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Protein

Hydroxymethylglutaryl-CoA synthase, mitochondrial

Gene

HMGCS2

Organism
Sus scrofa (Pig)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at transcript 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

Pathway: (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), 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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei80 – 801SubstrateBy similarity
Active sitei132 – 1321Proton donor/acceptorPROSITE-ProRule annotation
Active sitei166 – 1661Acyl-thioester intermediatePROSITE-ProRule annotation
Binding sitei204 – 2041SubstrateBy similarity
Binding sitei258 – 2581SubstrateBy similarity
Active sitei301 – 3011Proton donor/acceptorPROSITE-ProRule annotation
Binding sitei380 – 3801SubstrateBy similarity

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

BRENDAi2.3.3.10. 6170.
ReactomeiREACT_339425. 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
OrganismiSus scrofa (Pig)
Taxonomic identifieri9823 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
ProteomesiUP000008227 Componenti: Chromosome 4

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 3737MitochondrionCuratedAdd
BLAST
Chaini38 – 508471Hydroxymethylglutaryl-CoA synthase, mitochondrialPRO_0000013485Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei52 – 521N6-succinyllysineBy similarity
Modified residuei243 – 2431N6-acetyllysineBy similarity
Modified residuei256 – 2561N6-acetyllysine; alternateBy similarity
Modified residuei256 – 2561N6-succinyllysine; alternateBy similarity
Modified residuei306 – 3061N6-acetyllysineBy similarity
Modified residuei310 – 3101N6-acetyllysine; alternateBy similarity
Modified residuei310 – 3101N6-succinyllysine; alternateBy similarity
Modified residuei333 – 3331N6-succinyllysineBy similarity
Modified residuei342 – 3421N6-acetyllysine; alternateBy similarity
Modified residuei342 – 3421N6-succinyllysine; alternateBy similarity
Modified residuei350 – 3501N6-acetyllysine; alternateBy similarity
Modified residuei350 – 3501N6-succinyllysine; alternateBy similarity
Modified residuei354 – 3541N6-acetyllysine; alternateBy similarity
Modified residuei354 – 3541N6-succinyllysine; alternateBy similarity
Modified residuei358 – 3581N6-acetyllysine; alternateBy similarity
Modified residuei358 – 3581N6-succinyllysine; alternateBy similarity
Modified residuei433 – 4331PhosphoserineBy similarity
Modified residuei437 – 4371N6-acetyllysineBy similarity
Modified residuei440 – 4401PhosphoserineBy similarity
Modified residuei473 – 4731N6-acetyllysine; alternateBy similarity
Modified residuei473 – 4731N6-succinyllysine; alternateBy similarity

Post-translational modificationi

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

Keywords - PTMi

Acetylation, Phosphoprotein

Expressioni

Gene expression databases

GenevisibleiO02734. SS.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000007162.

Structurei

3D structure databases

ProteinModelPortaliO02734.
SMRiO02734. Positions 53-505.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the HMG-CoA synthase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG3425.
GeneTreeiENSGT00390000006096.
HOGENOMiHOG000012351.
HOVERGENiHBG051912.
InParanoidiO02734.
KOiK01641.
OMAiRIQLPWD.
OrthoDBiEOG741Z1W.
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.
IPR016038. Thiolase-like_subgr.
[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.

O02734-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQRLLTPVRQ VLRVKRAMQE ASFMPPLLPP AAHQRFSTVP AVPVAKADTW
60 70 80 90 100
PKDVGILALE VYFPAQYVDQ TDLEKFDNVE AGRYTVGLGQ THMGFCSVQE
110 120 130 140 150
DINSLCLTVV QRLMERTQLP WDSVGWLEVG TETIIDKSKS VKTVLMELFQ
160 170 180 190 200
DSGNTDIEGI DTTNACYGGT ASLFNAANWV ESSAWDGRYA VVVCGDIAVY
210 220 230 240 250
PRGNSRPTGG AGAVAMLVGP EAPLALERGL RGTHMENAYD FYKPNATSEY
260 270 280 290 300
PLVDGKLSIQ CYLRALDRCY TLYRQKIEKQ WKQAGIERHF TLDDLQFMIF
310 320 330 340 350
HTPFCKLVQK SLARLMFSDF LLADSDTQSS LYKGLEAFRG QKLEDTYANK
360 370 380 390 400
DIEKAFQKAS LDLFNKKTKP SLYLSLHNGN MYTSSLYGCL ASLLSQCSAQ
410 420 430 440 450
DLAGSRIGAF SYGSGLAASF YSLRVSQDAS PGSPLEKLVS SVSDLPERLA
460 470 480 490 500
SRKRVSPEEF TEIMNQREQY YHKVNFTPPG DPNSLFPGTW YLERVDELYR

RKYARHLV
Length:508
Mass (Da):56,934
Last modified:July 1, 1997 - v1
Checksum:i5479DE6F70B3C0F6
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U90884 mRNA. Translation: AAC48727.1.
CR956647 Genomic DNA. Translation: CAN13229.1.
RefSeqiNP_999545.1. NM_214380.2.
UniGeneiSsc.14479.

Genome annotation databases

EnsembliENSSSCT00000007357; ENSSSCP00000007162; ENSSSCG00000006716.
GeneIDi397673.
KEGGissc:397673.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U90884 mRNA. Translation: AAC48727.1.
CR956647 Genomic DNA. Translation: CAN13229.1.
RefSeqiNP_999545.1. NM_214380.2.
UniGeneiSsc.14479.

3D structure databases

ProteinModelPortaliO02734.
SMRiO02734. Positions 53-505.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9823.ENSSSCP00000007162.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSSSCT00000007357; ENSSSCP00000007162; ENSSSCG00000006716.
GeneIDi397673.
KEGGissc:397673.

Organism-specific databases

CTDi3158.

Phylogenomic databases

eggNOGiCOG3425.
GeneTreeiENSGT00390000006096.
HOGENOMiHOG000012351.
HOVERGENiHBG051912.
InParanoidiO02734.
KOiK01641.
OMAiRIQLPWD.
OrthoDBiEOG741Z1W.
TreeFamiTF105361.

Enzyme and pathway databases

UniPathwayiUPA00058; UER00102.
BRENDAi2.3.3.10. 6170.
ReactomeiREACT_339425. Synthesis of Ketone Bodies.

Gene expression databases

GenevisibleiO02734. SS.

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.
IPR016038. Thiolase-like_subgr.
[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...

Publicationsi

« Hide 'large scale' publications
  1. "Gene expression of mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase in a poorly ketogenic mammal: effect of starvation during the neonatal period of the piglet."
    Adams S.H., Alho C.S., Asins G., Hegardt F.G., Marrero P.F.
    Biochem. J. 324:65-73(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Liver.
  2. Porcine genome sequencing project
    Submitted (MAY-2007) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].

Entry informationi

Entry nameiHMCS2_PIG
AccessioniPrimary (citable) accession number: O02734
Secondary accession number(s): A5GFY7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: July 1, 1997
Last modified: June 24, 2015
This is version 107 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

External Data

Dasty 3

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 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.