1EZF

CRYSTAL STRUCTURE OF HUMAN SQUALENE SYNTHASE

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
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
Structure Motif: Primary M-CSA Annotation

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
B	d1ezfb_	All alpha proteins	Terpenoid synthases	Terpenoid synthases	Squalene synthase	Squalene synthase	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d1ezfa_	All alpha proteins	Terpenoid synthases	Terpenoid synthases	Squalene synthase	Squalene synthase	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d1ezfc_	All alpha proteins	Terpenoid synthases	Terpenoid synthases	Squalene synthase	Squalene synthase	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
B	SCOP2B Superfamily	Terpenoid synthases	8038853	3001615	SCOP2B (2022-06-29)
A	SCOP2 Family	Squalene synthase	8026474	4001456	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	Terpenoid synthases	8038853	3001615	SCOP2 (2022-06-29)
C	SCOP2B Superfamily	Terpenoid synthases	8038853	3001615	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)
B	SQS_PSY	e1ezfB1	A: alpha bundles	X: Terpenoid synthases (From Topology)	H: Terpenoid synthases (From Topology)	T: Terpenoid synthases	F: SQS_PSY	ECOD (1.6)
A	SQS_PSY	e1ezfA1	A: alpha bundles	X: Terpenoid synthases (From Topology)	H: Terpenoid synthases (From Topology)	T: Terpenoid synthases	F: SQS_PSY	ECOD (1.6)
C	SQS_PSY	e1ezfC1	A: alpha bundles	X: Terpenoid synthases (From Topology)	H: Terpenoid synthases (From Topology)	T: Terpenoid synthases	F: SQS_PSY	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
B	1.10.600.10	Mainly Alpha	Orthogonal Bundle	Farnesyl Diphosphate Synthase	Farnesyl Diphosphate Synthase	CATH (4.3.0)
A	1.10.600.10	Mainly Alpha	Orthogonal Bundle	Farnesyl Diphosphate Synthase	Farnesyl Diphosphate Synthase	CATH (4.3.0)
C	1.10.600.10	Mainly Alpha	Orthogonal Bundle	Farnesyl Diphosphate Synthase	Farnesyl Diphosphate Synthase	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C	PF00494	Squalene/phytoene synthase (SQS_PSY)	Squalene/phytoene synthase	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C	FARNESYL-DIPHOSPHATE FARNESYLTRANSFERASE	squalene synthase [NAD(P)H] activity prenyltransferase activity transferase activity transferase activity, transferring alkyl or aryl (other than methyl) groups catalytic activity farnesyltranstransferase activity cation binding ion binding binding metal ion binding small molecule binding	biosynthetic process steroid metabolic process lipid biosynthetic process primary metabolic process metabolic process cellular process steroid biosynthetic process lipid metabolic process farnesyl diphosphate metabolic process phospholipid metabolic process organophosphate metabolic process phosphate-containing compound metabolic process phosphorus metabolic process terpenoid metabolic process biosynthetic process steroid metabolic process lipid biosynthetic process primary metabolic process metabolic process cellular process steroid biosynthetic process lipid metabolic process farnesyl diphosphate metabolic process phospholipid metabolic process organophosphate metabolic process phosphate-containing compound metabolic process phosphorus metabolic process terpenoid metabolic process isoprenoid metabolic process secondary alcohol biosynthetic process small molecule biosynthetic process cholesterol biosynthetic process organic hydroxy compound metabolic process sterol metabolic process cholesterol metabolic process alcohol metabolic process secondary alcohol metabolic process sterol biosynthetic process organic hydroxy compound biosynthetic process alcohol biosynthetic process small molecule metabolic process	cellular anatomical structure membrane membrane-bounded organelle intracellular organelle intracellular anatomical structure organelle endoplasmic reticulum cytoplasm intracellular membrane-bounded organelle endomembrane system organelle subcompartment endoplasmic reticulum subcompartment nuclear outer membrane-endoplasmic reticulum membrane network organelle membrane cellular anatomical structure membrane membrane-bounded organelle intracellular organelle intracellular anatomical structure organelle endoplasmic reticulum cytoplasm intracellular membrane-bounded organelle endomembrane system organelle subcompartment endoplasmic reticulum subcompartment nuclear outer membrane-endoplasmic reticulum membrane network organelle membrane endoplasmic reticulum membrane

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C	IPR002060	Squalene/phytoene synthase	Family
A, B, C	IPR008949	Isoprenoid synthase domain superfamily	Homologous Superfamily
A, B, C	IPR044844	Trans-isoprenyl diphosphate synthases, eukaryotic-type	Family
A, B, C	IPR033904	Trans-isoprenyl diphosphate synthases, head-to-head	Domain
A, B, C	IPR019845	Squalene/phytoene synthase, conserved site	Conserved Site
A, B, C	IPR006449	Squalene synthase-like	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C	Pharos: P37268	phencyclidine abuse cannabis dependence cocaine dependence cocaine abuse Marijuana Abuse osteosarcoma pancreatic intraductal papillary-mucinous carcinoma polycystic ovary syndrome adrenal cortex carcinoma testicular germ cell tumor dermatomyositis hepatocellular carcinoma malignant mesothelioma medulloblastoma ovarian cancer phencyclidine abuse cannabis dependence cocaine dependence cocaine abuse Marijuana Abuse osteosarcoma pancreatic intraductal papillary-mucinous carcinoma polycystic ovary syndrome adrenal cortex carcinoma testicular germ cell tumor dermatomyositis hepatocellular carcinoma malignant mesothelioma medulloblastoma ovarian cancer pancreatic intraductal papillary-mucinous neoplasm progressive supranuclear palsy astrocytic tumor dilated cardiomyopathy interstitial cystitis lung cancer malignant pancreatic neoplasm oligodendroglioma pancreatic ductal adenocarcinoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia Pick disease subependymal giant cell astrocytoma Crohn disease leprosy lymphoplasmacytic lymphoma

Structure Motif Annotation: Mechanism and Catalytic Site Atlas M-CSA Database Homepage

Chains	Enzyme Name	Description	Catalytic Residues
A	squalene synthase M-CSA #264	Squalene synthase is a member of the Isoprenoid Synthase Type I superfamily. These enzymes catalyse the formation of squalene by the reductive dimerisation of two farnesyl diphosphate molecules in a two-step reaction (2 farnesyl diphosphate --> presqualene diphosphate; presqualene diphosphate + NAD(P)H --> squalene). In the human enzyme, the first half reaction occurs at one end of a large channel (surrounded by five alpha helices runs through the centre of the protein). Then the intermediate is thought to move into an enclosed pocket where the second half reaction occurs. This reaction occurs at the final branch point of the isoprenoid biosynthesis pathway, and is the first committed step in cholesterol biosynthesis.	Defined by 4 residues: TYR:A-141 [auth A-171]ARG:A-188 [auth A-218]ARG:A-198 [auth A-228]PHE:A-258 [auth A-288] \| Explore in 3D: M-CSA Motif Definition Extent of motif is too large to support Structure Motif searching. EC: 2.5.1.21 (PDB Primary Data)

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.