BioPAX pathway converted from "CSNK1A1 phosphorylates SMO dimer" in the Reactome database.

2.7.11

CSNK1A1 phosphorylates SMO dimer

Initial 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, 2014-10-30

Reactome DB_ID: 5632602

ciliary membraneGO0060170SMO dimer:CSNK1A1 [ciliary membrane]

SMO dimer:CSNK1A1

Reactome DB_ID: 5632507

ciliumGO0005929

UniProt:P48729 CSNK1A1

CSNK1A1

CSNK1A1FUNCTION 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.

Reactomehttp://www.reactome.orgHomo sapiens

NCBI Taxonomy9606UniProtP48729

Chain Coordinates

EQUAL

337

EQUAL

Reactome DB_ID: 5632597

SMO dimer [ciliary membrane]

SMO dimer

Reactome DB_ID: 5624094

UniProt:Q99835 SMO

SMO

SMOSMOHFUNCTION 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.

UniProtQ99835

EQUAL

787

EQUAL

Reactome Database ID Release 755632597Database identifier. Use 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-5632597

Reactome stable identifier. Use this 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-5632597.1Reactome Database ID Release 755632602Database identifier. Use 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-5632602

Reactome stable identifier. Use this 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-5632602.1

Reactome DB_ID: 5632460

ATP(4-) [ChEBI:30616]

ATP(4-)

Adenosine 5'-triphosphateatpATP

ChEBI30616

Reactome DB_ID: 5632624

pS588,S590, T593, S595-SMO dimer:CSNK1A1 [ciliary membrane]

pS588,S590, T593, S595-SMO dimer:CSNK1A1

Reactome DB_ID: 5632507

EQUAL

337

EQUAL

Reactome DB_ID: 5632621

pS588, S590, T593, S595-SMO dimer [ciliary membrane]

pS588, S590, T593, S595-SMO dimer

Reactome DB_ID: 5632525

O-phospho-L-serine at 588

588

EQUAL

O-phospho-L-serine [MOD:00046]

O-phospho-L-serine at 590

590

EQUAL

O-phospho-L-threonine at 593

593

EQUAL

O-phospho-L-threonine [MOD:00047]

O-phospho-L-serine at 595

595

EQUAL

787

EQUAL

Reactome Database ID Release 755632621Database identifier. Use 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-5632621

Reactome stable identifier. Use this 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-5632621.1Reactome Database ID Release 755632624Database identifier. Use 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-5632624

Reactome stable identifier. Use this 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-5632624.1

Reactome DB_ID: 5632457

ADP(3-) [ChEBI:456216]

ADP(3-)

ADP trianion5'-O-[(phosphonatooxy)phosphinato]adenosineADP

ChEBI456216PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 5632602

GO0004674

GO molecular function

Reactome Database ID Release 755632631Database identifier. Use 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 755632670Database identifier. Use 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-5632670

Reactome stable identifier. Use this 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