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Protein

Hydroxymethylglutaryl-CoA synthase, cytoplasmic

Gene

HMGCS1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

This enzyme condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is the substrate for HMG-CoA reductase.

Catalytic activityi

Acetyl-CoA + H2O + acetoacetyl-CoA = (S)-3-hydroxy-3-methylglutaryl-CoA + CoA.PROSITE-ProRule annotation

Pathwayi: (R)-mevalonate biosynthesis

This protein is involved in step 2 of the subpathway that synthesizes (R)-mevalonate from acetyl-CoA.
Proteins known to be involved in the 3 steps of the subpathway in this organism are:
  1. no protein annotated in this organism
  2. Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1), Hydroxymethylglutaryl-CoA synthase, mitochondrial (HMGCS2)
  3. 3-hydroxy-3-methylglutaryl coenzyme A reductase, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), 3-hydroxy-3-methylglutaryl coenzyme A reductase
This subpathway is part of the pathway (R)-mevalonate biosynthesis, which is itself part of Metabolic intermediate biosynthesis.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes (R)-mevalonate from acetyl-CoA, the pathway (R)-mevalonate biosynthesis and in Metabolic intermediate biosynthesis.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei95Proton donor/acceptorPROSITE-ProRule annotation1
Active sitei129Acyl-thioester intermediate1
Active sitei264Proton donor/acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

Cholesterol biosynthesis, Cholesterol metabolism, Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis, Steroid metabolism, Sterol biosynthesis, Sterol metabolism

Enzyme and pathway databases

BioCyciMetaCyc:ENSG00000112972-MONOMER.
ZFISH:ENSG00000112972-MONOMER.
BRENDAi2.3.3.10. 2681.
ReactomeiR-HSA-191273. Cholesterol biosynthesis.
R-HSA-1989781. PPARA activates gene expression.
R-HSA-2426168. Activation of gene expression by SREBF (SREBP).
UniPathwayiUPA00058; UER00102.

Chemistry databases

SwissLipidsiSLP:000000724.

Names & Taxonomyi

Protein namesi
Recommended name:
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (EC:2.3.3.10)
Short name:
HMG-CoA synthase
Alternative name(s):
3-hydroxy-3-methylglutaryl coenzyme A synthase
Gene namesi
Name:HMGCS1
Synonyms:HMGCS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:5007. HMGCS1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi129C → A or S: Loss of activity. 1 Publication1

Organism-specific databases

DisGeNETi3157.
OpenTargetsiENSG00000112972.
PharmGKBiPA29337.

Chemistry databases

GuidetoPHARMACOLOGYi638.

Polymorphism and mutation databases

BioMutaiHMGCS1.
DMDMi1708239.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002137471 – 520Hydroxymethylglutaryl-CoA synthase, cytoplasmicAdd BLAST520

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei4PhosphoserineCombined sources1
Modified residuei46N6-acetyllysineCombined sources1
Modified residuei273N6-acetyllysineCombined sources1
Modified residuei476PhosphothreonineCombined sources1
Modified residuei495PhosphoserineCombined sources1
Modified residuei516PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ01581.
MaxQBiQ01581.
PaxDbiQ01581.
PeptideAtlasiQ01581.
PRIDEiQ01581.

PTM databases

iPTMnetiQ01581.
PhosphoSitePlusiQ01581.
SwissPalmiQ01581.

Expressioni

Gene expression databases

BgeeiENSG00000112972.
CleanExiHS_HMGCS1.
ExpressionAtlasiQ01581. baseline and differential.
GenevisibleiQ01581. HS.

Organism-specific databases

HPAiCAB032907.
HPA036913.
HPA036914.

Interactioni

Protein-protein interaction databases

BioGridi109400. 31 interactors.
IntActiQ01581. 2 interactors.
STRINGi9606.ENSP00000322706.

Structurei

Secondary structure

1520
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi18 – 25Combined sources8
Beta strandi28 – 32Combined sources5
Helixi33 – 40Combined sources8
Helixi46 – 51Combined sources6
Beta strandi55 – 57Combined sources3
Helixi65 – 79Combined sources15
Helixi84 – 86Combined sources3
Beta strandi87 – 93Combined sources7
Beta strandi100 – 102Combined sources3
Helixi104 – 108Combined sources5
Helixi109 – 111Combined sources3
Turni112 – 116Combined sources5
Beta strandi124 – 127Combined sources4
Helixi128 – 130Combined sources3
Helixi131 – 143Combined sources13
Beta strandi152 – 161Combined sources10
Helixi169 – 171Combined sources3
Beta strandi173 – 184Combined sources12
Beta strandi186 – 189Combined sources4
Beta strandi195 – 198Combined sources4
Beta strandi203 – 205Combined sources3
Helixi218 – 247Combined sources30
Helixi255 – 257Combined sources3
Beta strandi259 – 263Combined sources5
Helixi268 – 285Combined sources18
Helixi289 – 291Combined sources3
Helixi293 – 295Combined sources3
Helixi299 – 301Combined sources3
Helixi306 – 308Combined sources3
Helixi313 – 322Combined sources10
Helixi324 – 330Combined sources7
Helixi333 – 335Combined sources3
Helixi336 – 341Combined sources6
Helixi345 – 347Combined sources3
Helixi348 – 359Combined sources12
Helixi362 – 365Combined sources4
Beta strandi369 – 376Combined sources8
Turni377 – 379Combined sources3
Beta strandi380 – 388Combined sources9
Helixi397 – 403Combined sources7
Turni404 – 407Combined sources4
Helixi408 – 413Combined sources6
Beta strandi415 – 417Combined sources3
Helixi420 – 433Combined sources14
Beta strandi453 – 458Combined sources6
Beta strandi464 – 468Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2P8UX-ray2.00A/B16-470[»]
ProteinModelPortaliQ01581.
SMRiQ01581.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ01581.

Family & Domainsi

Sequence similaritiesi

Belongs to the HMG-CoA synthase family.Curated

Phylogenomic databases

eggNOGiKOG1393. Eukaryota.
COG3425. LUCA.
GeneTreeiENSGT00390000006096.
HOGENOMiHOG000012351.
HOVERGENiHBG051912.
InParanoidiQ01581.
KOiK01641.
OMAiQRCISEE.
OrthoDBiEOG091G0791.
PhylomeDBiQ01581.
TreeFamiTF105361.

Family and domain databases

Gene3Di3.40.47.10. 1 hit.
InterProiIPR000590. HMG_CoA_synt_AS.
IPR013746. HMG_CoA_synt_C_dom.
IPR013528. HMG_CoA_synth_N.
IPR010122. HMG_CoA_synthase_euk.
IPR016039. Thiolase-like.
[Graphical view]
PfamiPF08540. HMG_CoA_synt_C. 1 hit.
PF01154. HMG_CoA_synt_N. 1 hit.
[Graphical view]
SUPFAMiSSF53901. SSF53901. 3 hits.
TIGRFAMsiTIGR01833. HMG-CoA-S_euk. 1 hit.
PROSITEiPS01226. HMG_COA_SYNTHASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q01581-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPGSLPLNAE ACWPKDVGIV ALEIYFPSQY VDQAELEKYD GVDAGKYTIG
60 70 80 90 100
LGQAKMGFCT DREDINSLCM TVVQNLMERN NLSYDCIGRL EVGTETIIDK
110 120 130 140 150
SKSVKTNLMQ LFEESGNTDI EGIDTTNACY GGTAAVFNAV NWIESSSWDG
160 170 180 190 200
RYALVVAGDI AVYATGNARP TGGVGAVALL IGPNAPLIFE RGLRGTHMQH
210 220 230 240 250
AYDFYKPDML SEYPIVDGKL SIQCYLSALD RCYSVYCKKI HAQWQKEGND
260 270 280 290 300
KDFTLNDFGF MIFHSPYCKL VQKSLARMLL NDFLNDQNRD KNSIYSGLEA
310 320 330 340 350
FGDVKLEDTY FDRDVEKAFM KASSELFSQK TKASLLVSNQ NGNMYTSSVY
360 370 380 390 400
GSLASVLAQY SPQQLAGKRI GVFSYGSGLA ATLYSLKVTQ DATPGSALDK
410 420 430 440 450
ITASLCDLKS RLDSRTGVAP DVFAENMKLR EDTHHLVNYI PQGSIDSLFE
460 470 480 490 500
GTWYLVRVDE KHRRTYARRP TPNDDTLDEG VGLVHSNIAT EHIPSPAKKV
510 520
PRLPATAAEP EAAVISNGEH
Length:520
Mass (Da):57,294
Last modified:October 1, 1996 - v2
Checksum:iC669212BF86CFF9B
GO

Sequence cautioni

The sequence AAH00297 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti248G → A in CAA47061 (PubMed:1358203).Curated1
Sequence conflicti251K → N in CAA47061 (PubMed:1358203).Curated1
Sequence conflicti299E → K in CAA47061 (PubMed:1358203).Curated1
Sequence conflicti364Q → H in CAA47061 (PubMed:1358203).Curated1
Sequence conflicti420P → Q in CAA47061 (PubMed:1358203).Curated1
Sequence conflicti519 – 520EH → VW in CAA47061 (PubMed:1358203).Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X66435 mRNA. Translation: CAA47061.1.
L25798 mRNA. Translation: AAA62411.1.
BT007302 mRNA. Translation: AAP35966.1.
AK315593 mRNA. Translation: BAG37965.1.
CH471119 Genomic DNA. Translation: EAW56054.1.
BC000297 mRNA. Translation: AAH00297.2. Different initiation.
CCDSiCCDS34154.1.
PIRiS27197.
S45497.
RefSeqiNP_001091742.1. NM_001098272.2.
NP_001311148.1. NM_001324219.1.
NP_001311149.1. NM_001324220.1.
NP_001311151.1. NM_001324222.1.
NP_001311152.1. NM_001324223.1.
NP_001311153.1. NM_001324224.1.
NP_001317592.1. NM_001330663.1.
NP_002121.4. NM_002130.7.
UniGeneiHs.397729.
Hs.741287.

Genome annotation databases

EnsembliENST00000325110; ENSP00000322706; ENSG00000112972.
ENST00000433297; ENSP00000399402; ENSG00000112972.
GeneIDi3157.
KEGGihsa:3157.
UCSCiuc003jnq.6. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X66435 mRNA. Translation: CAA47061.1.
L25798 mRNA. Translation: AAA62411.1.
BT007302 mRNA. Translation: AAP35966.1.
AK315593 mRNA. Translation: BAG37965.1.
CH471119 Genomic DNA. Translation: EAW56054.1.
BC000297 mRNA. Translation: AAH00297.2. Different initiation.
CCDSiCCDS34154.1.
PIRiS27197.
S45497.
RefSeqiNP_001091742.1. NM_001098272.2.
NP_001311148.1. NM_001324219.1.
NP_001311149.1. NM_001324220.1.
NP_001311151.1. NM_001324222.1.
NP_001311152.1. NM_001324223.1.
NP_001311153.1. NM_001324224.1.
NP_001317592.1. NM_001330663.1.
NP_002121.4. NM_002130.7.
UniGeneiHs.397729.
Hs.741287.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2P8UX-ray2.00A/B16-470[»]
ProteinModelPortaliQ01581.
SMRiQ01581.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109400. 31 interactors.
IntActiQ01581. 2 interactors.
STRINGi9606.ENSP00000322706.

Chemistry databases

GuidetoPHARMACOLOGYi638.
SwissLipidsiSLP:000000724.

PTM databases

iPTMnetiQ01581.
PhosphoSitePlusiQ01581.
SwissPalmiQ01581.

Polymorphism and mutation databases

BioMutaiHMGCS1.
DMDMi1708239.

Proteomic databases

EPDiQ01581.
MaxQBiQ01581.
PaxDbiQ01581.
PeptideAtlasiQ01581.
PRIDEiQ01581.

Protocols and materials databases

DNASUi3157.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000325110; ENSP00000322706; ENSG00000112972.
ENST00000433297; ENSP00000399402; ENSG00000112972.
GeneIDi3157.
KEGGihsa:3157.
UCSCiuc003jnq.6. human.

Organism-specific databases

CTDi3157.
DisGeNETi3157.
GeneCardsiHMGCS1.
HGNCiHGNC:5007. HMGCS1.
HPAiCAB032907.
HPA036913.
HPA036914.
MIMi142940. gene.
neXtProtiNX_Q01581.
OpenTargetsiENSG00000112972.
PharmGKBiPA29337.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1393. Eukaryota.
COG3425. LUCA.
GeneTreeiENSGT00390000006096.
HOGENOMiHOG000012351.
HOVERGENiHBG051912.
InParanoidiQ01581.
KOiK01641.
OMAiQRCISEE.
OrthoDBiEOG091G0791.
PhylomeDBiQ01581.
TreeFamiTF105361.

Enzyme and pathway databases

UniPathwayiUPA00058; UER00102.
BioCyciMetaCyc:ENSG00000112972-MONOMER.
ZFISH:ENSG00000112972-MONOMER.
BRENDAi2.3.3.10. 2681.
ReactomeiR-HSA-191273. Cholesterol biosynthesis.
R-HSA-1989781. PPARA activates gene expression.
R-HSA-2426168. Activation of gene expression by SREBF (SREBP).

Miscellaneous databases

ChiTaRSiHMGCS1. human.
EvolutionaryTraceiQ01581.
GenomeRNAii3157.
PROiQ01581.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000112972.
CleanExiHS_HMGCS1.
ExpressionAtlasiQ01581. baseline and differential.
GenevisibleiQ01581. HS.

Family and domain databases

Gene3Di3.40.47.10. 1 hit.
InterProiIPR000590. HMG_CoA_synt_AS.
IPR013746. HMG_CoA_synt_C_dom.
IPR013528. HMG_CoA_synth_N.
IPR010122. HMG_CoA_synthase_euk.
IPR016039. Thiolase-like.
[Graphical view]
PfamiPF08540. HMG_CoA_synt_C. 1 hit.
PF01154. HMG_CoA_synt_N. 1 hit.
[Graphical view]
SUPFAMiSSF53901. SSF53901. 3 hits.
TIGRFAMsiTIGR01833. HMG-CoA-S_euk. 1 hit.
PROSITEiPS01226. HMG_COA_SYNTHASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHMCS1_HUMAN
AccessioniPrimary (citable) accession number: Q01581
Secondary accession number(s): B2RDL8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: October 1, 1996
Last modified: November 30, 2016
This is version 183 of the entry and version 2 of the sequence. [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. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. 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.