Q02769 (FDFT_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Squalene synthase
Short name=SQS
Short name=SS
EC=2.5.1.21

Alternative name(s):
FPP:FPP farnesyltransferase
Farnesyl-diphosphate farnesyltransferase

Gene names

Name:

Fdft1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	416 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Critical branch point enzyme of isoprenoid biosynthesis that is thought to regulate the flux of isoprene intermediates through the sterol pathway.
Catalytic activity	2 farnesyl diphosphate + NAD(P)H = squalene + 2 diphosphate + NAD(P)+.
Cofactor	Magnesium.
Pathway	Terpene metabolism; lanosterol biosynthesis; lanosterol from farnesyl diphosphate: step 1/3.
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.4.
Disruption phenotype	Hypomorphic mutations in the Lss gene and in this gene were identified, as well as a null mutation in the Lss gene. Cataract onset is associated with the specific combination of Lss and Fdft1 mutant alleles that decrease cholesterol levels in cataractous lenses to about 57% of normal. Cholesterol insufficiency may cause the deficient proliferation of lens epithelial cells in Shumiya cataract rats, resulting in the loss of homeostatic epithelial cell control of the underlying fiber cells and ultimately cataractogenesis. Ref.5
Sequence similarities	Belongs to the phytoene/squalene synthase family.

Ontologies

Keywords
Biological process	Cholesterol biosynthesis Cholesterol metabolism Isoprene biosynthesis Lipid biosynthesis Lipid metabolism Steroid biosynthesis Steroid metabolism Sterol biosynthesis Sterol metabolism
Cellular component	Endoplasmic reticulum Membrane
Domain	Transmembrane Transmembrane helix
Ligand	Magnesium NADP
Molecular function	Oxidoreductase Transferase
Technical term	Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	cholesterol biosynthetic process Inferred from mutant phenotype Ref.5. Source: RGD farnesyl diphosphate metabolic process Inferred from mutant phenotype Ref.5. Source: RGD isoprenoid biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW intracellular membrane-bounded organelle Inferred from direct assay Ref.5. Source: RGD
Molecular_function	farnesyl-diphosphate farnesyltransferase activity Inferred from direct assay Ref.2. Source: RGD oxidoreductase activity Inferred from electronic annotation. Source: UniProtKB-KW squalene synthase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 416	416	Squalene synthase		PRO_0000067445
Regions
	Transmembrane	284 – 304	21	Helical; Potential
	Transmembrane	384 – 404	21	Helical; Potential
Natural variations
	Natural variant	1 – 64	64	Missing in truncated, active form.

Sequences

	Sequence		Length	Mass (Da)
	Q02769 [UniParc]. Last modified July 1, 1993. Version 1. Checksum: F4BC4D09C9F72169	FASTA	416	48,106
	10 20 30 40 50 60 MEFVKCLGHP EEFYNLLRFR MGGRRNFIPK MDRNSLSNSL KTCYKYLDQT SRSFAAVIQA 70 80 90 100 110 120 LDGDIRHAVC VFYLILRAMD TVEDDMAISV EKKIPLLRNF HTFLYEPEWR FTESKEKHRV 130 140 150 160 170 180 VLEDFPTISL EFRNLAEKYQ TVIADICHRM GCGMAEFLNK DVTSKQDWDK YCHYVAGLVG 190 200 210 220 230 240 IGLSRLFSAS EFEDPIVGED TECANSMGLF LQKTNIIRDY LEDQQEGRQF WPQEVWGKYV 250 260 270 280 290 300 KKLEDFVKPE NVDVAVKCLN ELITNALQHI PDVITYLSRL RNQSVFNFCA IPQVMAIATL 310 320 330 340 350 360 AACYNNHQVF KGVVKIRKGQ AVTLMMDATN MPAVKAIIYQ YIEEIYHRVP NSDPSASKAK 370 380 390 400 410 QLISNIRTQS LPNCQLISRS HYSPIYLSFI MLLAALSWQY LSTLSQVTED YVQREH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Solubilization, purification, and characterization of a truncated form of rat hepatic squalene synthetase." Shechter I., Klinger E., Rucker M.L., Engstrom R.G., Spirito J.A., Islam M.A., Boettcher B.R., Wienstein D.B. J. Biol. Chem. 267:8628-8635(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Molecular cloning, expression, and characterization of the cDNA for the rat hepatic squalene synthase." McKenzie T.L., Jiang G., Straubhaar J.R., Conrad D.G., Shechter I. J. Biol. Chem. 267:21368-21374(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Heart.
[4]	"Subcellular localization of squalene synthase in rat hepatic cells. Biochemical and immunochemical evidence." Stamellos K.D., Shackelford J.E., Schechter I., Jiang G., Conrad D.G., Keller G.-A., Krisans S.K. J. Biol. Chem. 268:12825-12836(1993) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION. Tissue: Liver.
[5]	"Lanosterol synthase mutations cause cholesterol deficiency-associated cataracts in the Shumiya cataract rat." Mori M., Li G., Abe I., Nakayama J., Guo Z., Sawashita J., Ugawa T., Nishizono S., Serikawa T., Higuchi K., Shumiya S. J. Clin. Invest. 116:395-404(2006) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M95591 mRNA. Translation: AAA42179.1. BC081810 mRNA. Translation: AAH81810.1.
IPI	IPI00210233.
PIR	A45105.
RefSeq	NP_062111.1. NM_019238.2.
UniGene	Rn.154404.
3D structure databases
ProteinModelPortal	Q02769.
SMR	Q02769. Positions 34-370.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000029808.
Proteomic databases
PaxDb	Q02769.
PRIDE	Q02769.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000032089; ENSRNOP00000029808; ENSRNOG00000021314.
GeneID	29580.
KEGG	rno:29580.
UCSC	RGD:61834. rat.
Organism-specific databases
CTD	2222.
RGD	61834. Fdft1.
Phylogenomic databases
eggNOG	COG1562.
GeneTree	ENSGT00390000016034.
HOGENOM	HOG000186940.
HOVERGEN	HBG002370.
InParanoid	Q02769.
KO	K00801.
OMA	ELRHAVC.
OrthoDB	EOG4QVCC2.
Enzyme and pathway databases
UniPathway	UPA00767; UER00751.
Gene expression databases
Genevestigator	Q02769.
GermOnline	ENSRNOG00000021314. Rattus norvegicus.
Family and domain databases
Gene3D	1.10.600.10. 1 hit.
InterPro	IPR002060. Squ/phyt_synthse. IPR006449. Squal_synth. IPR019845. Squalene/phytoene_synthase_CS. IPR008949. Terpenoid_synth. [Graphical view]
Pfam	PF00494. SQS_PSY. 1 hit. [Graphical view]
SUPFAM	SSF48576. Terpenoid_synth. 1 hit.
TIGRFAMs	TIGR01559. squal_synth. 1 hit.
PROSITE	PS01044. SQUALEN_PHYTOEN_SYN_1. 1 hit. PS01045. SQUALEN_PHYTOEN_SYN_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q02769.
ChEMBL	CHEMBL3815.
NextBio	609686.

Entry information

Entry name

FDFT_RAT

Accession

Primary (citable) accession number: Q02769

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	July 1, 1993
Last modified:	April 3, 2013
This is version 104 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program