Protein detail

SMO

Protein smoothened (Protein Gx)

Entry name SMO	UniProt ID Q99835	EVMP confidence score 0.50
Supporting publications (n) 1	Transmembrane count 7	Protein classification Cancer-related genesDisease related genesFDA approved drug targetsG-protein coupled receptorsHuman disease related genesPlasma proteinsPredicted membrane proteinsTransporters

EVMP confidence score

Annotation confidence score; open for threshold definitions.

Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40

Basic Information13

Protein Names

Protein smoothened (Protein Gx)

Protein Class (8)

Cancer-related genesDisease related genesFDA approved drug targetsG-protein coupled receptorsHuman disease related genesPlasma proteinsPredicted membrane proteinsTransporters

Protein Function (8)

Human disease related genes:Cancers:Cancers of eye, brain, and central nervous system
Transporters
Human disease related genes:Cancers:Skin cancers
G-protein coupled receptors:GPCRs excl olfactory receptors
Disease related genes
Cancer-related genes
G-protein coupled receptors:Family fz/smo receptors
FDA approved drug targets:Small molecule drugs

Transmembrane

234..254; Helical; Name=1; 263..283; Helical; Name=2; 315..335; Helical; Name=3; 359..379; Helical; Name=4; 403..423; Helical; Name=5; 452..472; Helical; Name=6; 525..545; Helical; Name=7

Transmembrane Count

Ensembl

ENSG00000128602

Entrez Gene Symbol

SMO

Gene Synonym (2)

FZD11SMOH

Gene Description

Smoothened, frizzled class receptor

Chromosome

Position

129188633-129213545

Supporting publications (n)

EVMP confidence score

0.50

Function & Pathway7

Protein Function (8)

Human disease related genes:Cancers:Cancers of eye, brain, and central nervous system
Transporters
Human disease related genes:Cancers:Skin cancers
G-protein coupled receptors:GPCRs excl olfactory receptors
Disease related genes
Cancer-related genes
G-protein coupled receptors:Family fz/smo receptors
FDA approved drug targets:Small molecule drugs

Cellular Component (15)

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Molecular Function (7)

Biological Process (3)

KEGG (5)

Reactome (11)

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Mediation Categories (4)

Clinical-translation mediationFusion and delivery mediationMetabolism mediationReceptor-signaling mediation

Relations & Evidence109

Ligand-Receptor Signaling (54)

54 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
cell_surface	cell_surface	Surfaceome	No	No	No	Yes	No
cell_surface	cell_surface	connectomeDB2020	No	No	No	Yes	No
cell_surface	cell_surface	OmniPath	No	No	No	Yes	No
receptor	receptor	talklr	No	Yes	No	Yes	No
receptor	receptor	scConnect	No	Yes	No	Yes	No
receptor	receptor	connectomeDB2020	No	Yes	No	Yes	No
receptor	receptor	iTALK	No	Yes	No	Yes	No
receptor	receptor	Almen2009	No	Yes	No	Yes	No
receptor	receptor	CellCellInteractions	No	Yes	No	Yes	No
receptor	receptor	EMBRACE	No	Yes	No	Yes	No

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Regulatory Interaction Network (36)

36 records.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
SMO	Q99835	EVC	P57679	Yes	Yes	No	SignaLink3	SignaLink3:22986504
SMO	Q99835	LBN	Q86UK5	Yes	Yes	No	SignaLink3	SignaLink3:22986504
ARBK1	P25098	SMO	Q99835	Yes	Yes	No	SPIKEWangSPIKE_LCSIGNOR	SIGNOR:21695114 SIGNOR:15618519 SPIKE_LC:15618519 SIGNOR:23074268 SPIKE:15618519
PTC1	Q13635	SMO	Q99835	Yes	Yes	Yes	WangNetPathSIGNORHPRDCui2007SignaLink3BioGRIDCancerCellMapSPIKE_LCSPIKE	SPIKE_LC:9811851 SPIKE:20207148 BioGRID:9811851 HPRD:9811851 SPIKE_LC:20207148 SPIKE_LC:20076617 NetPath:9811851 SIGNOR:12192414 SPIKE:20076617 NetPath:8906787 SIGNOR:14556242 SPIKE:9811851 SignaLink3:23331499 CancerCellMap:9811851 SignaLink3:14556242
PTC2	Q9Y6C5	SMO	Q99835	Yes	Yes	No	WangNetPathHPRDCui2007SignaLink3CancerCellMapSPIKE_LCSPIKE	SignaLink3:18988627 SignaLink3:9811851 SPIKE_LC:9811851 HPRD:9811851 NetPath:9811851 SPIKE:9811851 SignaLink3:23331499 CancerCellMap:9811851
SMO	Q99835	ARRB2	P32121	Yes	Yes	No	WangNetPathSIGNORHINTSPIKE_LCSPIKE	NetPath:15618519 SIGNOR:15618519 SPIKE_LC:15618519 SIGNOR:23074268 SPIKE:15618519 HINT:23877428 HINT:15618519
GSK3B	P49841	SMO	Q99835	Yes	Yes	Yes	WangCui2007SignaLink3	SignaLink3:15803137 SignaLink3:23331499
SMO	Q99835	KAPCA	P17612	Yes	Yes	Yes	SignaLink3ACSN	ACSN:20956384 ACSN:17688959 ACSN:18820483 SignaLink3:14611647 ACSN:20643644 ACSN:21209912 ACSN:17641202 ACSN:19592253 SignaLink3:23331499 ACSN:19549984 ACSN:20016067 ACSN:18997815
GRK6	P43250	SMO	Q99835	Yes	Yes	No	SignaLink3	SignaLink3:15618519 SignaLink3:23331499
ARRB1	P49407	SMO	Q99835	Yes	Yes	No	SignaLink3	SignaLink3:15618519 SignaLink3:23331499

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Protein Complex Composition (18)

18 records.

Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs
CDC5L CRNKL1 CYP3A5 EFTUD2 HSPA8 PRPF8 SMN1 SMOX SNRPA SNRPA1 SNRPD2 SNW1	P09012 P09661 P11142 P20815 P62316 Q13573 Q15029 Q16637 Q6P2Q9 Q99459 Q9BZJ0 Q9NWM0	1:1:1:1:1:1:1:1:1:1:1:1	NetworkBlastCompleat	Compleat:HC9140
DDRGK1 IMMT MSMO1 PDHA2 YARS2	P29803 Q15800 Q16891 Q96HY6 Q9Y2Z4	0:0:0:0:0	Havugimana2012	Havugimana2012:C_454
EVC SMO	P57679 Q99835	0:0	KEGG-MEDICUS
ENTREP3 HECW1 SMO	P81408 Q76N89 Q99835	0:0:0	hu.MAP2
GPR180 MSMO1	Q15800 Q86V85	0:0	hu.MAP
CRBN KDM4D SMOC1 TRPC4AP	Q6B0I6 Q8TEL6 Q96SW2 Q9H4F8	0:0:0:0	hu.MAP2
KDM4D SMOC1 TRPC4AP	Q6B0I6 Q8TEL6 Q9H4F8	0:0:0	hu.MAP2
SMO	Q99835	2	PDB	PDB:5l7dPDB:5v57PDB:7zi0PDB:4jkvPDB:5v56PDB:5l7i

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Isolation & Detection Technology (1)

1 record.

EV Isolation Method	Detection Method	Number of References	References
Differential UltracentrifugationDensity Gradient CentrifugationUltrafiltration / Tangential Flow FiltrationSize Exclusion Chromatography	Mass spectrometry	9	30950185 28396511 34623918 37786918 34817906 28986585 27894104 38321535 32089743

Sequence, Structure & Domains13

Sequences

Length

787

Mass

86,397

Sequence

MAAARPARGPELPLLGLLLLLLLGDPGRGAASSGNATGPGPRSAGGSARRSAAVTGPPPPLSHCGRAAPCEPLRYNVCLGSVLPYGATSTLLAGDSDSQEEAHGKLVLWSGLRNAPRCWAVIQPLLCAVYMPKCENDRVELPSRTLCQATRGPCAIVERERGWPDFLRCTPDRFPEGCTNEVQNIKFNSSGQCEVPLVRTDNPKSWYEDVEGCGIQCQNPLFTEAEHQDMHSYIAAFGAVTGLCTLFTLATFVADWRNSNRYPAVILFYVNACFFVGSIGWLAQFMDGARREIVCRADGTMRLGEPTSNETLSCVIIFVIVYYALMAGVVWFVVLTYAWHTSFKALGTTYQPLSGKTSYFHLLTWSLPFVLTVAILAVAQVDGDSVSGICFVGYKNYRYRAGFVLAPIGLVLIVGGYFLIRGVMTLFSIKSNHPGLLSEKAASKINETMLRLGIFGFLAFGFVLITFSCHFYDFFNQAEWERSFRDYVLCQANVTIGLPTKQPIPDCEIKNRPSLLVEKINLFAMFGTGIAMSTWVWTKATLLIWRRTWCRLTGQSDDEPKRIKKSKMIAKAFSKRHELLQNPGQELSFSMHTVSHDGPVAGLAFDLNEPSADVSSAWAQHVTKMVARRGAILPQDISVTPVATPVPPEEQANLWLVEAEISPELQKRLGRKKKRRKRKKEVCPLAPPPELHPPAPAPSTIPRLPQLPRQKCLVAAGAWGAGDSCRQGAWTLVSNPFCPEPSPPQDPFLPSAPAPVAWAHGRRQGLGPIHSRTNLMDTELMDADSDF

3D Structural Models

Turn

152..154; 165..167; 171..173; 182..184; 262..265; 354..356; 385..388

Helix

62..64; 99..109; 110..113; 116..130; 144..151; 155..160; 203..205; 224..254; 256..259; 266..282; 283..285; 289..294; 313..347; 361..378; 397..403; 405..432; 443..492; 515..532; 533..536; 539..548

Beta Strand

65..67; 76..78; 86..88; 90..92; 136..140; 176..178; 190..192; 197..199; 210..218; 299..301; 304..306; 308..310; 381..384; 389..395; 436..442; 496..498; 501..503; 554..558

3D Structure

Electron microscopy (5); X-ray crystallography (10)

Domain & Motif Annotations

Compositional Bias

38..53; Low complexity; 668..680; Basic residues; 685..699; Pro residues

Domain (CC)

The N-terminal extracellular domain mediates sterol-binding which is required for maximal activation of signaling (PubMed:24859340). Contains a second sterol-binding site within the seven-transmembrane pocket which is also required for activation (By similarity). The activating sterol is likely to be cholesterol (PubMed:35658032). The extracellular site is required for SHH-induced activity while the site within the transmembrane pocket regulates basal signaling in the absence of SHH (PubMed:35658032).

Domain (FT)

65..181; FZ

Region

30..60; Disordered; 538..569; Interaction with BBS5 and BBS7; 570..653; Required for interaction with PRKACA; 581..593; Interaction with DLG5; 667..704; Disordered

Protein Families

G-protein coupled receptor Fz/Smo family

Sequence Similarities

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

Clinical Relevance6

Disease Involvement (3)

Cancer-related genesDisease variantFDA approved drug targets

Related Diseases (6)

Basal cell carcinoma Brain cancer Chronic myelomonocytic leukaemia Ovarian cancer Skin cancer Solid tumour/cancer

Biomarker

Approved; Phase 2; Phase 1

Drug Targets

FDA approved drug targets

Drugs (13)

TALADEGIB GLASDEGIB VISMODEGIB SONIDEGIB PATIDEGIB NULL GEFITINIB ARSENIC TRIOXIDE TAK-441 GLASDEGIB MALEATE BMS-833923 PURMORPHAMINE LEQ506

Antibody (2)

CAB011446 CAB080590

Supporting Publications1

PMID	Title	Abstract
38938674	Gestational age at birth influences protein and RNA content in human milk extracellular vesicles.	No abstract available