Top Level Name

  ⌊ Superfamily (core) Isoprenoid Synthase Type I

    ⌊ Subgroup Squalene/Phytoene Synthase Like

     ⌊ Family squalene synthase

  ⌊ FunctionalDomain squalene synthase (ID 132135)

Superfamily Assignment Evidence Code(s) ISS
Family Assignment Evidence Code ISS
This entry was last updated onJune 10, 2017

References to Other Databases

Genbank

SpeciesGIAccessionProteome
Homo sapiens Taxon ID: 9606 913349 AAB33404.1 (Genbank) PRP URP

Uniprot

Protein NameAccessionEC Number Identifier
Squalene synthase P37268 2.5.1.21 FDFT_HUMAN (Swiss-Prot)

Sequence

Length of Enzyme (full-length): 417 | Length of Functional Domain: 369

1       10        20        30        40        50        60

MEFVKCLGHPEEFYNLVRFRIGGKRKVMPKMDQDSLSSSLKTCYRYLNQTSRSFAAVIQA
LDGEMRNAVCIFYLVLRALDTLEDDMTISVEKKVPLLHNFHSFLYQPDWRFMESKEKDRQ
VLEDFPTISLEFRNLAEKYQTVIADICRRMGIGMAEFLDKHVTSEQEWDKYCHYVAGLVG
IGLSRLFSASEFEDPLVGEDTERANSMGLFLQKTNIIRDYLEDQQGGREFWPQEVWSRYV
KKLGDFAKPENIDLAVQCLNELITNALHHIPDVITYLSRLRNQSVFNFCAIPQVMAIATL
AACYNNQQVFKGAVKIRKGQAVTLMMDATNMPAVKAIIYQYMEEIYHRIPDSNPSSSKTR
QIISTIRTQNLPNCQLISRSHYSPIYLSFVMLLAALSWQYLTTLSQVTEDYVQTGEH
This shows the full-length sequence of the enzyme. The region of the functional domain is highlighted in black letters, while the residual residues are shown in grey. The Superfamily domain, when present, is shown using underlining. In many cases the functional domain is the full-length sequence.
Conserved catalytic residues (as determined by automated alignment to family, subgroup, or superfamily HMMs) are shown with teal highlighting . Conserved catalytic residues which do not matched the Conserved Alignment Residue are shown with maroon highlighting . Information regarding their function can be found in the Conserved Residues section below.
FASTA formatted full-length sequence.
BLAST this sequence against SFLD.
Scan SFLD-HMMs with this sequence.

Conserved Residues
Superfamily CAR This EFD conserves 3/3 Superfamily-specific Conserved Alignment Residues.
Position Amino Acid Location Function Role Evidence Code Reference
80 Asp (D) side chain None --
84 Asp (D) side chain None --
215 Asn (N) side chain None --
Subgroup CAR This EFD conserves 7/7 Subgroup-specific Conserved Alignment Residues.
Position Amino Acid Location Function Role Evidence Code Reference
77 Arg (R) side chain None -- ICS PubMed:21098670
80 Asp (D) side chain Metal ligand metal ligand -- binding ICS
84 Asp (D) side chain Metal ligand metal ligand -- binding ICS
171 Tyr (Y) side chain facilitates removal of Mg2+ PPi product complex formed in both half-reactions increase electrophilicity -- spectator IME PubMed:21098670
215 Asn (N) side chain Metal ligand metal ligand -- binding ICS
219 Asp (D) side chain Metal ligand metal ligand -- binding ICS
223 Asp (D) side chain None -- IME PubMed:21098670
Family CAR This EFD conserves 9/9 Family-specific Conserved Alignment Residues.
Position Amino Acid Location Function Role Evidence Code Reference
77 Arg (R) side chain None -- ISS
80 Asp (D) side chain binds diphosphate moiety of substrate via Mg2+ metal ligand -- binding ISS PubMed:10896663
84 Asp (D) side chain binds diphosphate moiety of substrate via Mg2+ metal ligand -- binding ISS PubMed:10896663
171 Tyr (Y) side chain essential for catalysis--most likely for first reaction -- IME PubMed:9575210
218 Arg (R) side chain stabilizes diphosphate leaving group electrostatic stabiliser -- spectator ICS PubMed:10896663
219 Asp (D) side chain binds diphosphate moiety of substrate via Mg2+ metal ligand -- binding IME PubMed:9575210
223 Asp (D) side chain binds diphosphate moiety of substrate via Mg2+ metal ligand -- binding IME PubMed:9575210
228 Arg (R) side chain stabilizes diphosphate leaving group electrostatic stabiliser -- spectator ICS PubMed:10896663
288 Phe (F) side chain essential for catalysis--most likely for second reaction -- IME PubMed:9575210

Structures

PDB ID Title Molecule Name Number of
EFDs		 Resolution (Å) Mutant? Het group Links
3Q2Z Human Squalene Synthase In Complex With N-[(3R,5S)-7-Chloro-5-(2,3-Dimethoxyphenyl)-1-Neopentyl-2-Oxo-1,2,3,5-Tetrahydro-4,1-Benzoxazepine-3-Acetyl]-L-Aspartic Acid Squalene Synthase 37 2.0 Phosphate Ion • N-{[(3R,5S)-7-Chloro-5-(2,3-Dimethoxyphenyl)-1-(2,2-Dimethylpropyl)-2-Oxo-1,2,3,5-Tetrahydro-4,1-Benzoxazepin-3-Yl]Acetyl}-L-Aspartic Acid CSA • PDB • PDBSum
3Q30 Human Squalene Synthase In Complex With (2R,3R)-2-Carboxymethoxy-3-[5-(2-Naphthalenyl)Pentyl]Aminocarbonyl-3-[5-(2-Naphthalenyl) Pentyloxy]Propionic Acid Squalene Synthase 37 2.0 Magnesium Ion
(2 more ⇓) 		CSA • PDB • PDBSum
3ASX Human Squalene Synthase In Complex With 1-{4-[{4-Chloro-2-[(2-Chlorophenyl)(Hydroxy)Methyl]Phenyl}(2,2-Dimethylpropyl)Amino]-4-Oxobutanoyl}Piperidine-3-Carboxylic Acid Squalene Synthase 37 2.0 Phosphate Ion • (3R)-1-{4-[{4-Chloro-2-[(S)-(2-Chlorophenyl)(Hydroxy) Methyl]Phenyl}(2,2-Dimethylpropyl)Amino]-4-Oxobutanoyl}Piperidine-3-Carboxylic Acid CSA • PDB • PDBSum
3LEE Crystal Structure Of The Human Squalene Synthase Complexed With Bph-652 Squalene Synthetase 37 3.2 (1R)-4-(3-Phenoxyphenyl)-1-Phosphonobutane-1-Sulfonic Acid • Magnesium Ion CSA • PDB • PDBSum
3V66 Human Squalene Synthase In Complex With 2-(1-{2-[(4R,6S)-8-Chloro-6-(2,3-Dimethoxyphenyl)-4H,6H-Pyrrolo[1,2-A][4,1]Benzoxazepin-4-Yl]Acetyl}-4-Piperidinyl)Acetic Acid Squalene Synthase 37 1.8 Phosphate Ion • (1-{[(4R,6S)-8-Chloro-6-(2,3-Dimethoxyphenyl)-4H,6H-Pyrrolo[1,2-A][4,1]Benzoxazepin-4-Yl]Acetyl}Piperidin-4-Yl)Acetic Acid CSA • PDB • PDBSum
3VJ9 Crystal Structure Of The Human Squalene Synthase Squalene Synthase 37 1.52 Calcium Ion • Nickel (Ii) Ion CSA • PDB • PDBSum
3VJ8 Crystal Structure Of The Human Squalene Synthase Squalene Synthase 37 1.52 CSA • PDB • PDBSum
3VJC Crystal Structure Of The Human Squalene Synthase In Complex With Zaragozic Acid A Squalene Synthase 37 1.89 Zaragozic Acid A
(2 more ⇓) 		CSA • PDB • PDBSum
3VJB Crystal Structure Of The Human Squalene Synthase Squalene Synthase 37 2.05 CSA • PDB • PDBSum
3VJA Crystal Structure Of The Human Squalene Synthase Squalene Synthase 37 1.76 Nickel (Ii) Ion CSA • PDB • PDBSum
3WEH Crystal Structure Of The Human Squalene Synthase In Complex With Presqualene Pyrophosphate Squalene Synthase 37 1.87 Magnesium Ion • {(1R,2R,3R)-2-[(3E)-4,8-Dimethylnona-3,7-Dien-1-Yl]-2-Methyl-3-[(1E,5E)-2,6,10-Trimethylundeca-1,5,9-Trien-1-Yl]Cyclopropyl}Methyl Trihydrogen Diphosphate CSA • PDB • PDBSum
3WEG Crystal Structure Of The Human Squalene Synthase In Complex With Farnesyl Thiopyrophosphate And Magnesium Ion Squalene Synthase 37 1.75 Magnesium Ion • S-[(2E,6E)-3,7,11-Trimethyldodeca-2,6,10-Trienyl] Trihydrogen Thiodiphosphate CSA • PDB • PDBSum
3WEF Crystal Structure Of The Human Squalene Synthase In Complex With Farnesyl Thiopyrophosphate Squalene Synthase 37 2.35 S-[(2E,6E)-3,7,11-Trimethyldodeca-2,6,10-Trienyl] Trihydrogen Thiodiphosphate CSA • PDB • PDBSum
1EZF Crystal Structure Of Human Squalene Synthase Farnesyl-Diphosphate Farnesyltransferase 37 2.15 Yes N-{2-[Trans-7-Chloro-1-(2,2-Dimethyl-Propyl) -5-Naphthalen-1-Yl-2-Oxo-1,2,3,5-Tetrahydro-Benzo[E] [1, 4]Oxazepin-3-Yl]-Acetyl}-Aspartic Acid CSA • PDB • PDBSum
3WEK Crystal Structure Of The Human Squalene Synthase F288L Mutant In Complex With Presqualene Pyrophosphate Squalene Synthase 37 1.85 Yes Magnesium Ion • {(1R,2R,3R)-2-[(3E)-4,8-Dimethylnona-3,7-Dien-1-Yl]-2-Methyl-3-[(1E,5E)-2,6,10-Trimethylundeca-1,5,9-Trien-1-Yl]Cyclopropyl}Methyl Trihydrogen Diphosphate CSA • PDB • PDBSum
3WEI Crystal Structure Of The Human Squalene Synthase Y73A Mutant In Complex With Presqualene Pyrophosphate Squalene Synthase 37 1.79 Yes Manganese (Ii) Ion • {(1R,2R,3R)-2-[(3E)-4,8-Dimethylnona-3,7-Dien-1-Yl]-2-Methyl-3-[(1E,5E)-2,6,10-Trimethylundeca-1,5,9-Trien-1-Yl]Cyclopropyl}Methyl Trihydrogen Diphosphate CSA • PDB • PDBSum
3WEJ Crystal Structure Of The Human Squalene Synthase F288A Mutant In Complex With Presqualene Pyrophosphate Squalene Synthase 37 2.0 Yes Magnesium Ion • {(1R,2R,3R)-2-[(3E)-4,8-Dimethylnona-3,7-Dien-1-Yl]-2-Methyl-3-[(1E,5E)-2,6,10-Trimethylundeca-1,5,9-Trien-1-Yl]Cyclopropyl}Methyl Trihydrogen Diphosphate CSA • PDB • PDBSum
Percent identity and alignment length from the BLAST match of the Functional Domain sequence to the PDB sequence.
"Yes" indicates that a GI associated with this Functional Domain was mapped to the PDB ID via UniProtKB.

Curation History
Time Change Annotation Old Value New Value
April 30, 2014, 11:48 a.m. update curation agent sbrown setDomainBoundaries.py
update domain start position 38 2
EC number assigned by UniProtKB accession ID.