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Protein

Hydroxymethylglutaryl-CoA synthase, mitochondrial

Gene

HMGCS2

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 4 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.By similarity

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, mitochondrial (HMGCS2)
  3. 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), 3-hydroxy-3-methylglutaryl coenzyme A reductase (hmgcr)
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
Binding sitei80SubstrateBy similarity1
Active sitei132Proton donor/acceptorPROSITE-ProRule annotation1
Active sitei166Acyl-thioester intermediatePROSITE-ProRule annotation1
Binding sitei204SubstrateBy similarity1
Binding sitei258SubstrateBy similarity1
Active sitei301Proton donor/acceptorPROSITE-ProRule annotation1
Binding sitei380SubstrateBy similarity1

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

ReactomeiR-BTA-77111. Synthesis of Ketone Bodies.
UniPathwayiUPA00058; UER00102.

Names & Taxonomyi

Protein namesi
Recommended name:
Hydroxymethylglutaryl-CoA synthase, mitochondrial (EC:2.3.3.10)
Short name:
HMG-CoA synthase
Alternative name(s):
3-hydroxy-3-methylglutaryl coenzyme A synthase
Gene namesi
Name:HMGCS2
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 3

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 37MitochondrionCuratedAdd BLAST37
ChainiPRO_000023627638 – 508Hydroxymethylglutaryl-CoA synthase, mitochondrialAdd BLAST471

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei52N6-succinyllysineBy similarity1
Modified residuei243N6-acetyllysineBy similarity1
Modified residuei256N6-acetyllysine; alternateBy similarity1
Modified residuei256N6-succinyllysine; alternateBy similarity1
Modified residuei306N6-acetyllysineBy similarity1
Modified residuei310N6-acetyllysine; alternateBy similarity1
Modified residuei310N6-succinyllysine; alternate1 Publication1
Modified residuei333N6-succinyllysineBy similarity1
Modified residuei342N6-acetyllysine; alternateBy similarity1
Modified residuei342N6-succinyllysine; alternateBy similarity1
Modified residuei350N6-acetyllysine; alternateBy similarity1
Modified residuei350N6-succinyllysine; alternateBy similarity1
Modified residuei354N6-acetyllysine; alternateBy similarity1
Modified residuei354N6-succinyllysine; alternateBy similarity1
Modified residuei358N6-acetyllysine; alternateBy similarity1
Modified residuei358N6-succinyllysine; alternateBy similarity1
Modified residuei433PhosphoserineBy similarity1
Modified residuei437N6-acetyllysineBy similarity1
Modified residuei440PhosphoserineBy similarity1
Modified residuei447N6-acetyllysine; alternateBy similarity1
Modified residuei447N6-succinyllysine; alternateBy similarity1
Modified residuei456PhosphoserineBy similarity1
Modified residuei473N6-acetyllysine; alternateBy similarity1
Modified residuei473N6-succinyllysine; alternateBy similarity1
Modified residuei477PhosphoserineBy similarity1

Post-translational modificationi

Succinylated. Desuccinylated by SIRT5. Succinylation, at least at Lys-310, inhibits the enzymatic activity.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiQ2KIE6.
PeptideAtlasiQ2KIE6.
PRIDEiQ2KIE6.

Expressioni

Gene expression databases

BgeeiENSBTAG00000003898.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000005088.

Structurei

3D structure databases

ProteinModelPortaliQ2KIE6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the HMG-CoA synthase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG1393. Eukaryota.
COG3425. LUCA.
GeneTreeiENSGT00390000006096.
HOGENOMiHOG000012351.
HOVERGENiHBG051912.
InParanoidiQ2KIE6.
KOiK01641.
OMAiQWKQAGS.
OrthoDBiEOG091G0791.
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.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q2KIE6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQRLLTPVRQ VLQVKRVMQE ASLLPARLLP AAHPSFSTVP AVPLAKTDTW
60 70 80 90 100
PKDVGILAME VYFPAQYVDQ TELEKFNKVE AGRYTVGLGQ TQMGFCSVQE
110 120 130 140 150
DVNSLCLTVV QQLMERTQLP WDSVGRLEVG TETIIDKSKA VKTVLMELFQ
160 170 180 190 200
DSGNTDIEGI DTTNACYGGT ASLFNAANWM ESSSWDGRYA LVVCGDIAVY
210 220 230 240 250
PSGNARPTGG AGAVAMLVGP EAPLVLERGL RGTHMENVYD FYKPDVTSEY
260 270 280 290 300
PLVDGKLSIQ CYLRALDKCY AFYRQKIEKQ WKQAGIDRPF TLDDVQYMIF
310 320 330 340 350
HTPFCKLVQK SLARLMFNDF LLASGDTQTG IYKGLEAFRG LKLEDTYTNK
360 370 380 390 400
DVDKAFLKAS LNMFNKKTKN SLYLSTYNGN MYTSSLYGCL ASLLAHHSAQ
410 420 430 440 450
DLAGSRIGAF SYGSGLAASF FSFRVSQDAS PGSPLEKLVS STSDLQKRLA
460 470 480 490 500
SRKRVSPEEF TEIMNQREQY YHKMNFSPPG DKNSLFPGTW YLERVDELYR

RKYARRPV
Length:508
Mass (Da):56,895
Last modified:March 7, 2006 - v1
Checksum:i12F31AAFBAE986BF
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC112666 mRNA. Translation: AAI12667.1.
RefSeqiNP_001039348.1. NM_001045883.1.
XP_010801406.1. XM_010803104.2.
UniGeneiBt.9689.

Genome annotation databases

EnsembliENSBTAT00000005088; ENSBTAP00000005088; ENSBTAG00000003898.
GeneIDi503684.
KEGGibta:503684.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC112666 mRNA. Translation: AAI12667.1.
RefSeqiNP_001039348.1. NM_001045883.1.
XP_010801406.1. XM_010803104.2.
UniGeneiBt.9689.

3D structure databases

ProteinModelPortaliQ2KIE6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000005088.

Proteomic databases

PaxDbiQ2KIE6.
PeptideAtlasiQ2KIE6.
PRIDEiQ2KIE6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000005088; ENSBTAP00000005088; ENSBTAG00000003898.
GeneIDi503684.
KEGGibta:503684.

Organism-specific databases

CTDi3158.

Phylogenomic databases

eggNOGiKOG1393. Eukaryota.
COG3425. LUCA.
GeneTreeiENSGT00390000006096.
HOGENOMiHOG000012351.
HOVERGENiHBG051912.
InParanoidiQ2KIE6.
KOiK01641.
OMAiQWKQAGS.
OrthoDBiEOG091G0791.
TreeFamiTF105361.

Enzyme and pathway databases

UniPathwayiUPA00058; UER00102.
ReactomeiR-BTA-77111. Synthesis of Ketone Bodies.

Gene expression databases

BgeeiENSBTAG00000003898.

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 nameiHMCS2_BOVIN
AccessioniPrimary (citable) accession number: Q2KIE6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: March 7, 2006
Last modified: October 5, 2016
This is version 81 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. 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.