Human Disease Model Report: basal cell carcinoma, SMO-related

General Information

Name

basal cell carcinoma, SMO-related

FlyBase ID

FBhh0001201

Disease Ontology Term

basal cell carcinoma

Parent Disease

OMIM

Overview

In basal cell carcinoma, somatic variants of the Hedgehog signaling pathway gene SMO have been identified. Two such variants have been investigated in Drosophila, using analogous mutations in the orthologous fly gene, smo. Variant(s) implicated in human disease tested (as analogous mutation in fly gene): K580Q in the fly smo gene (corresponds to R562Q in the human SMO gene); W553L in the fly smo gene (corresponds to W535L in the human SMO gene).

Control of smo localization appears to be a crucial step in Hedgehog signaling in Drosophila. Mutations analogous to those associated with human tumors result in the smo protein being constitutively present at the cell surface. Overexpression of the oncogenic mutants causes significant changes in wing patterning and anterior outgrowth.

See also the human disease model 'cancer, epithelial, Notch signaling, Hedgehog signaling' (FBhh0001075).

[updated Feb. 2020 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: basal cell carcinoma, SMO-related

OMIM report

Human gene(s) implicated

Symptoms and phenotype

Cutaneous basal cell carcinoma (BCC) is the most common cancer among people of European ancestry (Stacey et al., 2009; pubmed:19578363). [from MIM:605462; 2020.02.26]

(OMIM, 2013-)

Genetics

The primary environmental risk factor for BCC is sun exposure, but genetics also has a substantial role. [from MIM:605462; 2020.02.26]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

The protein encoded by SMO is a G protein-coupled receptor that interacts with the patched protein, a receptor for hedgehog proteins. The encoded protein tranduces signals to other proteins after activation by a hedgehog protein/patched protein complex. [Gene Cards, SMO; 2020.02.26]

(FlyBase Curators, 2013-)

Mutations in hedgehog pathway genes, primarily genes encoding patched homologue 1 (PTCH1) and smoothened homologue (SMO), occur in basal-cell carcinoma (Von Hoff, et al., 2009; pubmed:19726763).

(FlyBase Curators, 2013-)

An orally active small molecule inhibitor of SMO is used as a therapeutic for metastatic or locally advanced basal-cell carcinoma (originally described in Von Hoff, et al., 2009; pubmed:19726763).

(FlyBase Curators, 2013-)

Abnormalities in the Hedgehog signaling pathway are found in basal cell carcinomas. [from MIM:605462; 2020.02.26]

(OMIM, 2013-)

External links

COSMIC gene: SMO
Gene2Function (human gene): SMO
Gene Cards: SMO
MedlinePlus (gene): SMO
KEGG Disease Pathways: Basal cell carcinoma
MARRVEL (human gene): SMO
NCBI MedGen: Basal cell carcinoma, multiple (BCC1)
NCBI (Entrez) gene: SMO; smoothened, frizzled class receptor

Disease synonyms

basal cell carcinoma, somatic

Related Diseases

Related human health report(s)

cancer, epithelial, Notch signaling, Hedgehog signaling

cancer, multiple, Hedgehog signaling pathway

Ortholog Information

Human gene(s) in FlyBase

Human gene (HGNC)

Symbol / Name

SMO; smoothened, frizzled class receptor

D. melanogaster ortholog (based on DIOPT)

Dmel\smo

(DIOPT, 2013-)

Comments on ortholog(s)

One to one: 1 human to 1 Drosophila.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\smo

Gene Snapshot

smoothened (smo) encodes a critical component of the Hedgehog signaling pathway. It is regulated by phosphorylation, dimerization, and cell-surface accumulation upon Hedgehog stimulation. The product of smo is also regulated by ubiquitin and other small molecules such as phospholipids. [Date last reviewed: 2019-03-14]

Molecular function (GO)

Cellular component (GO)

Gene Groups / Pathways

SMO
HH-SMOC

Comments on ortholog(s)

High-scoring ortholog of human SMO (1 Drosophila to 1 human). Dmel\smo shares 37% identity and 57% similarity with the human gene.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (37 groups)

smo

protein-protein

Interacting group

Assay

References

smo

pull down, anti tag western blot, fluorescent resonance energy transfer, fluorescence microscopy, autoradiography, anti bait coimmunoprecipitation, western blot, anti tag coimmunoprecipitation, bioluminescence resonance energy transfer, fluorescence technology

(Jiang et al., 2016, Maier et al., 2014, Fan et al., 2012, Chen et al., 2010, Walthall et al., 2007, Zhao et al., 2007)

smo - ci

anti bait coimmunoprecipitation, western blot, peptide massfingerprinting

(Walthall et al., 2007, Lum et al., 2003, Ruel et al., 2003)

smo - cos

anti tag coimmunoprecipitation, western blot, fluorescent resonance energy transfer, anti bait coimmunoprecipitation, tag visualisation, colocalization, fluorescence microscopy, inferred by author, anti tag western blot, pull down, peptide massfingerprinting, bioluminescence resonance energy transfer, fluorescence technology, two hybrid

(Li et al., 2014, Maier et al., 2014, Ranieri et al., 2014, Fan et al., 2012, Ranieri et al., 2012, Shi et al., 2011, Zhang et al., 2011, Liu et al., 2007, Ruel et al., 2007, Walthall et al., 2007, Zhang et al., 2005, Jia et al., 2003, Lum et al., 2003, Ogden et al., 2003, Ruel et al., 2003)

smo - Cul4

anti tag coimmunoprecipitation, anti tag western blot

(Li et al., 2018)

smo - flw

anti tag coimmunoprecipitation, western blot

(Su et al., 2011)

smo - fu

anti bait coimmunoprecipitation, western blot, bimolecular fluorescence complementation, fluorescence microscopy, anti tag coimmunoprecipitation, anti tag western blot, colocalization, inferred by author, two hybrid, peptide massfingerprinting

(Kubíková et al., 2023, Giordano et al., 2018, Ranieri et al., 2014, Ranieri et al., 2012, Malpel et al., 2007, Jia et al., 2003, Lum et al., 2003, Ogden et al., 2003, Ruel et al., 2003)

smo - Gβ13F

anti tag coimmunoprecipitation, anti tag western blot

(Li et al., 2018)

smo - gish

anti tag coimmunoprecipitation, anti tag western blot

(Li et al., 2016)

smo - Gprk2

anti tag coimmunoprecipitation, anti tag western blot, fluorescent resonance energy transfer, fluorescence microscopy, pull down

(Jiang et al., 2016, Chen et al., 2010)

smo - Herc4

anti tag coimmunoprecipitation, anti tag western blot

(Jiang et al., 2019)

smo - Hrs

anti tag coimmunoprecipitation, anti tag western blot, pull down, western blot

(Zhou et al., 2018, Fan et al., 2013)

smo - krz

anti tag coimmunoprecipitation, anti tag western blot, western blot

(Jiang et al., 2018, Zhang et al., 2017, Li et al., 2012, Molnar et al., 2011)

smo - mts

anti tag coimmunoprecipitation, western blot

(Su et al., 2011)

smo - pic

anti tag coimmunoprecipitation, anti tag western blot

(Li et al., 2018)

smo - Pka-C1

anti tag coimmunoprecipitation, western blot, bimolecular fluorescence complementation, fluorescence microscopy, anti tag western blot, anti bait coimmunoprecipitation

(Fan et al., 2019, Chen et al., 2017, Li et al., 2014, Ranieri et al., 2014)

smo - Pp1-13C

anti tag coimmunoprecipitation, western blot

(Su et al., 2011)

smo - Pp1-87B

anti tag coimmunoprecipitation, western blot

(Su et al., 2011)

smo - Pp1α-96A

anti tag coimmunoprecipitation, western blot

(Su et al., 2011)

smo - Pp4-19C

anti tag coimmunoprecipitation, anti tag western blot, pull down

(Jia et al., 2009)

smo - ptc

anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation

(Walthall et al., 2007, Johnson et al., 2000)

smo - Rack1

anti tag coimmunoprecipitation, anti tag western blot

(Li et al., 2020)

smo - smg

colocalization, fluorescence microscopy, inferred by author, anti tag coimmunoprecipitation, anti tag western blot, pull down, molecular weight estimation by staining, two hybrid, x-ray crystallography, isothermal titration calorimetry, predetermined participant

(Kubíková et al., 2023, Bruzzone et al., 2020)

smo - Smurf

anti tag coimmunoprecipitation, anti tag western blot

(Li et al., 2018, Huang et al., 2013)

smo - Sumo

anti tag coimmunoprecipitation, anti tag western blot

(Zhang et al., 2017)

smo - Sxl

anti bait coimmunoprecipitation, western blot

(Walthall et al., 2007)

smo - Ubi-p5E

anti tag coimmunoprecipitation, covalent binding, anti tag western blot

(Yang et al., 2013)

smo - Ubi-p63E

anti tag coimmunoprecipitation, covalent binding, anti tag western blot

(Yang et al., 2013)

smo - Uch-L5

anti tag coimmunoprecipitation, anti tag western blot, anti bait coimmunoprecipitation

(Zhou et al., 2018)

smo - Uch-L5R

anti tag coimmunoprecipitation, anti tag western blot

(Zhou et al., 2018)

smo - Ulp1

anti tag coimmunoprecipitation, anti tag western blot

(Zhang et al., 2017, Ma et al., 2016)

smo - Usp8

anti tag coimmunoprecipitation, anti tag western blot, pull down

(Li et al., 2020, Ma et al., 2016, Fan et al., 2013, Li et al., 2012, Xia et al., 2012)

smo - Vps36

anti tag coimmunoprecipitation, anti tag western blot

(Yang et al., 2013)

smo - wdb

anti tag coimmunoprecipitation, western blot, pull down

(Su et al., 2011)

RNA-RNA

Interacting group

Assay

References

smo - mir-5

fluorescence technology, luminiscence technology, necessary binding region, immunohistochemistry

(Wu et al., 2012)

smo - mir-12

fluorescence technology

(Friggi-Grelin et al., 2008)

smo - mir-283

fluorescence technology

(Friggi-Grelin et al., 2008)

smo - mir-960

luminiscence technology, necessary binding region, fluorescence technology, immunocytochemistry

(Gao et al., 2013)

Alleles Reported to Model Human Disease (Disease Ontology) (2 alleles)

smo

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

smo^RNAi.UAS.cUa

model of primary bacterial infectious disease

CEA

(Lee et al., 2015)

Modifiers Based on Experimental Evidence ( 1 )

Allele

Disease

Interaction

References

smo¹

ameliorates neurodegenerative disease

modeled by ptc^559.1

(Gazi et al., 2009)

Alleles Representing Disease-Implicated Variants

Genetic Tools, Stocks and Reagents

Sources of Stocks

Contact lab of origin for a reagent not available from a public stock center.

Bloomington Stock Center Disease Page

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

smo^{RNAi.3'UTR.UAS}

P{UAS-smo.RNAi.3'UTR}

y¹ w^*; P{UAS-smo.RNAi.WIZ}2 P{UAS-smo.RNAi.WIZ}8/CyO, P{Wee-P.ph0}2

y¹ v¹; P{TRiP.JF02363}attP2

y¹ v¹; P{TRiP.GL01472}attP2

smo^HMC03577

P{TRiP.HMC03577}

y¹ sc^* v¹ sev²¹; P{TRiP.HMC03577}attP40

y¹ v¹; P{TRiP.HMJ30064}attP40/CyO

smo^VSH330287

P{VSH330287}

P{VSH330287}attP40

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

smo^D16

loss of function allele

gamma ray

w^*; smo^D16 P{neoFRT}42D mam¹⁰ Egfr^f24/CyO, P{ActGFP}JMR1

smo¹

ethyl methanesulfonate

CyO / smo¹ cn¹ bw¹ speck¹

References (5)

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