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Entry version 193 (23 Feb 2022)
Sequence version 1 (01 Oct 1996)
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Protein

Hydroxymethylglutaryl-CoA synthase, mitochondrial

Gene

HMGCS2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Catalyzes the first irreversible step in ketogenesis, condensing acetyl-CoA to acetoacetyl-CoA to form HMG-CoA, which is converted by HMG-CoA reductase (HMGCR) into mevalonate.

3 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the 'Function' section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

  1. KM=87.3 µM for acetyl-CoA1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: (R)-mevalonate biosynthesis

This protein is involved in step 2 of the subpathway that synthesizes (R)-mevalonate from acetyl-CoA.Curated 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
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei80Substrate1 Publication1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei132Proton donor/acceptor1 Publication1
Active sitei166Acyl-thioester intermediatePROSITE-ProRule annotation1 Publication1
Binding sitei204Substrate1 Publication1
Binding sitei258Substrate1 Publication1
Active sitei301Proton donor/acceptor1 Publication1
Binding sitei380Substrate1 Publication1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionTransferase
Biological processCholesterol biosynthesis, Cholesterol metabolism, Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis, Steroid metabolism, Sterol biosynthesis, Sterol metabolism

Enzyme and pathway databases

BRENDA Comprehensive Enzyme Information System

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BRENDAi
2.3.3.10, 2681

Pathway Commons web resource for biological pathway data

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PathwayCommonsi
P54868

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-1989781, PPARA activates gene expression
R-HSA-77111, Synthesis of Ketone Bodies

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...
SignaLinki
P54868

UniPathway: a resource for the exploration and annotation of metabolic pathways

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UniPathwayi
UPA00058;UER00102

Chemistry databases

SwissLipids knowledge resource for lipid biology

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SwissLipidsi
SLP:000001249 [P54868-1]

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Hydroxymethylglutaryl-CoA synthase, mitochondrial (EC:2.3.3.103 Publications)
Short name:
HMG-CoA synthase
Alternative name(s):
3-hydroxy-3-methylglutaryl coenzyme A synthase
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:HMGCS2
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 1

Organism-specific databases

Human Gene Nomenclature Database

More...
HGNCi
HGNC:5008, HMGCS2

Online Mendelian Inheritance in Man (OMIM)

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MIMi
600234, gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_P54868

Eukaryotic Pathogen, Vector and Host Database Resources

More...
VEuPathDBi
HostDB:ENSG00000134240

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Keywords - Cellular componenti

Mitochondrion

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

3-hydroxy-3-methylglutaryl-CoA synthase-2 deficiency (HMGCS2D)7 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA metabolic disorder characterized by severe hypoketotic hypoglycemia, encephalopathy, and hepatomegaly.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_03275754V → M in HMGCS2D; abolished protein expression. 2 PublicationsCorresponds to variant dbSNP:rs28937320EnsemblClinVar.1
Natural variantiVAR_083500112R → W in HMGCS2D; decreased protein abundance; abolished enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs768707273Ensembl.1
Natural variantiVAR_083501144V → L in HMGCS2D; decreased protein abundance; stong reduction of enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs775528207Ensembl.1
Natural variantiVAR_032758167Y → C in HMGCS2D; abolished enzymatic activity. 2 PublicationsCorresponds to variant dbSNP:rs137852640EnsemblClinVar.1
Natural variantiVAR_083502168G → S in HMGCS2D. 1 PublicationCorresponds to variant dbSNP:rs746217014EnsemblClinVar.1
Natural variantiVAR_083503169G → D in HMGCS2D; decreased protein abundance; abolished enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs1237226874Ensembl.1
Natural variantiVAR_032711174F → L in HMGCS2D; reduced peptide level; strong reduction of enzymatic activity. 2 PublicationsCorresponds to variant dbSNP:rs137852636EnsemblClinVar.1
Natural variantiVAR_083504185W → R in HMGCS2D; strong decreased of protein expression; abolished enzymatic activity. 1 Publication1
Natural variantiVAR_083505188R → H in HMGCS2D; abolished protein expression. 2 PublicationsCorresponds to variant dbSNP:rs761373362Ensembl.1
Natural variantiVAR_032759212G → R in HMGCS2D; abolished protein expression. 2 PublicationsCorresponds to variant dbSNP:rs137852638EnsemblClinVar.1
Natural variantiVAR_083506232G → V in HMGCS2D; decreased protein abundance; abolished enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs1002548815EnsemblClinVar.1
Natural variantiVAR_083507266L → S in HMGCS2D; decreased protein abundance; abolished enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs918691885Ensembl.1
Natural variantiVAR_083508307M → T in HMGCS2D; abolished enzymatic activity. 2 Publications1
Natural variantiVAR_083509360S → P in HMGCS2D. 1 Publication1
Natural variantiVAR_083510388G → R in HMGCS2D; abolished protein expression. 1 PublicationCorresponds to variant dbSNP:rs752626288EnsemblClinVar.1
Natural variantiVAR_083511424 – 508Missing in HMGCS2D. 1 PublicationAdd BLAST85
Natural variantiVAR_083512470F → T in HMGCS2D; decreased protein abundance; abolished enzymatic activity; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_032760500R → H in HMGCS2D; abolished enzymatic activity. 2 PublicationsCorresponds to variant dbSNP:rs137852639EnsemblClinVar.1
Natural variantiVAR_083513503Y → C in HMGCS2D; decreased protein abundance; stong reduction of enzymatic activity. 1 Publication1
Natural variantiVAR_083514505R → Q in HMGCS2D; decreased protein abundance; stong reduction of enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs758519315Ensembl.1

Keywords - Diseasei

Disease variant

Organism-specific databases

DisGeNET

More...
DisGeNETi
3158

MalaCards human disease database

More...
MalaCardsi
HMGCS2
MIMi605911, phenotype

Open Targets

More...
OpenTargetsi
ENSG00000134240

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...
Orphaneti
35701, 3-hydroxy-3-methylglutaryl-CoA synthase deficiency

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA29338

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...
Pharosi
P54868, Tbio

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...
BioMutai
HMGCS2

Domain mapping of disease mutations (DMDM)

More...
DMDMi
1708234

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a transit peptide.<p><a href='/help/transit' target='_top'>More...</a></p>Transit peptidei1 – 37MitochondrionCuratedAdd BLAST37
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000001348338 – 508Hydroxymethylglutaryl-CoA synthase, mitochondrialAdd BLAST471

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei52N6-succinyllysineBy similarity1
Modified residuei83N6-acetyllysine; alternateBy similarity1
Modified residuei83N6-succinyllysine; alternateBy similarity1
Modified residuei221N6-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; alternateBy similarity1
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 residuei433PhosphoserineCombined sources1
Modified residuei437N6-acetyllysineBy similarity1
Modified residuei440PhosphoserineCombined sources1
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

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Succinylated. Desuccinylated by SIRT5. Succinylation, at least at Lys-83 and Lys-310, inhibits the enzymatic activity.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

jPOST - Japan Proteome Standard Repository/Database

More...
jPOSTi
P54868

MassIVE - Mass Spectrometry Interactive Virtual Environment

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MassIVEi
P54868

MaxQB - The MaxQuant DataBase

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MaxQBi
P54868

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
P54868

PeptideAtlas

More...
PeptideAtlasi
P54868

PRoteomics IDEntifications database

More...
PRIDEi
P54868

ProteomicsDB: a multi-organism proteome resource

More...
ProteomicsDBi
56743 [P54868-1]
56744 [P54868-2]

2D gel databases

REPRODUCTION-2DPAGE

More...
REPRODUCTION-2DPAGEi
IPI00008934

PTM databases

GlyGen: Computational and Informatics Resources for Glycoscience

More...
GlyGeni
P54868, 1 site, 1 O-linked glycan (1 site)

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
P54868

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
P54868

SwissPalm database of S-palmitoylation events

More...
SwissPalmi
P54868

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Expression in liver is 200-fold higher than in any other tissue. Low expression in colon, kidney, testis, and pancreas. Very low expression in heart and skeletal muscle (PubMed:7893153, PubMed:21952825, PubMed:16940161). Not detected in brain (PubMed:21952825).3 Publications
Highest expression detected in heart and skeletal muscle.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSG00000134240, Expressed in right lobe of liver and 161 other tissues

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
P54868, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
P54868, HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
ENSG00000134240, Tissue enriched (liver)

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer.

1 Publication

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

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BioGRIDi
109401, 12 interactors

Protein interaction database and analysis system

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IntActi
P54868, 6 interactors

Molecular INTeraction database

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MINTi
P54868

STRING: functional protein association networks

More...
STRINGi
9606.ENSP00000358414

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

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RNActi
P54868, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1508
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
P54868

Database of comparative protein structure models

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ModBasei
Search...

Protein Data Bank in Europe - Knowledge Base

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PDBe-KBi
Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...
EvolutionaryTracei
P54868

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
KOG1393, Eukaryota

Ensembl GeneTree

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GeneTreei
ENSGT00390000006096

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
CLU_008065_0_1_1

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
P54868

Identification of Orthologs from Complete Genome Data

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OMAi
HTPNCKL

Database for complete collections of gene phylogenies

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PhylomeDBi
P54868

TreeFam database of animal gene trees

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TreeFami
TF105361

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...
Gene3Di
3.40.47.10, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR000590, HMG_CoA_synt_AS
IPR013746, HMG_CoA_synt_C_dom
IPR013528, HMG_CoA_synth_N
IPR010122, HMG_CoA_synthase_euk
IPR016039, Thiolase-like

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF08540, HMG_CoA_synt_C, 1 hit
PF01154, HMG_CoA_synt_N, 1 hit

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF53901, SSF53901, 2 hits

TIGRFAMs; a protein family database

More...
TIGRFAMsi
TIGR01833, HMG-CoA-S_euk, 1 hit

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS01226, HMG_COA_SYNTHASE, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 3 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: P54868-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <p><strong>What is the canonical sequence?</strong><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MQRLLTPVKR ILQLTRAVQE TSLTPARLLP VAHQRFSTAS AVPLAKTDTW
60 70 80 90 100
PKDVGILALE VYFPAQYVDQ TDLEKYNNVE AGKYTVGLGQ TRMGFCSVQE
110 120 130 140 150
DINSLCLTVV QRLMERIQLP WDSVGRLEVG TETIIDKSKA VKTVLMELFQ
160 170 180 190 200
DSGNTDIEGI DTTNACYGGT ASLFNAANWM ESSSWDGRYA MVVCGDIAVY
210 220 230 240 250
PSGNARPTGG AGAVAMLIGP KAPLALERGL RGTHMENVYD FYKPNLASEY
260 270 280 290 300
PIVDGKLSIQ CYLRALDRCY TSYRKKIQNQ WKQAGSDRPF TLDDLQYMIF
310 320 330 340 350
HTPFCKMVQK SLARLMFNDF LSASSDTQTS LYKGLEAFGG LKLEDTYTNK
360 370 380 390 400
DLDKALLKAS QDMFDKKTKA SLYLSTHNGN MYTSSLYGCL ASLLSHHSAQ
410 420 430 440 450
ELAGSRIGAF SYGSGLAASF FSFRVSQDAA PGSPLDKLVS STSDLPKRLA
460 470 480 490 500
SRKCVSPEEF TEIMNQREQF YHKVNFSPPG DTNSLFPGTW YLERVDEQHR

RKYARRPV
Length:508
Mass (Da):56,635
Last modified:October 1, 1996 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iBD362D631F7C3C80
GO
Isoform 2 (identifier: P54868-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     187-228: Missing.

Show »
Length:466
Mass (Da):52,482
Checksum:i9D3C527559B74618
GO
Isoform 3 (identifier: P54868-3) [UniParc]FASTAAdd to basket
Also known as: HMGCS2delta41 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     229-283: Missing.

Show »
Length:453
Mass (Da):50,050
Checksum:i80C1D1EBB7403EC0
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti234H → Y in CAG33131 (Ref. 3) Curated1
Sequence conflicti385S → T in CAG33131 (Ref. 3) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03275754V → M in HMGCS2D; abolished protein expression. 2 PublicationsCorresponds to variant dbSNP:rs28937320EnsemblClinVar.1
Natural variantiVAR_083500112R → W in HMGCS2D; decreased protein abundance; abolished enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs768707273Ensembl.1
Natural variantiVAR_083501144V → L in HMGCS2D; decreased protein abundance; stong reduction of enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs775528207Ensembl.1
Natural variantiVAR_032758167Y → C in HMGCS2D; abolished enzymatic activity. 2 PublicationsCorresponds to variant dbSNP:rs137852640EnsemblClinVar.1
Natural variantiVAR_083502168G → S in HMGCS2D. 1 PublicationCorresponds to variant dbSNP:rs746217014EnsemblClinVar.1
Natural variantiVAR_083503169G → D in HMGCS2D; decreased protein abundance; abolished enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs1237226874Ensembl.1
Natural variantiVAR_032711174F → L in HMGCS2D; reduced peptide level; strong reduction of enzymatic activity. 2 PublicationsCorresponds to variant dbSNP:rs137852636EnsemblClinVar.1
Natural variantiVAR_083504185W → R in HMGCS2D; strong decreased of protein expression; abolished enzymatic activity. 1 Publication1
Natural variantiVAR_083505188R → H in HMGCS2D; abolished protein expression. 2 PublicationsCorresponds to variant dbSNP:rs761373362Ensembl.1
Natural variantiVAR_032759212G → R in HMGCS2D; abolished protein expression. 2 PublicationsCorresponds to variant dbSNP:rs137852638EnsemblClinVar.1
Natural variantiVAR_083506232G → V in HMGCS2D; decreased protein abundance; abolished enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs1002548815EnsemblClinVar.1
Natural variantiVAR_083507266L → S in HMGCS2D; decreased protein abundance; abolished enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs918691885Ensembl.1
Natural variantiVAR_083508307M → T in HMGCS2D; abolished enzymatic activity. 2 Publications1
Natural variantiVAR_083509360S → P in HMGCS2D. 1 Publication1
Natural variantiVAR_083510388G → R in HMGCS2D; abolished protein expression. 1 PublicationCorresponds to variant dbSNP:rs752626288EnsemblClinVar.1
Natural variantiVAR_083511424 – 508Missing in HMGCS2D. 1 PublicationAdd BLAST85
Natural variantiVAR_083512470F → T in HMGCS2D; decreased protein abundance; abolished enzymatic activity; requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_032760500R → H in HMGCS2D; abolished enzymatic activity. 2 PublicationsCorresponds to variant dbSNP:rs137852639EnsemblClinVar.1
Natural variantiVAR_083513503Y → C in HMGCS2D; decreased protein abundance; stong reduction of enzymatic activity. 1 Publication1
Natural variantiVAR_083514505R → Q in HMGCS2D; decreased protein abundance; stong reduction of enzymatic activity. 1 PublicationCorresponds to variant dbSNP:rs758519315Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_042892187 – 228Missing in isoform 2. 1 PublicationAdd BLAST42
Alternative sequenceiVSP_047445229 – 283Missing in isoform 3. 1 PublicationAdd BLAST55

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
X83618 mRNA Translation: CAA58593.1
U81859 U81858 Genomic DNA Translation: AAB72036.1
CR456850 mRNA Translation: CAG33131.1
AK303777 mRNA Translation: BAH14049.1
AL589734 Genomic DNA No translation available.
CH471122 Genomic DNA Translation: EAW56709.1
BC044217 mRNA Translation: AAH44217.1
U12788 mRNA Translation: AAA92673.1
U12789 mRNA Translation: AAA92674.1
GU433940 mRNA Translation: ADD21696.1

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS53353.1 [P54868-2]
CCDS905.1 [P54868-1]

Protein sequence database of the Protein Information Resource

More...
PIRi
S71623

NCBI Reference Sequences

More...
RefSeqi
NP_001159579.1, NM_001166107.1 [P54868-2]
NP_005509.1, NM_005518.3 [P54868-1]
XP_011539615.1, XM_011541313.1 [P54868-3]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000369406; ENSP00000358414; ENSG00000134240
ENST00000544913; ENSP00000439495; ENSG00000134240 [P54868-2]

Database of genes from NCBI RefSeq genomes

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GeneIDi
3158

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:3158

Matched Annotation from NCBI and EMBL-EBI (MANE) - Phase one

More...
MANE-Selecti
ENST00000369406.8; ENSP00000358414.3; NM_005518.4; NP_005509.1

UCSC genome browser

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UCSCi
uc001eid.4, human [P54868-1]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X83618 mRNA Translation: CAA58593.1
U81859 U81858 Genomic DNA Translation: AAB72036.1
CR456850 mRNA Translation: CAG33131.1
AK303777 mRNA Translation: BAH14049.1
AL589734 Genomic DNA No translation available.
CH471122 Genomic DNA Translation: EAW56709.1
BC044217 mRNA Translation: AAH44217.1
U12788 mRNA Translation: AAA92673.1
U12789 mRNA Translation: AAA92674.1
GU433940 mRNA Translation: ADD21696.1
CCDSiCCDS53353.1 [P54868-2]
CCDS905.1 [P54868-1]
PIRiS71623
RefSeqiNP_001159579.1, NM_001166107.1 [P54868-2]
NP_005509.1, NM_005518.3 [P54868-1]
XP_011539615.1, XM_011541313.1 [P54868-3]

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...
PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

More...
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2WYAX-ray1.70A/B/C/D51-508[»]
SMRiP54868
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi109401, 12 interactors
IntActiP54868, 6 interactors
MINTiP54868
STRINGi9606.ENSP00000358414

Chemistry databases

SwissLipidsiSLP:000001249 [P54868-1]

PTM databases

GlyGeniP54868, 1 site, 1 O-linked glycan (1 site)
iPTMnetiP54868
PhosphoSitePlusiP54868
SwissPalmiP54868

Genetic variation databases

BioMutaiHMGCS2
DMDMi1708234

2D gel databases

REPRODUCTION-2DPAGEiIPI00008934

Proteomic databases

jPOSTiP54868
MassIVEiP54868
MaxQBiP54868
PaxDbiP54868
PeptideAtlasiP54868
PRIDEiP54868
ProteomicsDBi56743 [P54868-1]
56744 [P54868-2]

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...
Antibodypediai
33918, 204 antibodies from 26 providers

The DNASU plasmid repository

More...
DNASUi
3158

Genome annotation databases

EnsembliENST00000369406; ENSP00000358414; ENSG00000134240
ENST00000544913; ENSP00000439495; ENSG00000134240 [P54868-2]
GeneIDi3158
KEGGihsa:3158
MANE-SelectiENST00000369406.8; ENSP00000358414.3; NM_005518.4; NP_005509.1
UCSCiuc001eid.4, human [P54868-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
3158
DisGeNETi3158

GeneCards: human genes, protein and diseases

More...
GeneCardsi
HMGCS2
HGNCiHGNC:5008, HMGCS2
HPAiENSG00000134240, Tissue enriched (liver)
MalaCardsiHMGCS2
MIMi600234, gene
605911, phenotype
neXtProtiNX_P54868
OpenTargetsiENSG00000134240
Orphaneti35701, 3-hydroxy-3-methylglutaryl-CoA synthase deficiency
PharmGKBiPA29338
VEuPathDBiHostDB:ENSG00000134240

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG1393, Eukaryota
GeneTreeiENSGT00390000006096
HOGENOMiCLU_008065_0_1_1
InParanoidiP54868
OMAiHTPNCKL
PhylomeDBiP54868
TreeFamiTF105361

Enzyme and pathway databases

UniPathwayiUPA00058;UER00102
BRENDAi2.3.3.10, 2681
PathwayCommonsiP54868
ReactomeiR-HSA-1989781, PPARA activates gene expression
R-HSA-77111, Synthesis of Ketone Bodies
SignaLinkiP54868

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...
BioGRID-ORCSi
3158, 10 hits in 1038 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
HMGCS2, human
EvolutionaryTraceiP54868

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
3158
PharosiP54868, Tbio

Protein Ontology

More...
PROi
PR:P54868
RNActiP54868, protein

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000134240, Expressed in right lobe of liver and 161 other tissues
ExpressionAtlasiP54868, baseline and differential
GenevisibleiP54868, HS

Family and domain databases

Gene3Di3.40.47.10, 1 hit
InterProiView protein in InterPro
IPR000590, HMG_CoA_synt_AS
IPR013746, HMG_CoA_synt_C_dom
IPR013528, HMG_CoA_synth_N
IPR010122, HMG_CoA_synthase_euk
IPR016039, Thiolase-like
PfamiView protein in Pfam
PF08540, HMG_CoA_synt_C, 1 hit
PF01154, HMG_CoA_synt_N, 1 hit
SUPFAMiSSF53901, SSF53901, 2 hits
TIGRFAMsiTIGR01833, HMG-CoA-S_euk, 1 hit
PROSITEiView protein in PROSITE
PS01226, HMG_COA_SYNTHASE, 1 hit

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiHMCS2_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P54868
Secondary accession number(s): B7Z8R3
, D3Y5K6, Q5SZU2, Q6IBF4
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: February 23, 2022
This is version 193 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with genetic variants
    List of human entries with genetic variants
  3. Human variants curated from literature reports
    Index of human variants curated from literature reports
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families
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