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Q02769

- FDFT_RAT

UniProt

Q02769 - FDFT_RAT

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Protein
Squalene synthase
Gene
Fdft1
Organism
Rattus norvegicus (Rat)
Status
Reviewed - 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

Magnesium.

Pathwayi

GO - Molecular functioni

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

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_196408. PPARA activates gene expression.
REACT_198613. 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: Chromosome 15

Organism-specific databases

RGDi61834. Fdft1.

Subcellular locationi

Endoplasmic reticulum membrane; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei284 – 30421Helical; Reviewed prediction
Add
BLAST
Transmembranei384 – 40421Helical; Reviewed prediction
Add
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 synthase
PRO_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.

Family & Domainsi

Sequence similaritiesi

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

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

Family and domain databases

Gene3Di1.10.600.10. 1 hit.
InterProiIPR002060. Squ/phyt_synthse.
IPR006449. Squal_synth.
IPR019845. Squalene/phytoene_synthase_CS.
IPR008949. Terpenoid_synth.
[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

MEFVKCLGHP EEFYNLLRFR MGGRRNFIPK MDRNSLSNSL KTCYKYLDQT    50
SRSFAAVIQA LDGDIRHAVC VFYLILRAMD TVEDDMAISV EKKIPLLRNF 100
HTFLYEPEWR FTESKEKHRV VLEDFPTISL EFRNLAEKYQ TVIADICHRM 150
GCGMAEFLNK DVTSKQDWDK YCHYVAGLVG IGLSRLFSAS EFEDPIVGED 200
TECANSMGLF LQKTNIIRDY LEDQQEGRQF WPQEVWGKYV KKLEDFVKPE 250
NVDVAVKCLN ELITNALQHI PDVITYLSRL RNQSVFNFCA IPQVMAIATL 300
AACYNNHQVF KGVVKIRKGQ AVTLMMDATN MPAVKAIIYQ YIEEIYHRVP 350
NSDPSASKAK QLISNIRTQS LPNCQLISRS HYSPIYLSFI MLLAALSWQY 400
LSTLSQVTED YVQREH 416
Length:416
Mass (Da):48,106
Last modified:July 1, 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:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
Links Updated
M95591 mRNA. Translation: AAA42179.1 .
BC081810 mRNA. Translation: AAH81810.1 .
PIRi A45105.
RefSeqi NP_062111.1. NM_019238.2.
UniGenei Rn.154404.

3D structure databases

ProteinModelPortali Q02769.
SMRi Q02769. Positions 34-370.
ModBasei Search...

Protein-protein interaction databases

MINTi MINT-4569367.
STRINGi 10116.ENSRNOP00000029808.

Chemistry

BindingDBi Q02769.
ChEMBLi CHEMBL3815.
GuidetoPHARMACOLOGYi 645.

Proteomic databases

PaxDbi Q02769.
PRIDEi Q02769.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSRNOT00000032089 ; ENSRNOP00000029808 ; ENSRNOG00000021314 .
GeneIDi 29580.
KEGGi rno:29580.
UCSCi RGD:61834. rat.

Organism-specific databases

CTDi 2222.
RGDi 61834. Fdft1.

Phylogenomic databases

eggNOGi COG1562.
GeneTreei ENSGT00390000016034.
HOGENOMi HOG000186940.
HOVERGENi HBG002370.
InParanoidi Q02769.
KOi K00801.
OMAi EMRHAVC.
OrthoDBi EOG7QRQTS.
PhylomeDBi Q02769.
TreeFami TF105316.

Enzyme and pathway databases

UniPathwayi UPA00767 ; UER00751 .
Reactomei REACT_196408. PPARA activates gene expression.
REACT_198613. Activation of gene expression by SREBF (SREBP).

Miscellaneous databases

NextBioi 609686.
PROi Q02769.

Gene expression databases

Genevestigatori Q02769.

Family and domain databases

Gene3Di 1.10.600.10. 1 hit.
InterProi IPR002060. Squ/phyt_synthse.
IPR006449. Squal_synth.
IPR019845. Squalene/phytoene_synthase_CS.
IPR008949. Terpenoid_synth.
[Graphical view ]
Pfami PF00494. SQS_PSY. 1 hit.
[Graphical view ]
SUPFAMi SSF48576. SSF48576. 1 hit.
TIGRFAMsi TIGR01559. squal_synth. 1 hit.
PROSITEi PS01044. SQUALEN_PHYTOEN_SYN_1. 1 hit.
PS01045. SQUALEN_PHYTOEN_SYN_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

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(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.

Entry informationi

Entry nameiFDFT_RAT
AccessioniPrimary (citable) accession number: Q02769
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: July 1, 1993
Last modified: September 3, 2014
This is version 113 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

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