P37268 (FDFT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Squalene synthase
Short name=SQS
Short name=SS
EC=2.5.1.21

Alternative name(s):
FPP:FPP farnesyltransferase
Farnesyl-diphosphate farnesyltransferase

Gene names

Name:

FDFT1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	417 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	2 farnesyl diphosphate + NAD(P)H = squalene + 2 diphosphate + NAD(P)+.
Cofactor	Magnesium.
Pathway	Terpene metabolism; lanosterol biosynthesis; lanosterol from farnesyl diphosphate: step 1/3.
Subunit structure	Monomer By similarity.
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein.
Sequence similarities	Belongs to the phytoene/squalene synthase family.

Ontologies

Keywords
Biological process	Cholesterol biosynthesis Cholesterol metabolism Isoprene biosynthesis Lipid biosynthesis Lipid metabolism Steroid biosynthesis Steroid metabolism Sterol biosynthesis Sterol metabolism
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Magnesium NADP
Molecular function	Oxidoreductase Transferase
Technical term	3D-structure Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological_process	cellular lipid metabolic process Traceable author statement. Source: Reactome cholesterol biosynthetic process Traceable author statement. Source: Reactome farnesyl diphosphate metabolic process Inferred from electronic annotation. Source: Compara isoprenoid biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	farnesyl-diphosphate farnesyltransferase activity Traceable author statement. Source: Reactome oxidoreductase activity Inferred from electronic annotation. Source: UniProtKB-KW squalene synthase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 417

417

Squalene synthase

PRO_0000067443

Regions

Transmembrane

284 – 304

21

Helical; Potential

Transmembrane

384 – 404

21

Helical; Potential

Natural variations

Natural variant

45

1

K → R Influences plasma cholesterol levels; associated with increased total cholesterol and non-high-density lipoprotein cholesterol. Ref.5 Ref.8
Corresponds to variant rs11549147 [ dbSNP | Ensembl ].

VAR_011786

Natural variant

392

1

L → P.
Corresponds to variant rs1804473 [ dbSNP | Ensembl ].

VAR_011787

Experimental info

Sequence conflict

353

1

D → N in AAB33404. Ref.4

Sequence conflict

402

1

T → A in CAA48896. Ref.3

Secondary structure

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417

Helix Strand Turn

Details...

Helix

38 – 51

14

Helix

52 – 54

3

Helix

55 – 59

5

Helix

65 – 84

20

Helix

90 – 103

14

Turn

117 – 119

3

Helix

120 – 123

4

Helix

125 – 134

10

Helix

137 – 156

20

Helix

157 – 159

3

Helix

165 – 175

11

Helix

177 – 189

13

Helix

195 – 199

5

Helix

201 – 218

18

Helix

220 – 225

6

Helix

233 – 236

4

Turn

237 – 239

3

Helix

243 – 247

5

Helix

249 – 251

3

Helix

252 – 267

16

Helix

270 – 278

9

Helix

283 – 303

21

Helix

307 – 310

4

Helix

318 – 327

10

Beta strand

328 – 330

3

Helix

331 – 346

16

Helix

356 – 368

13

Sequences

	Sequence		Length	Mass (Da)
	P37268 [UniParc]. Last modified October 1, 1994. Version 1. Checksum: D36CBC8382F827EC	FASTA	417	48,115
	10 20 30 40 50 60 MEFVKCLGHP EEFYNLVRFR IGGKRKVMPK MDQDSLSSSL KTCYKYLNQT SRSFAAVIQA 70 80 90 100 110 120 LDGEMRNAVC IFYLVLRALD TLEDDMTISV EKKVPLLHNF HSFLYQPDWR FMESKEKDRQ 130 140 150 160 170 180 VLEDFPTISL EFRNLAEKYQ TVIADICRRM GIGMAEFLDK HVTSEQEWDK YCHYVAGLVG 190 200 210 220 230 240 IGLSRLFSAS EFEDPLVGED TERANSMGLF LQKTNIIRDY LEDQQGGREF WPQEVWSRYV 250 260 270 280 290 300 KKLGDFAKPE NIDLAVQCLN ELITNALHHI PDVITYLSRL RNQSVFNFCA IPQVMAIATL 310 320 330 340 350 360 AACYNNQQVF KGAVKIRKGQ AVTLMMDATN MPAVKAIIYQ YMEEIYHRIP DSDPSSSKTR 370 380 390 400 410 QIISTIRTQN LPNCQLISRS HYSPIYLSFV MLLAALSWQY LTTLSQVTED YVQTGEH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Conservation between human and fungal squalene synthetases: similarities in structure, function, and regulation." Robinson G.W., Tsay Y.H., Kienzle B.K., Smith-Monroy C.A., Bishop R.W. Mol. Cell. Biol. 13:2706-2717(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Transcriptional regulation by lovastatin and 25-hydroxycholesterol in HepG2 cells and molecular cloning and expression of the cDNA for the human hepatic squalene synthase." Jiang G., McKenzie T.L., Conrad D.G., Shechter I. J. Biol. Chem. 268:12818-12824(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[3]	"Cloning, expression and characterisation of the cDNA encoding human hepatic squalene synthase, and its relationship to phytoene synthase." Summers C., Karst F., Charles A.D. Gene 136:185-192(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[4]	"Expression, purification, and characterization of the human squalene synthase: use of yeast and baculoviral systems." Soltis D.A., McMahon G., Caplan S.L., Dudas D.A., Chamberlin H.A., Vattay A., Dottavio D., Rucker M.L., Engstrom R.G., Cornell-Kennon S.A. Arch. Biochem. Biophys. 316:713-723(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[5]	"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], VARIANT ARG-45. Tissue: Lung, Muscle and Urinary bladder.
[6]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]	"Crystal structure of human squalene synthase. A key enzyme in cholesterol biosynthesis." Pandit J., Danley D.E., Schulte G.K., Mazzalupo S., Pauly T.A., Hayward C.M., Hamanaka E.S., Thompson J.F., Harwood H.J. Jr. J. Biol. Chem. 275:30610-30617(2000) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 39-370.
[8]	"K45R variant of squalene synthase increases total cholesterol levels in two study samples from a French Canadian population." Do R., Pare G., Montpetit A., Hudson T.J., Gaudet D., Engert J.C. Hum. Mutat. 29:689-694(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT ARG-45, ASSOCIATION WITH PLASMA CHOLESTEROL LEVELS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L06070 mRNA. Translation: AAA60582.1.
L06105 mRNA. Translation: AAA36645.1.
X69141 mRNA. Translation: CAA48896.1.
S76822 mRNA. Translation: AAB33404.1.
BC003573 mRNA. Translation: AAH03573.1.
BC009251 mRNA. Translation: AAH09251.1.
BC029641 mRNA. Translation: AAH29641.1.

IPI

IPI00020944.

PIR

A45998.
I38245.
I52090.

RefSeq

NP_004453.3. NM_004462.3.

UniGene

Hs.593928.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EZF	X-ray	2.15	A/B/C	35-370	[»]
3ASX	X-ray	2.00	A	31-370	[»]
3LEE	X-ray	3.20	A/B/C/D/E/F	31-370	[»]
3Q2Z	X-ray	2.00	A	31-370	[»]
3Q30	X-ray	2.00	A	31-370	[»]
3V66	X-ray	1.80	A	31-370	[»]
3VJ8	X-ray	1.52	A	31-370	[»]
3VJ9	X-ray	1.52	A	31-370	[»]
3VJA	X-ray	1.76	A/B	31-370	[»]
3VJB	X-ray	2.05	A/B/C/D/E/F	31-370	[»]
3VJC	X-ray	1.89	A/B/C/D/E/F	31-370	[»]

ProteinModelPortal

P37268.

ModBase

Search...

Protein-protein interaction databases

IntAct

P37268. 8 interactions.

MINT

MINT-1401726.

STRING

9606.ENSP00000220584.

PTM databases

PhosphoSite

P37268.

Polymorphism databases

DMDM

585126.

Proteomic databases

PaxDb

P37268.

PeptideAtlas

P37268.

PRIDE

P37268.

Protocols and materials databases

DNASU

2222.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000220584; ENSP00000220584; ENSG00000079459.

GeneID

2222.

KEGG

hsa:2222.

UCSC

uc003wuh.3. human.

Organism-specific databases

CTD

2222.

GeneCards

GC08P011653.

H-InvDB

HIX0168873.

HGNC

HGNC:3629. FDFT1.

HPA

HPA008874.

MIM

184420. gene.

neXtProt

NX_P37268.

PharmGKB

PA28073.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1562.

HOVERGEN

HBG002370.

InParanoid

P37268.

KO

K00801.

OMA

ELRHAVC.

OrthoDB

EOG4QVCC2.

PhylomeDB

P37268.

Enzyme and pathway databases

BioCyc

MetaCyc:HS01329-MONOMER.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P37268.

UniPathway

UPA00767; UER00751.

Gene expression databases

ArrayExpress

P37268.

Bgee

P37268.

CleanEx

HS_FDFT1.

Genevestigator

P37268.

GermOnline

ENSG00000079459. Homo sapiens.

Family and domain databases

Gene3D

1.10.600.10. 1 hit.

InterPro

IPR002060. Squ/phyt_synthse.
IPR006449. Squal_synth.
IPR019845. Squalene/phytoene_synthase_CS.
IPR008949. Terpenoid_synth.
[Graphical view]

Pfam

PF00494. SQS_PSY. 1 hit.
[Graphical view]

SUPFAM

SSF48576. Terpenoid_synth. 1 hit.

TIGRFAMs

TIGR01559. squal_synth. 1 hit.

PROSITE

PS01044. SQUALEN_PHYTOEN_SYN_1. 1 hit.
PS01045. SQUALEN_PHYTOEN_SYN_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P37268.

ChEMBL

CHEMBL3338.

ChiTaRS

FDFT1. human.

EvolutionaryTrace

P37268.

GenomeRNAi

2222.

NextBio

9013.

SOURCE

Search...

Entry information

Entry name

FDFT_HUMAN

Accession

Primary (citable) accession number: P37268
Secondary accession number(s): Q96GT0

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1994
Last sequence update:	October 1, 1994
Last modified:	May 1, 2013
This is version 142 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.