5L7D

Structure of human Smoothened in complex with cholesterol

External Resource: Annotation

Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations
Membrane Protein Annotation: OPM
Membrane Protein Annotation: PDBTM
Membrane Protein Annotation: MemProtMD
Membrane Protein Annotation: mpstruc

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	G protein-coupled receptor-like	8091112	3000473	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Cytochromes	8057879	3001526	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Cytochromes	8057879	3001526	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	G protein-coupled receptor-like	8091112	3000473	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	Frizzled	e5l7dA1	A: alpha bundles	X: Family A G protein-coupled receptor-like (From Topology)	H: Family A G protein-coupled receptor-like (From Topology)	T: Family A G protein-coupled receptor-like	F: Frizzled	ECOD (1.6)
A	Cytochrom_B562_1	e5l7dA2	A: alpha bundles	X: Four-helical up-and-down bundle	H: Cytochromes (From Topology)	T: Cytochromes	F: Cytochrom_B562_1	ECOD (1.6)
A	Fz	e5l7dA3	A: few secondary structure elements	X: Frizzled cysteine-rich domain-related (From Topology)	H: Frizzled cysteine-rich domain-related (From Topology)	T: Frizzled cysteine-rich domain-related	F: Fz	ECOD (1.6)
B	Frizzled	e5l7dB1	A: alpha bundles	X: Family A G protein-coupled receptor-like (From Topology)	H: Family A G protein-coupled receptor-like (From Topology)	T: Family A G protein-coupled receptor-like	F: Frizzled	ECOD (1.6)
B	Cytochrom_B562_1	e5l7dB2	A: alpha bundles	X: Four-helical up-and-down bundle	H: Cytochromes (From Topology)	T: Cytochromes	F: Cytochrom_B562_1	ECOD (1.6)
B	Fz	e5l7dB3	A: few secondary structure elements	X: Frizzled cysteine-rich domain-related (From Topology)	H: Frizzled cysteine-rich domain-related (From Topology)	T: Frizzled cysteine-rich domain-related	F: Fz	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	1.10.2000.10	Mainly Alpha	Orthogonal Bundle	Frizzled cysteine-rich domain	Frizzled cysteine-rich domain	CATH (4.3.0)
A	1.20.1070.10	Mainly Alpha	Up-down Bundle	Rhopdopsin 7-helix transmembrane proteins	Rhodopsin 7-helix transmembrane proteins	CATH (4.3.0)
B	1.10.2000.10	Mainly Alpha	Orthogonal Bundle	Frizzled cysteine-rich domain	Frizzled cysteine-rich domain	CATH (4.3.0)
B	1.20.1070.10	Mainly Alpha	Up-down Bundle	Rhopdopsin 7-helix transmembrane proteins	Rhodopsin 7-helix transmembrane proteins	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF07361	Cytochrome b562 (Cytochrom_B562)	Cytochrome b562	-	Family
A, B	PF01392	Fz domain (Fz)	Fz domain	Also known as the CRD (cysteine rich domain), the C6 box in MuSK receptor. This domain of unknown function has been independently identified by several groups [1,2,3,4]. The domain contains 10 conserved cysteines.	Domain
A, B	PF01534	Frizzled/Smoothened family membrane region (Frizzled)	Frizzled/Smoothened family membrane region	-	Family

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	Smoothened homolog,Soluble cytochrome b562,Smoothened homolog	binding organic cyclic compound binding tetrapyrrole binding heme binding electron transfer activity cation binding transition metal ion binding iron ion binding ion binding metal ion binding small molecule binding patched binding protein binding signaling receptor binding binding organic cyclic compound binding tetrapyrrole binding heme binding electron transfer activity cation binding transition metal ion binding iron ion binding ion binding metal ion binding small molecule binding patched binding protein binding signaling receptor binding molecular transducer activity G protein-coupled receptor activity transmembrane signaling receptor activity signaling receptor activity enzyme regulator activity enzyme inhibitor activity protein kinase regulator activity cAMP-dependent protein kinase regulator activity protein kinase inhibitor activity molecular function inhibitor activity molecular function regulator activity cAMP-dependent protein kinase inhibitor activity protein serine/threonine kinase inhibitor activity kinase inhibitor activity kinase regulator activity molecular sequestering activity protein sequestering activity sterol binding oxysterol binding steroid binding lipid binding protein kinase A catalytic subunit binding protein kinase A binding kinase binding enzyme binding protein kinase binding	electron transport chain metabolic process cellular process generation of precursor metabolites and energy cellular response to stimulus response to sterol response to stimulus response to lipid response to alcohol cellular response to organic cyclic compound response to oxygen-containing compound response to cholesterol cellular response to oxygen-containing compound cellular response to chemical stimulus electron transport chain metabolic process cellular process generation of precursor metabolites and energy cellular response to stimulus response to sterol response to stimulus response to lipid response to alcohol cellular response to organic cyclic compound response to oxygen-containing compound response to cholesterol cellular response to oxygen-containing compound cellular response to chemical stimulus cellular response to alcohol response to chemical cellular response to lipid cellular response to sterol cellular response to cholesterol response to organic cyclic compound developmental process cellular developmental process cell differentiation cell fate specification cell fate commitment neuroblast proliferation multicellular organismal process cell population proliferation nervous system development generation of neurons neurogenesis multicellular organism development anatomical structure development neural precursor cell proliferation system development pattern specification process digestive system development tube development midgut development digestive tract development regulation of protein stability biological regulation regulation of biological quality protein stabilization central nervous system development multicellular organismal-level homeostasis homeostatic process homeostasis of number of cells within a tissue anatomical structure homeostasis tissue homeostasis homeostasis of number of cells mammary gland epithelial cell differentiation epithelium development mammary gland development gland development animal organ development tissue development epithelial cell differentiation mammary gland epithelium development regulation of biological process signaling cell-cell signaling epithelial-mesenchymal cell signaling cell communication muscle cell migration myoblast migration cell migration cell motility regulation of biosynthetic process regulation of cellular process positive regulation of biological process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process positive regulation of macromolecule biosynthetic process regulation of gene expression positive regulation of metabolic process biosynthetic process positive regulation of gene expression positive regulation of biosynthetic process regulation of macromolecule biosynthetic process positive regulation of macromolecule metabolic process macromolecule metabolic process regulation of metabolic process positive regulation of cellular process anatomical structure morphogenesis pancreas morphogenesis pancreas development animal organ morphogenesis apoptotic process cell death programmed cell death regulation of protein modification process regulation of protein phosphorylation negative regulation of biological process negative regulation of phosphate metabolic process regulation of primary metabolic process regulation of phosphate metabolic process phosphate-containing compound metabolic process negative regulation of protein modification process negative regulation of cellular process protein metabolic process protein modification process phosphorus metabolic process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process protein phosphorylation phosphorylation regulation of protein metabolic process negative regulation of metabolic process primary metabolic process negative regulation of protein phosphorylation macromolecule modification negative regulation of phosphorus metabolic process regulation of phosphorylation regulation of phosphorus metabolic process negative regulation of phosphorylation cerebellum morphogenesis cerebellar cortex morphogenesis head development hindbrain morphogenesis brain development cerebellar cortex development cerebellum development metencephalon development hindbrain development protein localization establishment of protein localization cellular localization nitrogen compound transport nucleocytoplasmic transport transport nuclear transport intracellular transport protein localization to nucleus establishment of localization localization import into nucleus establishment of protein localization to organelle protein transport cellular macromolecule localization macromolecule localization protein localization to organelle establishment of localization in cell protein import into nucleus intracellular protein transport epidermis development molting cycle process hair cycle epidermis morphogenesis morphogenesis of an epithelium tissue morphogenesis skin development skin epidermis development hair follicle development molting cycle hair cycle process hair follicle morphogenesis regulation of localization regulation of protein localization positive regulation of nucleocytoplasmic transport positive regulation of establishment of protein localization regulation of protein localization to nucleus positive regulation of protein transport regulation of protein import into nucleus positive regulation of intracellular transport regulation of intracellular transport regulation of transport positive regulation of protein localization to nucleus regulation of establishment of protein localization positive regulation of protein import into nucleus regulation of nucleocytoplasmic transport regulation of protein transport positive regulation of transport regulation of cellular localization positive regulation of protein localization regulation of intracellular protein transport positive regulation of intracellular protein transport embryo development ending in birth or egg hatching chordate embryonic development embryo development in utero embryonic development forebrain development pallium development cerebral cortex development telencephalon development astrocyte differentiation cell development astrocyte activation glial cell development astrocyte development gliogenesis response to stress defense response cell activation glial cell differentiation glial cell activation inflammatory response neuroinflammatory response brain morphogenesis forebrain morphogenesis neural tube development regionalization dorsal/ventral pattern formation dorsal/ventral neural tube patterning neural tube patterning columnar/cuboidal epithelial cell development endocrine pancreas development type B pancreatic cell differentiation glandular epithelial cell development endocrine system development type B pancreatic cell development glandular epithelial cell differentiation epithelial cell development enteroendocrine cell differentiation columnar/cuboidal epithelial cell differentiation RNA metabolic process negative regulation of RNA biosynthetic process RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription nucleic acid biosynthetic process regulation of RNA metabolic process transcription by RNA polymerase II negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of transcription by RNA polymerase II negative regulation of DNA-templated transcription negative regulation of transcription by RNA polymerase II nucleobase-containing compound biosynthetic process nucleic acid metabolic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process regulation of DNA-templated transcription negative regulation of RNA metabolic process multicellular organism growth developmental growth growth positive regulation of DNA-templated transcription positive regulation of nucleobase-containing compound metabolic process positive regulation of transcription by RNA polymerase II positive regulation of RNA metabolic process positive regulation of RNA biosynthetic process heart morphogenesis embryonic heart tube development tube morphogenesis embryonic heart tube morphogenesis heart looping determination of bilateral symmetry epithelial tube morphogenesis embryonic organ development determination of left/right symmetry specification of symmetry embryonic organ morphogenesis heart development embryonic morphogenesis determination of heart left/right asymmetry circulatory system development left/right pattern formation regulation of somatic stem cell population maintenance regulation of developmental process regulation of stem cell population maintenance stem cell population maintenance somatic stem cell population maintenance regulation of multicellular organismal process maintenance of cell number ossification osteoblast differentiation cell surface receptor signaling pathway smoothened signaling pathway signal transduction myotube cell development skeletal muscle fiber development skeletal muscle tissue development muscle cell differentiation myotube differentiation striated muscle tissue development muscle structure development skeletal muscle organ development striated muscle cell development muscle cell development muscle tissue development muscle organ development striated muscle cell differentiation cardiac atrium morphogenesis cardiac chamber morphogenesis cardiac atrium development cardiac septum development cardiac septum morphogenesis cardiac chamber development atrial septum morphogenesis atrial septum development mesonephric epithelium development kidney epithelium development branching morphogenesis of an epithelial tube nephron tubule morphogenesis regulation of kidney development regulation of branching involved in ureteric bud morphogenesis positive regulation of developmental process nephron development regulation of morphogenesis of a branching structure regulation of animal organ morphogenesis positive regulation of multicellular organismal process mesonephric tubule development renal tubule morphogenesis nephron morphogenesis nephron epithelium morphogenesis nephron tubule development renal system development ureteric bud morphogenesis positive regulation of morphogenesis of an epithelium branching involved in ureteric bud morphogenesis renal tubule development regulation of morphogenesis of an epithelium regulation of anatomical structure morphogenesis nephron epithelium development ureteric bud development mesonephros development kidney morphogenesis morphogenesis of a branching structure positive regulation of branching involved in ureteric bud morphogenesis mesonephric tubule morphogenesis kidney development morphogenesis of a branching epithelium odontogenesis of dentin-containing tooth odontogenesis negative regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death negative regulation of apoptotic process ventral midline determination ventral midline development central nervous system neuron differentiation neuron differentiation positive regulation of cell communication positive regulation of signal transduction regulation of signal transduction positive regulation of response to stimulus positive regulation of smoothened signaling pathway regulation of smoothened signaling pathway regulation of signaling regulation of response to stimulus regulation of cell communication positive regulation of signaling regulation of cell differentiation regulation of epithelial cell differentiation negative regulation of cell differentiation regulation of multicellular organismal development negative regulation of epithelial cell differentiation negative regulation of developmental process spinal cord dorsal/ventral patterning spinal cord development spinal cord patterning positive regulation of mesenchymal cell proliferation positive regulation of cell population proliferation regulation of mesenchymal cell proliferation regulation of cell population proliferation mesenchymal cell proliferation positive regulation of epithelial cell proliferation regulation of epithelial cell proliferation epithelial cell proliferation diencephalon development thalamus development stem cell development neural crest cell differentiation neural crest cell development mesenchyme development mesenchymal cell migration stem cell differentiation ameboidal-type cell migration mesenchymal cell differentiation neural crest cell migration commissural neuron axon guidance axonogenesis cell projection organization plasma membrane bounded cell projection morphogenesis neuron projection development cell morphogenesis cellular component organization cell projection morphogenesis neuron projection morphogenesis cellular component organization or biogenesis plasma membrane bounded cell projection organization axon guidance axon development cell morphogenesis involved in neuron differentiation neuron projection guidance neuron development left/right axis specification axis specification regulation of heart morphogenesis blood vessel morphogenesis vasculogenesis vasculature development blood vessel development mesenchymal to epithelial transition involved in renal vesicle formation renal vesicle morphogenesis metanephric renal vesicle morphogenesis renal vesicle development metanephros development metanephric renal vesicle formation metanephros morphogenesis metanephric nephron development mesenchymal to epithelial transition involved in metanephric renal vesicle formation mesenchymal to epithelial transition involved in metanephros morphogenesis epithelial cell differentiation involved in kidney development mesenchymal to epithelial transition metanephric nephron morphogenesis cell differentiation involved in metanephros development cell differentiation involved in kidney development anatomical structure formation involved in morphogenesis renal vesicle formation positive regulation of locomotion regulation of cell motility positive regulation of cell migration regulation of locomotion positive regulation of cell motility regulation of cell migration locomotion regulation of growth regulation of developmental growth positive regulation of organ growth organ growth positive regulation of growth regulation of organ growth positive regulation of developmental growth regulation of multicellular organism growth positive regulation of multicellular organism growth dentate gyrus development hippocampus development limbic system development smooth muscle tissue development regulation of molecular function regulation of DNA binding regulation of binding negative regulation of binding negative regulation of molecular function negative regulation of DNA binding negative regulation of gene expression regulation of hair cycle regulation of hair follicle development negative regulation of hair follicle development negative regulation of multicellular organismal process detection of stimulus contact inhibition detection of cell density detection of biotic stimulus response to biotic stimulus lateral mesoderm development determination of left/right asymmetry in lateral mesoderm mesoderm development dopaminergic neuron differentiation positive regulation of nervous system development regulation of neuroblast proliferation regulation of neurogenesis regulation of cell development regulation of nervous system development positive regulation of cell differentiation positive regulation of neurogenesis regulation of neural precursor cell proliferation positive regulation of cell development positive regulation of neural precursor cell proliferation positive regulation of neuroblast proliferation anterior/posterior pattern specification somite development	cellular anatomical structure periplasmic space extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle cell projection ciliary tip cilium cellular anatomical structure periplasmic space extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space vesicle extracellular membrane-bounded organelle cell projection ciliary tip cilium plasma membrane bounded cell projection somatodendritic compartment dendrite dendritic tree neuron projection intracellular anatomical structure membrane intracellular vesicle intracellular membrane-bounded organelle intracellular organelle cytoplasmic vesicle membrane bounding membrane of organelle cytoplasmic vesicle vesicle membrane endocytic vesicle membrane cytoplasm organelle membrane endocytic vesicle Golgi apparatus endomembrane system endoplasmic reticulum-Golgi intermediate compartment non-motile cilium 9+0 non-motile cilium microtubule organizing center cytoskeleton membraneless organelle centriole intracellular membraneless organelle microtubule cytoskeleton cell periphery plasma membrane ciliary membrane plasma membrane region cell projection membrane endosome late endosome endoplasmic reticulum

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR010980	Cytochrome c/b562	Homologous Superfamily
A, B	IPR009155	Cytochrome b562	Family
A, B	IPR036790	Frizzled cysteine-rich domain superfamily	Homologous Superfamily
A, B	IPR041771	Smoothened, cysteine-rich domain	Domain
A, B	IPR017981	GPCR, family 2-like, 7TM	Domain
A, B	IPR000539	Frizzled/Smoothened, 7TM	Domain
A, B	IPR020067	Frizzled domain	Domain
A, B	IPR035683	Smoothened, 7TM	Domain
A, B	IPR015526	Frizzled/secreted frizzled-related protein	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: Q99835	curry-Jones syndrome skin basal cell carcinoma secretory meningioma ameloblastoma medulloblastoma acute promyelocytic leukemia meningioma ependymoblastoma fibrous meningioma Jaw Abnormalities skin neoplasm spinal meningioma transitional meningioma clear cell meningioma female infertility curry-Jones syndrome skin basal cell carcinoma secretory meningioma ameloblastoma medulloblastoma acute promyelocytic leukemia meningioma ependymoblastoma fibrous meningioma Jaw Abnormalities skin neoplasm spinal meningioma transitional meningioma clear cell meningioma female infertility gastrointestinal stromal tumor psammomatous meningioma intraorbital meningioma medulloepithelioma cerebral convexity meningioma meningothelial meningioma parasagittal meningioma intraventricular meningioma skin cancer angiomatous meningioma maxillary neoplasm benign meningioma cerebral primitive neuroectodermal tumor microcystic meningioma olfactory groove meningioma osteosarcoma polydactyly primitive neuroectodermal tumor acute myeloid leukemia lymphoplasmacyte-rich meningioma atypical teratoid rhabdoid tumor osteoarthritis papillary meningioma large cell medulloblastoma skin pigmented basal cell carcinoma basal cell carcinoma, susceptibility to, 1 brain cancer cutaneous lupus erythematosus osteoarthritis, hip glioblastoma intellectual disability lung cancer adamantinoma malignant ependymoma craniosynostosis

Membrane Protein Annotation: OPM OPM Database Homepage

Chains	External Link	Type	Class	Superfamily	Family
A, B	OPM	Transmembrane	Alpha-helical polytopic	Rhodopsin-like receptors and pumps	Frizzled/Smoothened family

Membrane Protein Annotation: PDBTM PDBTM Database Homepage

Chains	External Link	Comment
A, B	PDBTM	Annotated as membrane protein by PDBTM

Membrane Protein Annotation: MemProtMD MemProtMD Database Homepage

Chains	External Link	Comment
A, B	MemProtMD	Annotated as membrane protein by MemProtMD

Membrane Protein Annotation: mpstruc mpstruc Database Homepage

Chains	Resource Link	Group	Subgroup	Protein
A, B	mpstruc	TRANSMEMBRANE PROTEINS: ALPHA-HELICAL	G Protein-Coupled Receptors: Class F	Smoothened (SMO) receptor in complex with cholesterol (apo-SMOΔC)

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM157729.