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Protein

Squalene synthase

Gene

FDFT1

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

Functioni

Caution

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

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
UniPathwayiUPA00767; 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

PTM databases

iPTMnetiP37268
PhosphoSitePlusiP37268
SwissPalmiP37268

Expressioni

Gene expression databases

BgeeiENSG00000079459
CleanExiHS_FDFT1
ExpressionAtlasiP37268 baseline and differential
GenevisibleiP37268 HS

Organism-specific databases

HPAiHPA008874

Interactioni

Subunit structurei

Monomer.By similarity

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi10851633 interactors.
IntActiP37268 17 interactors.
STRINGi9606.ENSP00000220584

Chemistry databases

BindingDBiP37268

Structurei

Secondary structure

1417
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi38 – 51Combined sources14
Helixi52 – 54Combined sources3
Helixi55 – 59Combined sources5
Helixi65 – 84Combined sources20
Helixi90 – 103Combined sources14
Turni117 – 119Combined sources3
Helixi120 – 123Combined sources4
Helixi125 – 134Combined sources10
Helixi137 – 156Combined sources20
Helixi157 – 159Combined sources3
Helixi165 – 175Combined sources11
Helixi177 – 189Combined sources13
Beta strandi191 – 193Combined sources3
Helixi195 – 199Combined sources5
Helixi201 – 218Combined sources18
Helixi220 – 225Combined sources6
Helixi233 – 236Combined sources4
Turni237 – 239Combined sources3
Helixi243 – 247Combined sources5
Helixi249 – 251Combined sources3
Helixi252 – 267Combined sources16
Helixi270 – 278Combined sources9
Helixi283 – 303Combined sources21
Helixi307 – 310Combined sources4
Helixi318 – 327Combined sources10
Beta strandi328 – 330Combined sources3
Helixi331 – 346Combined sources16
Helixi356 – 368Combined sources13

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...

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
OMAiFNFVAIP
OrthoDBiEOG091G072P
PhylomeDBiP37268
TreeFamiTF105316

Family and domain databases

CDDicd00683 Trans_IPPS_HH, 1 hit
Gene3Di1.10.600.101 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
PfamiView protein in Pfam
PF00494 SQS_PSY, 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

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

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 [P37268-2]
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

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: April 25, 2018
This is version 191 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