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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

BioCyciZFISH:ENSG00000128602-MONOMER.
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.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:11119. SMO.

Subcellular locationi

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

GO - Cellular componenti

  • ciliary membrane Source: Reactome
  • ciliary tip Source: Reactome
  • cilium Source: BHF-UCL
  • 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
Complete GO annotation...

Keywords - Cellular componenti

Cell projection, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi6608.
MalaCardsiSMO.
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...)Sequence analysis1
Disulfide bondi70 ↔ 134PROSITE-ProRule annotation
Disulfide bondi78 ↔ 127PROSITE-ProRule annotation
Disulfide bondi118 ↔ 154PROSITE-ProRule annotation
Disulfide bondi147 ↔ 169PROSITE-ProRule annotation
Glycosylationi188N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi193 ↔ 213PROSITE-ProRule annotation1 Publication
Disulfide bondi217 ↔ 295PROSITE-ProRule annotation1 Publication
Glycosylationi309N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi314 ↔ 390PROSITE-ProRule annotation1 Publication
Disulfide bondi490 ↔ 507PROSITE-ProRule annotation1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ99835.
PaxDbiQ99835.
PeptideAtlasiQ99835.
PRIDEiQ99835.

PTM databases

iPTMnetiQ99835.
PhosphoSitePlusiQ99835.

Expressioni

Gene expression databases

BgeeiENSG00000128602.
CleanExiHS_SMO.
ExpressionAtlasiQ99835. baseline and differential.
GenevisibleiQ99835. HS.

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

GO - Molecular functioni

  • patched binding Source: BHF-UCL
  • Wnt-protein binding Source: GO_Central

Protein-protein interaction databases

BioGridi112492. 5 interactors.
DIPiDIP-34574N.
IntActiQ99835. 5 interactors.
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 strandi64 – 67Combined sources4
Beta strandi76 – 78Combined sources3
Beta strandi86 – 88Combined sources3
Beta strandi90 – 95Combined sources6
Helixi99 – 109Combined sources11
Helixi110 – 113Combined sources4
Helixi116 – 130Combined sources15
Beta strandi136 – 140Combined sources5
Helixi144 – 151Combined sources8
Turni152 – 154Combined sources3
Helixi155 – 160Combined sources6
Helixi165 – 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 strandi500 – 502Combined sources3
Helixi515 – 532Combined sources18
Helixi533 – 536Combined sources4
Helixi539 – 548Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
5L7DX-ray3.20A/B32-428[»]
A/B443-555[»]
5L7IX-ray3.30A/B32-428[»]
A/B443-555[»]
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

Sequence similaritiesi

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

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

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.
SM01330. Frizzled. 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)DescriptionActionsGraphical viewLength
Natural variantiVAR_037891473D → H.Corresponds to variant rs17710891dbSNPEnsembl.1
Natural variantiVAR_007848535W → L in basal cell carcinoma samples; somatic mutation. 1 PublicationCorresponds to variant rs121918347dbSNPEnsembl.1
Natural variantiVAR_007849562R → Q in basal cell carcinoma samples; somatic mutation. 1 PublicationCorresponds to variant rs121918348dbSNPEnsembl.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

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
PDB 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[»]
5L7DX-ray3.20A/B32-428[»]
A/B443-555[»]
5L7IX-ray3.30A/B32-428[»]
A/B443-555[»]
ProteinModelPortaliQ99835.
SMRiQ99835.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112492. 5 interactors.
DIPiDIP-34574N.
IntActiQ99835. 5 interactors.
STRINGi9606.ENSP00000249373.

Chemistry databases

BindingDBiQ99835.
ChEMBLiCHEMBL5971.
DrugBankiDB01047. Fluocinonide.
DB06786. Halcinonide.
DB09143. Sonidegib.
DB08828. Vismodegib.
GuidetoPHARMACOLOGYi239.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiQ99835.
PhosphoSitePlusiQ99835.

Polymorphism and mutation databases

BioMutaiSMO.
DMDMi6226142.

Proteomic databases

EPDiQ99835.
PaxDbiQ99835.
PeptideAtlasiQ99835.
PRIDEiQ99835.

Protocols and materials databases

DNASUi6608.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000249373; ENSP00000249373; ENSG00000128602.
GeneIDi6608.
KEGGihsa:6608.
UCSCiuc003vor.4. human.

Organism-specific databases

CTDi6608.
DisGeNETi6608.
GeneCardsiSMO.
HGNCiHGNC:11119. SMO.
HPAiCAB011446.
HPA044232.
MalaCardsiSMO.
MIMi601500. gene.
neXtProtiNX_Q99835.
OpenTargetsiENSG00000128602.
PharmGKBiPA35968.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000128602-MONOMER.
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.

Miscellaneous databases

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

Gene expression databases

BgeeiENSG00000128602.
CleanExiHS_SMO.
ExpressionAtlasiQ99835. baseline and differential.
GenevisibleiQ99835. HS.

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.
SM01330. Frizzled. 1 hit.
[Graphical view]
SUPFAMiSSF63501. SSF63501. 1 hit.
PROSITEiPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetiSearch...

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: November 30, 2016
This is version 170 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

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 one 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.