromosomes during mitosis (PubMed:11955436, PubMed:1409656, PubMed:18305108). May play a role in keratin cytoskeleton disassembly and thereby, it may regulate epithelial cell migration (PubMed:23902688).SUBUNIT Monomer. Interacts with the Axin complex. Interacts with TUT1, leading to TUT1 phosphorylation. Interacts with FAM83H; recruits CSNK1A1 to keratin filaments (PubMed:23902688).SIMILARITY Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily.Homo sapiensNCBI Taxonomy9606UniProtP487292EQUAL337EQUALReactome Database ID Release 735632507Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5632507ReactomeR-HSA-56325072Reactome stable identifier. Use this 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-5632507.2Reactomehttp://www.reactome.org1SMO dimerReactome DB_ID: 5632597SMOSmoothened homologSMO_HUMANReactome DB_ID: 5624094UniProt:Q99835 SMOSMOSMOHFUNCTION G protein-coupled receptor that probably associates with the patched protein (PTCH) to transduce the hedgehog's proteins signal. Binding of sonic hedgehog (SHH) to its receptor patched is thought to prevent normal inhibition by patched of smoothened (SMO). Required for the accumulation of KIF7, GLI2 and GLI3 in the cilia (PubMed:19592253). Interacts with DLG5 at the ciliary base to induce the accumulation of KIF7 and GLI2 at the ciliary tip for GLI2 activation (By similarity).SUBUNIT Homodimer (PubMed:23636324). Interacts with ARRB2 (By similarity). Interacts with KIF7 (PubMed:19592253). Interacts with BBS5 and BBS7; the interactions are indicative for the association of SMO with the BBsome complex to facilitate ciliary localization of SMO (PubMed:22072986). Interacts with DLG5 and SDCBP (By similarity). Interacts with GAS8/DRC4 (PubMed:21659505).SIMILARITY Belongs to the G-protein coupled receptor Fz/Smo family.UniProtQ9983528EQUAL787EQUALReactome Database ID Release 735624094Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5624094ReactomeR-HSA-56240941Reactome stable identifier. Use this 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-5624094.12Reactome Database ID Release 735632597Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5632597ReactomeR-HSA-56325971Reactome stable identifier. Use this 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-5632597.11Reactome Database ID Release 735632602Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5632602ReactomeR-HSA-56326021Reactome stable identifier. Use this 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-5632602.1ATPAdenosine 5'-triphosphateATP(4-)Reactome DB_ID: 5632460ATP(4-) [ChEBI:30616]ATP(4-)ATPatpAdenosine 5'-triphosphateChEBICHEBI:30616Reactome Database ID Release 735632460Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5632460ReactomeR-ALL-56324604Reactome stable identifier. Use this 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-5632460.4COMPOUNDC00002additional informationMIMI:03618pS588,S590, T593, S595-SMO dimer:CSNK1A1Reactome DB_ID: 5632624pS588, S590, T593, S595-SMO dimerReactome DB_ID: 5632621SMO_HUMANpS588, S590, T593, S595-SMOSmoothened homologReactome DB_ID: 5632525588EQUALO-phospho-L-serineMODMOD:00046590EQUAL593EQUALO-phospho-L-threonineMODMOD:00047595EQUAL28EQUAL787EQUALReactome Database ID Release 735632525Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5632525ReactomeR-HSA-56325251Reactome stable identifier. Use this 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-5632525.12Reactome Database ID Release 735632621Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5632621ReactomeR-HSA-56326211Reactome stable identifier. Use this 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-5632621.111Reactome Database ID Release 735632624Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5632624ReactomeR-HSA-56326241Reactome stable identifier. Use this 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-5632624.1ADPAdenosine 5'-diphosphateADP(3-)Reactome DB_ID: 5632457ADP(3-) [ChEBI:456216]ADP(3-)ADP5'-O-[(phosphonatooxy)phosphinato]adenosineADP trianionChEBICHEBI:456216Reactome Database ID Release 735632457Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5632457ReactomeR-ALL-56324574Reactome stable identifier. Use this 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-5632457.4COMPOUNDC000088ACTIVATIONactiveUnit: #Protein1GENE ONTOLOGYGO:0004674gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 735632631Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5632631Reactome Database ID Release 735632670Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=5632670ReactomeR-HSA-56326701Reactome stable identifier. Use this 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-5632670.121695114Pubmed2011Sonic Hedgehog dependent phosphorylation by CK1? and GRK2 is required for ciliary accumulation and activation of smoothenedChen, YongbinSasai, NoriakiMa, GuoqiangYue, TaoJia, JianhangBriscoe, JamesJiang, JinPLoS Biol. 9:e100108320844016Pubmed2010G protein-coupled receptor kinase 2 promotes high-level Hedgehog signaling by regulating the active state of Smo through kinase-dependent and kinase-independent mechanisms in DrosophilaChen, YongbinLi, ShuangTong, ChaoZhao, YunWang, BingLiu, YajuanJia, JianhangJiang, JinGenes Dev. 24:2054-6717960137Pubmed2007Hedgehog regulates smoothened activity by inducing a conformational switchZhao, YTong, CJiang, JNature 450:252-8