SMO_RAT
ID SMO_RAT Reviewed; 793 AA.
AC P97698;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Smoothened homolog;
DE Short=SMO;
DE Flags: Precursor;
GN Name=Smo; Synonyms=Smoh;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Embryo;
RX PubMed=8906787; DOI=10.1038/384129a0;
RA Stone D.M., Hynes M., Armanini M., Swanson T.A., Gu Q., Johnson R.L.,
RA Scott M.P., Pennica D., Goddard A., Phillips H., Noll M., Hooper J.E.,
RA de Sauvage F., Rosenthal A.;
RT "The tumour-suppressor gene patched encodes a candidate receptor for Sonic
RT hedgehog.";
RL Nature 384:129-134(1996).
CC -!- FUNCTION: G protein-coupled receptor that probably associates with the
CC patched protein (PTCH) to transduce the hedgehog's proteins signal.
CC Binding of sonic hedgehog (SHH) to its receptor patched is thought to
CC prevent normal inhibition by patched of smoothened (SMO). Required for
CC the accumulation of KIF7, GLI2 and GLI3 in the cilia. Interacts with
CC DLG5 at the ciliary base to induce the accumulation of KIF7 and GLI2 at
CC the ciliary tip for GLI2 activation. {ECO:0000250|UniProtKB:P56726,
CC ECO:0000250|UniProtKB:Q99835}.
CC -!- SUBUNIT: Homodimer. Interacts with ARRB2. Interacts with KIF7.
CC Interacts with BBS5 and BBS7; the interactions are indicative for the
CC association of SMO with the BBsome complex to facilitate ciliary
CC localization of SMO. Interacts with DLG5 and SDCBP. Interacts with
CC GAS8/DRC4. {ECO:0000250|UniProtKB:P56726,
CC ECO:0000250|UniProtKB:Q99835}.
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. Cell
CC projection, cilium {ECO:0000250|UniProtKB:P56726}.
CC -!- TISSUE SPECIFICITY: In embryo, found in the early neural folds and
CC neural tube, pre-somitic mesoderm and somites, developing limb bud,
CC gut, eye, testes, cartilage, muscle, lung, epiglottis, thymus, tongue,
CC jaw, taste buds, teeth, and skin. In adult, found in multiple tissues
CC including heart, brain, liver, lung, skeletal muscle, kidney and
CC testis.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor Fz/Smo family.
CC {ECO:0000305}.
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DR EMBL; U84402; AAB41789.1; -; mRNA.
DR RefSeq; NP_036939.1; NM_012807.1.
DR AlphaFoldDB; P97698; -.
DR SMR; P97698; -.
DR STRING; 10116.ENSRNOP00000011356; -.
DR ChEMBL; CHEMBL1795175; -.
DR GlyGen; P97698; 3 sites.
DR iPTMnet; P97698; -.
DR PhosphoSitePlus; P97698; -.
DR PaxDb; P97698; -.
DR GeneID; 25273; -.
DR KEGG; rno:25273; -.
DR UCSC; RGD:3726; rat.
DR CTD; 6608; -.
DR RGD; 3726; Smo.
DR eggNOG; KOG3577; Eukaryota.
DR InParanoid; P97698; -.
DR OrthoDB; 509772at2759; -.
DR PhylomeDB; P97698; -.
DR Reactome; R-RNO-5610787; Hedgehog 'off' state.
DR Reactome; R-RNO-5620922; BBSome-mediated cargo-targeting to cilium.
DR Reactome; R-RNO-5632684; Hedgehog 'on' state.
DR Reactome; R-RNO-5635838; Activation of SMO.
DR PRO; PR:P97698; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0097731; C:9+0 non-motile cilium; ISO:RGD.
DR GO; GO:0044295; C:axonal growth cone; IDA:RGD.
DR GO; GO:0005814; C:centriole; ISO:RGD.
DR GO; GO:0060170; C:ciliary membrane; ISO:RGD.
DR GO; GO:0005929; C:cilium; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0044294; C:dendritic growth cone; IDA:RGD.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0014069; C:postsynaptic density; IDA:RGD.
DR GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW.
DR GO; GO:0005113; F:patched binding; ISO:RGD.
DR GO; GO:0009952; P:anterior/posterior pattern specification; ISO:RGD.
DR GO; GO:0048143; P:astrocyte activation; ISO:RGD.
DR GO; GO:0060413; P:atrial septum morphogenesis; ISO:RGD.
DR GO; GO:0048846; P:axon extension involved in axon guidance; IMP:RGD.
DR GO; GO:0048468; P:cell development; ISO:RGD.
DR GO; GO:0001708; P:cell fate specification; ISO:RGD.
DR GO; GO:0071397; P:cellular response to cholesterol; ISO:RGD.
DR GO; GO:0007417; P:central nervous system development; ISO:RGD.
DR GO; GO:0021953; P:central nervous system neuron differentiation; ISO:RGD.
DR GO; GO:0021696; P:cerebellar cortex morphogenesis; ISO:RGD.
DR GO; GO:0021987; P:cerebral cortex development; ISO:RGD.
DR GO; GO:0071679; P:commissural neuron axon guidance; IMP:RGD.
DR GO; GO:0060242; P:contact inhibition; ISO:RGD.
DR GO; GO:0021542; P:dentate gyrus development; ISO:RGD.
DR GO; GO:0003140; P:determination of left/right asymmetry in lateral mesoderm; ISS:UniProtKB.
DR GO; GO:0007368; P:determination of left/right symmetry; ISO:RGD.
DR GO; GO:0048589; P:developmental growth; ISO:RGD.
DR GO; GO:0048565; P:digestive tract development; ISO:RGD.
DR GO; GO:0021904; P:dorsal/ventral neural tube patterning; ISO:RGD.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; ISO:RGD.
DR GO; GO:0048568; P:embryonic organ development; ISO:RGD.
DR GO; GO:0060684; P:epithelial-mesenchymal cell signaling; ISO:RGD.
DR GO; GO:0021561; P:facial nerve development; IEP:RGD.
DR GO; GO:0048853; P:forebrain morphogenesis; ISS:UniProtKB.
DR GO; GO:0031069; P:hair follicle morphogenesis; ISO:RGD.
DR GO; GO:0001947; P:heart looping; ISS:UniProtKB.
DR GO; GO:0003007; P:heart morphogenesis; ISO:RGD.
DR GO; GO:0048873; P:homeostasis of number of cells within a tissue; ISO:RGD.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:0070986; P:left/right axis specification; ISO:RGD.
DR GO; GO:0060644; P:mammary gland epithelial cell differentiation; ISO:RGD.
DR GO; GO:0060231; P:mesenchymal to epithelial transition; IMP:RGD.
DR GO; GO:0072285; P:mesenchymal to epithelial transition involved in metanephric renal vesicle formation; ISS:UniProtKB.
DR GO; GO:0007494; P:midgut development; ISS:UniProtKB.
DR GO; GO:0035264; P:multicellular organism growth; ISO:RGD.
DR GO; GO:0051451; P:myoblast migration; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0043392; P:negative regulation of DNA binding; ISS:UniProtKB.
DR GO; GO:0030857; P:negative regulation of epithelial cell differentiation; ISO:RGD.
DR GO; GO:0010629; P:negative regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0051799; P:negative regulation of hair follicle development; ISO:RGD.
DR GO; GO:2000346; P:negative regulation of hepatocyte proliferation; IMP:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:RGD.
DR GO; GO:1901215; P:negative regulation of neuron death; IDA:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0001755; P:neural crest cell migration; ISO:RGD.
DR GO; GO:0031102; P:neuron projection regeneration; IEP:RGD.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; ISO:RGD.
DR GO; GO:0001503; P:ossification; ISO:RGD.
DR GO; GO:0001649; P:osteoblast differentiation; IEP:RGD.
DR GO; GO:0033687; P:osteoblast proliferation; IEP:RGD.
DR GO; GO:0061113; P:pancreas morphogenesis; ISO:RGD.
DR GO; GO:0007389; P:pattern specification process; ISO:RGD.
DR GO; GO:0010508; P:positive regulation of autophagy; IDA:RGD.
DR GO; GO:0090190; P:positive regulation of branching involved in ureteric bud morphogenesis; ISS:UniProtKB.
DR GO; GO:0030335; P:positive regulation of cell migration; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:RGD.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISS:UniProtKB.
DR GO; GO:2000491; P:positive regulation of hepatic stellate cell activation; IMP:RGD.
DR GO; GO:0007228; P:positive regulation of hh target transcription factor activity; ISS:UniProtKB.
DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; ISO:RGD.
DR GO; GO:0040018; P:positive regulation of multicellular organism growth; ISO:RGD.
DR GO; GO:2000179; P:positive regulation of neural precursor cell proliferation; IMP:RGD.
DR GO; GO:0002052; P:positive regulation of neuroblast proliferation; ISO:RGD.
DR GO; GO:0046622; P:positive regulation of organ growth; ISO:RGD.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; ISO:RGD.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:1904754; P:positive regulation of vascular associated smooth muscle cell migration; IMP:RGD.
DR GO; GO:0034504; P:protein localization to nucleus; ISO:RGD.
DR GO; GO:0050821; P:protein stabilization; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:2000826; P:regulation of heart morphogenesis; ISO:RGD.
DR GO; GO:2000036; P:regulation of stem cell population maintenance; ISO:RGD.
DR GO; GO:0010033; P:response to organic substance; IEP:RGD.
DR GO; GO:0009611; P:response to wounding; IEP:RGD.
DR GO; GO:0048741; P:skeletal muscle fiber development; ISO:RGD.
DR GO; GO:0048745; P:smooth muscle tissue development; ISO:RGD.
DR GO; GO:0007224; P:smoothened signaling pathway; ISS:UniProtKB.
DR GO; GO:0021938; P:smoothened signaling pathway involved in regulation of cerebellar granule cell precursor cell proliferation; ISO:RGD.
DR GO; GO:0021910; P:smoothened signaling pathway involved in ventral spinal cord patterning; ISO:RGD.
DR GO; GO:0061053; P:somite development; ISS:UniProtKB.
DR GO; GO:0007283; P:spermatogenesis; IEP:RGD.
DR GO; GO:0021794; P:thalamus development; ISO:RGD.
DR GO; GO:0003323; P:type B pancreatic cell development; ISO:RGD.
DR GO; GO:0001570; P:vasculogenesis; ISO:RGD.
DR GO; GO:0007371; P:ventral midline determination; ISO:RGD.
DR CDD; cd15030; 7tmF_SMO_homolog; 1.
DR CDD; cd07451; CRD_SMO; 1.
DR Gene3D; 1.10.2000.10; -; 1.
DR InterPro; IPR015526; Frizzled/SFRP.
DR InterPro; IPR000539; Frizzled/Smoothened_TM.
DR InterPro; IPR020067; Frizzled_dom.
DR InterPro; IPR036790; Frizzled_dom_sf.
DR InterPro; IPR017981; GPCR_2-like.
DR InterPro; IPR026544; SMO.
DR InterPro; IPR035683; SMO_7TM.
DR InterPro; IPR041771; SMO_CRD.
DR PANTHER; PTHR11309; PTHR11309; 1.
DR PANTHER; PTHR11309:SF35; PTHR11309:SF35; 1.
DR Pfam; PF01534; Frizzled; 1.
DR Pfam; PF01392; Fz; 1.
DR PRINTS; PR00489; FRIZZLED.
DR SMART; SM00063; FRI; 1.
DR SMART; SM01330; Frizzled; 1.
DR SUPFAM; SSF63501; SSF63501; 1.
DR PROSITE; PS50038; FZ; 1.
DR PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1.
PE 2: Evidence at transcript level;
KW Cell projection; Developmental protein; Disulfide bond;
KW G-protein coupled receptor; Glycoprotein; Membrane; Receptor;
KW Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix.
FT SIGNAL 1..30
FT /evidence="ECO:0000255"
FT CHAIN 31..793
FT /note="Smoothened homolog"
FT /id="PRO_0000013017"
FT TOPO_DOM 31..237
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 238..258
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 259..266
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 267..287
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 288..318
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 319..339
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 340..362
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 363..383
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 384..406
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 407..427
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 428..455
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 456..476
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 477..528
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 529..549
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 550..793
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 69..185
FT /note="FZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT REGION 35..61
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 542..573
FT /note="Interaction with BBS5 and BBS7"
FT /evidence="ECO:0000250|UniProtKB:P56726"
FT REGION 585..597
FT /note="Interaction with DLG5"
FT /evidence="ECO:0000250|UniProtKB:P56726"
FT REGION 674..702
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 38
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 192
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 497
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 74..138
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 82..131
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 122..158
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 151..173
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 197..217
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 221..299
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 318..394
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DISULFID 494..511
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
SQ SEQUENCE 793 AA; 87376 MW; 27B88178B2565FB9 CRC64;
MAAGRPVRGP ELAPRRLLQL LLLVLLGGRG RGAALSGNVT GPGPRSAGGS ARRNAPVTSP
PPPLLSHCGR AAHCEPLRYN VCLGSALPYG ATTTLLAGDS DSQEEAHSKL VLWSGLRNAP
RCWAVIQPLL CAVYMPKCEN DRVELPSRTL CQATRGPCAI VERERGWPDF LRCTPDHFPE
GCPNEVQNIK FNSSGQCEAP LVRTDNPKSW YEDVEGCGIQ CQNPLFTEAE HQDMHSYIAA
FGAVTGLCTL FTLATFVADW RNSNRYPAVI LFYVNACFFV GSIGWLAQFM DGARREIVCR
ADGTMRFGEP TSSETLSCVI IFVIVYYALM AGVVWFVVLT YAWHTSFKAL GTTYQPLSGK
TSYFHLLTWS LPFVLTVAIL AVAQVDGDSV SGICFVGYKN YRYRAGFVLA PIGLVLIVGG
YFLIRGVMTL FSIKSNHPGL LSEKAASKIN ETMLRLGIFG FLAFGFVLIT FSCHFYDFFN
QAEWERSFRD YVLCQANVTI GLPTKKPIPD CEIKNRPSLL VEKINLFAMF GTGIAMSTWV
WTKATLLIWR RTWCRLTGHS DDEPKRIKKS KMIAKAFSKR RELLQNPGQE LSFSMHTVSH
DGPVAGLAFE LNEPSADVSS AWAQHVTKMV ARRGAILPQD VSVTPVATPV PPEEQANLWL
VEAEISPELE KRLGRKKKRR KRKKEVCPLG PAPELHHSAP VPATSAVPRL PQLPRQKCLV
AANAWGTGEP CRQGAWTVVS NPFCPEPSPH QDPFLPGASA PRVWAQGRLQ GLGSIHSRTN
LMEAELLDAD SDF
