Smo
entrez
319757
canonical
uniprot
P56726
canonical
ensembl
ENSMUSG00000001761
resolver
ensp
ENSMUSP00000001812
resolver
enst
ENSMUST00000001812
resolver
genesymbol
Smo
resolver
genesymbol_syn
Smoh
resolver
uniprot
Q4VBD5
resolver
uniprot
Q8BJN8
resolver
uniprot_entry
Q4VBD5_MOUSE
resolver
uniprot_entry
Q8BJN8_MOUSE
resolver
uniprot_entry
SMO_MOUSE
resolver
amino_acid_sequence
MAAGRPVRGPELAPRRLLQLLLLVLLGGPGRGAALSGNVTGPGPHSASGSSRRDVPVTSPPPPLLSHCGRAAHCEPLRYNVCLGSALPYGATTTLLAGDSDSQEEAHGKLVLWSGLRNAPRCWAVIQPLLCAVYMPKCENDRVELPSRTLCQATRGPCAIVERERGWPDFLRCTPDHFPEGCPNEVQNIKFNSSGQCEAPLVRTDNPKSWYEDVEGCGIQCQNPLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARREIVCRADGTMRFGEPTSSETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPGLLSEKAASKINETMLRLGIFGFLAFGFVLITFSCHFYDFFNQAEWERSFRDYVLCQANVTIGLPTKKPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKATLLIWRRTWCRLTGHSDDEPKRIKKSKMIAKAFSKRRELLQNPGQELSFSMHTVSHDGPVAGLAFDLNEPSADVSSAWAQHVTKMVARRGAILPQDVSVTPVATPVPPEEQANMWLVEAEISPELEKRLGRKKKRRKRKKEVCPLRPAPELHHSAPVPATSAVPRLPQLPRQKCLVAANAWGTGESCRQGAWTLVSNPFCPEPSPHQDPFLPGASAPRVWAQGRLQGLGSIHSRTNLMEAEILDADSDF
uniprot
proteins
function
FUNCTION: G protein-coupled receptor, which transduces the smoothened signaling pathway (PubMed:16707575, PubMed:16885213, PubMed:17200122, PubMed:22231273, PubMed:23954590, PubMed:25644602, PubMed:27437577, PubMed:27545348, PubMed:27705744, PubMed:29804838, PubMed:30340023, PubMed:31263273, PubMed:31657721, PubMed:33886552). Activated by cholesterol in response to hedgehog (DHH, IHH or SHH) morphogens (PubMed:16707575, PubMed:17200122, PubMed:22231273, PubMed:23954590, PubMed:27437577, PubMed:27545348, PubMed:27705744, PubMed:29804838, PubMed:31657721). In absence of hedgehog, SMO is inactivated by patched protein (PTCH1 or PTCH2), which prevents SMO access to cholesterol (PubMed:17641202, PubMed:31657721). In response to hedgehog-binding to pathched, inhibition is relieved, promoting SMO translocation to primary cilium and activation by cholesterol: cholesterol causes a conformation change that triggers signaling via G protein G(i), mediating inhibition of adenylate cyclase activity and decreassed production of cAMP (PubMed:16885213). Decreased cAMP levels then inhibit protein kinase A (PKA) and promote release of GLI (GLI1, GLI2 and GLI3) transcription factors, which activate expression of target genes (By similarity). Active SMO also directly inhibits PKA by sequestering its catalytic subunit, PRKACA, at the cell membrane, preventing PRKACA-mediated phosphorylation and subsequent processing of GLI transcription factors (PubMed:33886552, PubMed:39138140). Active SMO also promotes the removal of GPR161, a key inhibitor of the smoothened signaling pathway, from primary cilia (PubMed:23332756). {ECO:0000250|UniProtKB:Q99835, ECO:0000269|PubMed:16707575, ECO:0000269|PubMed:16885213, ECO:0000269|PubMed:17200122, ECO:0000269|PubMed:17641202, ECO:0000269|PubMed:22231273, ECO:0000269|PubMed:23332756, ECO:0000269|PubMed:23954590, ECO:0000269|PubMed:25644602, ECO:0000269|PubMed:27437577, ECO:0000269|PubMed:27545348, ECO:0000269|PubMed:27705744, ECO:0000269|PubMed:29804838, ECO:0000269|PubMed:30340023, ECO:0000269|PubMed:31263273, ECO:0000269|PubMed:31657721, ECO:0000269|PubMed:33886552, ECO:0000269|PubMed:39138140}.
uniprot
proteins
mass_dalton
87450
uniprot
proteins
mutagenesis
MUTAGEN 88; /note="P->N: No effect on sterol binding."; /evidence="ECO:0000269|PubMed:24171105"; MUTAGEN 89; /note="Y->A: No effect on sterol binding."; /evidence="ECO:0000269|PubMed:23954590"; MUTAGEN 99; /note="D->A: Loss of cholesterol binding and reduced SHH-induced activation. No effect on basal signaling."; /evidence="ECO:0000269|PubMed:27437577, ECO:0000269|PubMed:35658032"; MUTAGEN 99; /note="D->N: Abolished cholesterylation and activation; the protein is refractory to activation in response to hedgehog. Knockin mice are embryonic lethal and display rightward-loop defects and severe pericardial edema."; /evidence="ECO:0000269|PubMed:28344083"; MUTAGEN 112..119; /note="LWSGLRNA->DYYALKHV: Loss of sterol binding."; /evidence="ECO:0000269|PubMed:23831757"; MUTAGEN 112; /note="L->A,D: Reduced sterol binding."; /evidence="ECO:0000269|PubMed:24171105"; MUTAGEN 112; /note="L->D: Loss of sterol binding and reduced response to SHH."; /evidence="ECO:0000269|PubMed:23831757"; MUTAGEN 113; /note="W->Y,A: Loss of sterol binding and reduced response to SHH."; /evidence="ECO:0000269|PubMed:23831757, ECO:0000269|PubMed:23954590"; MUTAGEN 114; /note="S->Y: No effect on sterol binding."; /evidence="ECO:0000269|PubMed:23831757"; MUTAGEN 115; /note="G->F: Reduced sterol binding. Impaired response to oxysterol without affecting response to cholesterol."; /evidence="ECO:0000269|PubMed:23954590, ECO:0000269|PubMed:24171105, ECO:0000269|PubMed:27705744"; MUTAGEN 116; /note="L->A: Reduced sterol binding."; /evidence="ECO:0000269|PubMed:23954590, ECO:0000269|PubMed:24171105"; MUTAGEN 118; /note="N->A: No effect on sterol binding."; /evidence="ECO:0000269|PubMed:24171105"; MUTAGEN 120; /note="P->A,E,G: No effect on sterol binding."; /evidence="ECO:0000269|PubMed:24171105"; MUTAGEN 128; /note="P->S,E,R: No effect on sterol binding."; /evidence="ECO:0000269|PubMed:23954590, ECO:0000269|PubMed:24171105"; MUTAGEN 134; /note="Y->F: Reduced cholesterol-binding, preventing activation."; /evidence="ECO:0000269|PubMed:24171105, ECO:0000269|PubMed:27437577"; MUTAGEN 137; /note="K->A: No effect on sterol binding."; /evidence="ECO:0000269|PubMed:23954590"; MUTAGEN 139; /note="E->A: No effect on sterol binding."; /evidence="ECO:0000269|PubMed:23954590"; MUTAGEN 140; /note="N->A: No effect on sterol binding."; /evidence="ECO:0000269|PubMed:23954590"; MUTAGEN 144; /note="E->A: No effect on sterol binding."; /evidence="ECO:0000269|PubMed:23954590"; MUTAGEN 150; /note="L->A,D,S: No effect on sterol binding."; /evidence="ECO:0000269|PubMed:24171105"; MUTAGEN 151; /note="C->Y: Reduced protein levels, reduced activity and loss of localization to cilia."; /evidence="ECO:0000269|PubMed:19464178"; MUTAGEN 162; /note="E->A: No effect on sterol binding."; /evidence="ECO:0000269|PubMed:24171105"; MUTAGEN 164; /note="E->L: Reduced sterol-binding."; /evidence="ECO:0000269|PubMed:27545348"; MUTAGEN 165; /note="R->A,E: No effect on sterol binding."; /evidence="ECO:0000269|PubMed:24171105"; MUTAGEN 166; /note="G->F: Reduced sterol binding."; /evidence="ECO:0000269|PubMed:24171105"; MUTAGEN 168; /note="P->A: Reduced sterol binding."; /evidence="ECO:0000269|PubMed:23954590, ECO:0000269|PubMed:24171105"; MUTAGEN 170; /note="F->A: Reduced sterol binding."; /evidence="ECO:0000269|PubMed:24171105"; MUTAGEN 333; /note="V->F: Failure to localize to primary cilia. Loss of cholesterol-induced activity."; /evidence="ECO:0000269|PubMed:31263273, ECO:0000269|PubMed:35658032"; MUTAGEN 398; /note="Y->F: Remains responsive to SHH and 20S-hydroxycholesterol. Reduced basal signaling."; /evidence="ECO:0000269|PubMed:31263273, ECO:0000269|PubMed:35658032"; MUTAGEN 408; /note="V->F: Loss of activity."; /evidence="ECO:0000269|PubMed:31263273"; MUTAGEN 412; /note="I->F: Loss of activity."; /evidence="ECO:0000269|PubMed:31263273"; MUTAGEN 420; /note="G->F: Reduced activity in response to SHH."; /evidence="ECO:0000269|PubMed:31263273"; MUTAGEN 455; /note="R->A,Q,E: Constitutively active smoothened signaling."; /evidence="ECO:0000269|PubMed:29804838"; MUTAGEN 463; /note="A->F: Loss of activity in response to SHH."; /evidence="ECO:0000269|PubMed:31263273"; MUTAGEN 470; /note="T->Q: Loss of cholesterol-induced activity."; /evidence="ECO:0000269|PubMed:31263273"; MUTAGEN 477; /note="D->G: Does not affect cholesterol-binding and activation."; /evidence="ECO:0000269|PubMed:27705744"; MUTAGEN 549..550; /note="WR->AA: Loss of activity and cilium localization."; /evidence="ECO:0000269|PubMed:16136078
uniprot
proteins
post_translational_modification
PTM: Phosphorylation by GRK2 and/GRK3 kinases promotes interaction with protein kinase A catalytic subunit PRKACA. {ECO:0000269|PubMed:33886552}.
uniprot
proteins
protein_family
G protein-coupled receptor Fz/Smo family
uniprot
proteins
pubmed
11517919
uniprot
proteins
pubmed
15618519
uniprot
proteins
pubmed
16136078
uniprot
proteins
pubmed
16707575
uniprot
proteins
pubmed
16885213
uniprot
proteins
pubmed
17199044
uniprot
proteins
pubmed
17200122
uniprot
proteins
pubmed
17641202
uniprot
proteins
pubmed
18497258
uniprot
proteins
pubmed
19464178
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
21659505
uniprot
proteins
pubmed
22072986
uniprot
proteins
pubmed
22231273
uniprot
proteins
pubmed
23332756
uniprot
proteins
pubmed
23831757
uniprot
proteins
pubmed
23954590
uniprot
proteins
pubmed
24171105
uniprot
proteins
pubmed
25644602
uniprot
proteins
pubmed
27437577
uniprot
proteins
pubmed
27545348
uniprot
proteins
pubmed
27705744
uniprot
proteins
pubmed
28344083
uniprot
proteins
pubmed
29804838
uniprot
proteins
pubmed
30340023
uniprot
proteins
pubmed
31263273
uniprot
proteins
pubmed
31657721
uniprot
proteins
pubmed
33886552
uniprot
proteins
pubmed
35658032
uniprot
proteins
pubmed
39138140
uniprot
proteins
pubmed
9196051
uniprot
proteins
sequence_length
793
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16136078, ECO:0000269|PubMed:33886552}; Multi-pass membrane protein {ECO:0000269|PubMed:31263273}. Cell projection, cilium membrane {ECO:0000269|PubMed:16136078, ECO:0000269|PubMed:17641202, ECO:0000269|PubMed:18497258, ECO:0000269|PubMed:19464178, ECO:0000269|PubMed:21659505, ECO:0000269|PubMed:22231273, ECO:0000269|PubMed:23831757, ECO:0000269|PubMed:25644602, ECO:0000269|PubMed:35658032, ECO:0000269|PubMed:39138140}; Multi-pass membrane protein {ECO:0000269|PubMed:31263273}. Note=Translocates to primary cilium in response to hedgehog (DHH, IHH or SHH) morphogens (PubMed:16136078, PubMed:17641202, PubMed:19464178). Cilium localization is mediated via a beta-arrestin and KIF3A-dependent mechanism (PubMed:18497258). {ECO:0000269|PubMed:16136078, ECO:0000269|PubMed:17641202, ECO:0000269|PubMed:18497258, ECO:0000269|PubMed:19464178}.
uniprot
proteins
transmembrane_region
TRANSMEM 236..258; /note="Helical; Name=1"; /evidence="ECO:0000269|PubMed:31263273, ECO:0007744|PDB:6O3C"; TRANSMEM 269..289; /note="Helical; Name=2"; /evidence="ECO:0000269|PubMed:31263273, ECO:0007744|PDB:6O3C"; TRANSMEM 317..341; /note="Helical; Name=3"; /evidence="ECO:0000269|PubMed:31263273, ECO:0007744|PDB:6O3C"; TRANSMEM 363..382; /note="Helical; Name=4"; /evidence="ECO:0000269|PubMed:31263273, ECO:0007744|PDB:6O3C"; TRANSMEM 403..428; /note="Helical; Name=5"; /evidence="ECO:0000269|PubMed:31263273, ECO:0007744|PDB:6O3C"; TRANSMEM 451..475; /note="Helical; Name=6"; /evidence="ECO:0000269|PubMed:31263273, ECO:0007744|PDB:6O3C"; TRANSMEM 523..542; /note="Helical; Name=7"; /evidence="ECO:0000269|PubMed:31263273, ECO:0007744|PDB:6O3C
uniprot
proteins