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UniProtKB - Q99835 (SMO_HUMAN)

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Protein

Smoothened homolog

Gene

SMO

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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, 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).By similarity1 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
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionDevelopmental protein, G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-HSA-373080 Class B/2 (Secretin family receptors)
R-HSA-5610787 Hedgehog 'off' state
R-HSA-5620922 BBSome-mediated cargo-targeting to cilium
R-HSA-5632684 Hedgehog 'on' state
R-HSA-5635838 Activation of SMO
SignaLinkiQ99835
SIGNORiQ99835

Protein family/group databases

TCDBi9.A.14.16.4 the g-protein-coupled receptor (gpcr) family

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000128602.9
HGNCiHGNC:11119 SMO
MIMi601500 gene
neXtProtiNX_Q99835

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini28 – 233ExtracellularSequence analysisAdd BLAST206
Transmembranei234 – 254Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini255 – 262CytoplasmicSequence analysis8
Transmembranei263 – 283Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini284 – 314ExtracellularSequence analysisAdd BLAST31
Transmembranei315 – 335Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini336 – 358CytoplasmicSequence analysisAdd BLAST23
Transmembranei359 – 379Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini380 – 402ExtracellularSequence analysisAdd BLAST23
Transmembranei403 – 423Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini424 – 451CytoplasmicSequence analysisAdd BLAST28
Transmembranei452 – 472Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini473 – 524ExtracellularSequence analysisAdd BLAST52
Transmembranei525 – 545Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini546 – 787CytoplasmicSequence analysisAdd BLAST242

Keywords - Cellular componenti

Cell projection, Membrane

Pathology & Biotechi

Involvement in diseasei

Curry-Jones syndrome (CRJS)2 Publications
The disease is caused by mutations affecting the gene represented in this entry. 8 individuals have been identified with the disease-causing mutation Phe-412 and all were mosaic. The mutation could not be reliably detected in blood, greatest success rates were obtained with affected tissues obtained by invasive procedures. It is thought that the mutation has arisen postzygotically early during embryonic development (PubMed:27236920). This mutation has also been identified in ameloblastoma, medulloblastoma, meningioma, and basal cell carcinoma, and has been reported as the oncogenic driver in some of these tumors (PubMed:24859340).2 Publications
Disease descriptionA multisystem disorder characterized by patchy skin lesions, polysyndactyly, diverse cerebral malformations, unicoronal craniosynostosis, iris colobomas, microphthalmia, and intestinal malrotation with myofibromas or hamartomas.
See also OMIM:601707
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_077087412L → F in CRJS; constitutive activation of the smoothened signaling pathway. 2 PublicationsCorresponds to variant dbSNP:rs879255280EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi6608
MalaCardsiSMO
MIMi601707 phenotype
OpenTargetsiENSG00000128602
PharmGKBiPA35968

Chemistry databases

ChEMBLiCHEMBL5971
DrugBankiDB01047 Fluocinonide
DB06786 Halcinonide
DB09143 Sonidegib
DB08828 Vismodegib
GuidetoPHARMACOLOGYi239

Polymorphism and mutation databases

BioMutaiSMO
DMDMi6226142

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 27Sequence analysisAdd BLAST27
ChainiPRO_000001301528 – 787Smoothened homologAdd BLAST760

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi35N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi70 ↔ 134PROSITE-ProRule annotation
Disulfide bondi78 ↔ 127PROSITE-ProRule annotation
Disulfide bondi118 ↔ 154PROSITE-ProRule annotation
Disulfide bondi147 ↔ 169PROSITE-ProRule annotation
Glycosylationi188N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi193 ↔ 213PROSITE-ProRule annotation1 Publication
Disulfide bondi217 ↔ 295PROSITE-ProRule annotation1 Publication
Glycosylationi309N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi314 ↔ 390PROSITE-ProRule annotation1 Publication
Disulfide bondi490 ↔ 507PROSITE-ProRule annotation1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ99835
PaxDbiQ99835
PeptideAtlasiQ99835
PRIDEiQ99835
ProteomicsDBi78499

PTM databases

iPTMnetiQ99835
PhosphoSitePlusiQ99835

Expressioni

Gene expression databases

BgeeiENSG00000128602
CleanExiHS_SMO
ExpressionAtlasiQ99835 baseline and differential
GenevisibleiQ99835 HS

Organism-specific databases

HPAiCAB011446

Interactioni

Subunit structurei

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).By similarity4 Publications

GO - Molecular functioni

  • patched binding Source: BHF-UCL
  • Wnt-protein binding Source: GO_Central
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi112492, 8 interactors
DIPiDIP-34574N
IntActiQ99835, 7 interactors
MINTiQ99835
STRINGi9606.ENSP00000249373

Chemistry databases

BindingDBiQ99835

Structurei

Secondary structure

1787
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi65 – 67Combined sources3
Beta strandi76 – 78Combined sources3
Beta strandi86 – 88Combined sources3
Beta strandi90 – 92Combined sources3
Helixi99 – 109Combined sources11
Helixi110 – 113Combined sources4
Helixi116 – 130Combined sources15
Beta strandi136 – 140Combined sources5
Helixi144 – 151Combined sources8
Turni152 – 154Combined sources3
Helixi155 – 160Combined sources6
Turni165 – 167Combined sources3
Turni171 – 173Combined sources3
Turni182 – 184Combined sources3
Beta strandi190 – 192Combined sources3
Beta strandi197 – 199Combined sources3
Helixi203 – 205Combined sources3
Beta strandi210 – 218Combined sources9
Helixi224 – 254Combined sources31
Helixi256 – 259Combined sources4
Turni262 – 265Combined sources4
Helixi266 – 282Combined sources17
Helixi283 – 285Combined sources3
Helixi289 – 294Combined sources6
Beta strandi299 – 301Combined sources3
Beta strandi304 – 306Combined sources3
Beta strandi308 – 310Combined sources3
Helixi313 – 347Combined sources35
Turni354 – 356Combined sources3
Helixi361 – 378Combined sources18
Beta strandi381 – 384Combined sources4
Turni385 – 388Combined sources4
Beta strandi389 – 395Combined sources7
Helixi397 – 403Combined sources7
Helixi405 – 432Combined sources28
Beta strandi436 – 442Combined sources7
Helixi443 – 492Combined sources50
Beta strandi501 – 503Combined sources3
Helixi515 – 532Combined sources18
Helixi533 – 536Combined sources4
Helixi539 – 548Combined sources10
Beta strandi554 – 558Combined sources5

3D structure databases

ProteinModelPortaliQ99835
SMRiQ99835
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini65 – 181FZPROSITE-ProRule annotationAdd BLAST117

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni538 – 569Interaction with BBS5 and BBS71 PublicationAdd BLAST32
Regioni581 – 593Interaction with DLG5By similarityAdd BLAST13

Sequence similaritiesi

Belongs to the G-protein coupled receptor Fz/Smo family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3577 Eukaryota
ENOG410XRC8 LUCA
GeneTreeiENSGT00760000118864
HOGENOMiHOG000252964
HOVERGENiHBG000352
InParanoidiQ99835
KOiK06226
OMAiKNSNRYP
OrthoDBiEOG091G04OK
PhylomeDBiQ99835
TreeFamiTF106460

Family and domain databases

CDDicd15030 7tmF_SMO_homolog, 1 hit
Gene3Di1.10.2000.10, 1 hit
InterProiView protein in InterPro
IPR015526 Frizzled/SFRP
IPR000539 Frizzled/Smoothened_TM
IPR020067 Frizzled_dom
IPR036790 Frizzled_dom_sf
IPR017981 GPCR_2-like
IPR026544 SMO
IPR035683 SMO_7TM
PANTHERiPTHR11309 PTHR11309, 1 hit
PTHR11309:SF35 PTHR11309:SF35, 1 hit
PfamiView protein in Pfam
PF01534 Frizzled, 1 hit
PF01392 Fz, 1 hit
PRINTSiPR00489 FRIZZLED
SMARTiView protein in SMART
SM00063 FRI, 1 hit
SM01330 Frizzled, 1 hit
SUPFAMiSSF63501 SSF63501, 1 hit
PROSITEiView protein in PROSITE
PS50038 FZ, 1 hit
PS50261 G_PROTEIN_RECEP_F2_4, 1 hit

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_077087412L → F in CRJS; constitutive activation of the smoothened signaling pathway. 2 PublicationsCorresponds to variant dbSNP:rs879255280EnsemblClinVar.1
Natural variantiVAR_037891473D → H. Corresponds to variant dbSNP:rs17710891EnsemblClinVar.1
Natural variantiVAR_007848535W → L in basal cell carcinoma and ameloblastoma samples; somatic mutation; constitutive activation of the smoothened signaling pathway. 2 PublicationsCorresponds to variant dbSNP:rs121918347EnsemblClinVar.1
Natural variantiVAR_007849562R → Q in basal cell carcinoma samples; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs121918348EnsemblClinVar.1

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.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSMO_HUMAN
AccessioniPrimary (citable) accession number: Q99835
Secondary accession number(s): A4D1K5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 1, 1997
Last modified: June 20, 2018
This is version 185 of the entry and version 1 of the sequence. See 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

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