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Protein

Squalene synthase

Gene

FDFT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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

  • farnesyl-diphosphate farnesyltransferase activity Source: GO_Central
  • squalene synthase activity Source: GO_Central

GO - Biological processi

Keywordsi

Molecular functionMultifunctional enzyme, Transferase
Biological processCholesterol biosynthesis, Cholesterol metabolism, Isoprene biosynthesis, Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis, Steroid metabolism, Sterol biosynthesis, Sterol metabolism
LigandMagnesium, NADP

Enzyme and pathway databases

BioCyciMetaCyc:HS01329-MONOMER
BRENDAi2.5.1.21 2681
ReactomeiR-HSA-191273 Cholesterol biosynthesis
R-HSA-1989781 PPARA activates gene expression
R-HSA-2426168 Activation of gene expression by SREBF (SREBP)
SABIO-RKiP37268
UniPathwayi
UPA00767;UER00751

Chemistry databases

SwissLipidsiSLP:000000138

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000079459.12
HGNCiHGNC:3629 FDFT1
MIMi184420 gene
neXtProtiNX_P37268

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi2222
OpenTargetsiENSG00000079459
PharmGKBiPA28073

Chemistry databases

ChEMBLiCHEMBL3338
DrugBankiDB05317 TAK-475
GuidetoPHARMACOLOGYi645

Polymorphism and mutation databases

BioMutaiFDFT1
DMDMi585126

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000674431 – 417Squalene synthaseAdd BLAST417

Proteomic databases

EPDiP37268
PaxDbiP37268
PeptideAtlasiP37268
PRIDEiP37268
ProteomicsDBi55271

PTM databases

iPTMnetiP37268
PhosphoSitePlusiP37268
SwissPalmiP37268

Expressioni

Gene expression databases

BgeeiENSG00000079459 Expressed in 237 organ(s), highest expression level in testis
CleanExiHS_FDFT1
ExpressionAtlasiP37268 baseline and differential
GenevisibleiP37268 HS

Organism-specific databases

HPAiHPA008874

Interactioni

Subunit structurei

Monomer.By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
CREB3O43889-23EBI-714550,EBI-625022

Protein-protein interaction databases

BioGridi108516, 33 interactors
IntActiP37268, 26 interactors
STRINGi9606.ENSP00000220584

Chemistry databases

BindingDBiP37268

Structurei

Secondary structure

1417
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP37268
SMRiP37268
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP37268

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
InParanoidiP37268
KOiK00801
OMAiNGPNEKD
OrthoDBiEOG091G072P
PhylomeDBiP37268
TreeFamiTF105316

Family and domain databases

CDDicd00683 Trans_IPPS_HH, 1 hit
Gene3Di1.10.600.10, 1 hit
InterProiView protein in InterPro
IPR008949 Isoprenoid_synthase_dom_sf
IPR002060 Squ/phyt_synthse
IPR006449 Squal_synth-like
IPR019845 Squalene/phytoene_synthase_CS
IPR033904 Trans_IPPS_HH
SFLDiSFLDG01018 Squalene/Phytoene_Synthase_Lik, 1 hit
SUPFAMiSSF48576 SSF48576, 1 hit
TIGRFAMsiTIGR01559 squal_synth, 1 hit
PROSITEiView protein in PROSITE
PS01044 SQUALEN_PHYTOEN_SYN_1, 1 hit
PS01045 SQUALEN_PHYTOEN_SYN_2, 1 hit

Sequences (5+)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 5 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P37268-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MEFVKCLGHP EEFYNLVRFR IGGKRKVMPK MDQDSLSSSL KTCYKYLNQT
60 70 80 90 100
SRSFAAVIQA LDGEMRNAVC IFYLVLRALD TLEDDMTISV EKKVPLLHNF
110 120 130 140 150
HSFLYQPDWR FMESKEKDRQ VLEDFPTISL EFRNLAEKYQ TVIADICRRM
160 170 180 190 200
GIGMAEFLDK HVTSEQEWDK YCHYVAGLVG IGLSRLFSAS EFEDPLVGED
210 220 230 240 250
TERANSMGLF LQKTNIIRDY LEDQQGGREF WPQEVWSRYV KKLGDFAKPE
260 270 280 290 300
NIDLAVQCLN ELITNALHHI PDVITYLSRL RNQSVFNFCA IPQVMAIATL
310 320 330 340 350
AACYNNQQVF KGAVKIRKGQ AVTLMMDATN MPAVKAIIYQ YMEEIYHRIP
360 370 380 390 400
DSDPSSSKTR QIISTIRTQN LPNCQLISRS HYSPIYLSFV MLLAALSWQY
410
LTTLSQVTED YVQTGEH
Length:417
Mass (Da):48,115
Last modified:October 1, 1994 - v1
Checksum:iD36CBC8382F827EC
GO
Isoform 2 (identifier: P37268-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-64: Missing.

Note: No experimental confirmation available.
Show »
Length:353
Mass (Da):40,770
Checksum:i45DC1E8B9F179D2B
GO
Isoform 3 (identifier: P37268-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-85: Missing.

Note: No experimental confirmation available.
Show »
Length:332
Mass (Da):38,317
Checksum:iD58BAF0FA5DC6E5F
GO
Isoform 4 (identifier: P37268-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-111: Missing.

Note: No experimental confirmation available.
Show »
Length:306
Mass (Da):35,101
Checksum:iC237E92AAE66264A
GO
Isoform 5 (identifier: P37268-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     128-170: Missing.

Note: No experimental confirmation available.
Show »
Length:374
Mass (Da):43,060
Checksum:iC9F61FDC11FAA49B
GO

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PNM1E9PNM1_HUMAN
Squalene synthase
FDFT1
410Annotation score:
E9PJG4E9PJG4_HUMAN
Squalene synthase
FDFT1
150Annotation score:
A0A1W2PQ47A0A1W2PQ47_HUMAN
Squalene synthase
FDFT1
476Annotation score:
E9PS69E9PS69_HUMAN
Squalene synthase
FDFT1
113Annotation score:
E9PSH1E9PSH1_HUMAN
Squalene synthase
FDFT1
67Annotation score:
E9PNJ2E9PNJ2_HUMAN
Squalene synthase
FDFT1
51Annotation score:
E9PQ90E9PQ90_HUMAN
Squalene synthase
FDFT1
45Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti353D → N in AAB33404 (PubMed:7864626).Curated1
Sequence conflicti402T → A in CAA48896 (PubMed:8294001).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01178645K → R Influences plasma cholesterol levels; associated with increased total cholesterol and non-high-density lipoprotein cholesterol. 2 PublicationsCorresponds to variant dbSNP:rs4731Ensembl.1
Natural variantiVAR_011787392L → P. Corresponds to variant dbSNP:rs1804473Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0565171 – 111Missing in isoform 4. 1 PublicationAdd BLAST111
Alternative sequenceiVSP_0562821 – 85Missing in isoform 3. 1 PublicationAdd BLAST85
Alternative sequenceiVSP_0562831 – 64Missing in isoform 2. 1 PublicationAdd BLAST64
Alternative sequenceiVSP_056518128 – 170Missing in isoform 5. 1 PublicationAdd BLAST43

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L06070 mRNA Translation: AAA60582.1
L06105 mRNA Translation: AAA36645.1
X69141 mRNA Translation: CAA48896.1
S76822 mRNA Translation: AAB33404.1
AK057726 mRNA Translation: BAG51957.1
AK293545 mRNA Translation: BAH11529.1
AK296043 mRNA Translation: BAG58807.1
AK300059 mRNA Translation: BAG61868.1
AK315993 mRNA Translation: BAH14364.1
AK316351 mRNA Translation: BAH14722.1
AK316531 mRNA Translation: BAH14902.1
AK316534 mRNA Translation: BAH14905.1
AC069185 Genomic DNA No translation available.
BC003573 mRNA Translation: AAH03573.1
BC009251 mRNA Translation: AAH09251.1
BC029641 mRNA Translation: AAH29641.1
CCDSiCCDS5985.1 [P37268-1]
CCDS75696.1 [P37268-2]
CCDS75697.1 [P37268-3]
PIRiA45998
I38245
I52090
RefSeqiNP_001274671.1, NM_001287742.1 [P37268-1]
NP_001274672.1, NM_001287743.1 [P37268-1]
NP_001274673.1, NM_001287744.1 [P37268-2]
NP_001274674.1, NM_001287745.1 [P37268-2]
NP_001274676.1, NM_001287747.1 [P37268-2]
NP_001274677.1, NM_001287748.1 [P37268-2]
NP_001274678.1, NM_001287749.1 [P37268-2]
NP_001274679.1, NM_001287750.1
NP_001274680.1, NM_001287751.1 [P37268-3]
NP_001274685.1, NM_001287756.1
NP_004453.3, NM_004462.4 [P37268-1]
XP_016868706.1, XM_017013217.1
UniGeneiHs.593928

Genome annotation databases

EnsembliENST00000220584; ENSP00000220584; ENSG00000079459 [P37268-1]
ENST00000443614; ENSP00000390367; ENSG00000079459 [P37268-5]
ENST00000525777; ENSP00000436069; ENSG00000079459 [P37268-3]
ENST00000528643; ENSP00000431649; ENSG00000079459 [P37268-3]
ENST00000528812; ENSP00000431749; ENSG00000079459 [P37268-2]
ENST00000530664; ENSP00000432331; ENSG00000079459 [P37268-2]
ENST00000538689; ENSP00000444248; ENSG00000079459 [P37268-2]
ENST00000615631; ENSP00000481481; ENSG00000079459 [P37268-1]
ENST00000618539; ENSP00000480828; ENSG00000079459 [P37268-1]
ENST00000622850; ENSP00000484122; ENSG00000079459 [P37268-2]
ENST00000623368; ENSP00000485229; ENSG00000079459 [P37268-2]
GeneIDi2222
KEGGihsa:2222
UCSCiuc003wuh.4 human [P37268-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L06070 mRNA Translation: AAA60582.1
L06105 mRNA Translation: AAA36645.1
X69141 mRNA Translation: CAA48896.1
S76822 mRNA Translation: AAB33404.1
AK057726 mRNA Translation: BAG51957.1
AK293545 mRNA Translation: BAH11529.1
AK296043 mRNA Translation: BAG58807.1
AK300059 mRNA Translation: BAG61868.1
AK315993 mRNA Translation: BAH14364.1
AK316351 mRNA Translation: BAH14722.1
AK316531 mRNA Translation: BAH14902.1
AK316534 mRNA Translation: BAH14905.1
AC069185 Genomic DNA No translation available.
BC003573 mRNA Translation: AAH03573.1
BC009251 mRNA Translation: AAH09251.1
BC029641 mRNA Translation: AAH29641.1
CCDSiCCDS5985.1 [P37268-1]
CCDS75696.1 [P37268-2]
CCDS75697.1 [P37268-3]
PIRiA45998
I38245
I52090
RefSeqiNP_001274671.1, NM_001287742.1 [P37268-1]
NP_001274672.1, NM_001287743.1 [P37268-1]
NP_001274673.1, NM_001287744.1 [P37268-2]
NP_001274674.1, NM_001287745.1 [P37268-2]
NP_001274676.1, NM_001287747.1 [P37268-2]
NP_001274677.1, NM_001287748.1 [P37268-2]
NP_001274678.1, NM_001287749.1 [P37268-2]
NP_001274679.1, NM_001287750.1
NP_001274680.1, NM_001287751.1 [P37268-3]
NP_001274685.1, NM_001287756.1
NP_004453.3, NM_004462.4 [P37268-1]
XP_016868706.1, XM_017013217.1
UniGeneiHs.593928

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EZFX-ray2.15A/B/C31-370[»]
3ASXX-ray2.00A31-370[»]
3LEEX-ray3.20A/B/C/D/E/F31-370[»]
3Q2ZX-ray2.00A31-370[»]
3Q30X-ray2.00A31-370[»]
3V66X-ray1.80A31-370[»]
3VJ8X-ray1.52A31-370[»]
3VJ9X-ray1.52A31-370[»]
3VJAX-ray1.76A/B31-370[»]
3VJBX-ray2.05A/B/C/D/E/F31-370[»]
3VJCX-ray1.89A/B/C/D/E/F31-370[»]
3WC9X-ray2.82A/B/C/D/E/F31-370[»]
3WCDX-ray2.75A/B/C/D/E/F31-370[»]
3WCFX-ray2.22A/B/C/D/E/F31-370[»]
3WCHX-ray2.50A/B/C/D/E/F31-370[»]
3WCIX-ray2.30A/B/C/D/E/F31-370[»]
3WCJX-ray2.20A/B/C/D/E/F31-370[»]
3WCLX-ray2.24A/B/C/D/E/F31-370[»]
3WCMX-ray2.06A/B/C/D/E/F31-370[»]
3WEFX-ray2.35A/B/C/D/E/F31-370[»]
3WEGX-ray1.75A31-370[»]
3WEHX-ray1.87A31-370[»]
3WEIX-ray1.79A31-370[»]
3WEJX-ray2.00A31-370[»]
3WEKX-ray1.85A31-370[»]
3WSAX-ray2.90A/B/C/D/E/F31-370[»]
ProteinModelPortaliP37268
SMRiP37268
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108516, 33 interactors
IntActiP37268, 26 interactors
STRINGi9606.ENSP00000220584

Chemistry databases

BindingDBiP37268
ChEMBLiCHEMBL3338
DrugBankiDB05317 TAK-475
GuidetoPHARMACOLOGYi645
SwissLipidsiSLP:000000138

PTM databases

iPTMnetiP37268
PhosphoSitePlusiP37268
SwissPalmiP37268

Polymorphism and mutation databases

BioMutaiFDFT1
DMDMi585126

Proteomic databases

EPDiP37268
PaxDbiP37268
PeptideAtlasiP37268
PRIDEiP37268
ProteomicsDBi55271

Protocols and materials databases

DNASUi2222
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000220584; ENSP00000220584; ENSG00000079459 [P37268-1]
ENST00000443614; ENSP00000390367; ENSG00000079459 [P37268-5]
ENST00000525777; ENSP00000436069; ENSG00000079459 [P37268-3]
ENST00000528643; ENSP00000431649; ENSG00000079459 [P37268-3]
ENST00000528812; ENSP00000431749; ENSG00000079459 [P37268-2]
ENST00000530664; ENSP00000432331; ENSG00000079459 [P37268-2]
ENST00000538689; ENSP00000444248; ENSG00000079459 [P37268-2]
ENST00000615631; ENSP00000481481; ENSG00000079459 [P37268-1]
ENST00000618539; ENSP00000480828; ENSG00000079459 [P37268-1]
ENST00000622850; ENSP00000484122; ENSG00000079459 [P37268-2]
ENST00000623368; ENSP00000485229; ENSG00000079459 [P37268-2]
GeneIDi2222
KEGGihsa:2222
UCSCiuc003wuh.4 human [P37268-1]

Organism-specific databases

CTDi2222
DisGeNETi2222
EuPathDBiHostDB:ENSG00000079459.12
GeneCardsiFDFT1
H-InvDBiHIX0168873
HGNCiHGNC:3629 FDFT1
HPAiHPA008874
MIMi184420 gene
neXtProtiNX_P37268
OpenTargetsiENSG00000079459
PharmGKBiPA28073
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1459 Eukaryota
COG1562 LUCA
GeneTreeiENSGT00390000016034
HOGENOMiHOG000186940
HOVERGENiHBG002370
InParanoidiP37268
KOiK00801
OMAiNGPNEKD
OrthoDBiEOG091G072P
PhylomeDBiP37268
TreeFamiTF105316

Enzyme and pathway databases

UniPathwayi
UPA00767;UER00751

BioCyciMetaCyc:HS01329-MONOMER
BRENDAi2.5.1.21 2681
ReactomeiR-HSA-191273 Cholesterol biosynthesis
R-HSA-1989781 PPARA activates gene expression
R-HSA-2426168 Activation of gene expression by SREBF (SREBP)
SABIO-RKiP37268

Miscellaneous databases

ChiTaRSiFDFT1 human
EvolutionaryTraceiP37268
GenomeRNAii2222
PROiPR:P37268
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000079459 Expressed in 237 organ(s), highest expression level in testis
CleanExiHS_FDFT1
ExpressionAtlasiP37268 baseline and differential
GenevisibleiP37268 HS

Family and domain databases

CDDicd00683 Trans_IPPS_HH, 1 hit
Gene3Di1.10.600.10, 1 hit
InterProiView protein in InterPro
IPR008949 Isoprenoid_synthase_dom_sf
IPR002060 Squ/phyt_synthse
IPR006449 Squal_synth-like
IPR019845 Squalene/phytoene_synthase_CS
IPR033904 Trans_IPPS_HH
SFLDiSFLDG01018 Squalene/Phytoene_Synthase_Lik, 1 hit
SUPFAMiSSF48576 SSF48576, 1 hit
TIGRFAMsiTIGR01559 squal_synth, 1 hit
PROSITEiView protein in PROSITE
PS01044 SQUALEN_PHYTOEN_SYN_1, 1 hit
PS01045 SQUALEN_PHYTOEN_SYN_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiFDFT_HUMAN
AccessioniPrimary (citable) accession number: P37268
Secondary accession number(s): B3KQ95
, B4DJE5, B4DT56, B7Z1J3, Q96GT0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: October 1, 1994
Last modified: November 7, 2018
This is version 197 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
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