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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: lanosterol biosynthesis

This protein is involved in step 1 of the subpathway that synthesizes lanosterol from farnesyl diphosphate.
Proteins known to be involved in the 3 steps of the subpathway in this organism are:
  1. Squalene synthase (Fdft1)
  2. Squalene monooxygenase (Sqle)
  3. Lanosterol synthase (Lss)
This subpathway is part of the pathway lanosterol biosynthesis, which is itself part of Terpene metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes lanosterol from farnesyl diphosphate, the pathway lanosterol biosynthesis and in Terpene metabolism.

GO - Molecular functioni

GO - Biological processi

  • cholesterol biosynthetic process Source: RGD
  • ergosterol biosynthetic process Source: InterPro
  • farnesyl diphosphate metabolic process Source: RGD
  • 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

ReactomeiR-RNO-191273. Cholesterol biosynthesis.
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
Proteomesi
  • UP000002494 Componenti: Chromosome 15

Organism-specific databases

RGDi61834. Fdft1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei284 – 304HelicalSequence analysisAdd BLAST21
Transmembranei384 – 404HelicalSequence analysisAdd BLAST21

GO - Cellular componenti

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

Chemistry databases

ChEMBLiCHEMBL3815.
GuidetoPHARMACOLOGYi645.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000674451 – 416Squalene synthaseAdd BLAST416

Proteomic databases

PaxDbiQ02769.
PRIDEiQ02769.

Expressioni

Gene expression databases

BgeeiENSRNOG00000021314.
GenevisibleiQ02769. RN.

Interactioni

Protein-protein interaction databases

MINTiMINT-4569367.
STRINGi10116.ENSRNOP00000029808.

Chemistry databases

BindingDBiQ02769.

Structurei

3D structure databases

ProteinModelPortaliQ02769.
SMRiQ02769.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the phytoene/squalene synthase family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1459. Eukaryota.
COG1562. LUCA.
GeneTreeiENSGT00390000016034.
HOGENOMiHOG000186940.
HOVERGENiHBG002370.
InParanoidiQ02769.
KOiK00801.
OMAiFHTYLYQ.
OrthoDBiEOG091G072P.
PhylomeDBiQ02769.
TreeFamiTF105316.

Family and domain databases

CDDicd00683. Trans_IPPS_HH. 1 hit.
Gene3Di1.10.600.10. 1 hit.
InterProiIPR008949. Isoprenoid_synthase_dom.
IPR002060. Squ/phyt_synthse.
IPR006449. Squal_synth.
IPR019845. Squalene/phytoene_synthase_CS.
IPR033904. Trans_IPPS_HH.
[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:July 1, 1993 - v1
Checksum:iF4BC4D09C9F72169
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti1 – 64Missing in truncated, active form. Add BLAST64

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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-4569367.
STRINGi10116.ENSRNOP00000029808.

Chemistry databases

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

eggNOGiKOG1459. Eukaryota.
COG1562. LUCA.
GeneTreeiENSGT00390000016034.
HOGENOMiHOG000186940.
HOVERGENiHBG002370.
InParanoidiQ02769.
KOiK00801.
OMAiFHTYLYQ.
OrthoDBiEOG091G072P.
PhylomeDBiQ02769.
TreeFamiTF105316.

Enzyme and pathway databases

UniPathwayiUPA00767; UER00751.
ReactomeiR-RNO-191273. Cholesterol biosynthesis.

Miscellaneous databases

PROiQ02769.

Gene expression databases

BgeeiENSRNOG00000021314.
GenevisibleiQ02769. RN.

Family and domain databases

CDDicd00683. Trans_IPPS_HH. 1 hit.
Gene3Di1.10.600.10. 1 hit.
InterProiIPR008949. Isoprenoid_synthase_dom.
IPR002060. Squ/phyt_synthse.
IPR006449. Squal_synth.
IPR019845. Squalene/phytoene_synthase_CS.
IPR033904. Trans_IPPS_HH.
[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...

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: November 30, 2016
This is version 128 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

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 one 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.