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Entry version 185 (17 Jun 2020)
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
    Proteins known to be involved in the 3 steps of the subpathway in this organism are:
    1. no protein annotated in this organism
    2. 3-hydroxy-3-methylglutaryl coenzyme A synthase (HMGCS1), 3-hydroxy-3-methylglutaryl coenzyme A synthase, Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1), 3-hydroxy-3-methylglutaryl coenzyme A synthase, Hydroxymethylglutaryl-CoA synthase, mitochondrial (HMGCS2), 3-hydroxy-3-methylglutaryl coenzyme A synthase, 3-hydroxy-3-methylglutaryl coenzyme A synthase
    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
    <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

    BioCyc Collection of Pathway/Genome Databases

    More...
    BioCyci
    MetaCyc:HS05836-MONOMER

    BRENDA Comprehensive Enzyme Information System

    More...
    BRENDAi
    2.3.3.10 2681

    Reactome - a knowledgebase of biological pathways and processes

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

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

    More...
    UniPathwayi
    UPA00058;UER00102

    Chemistry databases

    SwissLipids knowledge resource for lipid biology

    More...
    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

    Eukaryotic Pathogen Database Resources

    More...
    EuPathDBi
    HostDB:ENSG00000134240.11

    Human Gene Nomenclature Database

    More...
    HGNCi
    HGNC:5008 HMGCS2

    Online Mendelian Inheritance in Man (OMIM)

    More...
    MIMi
    600234 gene

    neXtProt; the human protein knowledge platform

    More...
    neXtProti
    NX_P54868

    <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

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

    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 mutations 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 Publication1
    Natural variantiVAR_083501144V → L in HMGCS2D; decreased protein abundance; stong reduction of enzymatic activity. 1 Publication1
    Natural variantiVAR_032758167Y → C in HMGCS2D; abolished enzymatic activity. 2 PublicationsCorresponds to variant dbSNP:rs137852640EnsemblClinVar.1
    Natural variantiVAR_083502168G → S in HMGCS2D. 1 Publication1
    Natural variantiVAR_083503169G → D in HMGCS2D; decreased protein abundance; abolished enzymatic activity. 1 Publication1
    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 Publications1
    Natural variantiVAR_032759212G → R in HMGCS2D; abolished protein expression. 2 PublicationsCorresponds to variant dbSNP:rs137852638Ensembl.1
    Natural variantiVAR_083506232G → V in HMGCS2D; decreased protein abundance; abolished enzymatic activity. 1 Publication1
    Natural variantiVAR_083507266L → S in HMGCS2D; decreased protein abundance; abolished enzymatic activity. 1 Publication1
    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 Publication1
    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:rs137852639Ensembl.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 Publication1

    Keywords - Diseasei

    Disease mutation

    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

    More...
    PharmGKBi
    PA29338

    Miscellaneous databases

    Pharos NIH Druggable Genome Knowledgebase

    More...
    Pharosi
    P54868 Tbio

    Polymorphism and mutation 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

    More...
    MassIVEi
    P54868

    MaxQB - The MaxQuant DataBase

    More...
    MaxQBi
    P54868

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

    More...
    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

    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

    More...
    Bgeei
    ENSG00000134240 Expressed in right lobe of liver and 142 other tissues

    ExpressionAtlas, Differential and Baseline Expression

    More...
    ExpressionAtlasi
    P54868 baseline and differential

    Genevisible search portal to normalized and curated expression data from Genevestigator

    More...
    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

    Protein-protein interaction databases

    The Biological General Repository for Interaction Datasets (BioGRID)

    More...
    BioGRIDi
    109401, 7 interactors

    Protein interaction database and analysis system

    More...
    IntActi
    P54868, 4 interactors

    Molecular INTeraction database

    More...
    MINTi
    P54868

    STRING: functional protein association networks

    More...
    STRINGi
    9606.ENSP00000358414

    Miscellaneous databases

    RNAct, Protein-RNA interaction predictions for model organisms.

    More...
    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

    More...
    SMRi
    P54868

    Database of comparative protein structure models

    More...
    ModBasei
    Search...

    Protein Data Bank in Europe - Knowledge Base

    More...
    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

    More...
    eggNOGi
    KOG1393 Eukaryota
    COG3425 LUCA

    Ensembl GeneTree

    More...
    GeneTreei
    ENSGT00390000006096

    The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

    More...
    HOGENOMi
    CLU_008065_0_1_1

    InParanoid: Eukaryotic Ortholog Groups

    More...
    InParanoidi
    P54868

    KEGG Orthology (KO)

    More...
    KOi
    K01641

    Identification of Orthologs from Complete Genome Data

    More...
    OMAi
    EVKHACY

    Database for complete collections of gene phylogenies

    More...
    PhylomeDBi
    P54868

    TreeFam database of animal gene trees

    More...
    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

    More...
    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. This section is only present in reviewed entries, i.e. in UniProtKB/Swiss-Prot.<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 <div> <p><b>What is the canonical sequence?</b><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 Publication1
    Natural variantiVAR_083501144V → L in HMGCS2D; decreased protein abundance; stong reduction of enzymatic activity. 1 Publication1
    Natural variantiVAR_032758167Y → C in HMGCS2D; abolished enzymatic activity. 2 PublicationsCorresponds to variant dbSNP:rs137852640EnsemblClinVar.1
    Natural variantiVAR_083502168G → S in HMGCS2D. 1 Publication1
    Natural variantiVAR_083503169G → D in HMGCS2D; decreased protein abundance; abolished enzymatic activity. 1 Publication1
    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 Publications1
    Natural variantiVAR_032759212G → R in HMGCS2D; abolished protein expression. 2 PublicationsCorresponds to variant dbSNP:rs137852638Ensembl.1
    Natural variantiVAR_083506232G → V in HMGCS2D; decreased protein abundance; abolished enzymatic activity. 1 Publication1
    Natural variantiVAR_083507266L → S in HMGCS2D; decreased protein abundance; abolished enzymatic activity. 1 Publication1
    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 Publication1
    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:rs137852639Ensembl.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 Publication1

    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

    More...
    EMBLi

    GenBank nucleotide sequence database

    More...
    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 [P54868-1]
    ENST00000544913; ENSP00000439495; ENSG00000134240 [P54868-2]

    Database of genes from NCBI RefSeq genomes

    More...
    GeneIDi
    3158

    KEGG: Kyoto Encyclopedia of Genes and Genomes

    More...
    KEGGi
    hsa:3158

    UCSC genome browser

    More...
    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

    More...
    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, 7 interactors
    IntActiP54868, 4 interactors
    MINTiP54868
    STRINGi9606.ENSP00000358414

    Chemistry databases

    SwissLipidsiSLP:000001249 [P54868-1]

    PTM databases

    iPTMnetiP54868
    PhosphoSitePlusiP54868
    SwissPalmiP54868

    Polymorphism and mutation 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 187 antibodies

    Genome annotation databases

    EnsembliENST00000369406; ENSP00000358414; ENSG00000134240 [P54868-1]
    ENST00000544913; ENSP00000439495; ENSG00000134240 [P54868-2]
    GeneIDi3158
    KEGGihsa:3158
    UCSCiuc001eid.4 human [P54868-1]

    Organism-specific databases

    Comparative Toxicogenomics Database

    More...
    CTDi
    3158
    DisGeNETi3158
    EuPathDBiHostDB:ENSG00000134240.11

    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

    GenAtlas: human gene database

    More...
    GenAtlasi
    Search...

    Phylogenomic databases

    eggNOGiKOG1393 Eukaryota
    COG3425 LUCA
    GeneTreeiENSGT00390000006096
    HOGENOMiCLU_008065_0_1_1
    InParanoidiP54868
    KOiK01641
    OMAiEVKHACY
    PhylomeDBiP54868
    TreeFamiTF105361

    Enzyme and pathway databases

    UniPathwayiUPA00058;UER00102
    BioCyciMetaCyc:HS05836-MONOMER
    BRENDAi2.3.3.10 2681
    ReactomeiR-HSA-1989781 PPARA activates gene expression
    R-HSA-77111 Synthesis of Ketone Bodies

    Miscellaneous databases

    BioGRID ORCS database of CRISPR phenotype screens

    More...
    BioGRID-ORCSi
    3158 2 hits in 788 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 142 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

    ProtoNet; Automatic hierarchical classification of proteins

    More...
    ProtoNeti
    Search...

    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: June 17, 2020
    This is version 185 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. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. SIMILARITY comments
      Index of protein domains and families
    4. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    5. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    6. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    7. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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