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Protein

Squalene synthase

Gene

Fdft1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Critical branch point enzyme of isoprenoid biosynthesis that is thought to regulate the flux of isoprene intermediates through the sterol pathway.

Catalytic activityi

2 farnesyl diphosphate + NAD(P)H = squalene + 2 diphosphate + NAD(P)+.

Cofactori

Pathwayi

GO - Molecular functioni

  1. farnesyl-diphosphate farnesyltransferase activity Source: RGD
  2. oxidoreductase activity Source: UniProtKB-KW
  3. squalene synthase activity Source: UniProtKB-EC

GO - Biological processi

  1. cholesterol biosynthetic process Source: RGD
  2. farnesyl diphosphate metabolic process Source: RGD
  3. isoprenoid biosynthetic process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Oxidoreductase, Transferase

Keywords - Biological processi

Cholesterol biosynthesis, Cholesterol metabolism, Isoprene biosynthesis, Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis, Steroid metabolism, Sterol biosynthesis, Sterol metabolism

Keywords - Ligandi

Magnesium, NADP

Enzyme and pathway databases

ReactomeiREACT_275030. Cholesterol biosynthesis.
REACT_285313. PPARA activates gene expression.
REACT_341940. Activation of gene expression by SREBF (SREBP).
UniPathwayiUPA00767; UER00751.

Names & Taxonomyi

Protein namesi
Recommended name:
Squalene synthase (EC:2.5.1.21)
Short name:
SQS
Short name:
SS
Alternative name(s):
FPP:FPP farnesyltransferase
Farnesyl-diphosphate farnesyltransferase
Gene namesi
Name:Fdft1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494 Componenti: Chromosome 15

Organism-specific databases

RGDi61834. Fdft1.

Subcellular locationi

Endoplasmic reticulum membrane 1 Publication; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei284 – 30421HelicalSequence AnalysisAdd
BLAST
Transmembranei384 – 40421HelicalSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. endoplasmic reticulum membrane Source: UniProtKB-SubCell
  2. integral component of membrane Source: UniProtKB-KW
  3. intracellular membrane-bounded organelle Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Disruption phenotypei

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.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 416416Squalene synthasePRO_0000067445Add
BLAST

Proteomic databases

PaxDbiQ02769.
PRIDEiQ02769.

Expressioni

Gene expression databases

GenevestigatoriQ02769.

Interactioni

Protein-protein interaction databases

MINTiMINT-4569367.
STRINGi10116.ENSRNOP00000029808.

Structurei

3D structure databases

ProteinModelPortaliQ02769.
SMRiQ02769. Positions 34-370.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the phytoene/squalene synthase family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG1562.
GeneTreeiENSGT00390000016034.
HOGENOMiHOG000186940.
HOVERGENiHBG002370.
InParanoidiQ02769.
KOiK00801.
OMAiFHTYLYQ.
OrthoDBiEOG7QRQTS.
PhylomeDBiQ02769.
TreeFamiTF105316.

Family and domain databases

Gene3Di1.10.600.10. 1 hit.
InterProiIPR008949. Isoprenoid_synthase_dom.
IPR002060. Squ/phyt_synthse.
IPR006449. Squal_synth.
IPR019845. Squalene/phytoene_synthase_CS.
[Graphical view]
PfamiPF00494. SQS_PSY. 1 hit.
[Graphical view]
SUPFAMiSSF48576. SSF48576. 1 hit.
TIGRFAMsiTIGR01559. squal_synth. 1 hit.
PROSITEiPS01044. SQUALEN_PHYTOEN_SYN_1. 1 hit.
PS01045. SQUALEN_PHYTOEN_SYN_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q02769-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEFVKCLGHP EEFYNLLRFR MGGRRNFIPK MDRNSLSNSL KTCYKYLDQT
60 70 80 90 100
SRSFAAVIQA LDGDIRHAVC VFYLILRAMD TVEDDMAISV EKKIPLLRNF
110 120 130 140 150
HTFLYEPEWR FTESKEKHRV VLEDFPTISL EFRNLAEKYQ TVIADICHRM
160 170 180 190 200
GCGMAEFLNK DVTSKQDWDK YCHYVAGLVG IGLSRLFSAS EFEDPIVGED
210 220 230 240 250
TECANSMGLF LQKTNIIRDY LEDQQEGRQF WPQEVWGKYV KKLEDFVKPE
260 270 280 290 300
NVDVAVKCLN ELITNALQHI PDVITYLSRL RNQSVFNFCA IPQVMAIATL
310 320 330 340 350
AACYNNHQVF KGVVKIRKGQ AVTLMMDATN MPAVKAIIYQ YIEEIYHRVP
360 370 380 390 400
NSDPSASKAK QLISNIRTQS LPNCQLISRS HYSPIYLSFI MLLAALSWQY
410
LSTLSQVTED YVQREH
Length:416
Mass (Da):48,106
Last modified:June 30, 1993 - v1
Checksum:iF4BC4D09C9F72169
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti1 – 6464Missing in truncated, active form.
Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M95591 mRNA. Translation: AAA42179.1.
BC081810 mRNA. Translation: AAH81810.1.
PIRiA45105.
RefSeqiNP_062111.1. NM_019238.2.
UniGeneiRn.154404.

Genome annotation databases

EnsembliENSRNOT00000032089; ENSRNOP00000029808; ENSRNOG00000021314.
GeneIDi29580.
KEGGirno:29580.
UCSCiRGD:61834. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M95591 mRNA. Translation: AAA42179.1.
BC081810 mRNA. Translation: AAH81810.1.
PIRiA45105.
RefSeqiNP_062111.1. NM_019238.2.
UniGeneiRn.154404.

3D structure databases

ProteinModelPortaliQ02769.
SMRiQ02769. Positions 34-370.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-4569367.
STRINGi10116.ENSRNOP00000029808.

Chemistry

BindingDBiQ02769.
ChEMBLiCHEMBL3815.
GuidetoPHARMACOLOGYi645.

Proteomic databases

PaxDbiQ02769.
PRIDEiQ02769.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000032089; ENSRNOP00000029808; ENSRNOG00000021314.
GeneIDi29580.
KEGGirno:29580.
UCSCiRGD:61834. rat.

Organism-specific databases

CTDi2222.
RGDi61834. Fdft1.

Phylogenomic databases

eggNOGiCOG1562.
GeneTreeiENSGT00390000016034.
HOGENOMiHOG000186940.
HOVERGENiHBG002370.
InParanoidiQ02769.
KOiK00801.
OMAiFHTYLYQ.
OrthoDBiEOG7QRQTS.
PhylomeDBiQ02769.
TreeFamiTF105316.

Enzyme and pathway databases

UniPathwayiUPA00767; UER00751.
ReactomeiREACT_275030. Cholesterol biosynthesis.
REACT_285313. PPARA activates gene expression.
REACT_341940. Activation of gene expression by SREBF (SREBP).

Miscellaneous databases

NextBioi609686.
PROiQ02769.

Gene expression databases

GenevestigatoriQ02769.

Family and domain databases

Gene3Di1.10.600.10. 1 hit.
InterProiIPR008949. Isoprenoid_synthase_dom.
IPR002060. Squ/phyt_synthse.
IPR006449. Squal_synth.
IPR019845. Squalene/phytoene_synthase_CS.
[Graphical view]
PfamiPF00494. SQS_PSY. 1 hit.
[Graphical view]
SUPFAMiSSF48576. SSF48576. 1 hit.
TIGRFAMsiTIGR01559. squal_synth. 1 hit.
PROSITEiPS01044. SQUALEN_PHYTOEN_SYN_1. 1 hit.
PS01045. SQUALEN_PHYTOEN_SYN_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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(1991) [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(1991) [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(2003) [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(1992) [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(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiFDFT_RAT
AccessioniPrimary (citable) accession number: Q02769
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 30, 1993
Last sequence update: June 30, 1993
Last modified: March 31, 2015
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.