Protein detail

SMO

Protein smoothened (Protein Gx)

Protein symbol SMO	UniProt ID Q99835	EVMP score 0.50
Frequency 1	Transmembrane count 7	Protein classification Cancer-related genesDisease related genesFDA approved drug targetsG-protein coupled receptorsHuman disease related genesPlasma proteinsPredicted membrane proteinsTransporters

Basic Information

Protein Names

Protein smoothened (Protein Gx)

Protein Class

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

Protein Function

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

FZD11SMOH

Gene Description

Smoothened, frizzled class receptor

Chromosome

Position

129188633-129213545

Frequency

EVMP Score

0.50

Fluorescence & Localization

Function & Pathway

Protein Function

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

Molecular Function

Biological Process

KEGG

Reactome

Mediation Categories

Clinical-translation mediationFusion and delivery mediationMetabolism mediationReceptor-signaling mediation

Relations & Evidence

Enzyme-Mediated Modification

0 records.

Ligand-Receptor Signaling

54 records.

Category	Parent	Database	Transmitter	Receiver	Secreted	Plasma Membrane (Transmembrane)	Plasma Membrane (Peripheral)
receptor	receptor	HPMR	No	Yes	No	Yes	No
receptor	receptor	CellTalkDB	No	Yes	No	Yes	No
receptor	receptor	Surfaceome	No	Yes	No	Yes	No
receptor	receptor	Ramilowski2015	No	Yes	No	Yes	No
receptor	receptor	Kirouac2010	No	Yes	No	Yes	No
gpcr	receptor	DGIdb	No	Yes	No	Yes	No
receptor	receptor	LRdb	No	Yes	No	Yes	No
receptor	receptor	Baccin2019	No	Yes	No	Yes	No
frizzled	receptor	Almen2009	No	Yes	No	Yes	No
gpcr	receptor	Almen2009	No	Yes	No	Yes	No

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Regulatory Interaction Network

36 records.

Source Protein Symbol	Source UniProt ID	Target Protein Symbol	Target UniProt ID	Is Directed	Is Stimulation	Is Inhibition	Database	References
SMO	Q99835	GBB3	P16520	Yes	Yes	No	SIGNOR	SIGNOR:16885213 SIGNOR:17251915 SIGNOR:23074268
SMO	Q99835	FYN	P06241	Yes	Yes	No	SIGNOR	SIGNOR:23074268 SIGNOR:18455992
SMO	Q99835	GNAI2	P04899	Yes	Yes	No	WangSIGNOR	SIGNOR:16885213 SIGNOR:23074268
SMO	Q99835	GBB2	P62879	Yes	Yes	No	SIGNOR	SIGNOR:16885213 SIGNOR:23074268
SMO	Q99835	GNAT2	P19087	Yes	Yes	No	SIGNOR	SIGNOR:16885213 SIGNOR:23074268
SMO	Q99835	GBG12	Q9UBI6	Yes	Yes	No	SIGNOR	SIGNOR:17251915
CERU	P00450	SMO	Q99835	Yes	No	Yes	SIGNOR	SIGNOR:16885213
SMO	Q99835	GBG2	P59768	Yes	Yes	No	WangSIGNOR	SIGNOR:16885213 SIGNOR:23074268
SMO	Q99835	TIAM1	Q13009	Yes	Yes	No	SIGNOR	SIGNOR:23074268 SIGNOR:20654717
SGK1	O00141	SMO	Q99835	Yes	No	Yes	SIGNOR	SIGNOR:25790864

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Protein Complex Composition

18 records.

Component Name	Component Gene Symbols	Component UniProt ID	Stoichiometry	Database	Database IDs
PTCH2_SMO	PTCH2 SMO	Q99835 Q9Y6C5	0:0	CellChatDB
	BET1 GOSR2 MSMO1 SAR1B SEC22B SEC23A SEC24B STX5 SURF4 TMED10 TMED2 TMED7 TMED9 TMEM97 UBC	O14653 O15155 O15260 O75396 O95487 P0CG48 P49755 Q13190 Q15363 Q15436 Q15800 Q5BJF2 Q9BVK6 Q9Y3B3 Q9Y6B6	1:1:1:1:1:1:1:1:1:1:1:1:1:1:1	NetworkBlastCompleat	Compleat:HC8394
	ATP13A1 ATP9A CYP26C1 ELOVL6 EMC2 EPB42 MSMO1 SACM1L SC5D SPCS2 SURF4 TMED10 TMED7 TMED9 UBC	O15260 O75110 O75845 P0CG48 P16452 P49755 Q15005 Q15006 Q15800 Q6V0L0 Q9BVK6 Q9H5J4 Q9HD20 Q9NTJ5 Q9Y3B3	1:1:1:1:1:1:1:1:1:1:1:1:1:1:1	NetworkBlastCompleat	Compleat:HC3993
	ARV1 ATP13A1 CYP26C1 DDOST EMC2 MSMO1 SACM1L SURF4 TMED10 TMED2 TMED5 TMED7 TMED9 UBC ZMPSTE24	O15260 O75844 P0CG48 P39656 P49755 Q15006 Q15363 Q15800 Q6V0L0 Q9BVK6 Q9H2C2 Q9HD20 Q9NTJ5 Q9Y3A6 Q9Y3B3	1:1:1:1:1:1:1:1:1:1:1:1:1:1:1	NetworkBlastCompleat	Compleat:HC7817
	ATP13A1 CEPT1 CYP26C1 EMC2 EMC3 MSMO1 RPN2 SACM1L SURF4 TMED10 TMED2 TMED5 TMED7 TMED9 UBC	O15260 P04844 P0CG48 P49755 Q15006 Q15363 Q15800 Q6V0L0 Q9BVK6 Q9HD20 Q9NTJ5 Q9P0I2 Q9Y3A6 Q9Y3B3 Q9Y6K0	1:1:1:1:1:1:1:1:1:1:1:1:1:1:1	NetworkBlastCompleat	Compleat:HC6536
	ATP13A1 EMC2 MSMO1 SACM1L SEC11A SPCS1 SPCS2 SPCS3 SURF4 TMED10 TMED2 TMED5 TMED7 TMED9 UBC	O15260 P0CG48 P49755 P61009 P67812 Q15005 Q15006 Q15363 Q15800 Q9BVK6 Q9HD20 Q9NTJ5 Q9Y3A6 Q9Y3B3 Q9Y6A9	1:1:1:1:1:1:1:1:1:1:1:1:1:1:1	NetworkBlastCompleat	Compleat:HC9614
	ATP13A1 CEPT1 CYP26C1 EMC2 MSMO1 SACM1L SPCS1 SPCS3 SURF4 TMED10 TMED2 TMED5 TMED7 TMED9 UBC	O15260 P0CG48 P49755 P61009 Q15006 Q15363 Q15800 Q6V0L0 Q9BVK6 Q9HD20 Q9NTJ5 Q9Y3A6 Q9Y3B3 Q9Y6A9 Q9Y6K0	1:1:1:1:1:1:1:1:1:1:1:1:1:1:1	NetworkBlastCompleat	Compleat:HC4231
	ATP13A1 CYP26C1 EMC2 MSMO1 SACM1L SEC11C SPCS1 SPCS2 SURF4 TMED10 TMED2 TMED5 TMED7 TMED9 UBC	O15260 P0CG48 P49755 Q15005 Q15006 Q15363 Q15800 Q6V0L0 Q9BVK6 Q9BY50 Q9HD20 Q9NTJ5 Q9Y3A6 Q9Y3B3 Q9Y6A9	1:1:1:1:1:1:1:1:1:1:1:1:1:1:1	NetworkBlastCompleat	Compleat:HC5011
	ATP13A1 CERS6 CYP26C1 GPAA1 MSMO1 PIGK PIGS PIGT RAC2 SACM1L SV2A UBC	O43292 P0CG48 P15153 Q15800 Q6V0L0 Q6ZMG9 Q7L0J3 Q92643 Q969N2 Q96S52 Q9HD20 Q9NTJ5	1:1:1:1:1:1:1:1:1:1:1:1	NetworkBlastCompleat	Compleat:HC7406
	ACTL6A DMAP1 EPC2 HSPA4 ING3 KAT5 MEAF6 MORF4L1 MORF4L2 MRGBP SET SMOX TRRAP VPS72 YEATS4	O95619 O96019 P34932 Q01105 Q15014 Q15906 Q52LR7 Q92993 Q9HAF1 Q9NPF5 Q9NV56 Q9NWM0 Q9NXR8 Q9UBU8 Q9Y4A5	1:1:1:1:1:1:1:1:1:1:1:1:1:1:1	NetworkBlastCompleat	Compleat:HC5441

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Isolation & Detection Technology

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 & Domains

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 Relevance

Disease Involvement

Cancer-related genesDisease variantFDA approved drug targets

Related Diseases

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

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

Antibody

CAB011446 CAB080590