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Protein

Smoothened homolog

Gene

SMO

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 and GLI3 in the cilia.1 Publication

GO - Molecular functioni

  • drug binding Source: UniProtKB
  • G-protein coupled receptor activity Source: GO_Central
  • patched binding Source: BHF-UCL
  • Wnt-protein binding Source: GO_Central

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_18372. Class B/2 (Secretin family receptors).
REACT_267753. Activation of SMO.
REACT_267948. BBSome-mediated cargo-targeting to cilium.
REACT_268323. Hedgehog 'off' state.
SignaLinkiQ99835.

Names & Taxonomyi

Protein namesi
Recommended name:
Smoothened homolog
Short name:
SMO
Alternative name(s):
Protein Gx
Gene namesi
Name:SMO
Synonyms:SMOH
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:11119. SMO.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini28 – 233206ExtracellularSequence AnalysisAdd
BLAST
Transmembranei234 – 25421Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini255 – 2628CytoplasmicSequence Analysis
Transmembranei263 – 28321Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini284 – 31431ExtracellularSequence AnalysisAdd
BLAST
Transmembranei315 – 33521Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini336 – 35823CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei359 – 37921Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini380 – 40223ExtracellularSequence AnalysisAdd
BLAST
Transmembranei403 – 42321Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini424 – 45128CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei452 – 47221Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini473 – 52452ExtracellularSequence AnalysisAdd
BLAST
Transmembranei525 – 54521Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini546 – 787242CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  • ciliary membrane Source: Reactome
  • ciliary tip Source: Reactome
  • endocytic vesicle membrane Source: Reactome
  • extracellular exosome Source: UniProtKB
  • integral component of membrane Source: GO_Central
  • intracellular membrane-bounded organelle Source: BHF-UCL
  • plasma membrane Source: UniProtKB
  • primary cilium Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA35968.

Chemistry

DrugBankiDB01047. Fluocinonide.
DB08828. Vismodegib.

Polymorphism and mutation databases

BioMutaiSMO.
DMDMi6226142.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2727Sequence AnalysisAdd
BLAST
Chaini28 – 787760Smoothened homologPRO_0000013015Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi35 – 351N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi70 ↔ 134PROSITE-ProRule annotation
Disulfide bondi78 ↔ 127PROSITE-ProRule annotation
Disulfide bondi118 ↔ 154PROSITE-ProRule annotation
Disulfide bondi147 ↔ 169PROSITE-ProRule annotation
Glycosylationi188 – 1881N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi193 ↔ 213PROSITE-ProRule annotation1 Publication
Disulfide bondi217 ↔ 295PROSITE-ProRule annotation1 Publication
Glycosylationi309 – 3091N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi314 ↔ 390PROSITE-ProRule annotation1 Publication
Disulfide bondi490 ↔ 507PROSITE-ProRule annotation1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ99835.
PRIDEiQ99835.

PTM databases

PhosphoSiteiQ99835.

Expressioni

Gene expression databases

BgeeiQ99835.
CleanExiHS_SMO.
ExpressionAtlasiQ99835. baseline and differential.
GenevestigatoriQ99835.

Organism-specific databases

HPAiCAB011446.
HPA044232.

Interactioni

Subunit structurei

Homodimer. Interacts with ARRB2. Interacts with KIF7. Interacts with BBS5 and BBS7; the interactions are indicative for the association of SMO with the BBsome complex to facilitate ciliary localization of SMO.3 Publications

Protein-protein interaction databases

BioGridi112492. 4 interactions.
DIPiDIP-34574N.
IntActiQ99835. 5 interactions.
STRINGi9606.ENSP00000249373.

Structurei

Secondary structure

1
787
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi190 – 1923Combined sources
Beta strandi197 – 1993Combined sources
Helixi203 – 2053Combined sources
Beta strandi210 – 2189Combined sources
Helixi224 – 25431Combined sources
Helixi256 – 2594Combined sources
Turni262 – 2654Combined sources
Helixi266 – 28217Combined sources
Helixi283 – 2853Combined sources
Helixi289 – 2946Combined sources
Beta strandi299 – 3013Combined sources
Beta strandi304 – 3063Combined sources
Helixi313 – 34735Combined sources
Turni354 – 3563Combined sources
Helixi361 – 37818Combined sources
Beta strandi381 – 3844Combined sources
Turni385 – 3884Combined sources
Beta strandi389 – 3957Combined sources
Helixi397 – 4037Combined sources
Helixi405 – 43228Combined sources
Beta strandi436 – 4427Combined sources
Helixi443 – 49250Combined sources
Helixi515 – 53218Combined sources
Helixi533 – 5364Combined sources
Helixi539 – 54810Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4JKVX-ray2.45A/B190-555[»]
4N4WX-ray2.80A190-555[»]
4O9RX-ray3.20A190-433[»]
A441-555[»]
4QIMX-ray2.61A190-433[»]
A441-555[»]
4QINX-ray2.60A190-433[»]
A441-555[»]
ProteinModelPortaliQ99835.
SMRiQ99835. Positions 55-175, 190-553.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini65 – 181117FZPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni538 – 56932Interaction with BBS5 and BBS7Add
BLAST

Sequence similaritiesi

Contains 1 FZ (frizzled) domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG312505.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000252964.
HOVERGENiHBG000352.
InParanoidiQ99835.
KOiK06226.
OMAiKNSNRYP.
OrthoDBiEOG74J972.
PhylomeDBiQ99835.
TreeFamiTF106460.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR017981. GPCR_2-like.
IPR026544. SMO.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF35. PTHR11309:SF35. 1 hit.
PfamiPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSiPR00489. FRIZZLED.
SMARTiSM00063. FRI. 1 hit.
[Graphical view]
SUPFAMiSSF63501. SSF63501. 1 hit.
PROSITEiPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q99835-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAAARPARGP ELPLLGLLLL LLLGDPGRGA ASSGNATGPG PRSAGGSARR
60 70 80 90 100
SAAVTGPPPP LSHCGRAAPC EPLRYNVCLG SVLPYGATST LLAGDSDSQE
110 120 130 140 150
EAHGKLVLWS GLRNAPRCWA VIQPLLCAVY MPKCENDRVE LPSRTLCQAT
160 170 180 190 200
RGPCAIVERE RGWPDFLRCT PDRFPEGCTN EVQNIKFNSS GQCEVPLVRT
210 220 230 240 250
DNPKSWYEDV EGCGIQCQNP LFTEAEHQDM HSYIAAFGAV TGLCTLFTLA
260 270 280 290 300
TFVADWRNSN RYPAVILFYV NACFFVGSIG WLAQFMDGAR REIVCRADGT
310 320 330 340 350
MRLGEPTSNE TLSCVIIFVI VYYALMAGVV WFVVLTYAWH TSFKALGTTY
360 370 380 390 400
QPLSGKTSYF HLLTWSLPFV LTVAILAVAQ VDGDSVSGIC FVGYKNYRYR
410 420 430 440 450
AGFVLAPIGL VLIVGGYFLI RGVMTLFSIK SNHPGLLSEK AASKINETML
460 470 480 490 500
RLGIFGFLAF GFVLITFSCH FYDFFNQAEW ERSFRDYVLC QANVTIGLPT
510 520 530 540 550
KQPIPDCEIK NRPSLLVEKI NLFAMFGTGI AMSTWVWTKA TLLIWRRTWC
560 570 580 590 600
RLTGQSDDEP KRIKKSKMIA KAFSKRHELL QNPGQELSFS MHTVSHDGPV
610 620 630 640 650
AGLAFDLNEP SADVSSAWAQ HVTKMVARRG AILPQDISVT PVATPVPPEE
660 670 680 690 700
QANLWLVEAE ISPELQKRLG RKKKRRKRKK EVCPLAPPPE LHPPAPAPST
710 720 730 740 750
IPRLPQLPRQ KCLVAAGAWG AGDSCRQGAW TLVSNPFCPE PSPPQDPFLP
760 770 780
SAPAPVAWAH GRRQGLGPIH SRTNLMDTEL MDADSDF
Length:787
Mass (Da):86,397
Last modified:May 1, 1997 - v1
Checksum:i8B4C459B34D13F83
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti473 – 4731D → H.
Corresponds to variant rs17710891 [ dbSNP | Ensembl ].
VAR_037891
Natural varianti535 – 5351W → L in basal cell carcinoma samples; somatic mutation. 1 Publication
VAR_007848
Natural varianti562 – 5621R → Q in basal cell carcinoma samples; somatic mutation. 1 Publication
VAR_007849

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U84401 mRNA. Translation: AAB41788.1.
AF114821, AF114819, AF114820 Genomic DNA. Translation: AAD17202.1.
AF120103 mRNA. Translation: AAF31757.1.
AF071494 mRNA. Translation: AAC24863.1.
CH236950 Genomic DNA. Translation: EAL24102.1.
CH471070 Genomic DNA. Translation: EAW83715.1.
BC009989 mRNA. Translation: AAH09989.1.
CCDSiCCDS5811.1.
RefSeqiNP_005622.1. NM_005631.4.
UniGeneiHs.437846.

Genome annotation databases

EnsembliENST00000249373; ENSP00000249373; ENSG00000128602.
GeneIDi6608.
KEGGihsa:6608.
UCSCiuc003vor.3. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U84401 mRNA. Translation: AAB41788.1.
AF114821, AF114819, AF114820 Genomic DNA. Translation: AAD17202.1.
AF120103 mRNA. Translation: AAF31757.1.
AF071494 mRNA. Translation: AAC24863.1.
CH236950 Genomic DNA. Translation: EAL24102.1.
CH471070 Genomic DNA. Translation: EAW83715.1.
BC009989 mRNA. Translation: AAH09989.1.
CCDSiCCDS5811.1.
RefSeqiNP_005622.1. NM_005631.4.
UniGeneiHs.437846.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4JKVX-ray2.45A/B190-555[»]
4N4WX-ray2.80A190-555[»]
4O9RX-ray3.20A190-433[»]
A441-555[»]
4QIMX-ray2.61A190-433[»]
A441-555[»]
4QINX-ray2.60A190-433[»]
A441-555[»]
ProteinModelPortaliQ99835.
SMRiQ99835. Positions 55-175, 190-553.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112492. 4 interactions.
DIPiDIP-34574N.
IntActiQ99835. 5 interactions.
STRINGi9606.ENSP00000249373.

Chemistry

BindingDBiQ99835.
ChEMBLiCHEMBL5971.
DrugBankiDB01047. Fluocinonide.
DB08828. Vismodegib.
GuidetoPHARMACOLOGYi239.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSiteiQ99835.

Polymorphism and mutation databases

BioMutaiSMO.
DMDMi6226142.

Proteomic databases

PaxDbiQ99835.
PRIDEiQ99835.

Protocols and materials databases

DNASUi6608.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000249373; ENSP00000249373; ENSG00000128602.
GeneIDi6608.
KEGGihsa:6608.
UCSCiuc003vor.3. human.

Organism-specific databases

CTDi6608.
GeneCardsiGC07P128828.
HGNCiHGNC:11119. SMO.
HPAiCAB011446.
HPA044232.
MIMi601500. gene.
neXtProtiNX_Q99835.
PharmGKBiPA35968.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG312505.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000252964.
HOVERGENiHBG000352.
InParanoidiQ99835.
KOiK06226.
OMAiKNSNRYP.
OrthoDBiEOG74J972.
PhylomeDBiQ99835.
TreeFamiTF106460.

Enzyme and pathway databases

ReactomeiREACT_18372. Class B/2 (Secretin family receptors).
REACT_267753. Activation of SMO.
REACT_267948. BBSome-mediated cargo-targeting to cilium.
REACT_268323. Hedgehog 'off' state.
SignaLinkiQ99835.

Miscellaneous databases

ChiTaRSiSMO. human.
GeneWikiiSmoothened.
GenomeRNAii6608.
NextBioi25725.
PROiQ99835.
SOURCEiSearch...

Gene expression databases

BgeeiQ99835.
CleanExiHS_SMO.
ExpressionAtlasiQ99835. baseline and differential.
GenevestigatoriQ99835.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR017981. GPCR_2-like.
IPR026544. SMO.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF35. PTHR11309:SF35. 1 hit.
PfamiPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSiPR00489. FRIZZLED.
SMARTiSM00063. FRI. 1 hit.
[Graphical view]
SUPFAMiSSF63501. SSF63501. 1 hit.
PROSITEiPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Embryonic lung.
  2. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-535 AND GLN-562.
  3. "Cloning and identification of Gx gene in NPC."
    Jiang N., Zeng Z.Y., Li G.Y.
    Submitted (JAN-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  4. "Human chromosome 7: DNA sequence and biology."
    Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S.
    , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
    Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Brain.
  7. "The mammalian Cos2 homolog Kif7 plays an essential role in modulating Hh signal transduction during development."
    Endoh-Yamagami S., Evangelista M., Wilson D., Wen X., Theunissen J.W., Phamluong K., Davis M., Scales S.J., Solloway M.J., de Sauvage F.J., Peterson A.S.
    Curr. Biol. 19:1320-1326(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH KIF7.
  8. "A novel protein LZTFL1 regulates ciliary trafficking of the BBSome and Smoothened."
    Seo S., Zhang Q., Bugge K., Breslow D.K., Searby C.C., Nachury M.V., Sheffield V.C.
    PLoS Genet. 7:E1002358-E1002358(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: ASSOCIATION WITH THE BBSOME COMPLEX, INTERACTION WITH BBS5 AND BBS7, SUBCELLULAR LOCATION.
  9. "Structure of the human smoothened receptor bound to an antitumour agent."
    Wang C., Wu H., Katritch V., Han G.W., Huang X.P., Liu W., Siu F.Y., Roth B.L., Cherezov V., Stevens R.C.
    Nature 497:338-343(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.45 ANGSTROMS) OF 190-555 IN COMPLEX WITH ANTAGONIST, SUBUNIT, DISULFIDE BONDS.

Entry informationi

Entry nameiSMO_HUMAN
AccessioniPrimary (citable) accession number: Q99835
Secondary accession number(s): A4D1K5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 1, 1997
Last modified: May 27, 2015
This is version 155 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.