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UniProtKB - P35914 (HMGCL_HUMAN)

Entry version 189 (11 Dec 2019)
Sequence version 2 (25 Oct 2002)
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Protein

Hydroxymethylglutaryl-CoA lyase, mitochondrial

Gene

HMGCL

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

Mitochondrial 3-hydroxymethyl-3-methylglutaryl-CoA lyase that catalyzes a cation-dependent cleavage of (S)-3-hydroxy-3-methylglutaryl-CoA into acetyl-CoA and acetoacetate, a key step in ketogenesis. Terminal step in leucine catabolism. Ketone bodies (beta-hydroxybutyrate, acetoacetate and acetone) are essential as an alternative source of energy to glucose, as lipid precursors and as regulators of metabolism.3 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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 provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

a divalent metal cation1 Publication

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Stimulated by reducing agents such as dithiothreitol (DTT).1 Publication

<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=200 µM for magnesium ion2 Publications
  2. KM=48 µM for HMG-CoA2 Publications
  1. Vmax=191 µmol/min/mg enzyme2 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section describes the metabolic pathway(s) associated with a protein.<p><a href='/help/pathway' target='_top'>More...</a></p>Pathwayi: (S)-3-hydroxy-3-methylglutaryl-CoA degradation

This protein is involved in step 1 of the subpathway that synthesizes acetoacetate from (S)-3-hydroxy-3-methylglutaryl-CoA.
Proteins known to be involved in this subpathway in this organism are:
  1. Hydroxymethylglutaryl-CoA lyase, mitochondrial (HMGCL), 3-hydroxy-3-methylglutaryl-CoA lyase, cytoplasmic (HMGCLL1)
This subpathway is part of the pathway (S)-3-hydroxy-3-methylglutaryl-CoA degradation, which is itself part of Metabolic intermediate metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes acetoacetate from (S)-3-hydroxy-3-methylglutaryl-CoA, the pathway (S)-3-hydroxy-3-methylglutaryl-CoA degradation and in Metabolic intermediate metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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 sitei41Substrate1
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the ‘Description’ field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi42Divalent metal cation1
Metal bindingi233Divalent metal cation1
Metal bindingi235Divalent metal cation1
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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 sitei266PROSITE-ProRule annotation1
Metal bindingi275Divalent metal cation1

<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

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<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 functionLyase
LigandMetal-binding

Enzyme and pathway databases

BioCyc Collection of Pathway/Genome Databases

More...BioCyci		MetaCyc:HS04116-MONOMER

BRENDA Comprehensive Enzyme Information System

More...BRENDAi		4.1.3.4 2681

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-77111 Synthesis of Ketone Bodies
R-HSA-9033241 Peroxisomal protein import

SABIO-RK: Biochemical Reaction Kinetics Database

More...SABIO-RKi		P35914

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

More...UniPathwayi		UPA00896;UER00863

Chemistry databases

SwissLipids knowledge resource for lipid biology

More...SwissLipidsi		SLP:000001292 [P35914-1]

<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_and_taxonomy_section">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 lyase, mitochondrial (EC:4.1.3.42 Publications)
Short name:
HL
Short name:
HMG-CoA lyase
Alternative name(s):
3-hydroxy-3-methylglutarate-CoA lyase
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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:HMGCL
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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_and_taxonomy_section">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_and_taxonomy_section">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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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_manual">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:ENSG00000117305.14

Human Gene Nomenclature Database

More...HGNCi		HGNC:5005 HMGCL

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		613898 gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P35914

<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, Peroxisome

<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 lyase deficiency (HMGCLD)10 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disease affecting ketogenesis and L-leucine catabolism. The disease usually appears in the first year of life after a fasting period and its clinical acute symptoms include vomiting, seizures, metabolic acidosis, hypoketotic hypoglycemia and lethargy. These symptoms sometimes progress to coma, with fatal outcome in some cases.
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_05844037E → K in HMGCLD; activity lower than 5% respect to the wild-type. 1 Publication1
Natural variantiVAR_00374441R → Q in HMGCLD; loss of activity and of proton exchange. 2 PublicationsCorresponds to variant dbSNP:rs121964997EnsemblClinVar.1
Natural variantiVAR_00374542D → E in HMGCLD; reduced activity. 1 Publication1
Natural variantiVAR_00374642D → G in HMGCLD; loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs1467902610Ensembl.1
Natural variantiVAR_00374742D → H in HMGCLD; loss of activity. 1 Publication1
Natural variantiVAR_05844148K → N in HMGCLD; abolishes almost all enzymatic activity. 1 Publication1
Natural variantiVAR_00374870V → L in HMGCLD. Corresponds to variant dbSNP:rs121964996EnsemblClinVar.1
Natural variantiVAR_05844275S → R in HMGCLD. 1 PublicationCorresponds to variant dbSNP:rs1357942068Ensembl.1
Natural variantiVAR_058443142S → F in HMGCLD; activity lower than 5% respect to the wild-type. 1 Publication1
Natural variantiVAR_065453165R → Q in HMGCLD. 1 PublicationCorresponds to variant dbSNP:rs199587895EnsemblClinVar.1
Natural variantiVAR_058444174C → Y in HMGCLD; activity lower than 5% respect to the wild-type. 1 PublicationCorresponds to variant dbSNP:rs765475941Ensembl.1
Natural variantiVAR_058445192F → S in HMGCLD; activity lower than 5% respect to the wild-type. 1 Publication1
Natural variantiVAR_058446200I → F in HMGCLD; activity lower than 5% respect to the wild-type. 1 Publication1
Natural variantiVAR_058447201S → Y in HMGCLD. 1 PublicationCorresponds to variant dbSNP:rs760106433EnsemblClinVar.1
Natural variantiVAR_058448203G → E in HMGCLD; complete loss of activity. 1 PublicationCorresponds to variant dbSNP:rs1553131940EnsemblClinVar.1
Natural variantiVAR_058449204D → N in HMGCLD. 1 Publication1
Natural variantiVAR_003749233H → R in HMGCLD; loss of activity. 3 PublicationsCorresponds to variant dbSNP:rs727503963EnsemblClinVar.1
Natural variantiVAR_058450263L → P in HMGCLD. 1 Publication1
Natural variantiVAR_014202279E → K in HMGCLD. 1 PublicationCorresponds to variant dbSNP:rs121964998EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi37E → D: Normal activity. 1 Publication1
Mutagenesisi41R → M: Reduced activity, and loss of proton exchange. 1 Publication1
Mutagenesisi42D → A or N: Loss of activity, and reduced proton exchange rate. 2 Publications1
Mutagenesisi72E → A: Loss of activity, and reduced affinity for metal cofactor and substrate. 1 Publication1
Mutagenesisi204D → A: Reduced activity, and reduced affinity for metal cofactor and substrate. 1 Publication1
Mutagenesisi233H → A: Loss of activity, and reduced proton exchange rate. 2 Publications1
Mutagenesisi266C → A: Loss of activity. 1
Mutagenesisi279E → A: Reduced thermal stability, but normal activity. 1 Publication1
Mutagenesisi280D → A: Normal activity. 1 Publication1
Mutagenesisi323C → S: Abolishes interchain homodimerization. Exhibits no DTT stimulated activity. 2 Publications1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNET

More...DisGeNETi		3155

MalaCards human disease database

More...MalaCardsi		HMGCL
MIMi246450 phenotype

Open Targets

More...OpenTargetsi		ENSG00000117305

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

More...Orphaneti		20 3-hydroxy-3-methylglutaric aciduria

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA29336

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		P35914 Tbio

Chemistry databases

Drug and drug target database

More...DrugBanki		DB04594 3-hydroxyglutaric acid

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		HMGCL

Domain mapping of disease mutations (DMDM)

More...DMDMi		24418852

<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 – 27MitochondrionAdd BLAST27
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000001347828 – 325Hydroxymethylglutaryl-CoA lyase, mitochondrialAdd BLAST298

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 residuei48N6-acetyllysine; alternateCombined sources1
Modified residuei48N6-succinyllysine; alternateBy similarity1
Modified residuei111N6-acetyllysineBy similarity1
Modified residuei137N6-acetyllysine; alternateBy similarity1
Modified residuei137N6-succinyllysine; alternateBy similarity1
Modified residuei179N6-acetyllysine; alternateBy similarity1
Modified residuei179N6-succinyllysine; alternateBy similarity1
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi323Interchain1 Publication
Modified residuei324N6-acetyllysineBy similarity1

Keywords - PTMi

Acetylation, Disulfide bond

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		P35914

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		P35914

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		P35914

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

More...PaxDbi		P35914

PeptideAtlas

More...PeptideAtlasi		P35914

PRoteomics IDEntifications database

More...PRIDEi		P35914

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		55164 [P35914-1]
55165 [P35914-2]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P35914

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

More...PhosphoSitePlusi		P35914

<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

Highest expression in liver. Expressed in pancreas, kidney, intestine, testis, fibroblasts and lymphoblasts. Very low expression in brain and skeletal muscle. The relative expression of isoform 2 (at mRNA level) is highest in heart (30%), skeletal muscle (22%), and brain (14%).1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000117305 Expressed in 228 organ(s), highest expression level in right lobe of liver

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P35914 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P35914 HS

Organism-specific databases

Human Protein Atlas

More...HPAi		HPA004727

<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_section">'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_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer; disulfide-linked. Can also form homotetramers.

2 Publications

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...BioGridi		109398, 25 interactors

Protein interaction database and analysis system

More...IntActi		P35914, 11 interactors

Molecular INTeraction database

More...MINTi		P35914

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000363614

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		P35914 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

1325
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		P35914

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		P35914

<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

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini33 – 300Pyruvate carboxyltransferasePROSITE-ProRule annotationAdd BLAST268

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi323 – 325Microbody targeting signalSequence analysis3

<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

Belongs to the HMG-CoA lyase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG2368 Eukaryota
COG0119 LUCA

Ensembl GeneTree

More...GeneTreei		ENSGT00940000158484

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		HOG000219757

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P35914

KEGG Orthology (KO)

More...KOi		K01640

Identification of Orthologs from Complete Genome Data

More...OMAi		FGGCPMA

Database of Orthologous Groups

More...OrthoDBi		1029775at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		P35914

TreeFam database of animal gene trees

More...TreeFami		TF105363

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		3.20.20.70, 1 hit

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR013785 Aldolase_TIM
IPR000138 HMG_CoA_lyase_AS
IPR000891 PYR_CT

Pfam protein domain database

More...Pfami		View protein in Pfam
PF00682 HMGL-like, 1 hit

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS01062 HMG_COA_LYASE, 1 hit
PS50991 PYR_CT, 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_length">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_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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

This entry has 3 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: P35914-1) [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.

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MAAMRKALPR RLVGLASLRA VSTSSMGTLP KRVKIVEVGP RDGLQNEKNI 
        60         70         80         90        100
VSTPVKIKLI DMLSEAGLSV IETTSFVSPK WVPQMGDHTE VLKGIQKFPG 
       110        120        130        140        150
INYPVLTPNL KGFEAAVAAG AKEVVIFGAA SELFTKKNIN CSIEESFQRF 
       160        170        180        190        200
DAILKAAQSA NISVRGYVSC ALGCPYEGKI SPAKVAEVTK KFYSMGCYEI 
       210        220        230        240        250
SLGDTIGVGT PGIMKDMLSA VMQEVPLAAL AVHCHDTYGQ ALANTLMALQ 
       260        270        280        290        300
MGVSVVDSSV AGLGGCPYAQ GASGNLATED LVYMLEGLGI HTGVNLQKLL 
       310        320 
EAGNFICQAL NRKTSSKVAQ ATCKL
Length:325
Mass (Da):34,360
Last modified:October 25, 2002 - v2
<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:iB82B2488A10D6980
GO
Isoform 2 (identifier: P35914-2) [UniParc]FASTAAdd to basket
Also known as: HMGCS2delta5,6

The sequence of this isoform differs from the canonical sequence as follows:
     117-187: Missing.

Note: The transcript is not translated, but would result in a catalytically impaired product if it was.Curated
Show »
Length:254
Mass (Da):26,910
Checksum:iFAD9D90A1A62F3AD
GO
Isoform 3 (identifier: P35914-3) [UniParc]FASTAAdd to basket
Also known as: HMGCS2delta5,6,7

The sequence of this isoform differs from the canonical sequence as follows:
     117-187: Missing.
     188-250: Missing.

Note: Very low expression. The transcript is not translated, but would result in a catalytically inactive product if it was.Curated
Show »
Length:191
Mass (Da):20,222
Checksum:iD5540BECDB75D854
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0Y2L7H0Y2L7_HUMAN
Hydroxymethylglutaryl-CoA lyase, mi...
HMGCL
182Annotation score:

Annotation score:1 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 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 conflicti243A → T in AAA92733 (PubMed:8440722).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05844037E → K in HMGCLD; activity lower than 5% respect to the wild-type. 1 Publication1
Natural variantiVAR_00374441R → Q in HMGCLD; loss of activity and of proton exchange. 2 PublicationsCorresponds to variant dbSNP:rs121964997EnsemblClinVar.1
Natural variantiVAR_00374542D → E in HMGCLD; reduced activity. 1 Publication1
Natural variantiVAR_00374642D → G in HMGCLD; loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs1467902610Ensembl.1
Natural variantiVAR_00374742D → H in HMGCLD; loss of activity. 1 Publication1
Natural variantiVAR_05844148K → N in HMGCLD; abolishes almost all enzymatic activity. 1 Publication1
Natural variantiVAR_00374870V → L in HMGCLD. Corresponds to variant dbSNP:rs121964996EnsemblClinVar.1
Natural variantiVAR_05844275S → R in HMGCLD. 1 PublicationCorresponds to variant dbSNP:rs1357942068Ensembl.1
Natural variantiVAR_058443142S → F in HMGCLD; activity lower than 5% respect to the wild-type. 1 Publication1
Natural variantiVAR_065453165R → Q in HMGCLD. 1 PublicationCorresponds to variant dbSNP:rs199587895EnsemblClinVar.1
Natural variantiVAR_058444174C → Y in HMGCLD; activity lower than 5% respect to the wild-type. 1 PublicationCorresponds to variant dbSNP:rs765475941Ensembl.1
Natural variantiVAR_058445192F → S in HMGCLD; activity lower than 5% respect to the wild-type. 1 Publication1
Natural variantiVAR_058446200I → F in HMGCLD; activity lower than 5% respect to the wild-type. 1 Publication1
Natural variantiVAR_058447201S → Y in HMGCLD. 1 PublicationCorresponds to variant dbSNP:rs760106433EnsemblClinVar.1
Natural variantiVAR_058448203G → E in HMGCLD; complete loss of activity. 1 PublicationCorresponds to variant dbSNP:rs1553131940EnsemblClinVar.1
Natural variantiVAR_058449204D → N in HMGCLD. 1 Publication1
Natural variantiVAR_003749233H → R in HMGCLD; loss of activity. 3 PublicationsCorresponds to variant dbSNP:rs727503963EnsemblClinVar.1
Natural variantiVAR_058450263L → P in HMGCLD. 1 Publication1
Natural variantiVAR_014202279E → K in HMGCLD. 1 PublicationCorresponds to variant dbSNP:rs121964998EnsemblClinVar.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_047444117 – 187Missing in isoform 2 and isoform 3. 2 PublicationsAdd BLAST71
Alternative sequenceiVSP_043788188 – 250Missing in isoform 3. 1 PublicationAdd BLAST63

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
L07033 mRNA Translation: AAA92733.1
AK300733 mRNA Translation: BAG62406.1
AK313869 mRNA Translation: BAG36597.1
BT009792 mRNA Translation: AAP88794.1
CR456884 mRNA Translation: CAG33165.1
AL031295 Genomic DNA No translation available.
AL590728 Genomic DNA No translation available.
CH471134 Genomic DNA Translation: EAW95094.1
BC010570 mRNA Translation: AAH10570.1
AH003700 Genomic DNA Translation: AAB19099.1
FJ472654 mRNA Translation: ACK58684.1
GU433941 mRNA Translation: ADD21697.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS243.1 [P35914-1]
CCDS53279.1 [P35914-2]

Protein sequence database of the Protein Information Resource

More...PIRi		A45470

NCBI Reference Sequences

More...RefSeqi		NP_000182.2, NM_000191.2 [P35914-1]
NP_001159531.1, NM_001166059.1 [P35914-2]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000374490; ENSP00000363614; ENSG00000117305 [P35914-1]
ENST00000436439; ENSP00000389281; ENSG00000117305 [P35914-2]

Database of genes from NCBI RefSeq genomes

More...GeneIDi		3155

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:3155

UCSC genome browser

More...UCSCi		uc001bib.4 human [P35914-1]

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
L07033 mRNA Translation: AAA92733.1
AK300733 mRNA Translation: BAG62406.1
AK313869 mRNA Translation: BAG36597.1
BT009792 mRNA Translation: AAP88794.1
CR456884 mRNA Translation: CAG33165.1
AL031295 Genomic DNA No translation available.
AL590728 Genomic DNA No translation available.
CH471134 Genomic DNA Translation: EAW95094.1
BC010570 mRNA Translation: AAH10570.1
AH003700 Genomic DNA Translation: AAB19099.1
FJ472654 mRNA Translation: ACK58684.1
GU433941 mRNA Translation: ADD21697.1
CCDSiCCDS243.1 [P35914-1]
CCDS53279.1 [P35914-2]
PIRiA45470
RefSeqiNP_000182.2, NM_000191.2 [P35914-1]
NP_001159531.1, NM_001166059.1 [P35914-2]

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
2CW6X-ray2.10A/B/C/D/E/F28-325[»]
3MP3X-ray2.40A/B/C/D/E/F28-325[»]
3MP4X-ray2.20A/B/C/D/E/F28-325[»]
3MP5X-ray2.25A/B/C/D/E/F28-325[»]
SMRiP35914
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGridi109398, 25 interactors
IntActiP35914, 11 interactors
MINTiP35914
STRINGi9606.ENSP00000363614

Chemistry databases

DrugBankiDB04594 3-hydroxyglutaric acid
SwissLipidsiSLP:000001292 [P35914-1]

PTM databases

iPTMnetiP35914
PhosphoSitePlusiP35914

Polymorphism and mutation databases

BioMutaiHMGCL
DMDMi24418852

Proteomic databases

EPDiP35914
jPOSTiP35914
MassIVEiP35914
PaxDbiP35914
PeptideAtlasiP35914
PRIDEiP35914
ProteomicsDBi55164 [P35914-1]
55165 [P35914-2]

Protocols and materials databases

The DNASU plasmid repository

More...DNASUi		3155

Genome annotation databases

EnsembliENST00000374490; ENSP00000363614; ENSG00000117305 [P35914-1]
ENST00000436439; ENSP00000389281; ENSG00000117305 [P35914-2]
GeneIDi3155
KEGGihsa:3155
UCSCiuc001bib.4 human [P35914-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		3155
DisGeNETi3155
EuPathDBiHostDB:ENSG00000117305.14

GeneCards: human genes, protein and diseases

More...GeneCardsi		HMGCL
HGNCiHGNC:5005 HMGCL
HPAiHPA004727
MalaCardsiHMGCL
MIMi246450 phenotype
613898 gene
neXtProtiNX_P35914
OpenTargetsiENSG00000117305
Orphaneti20 3-hydroxy-3-methylglutaric aciduria
PharmGKBiPA29336

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG2368 Eukaryota
COG0119 LUCA
GeneTreeiENSGT00940000158484
HOGENOMiHOG000219757
InParanoidiP35914
KOiK01640
OMAiFGGCPMA
OrthoDBi1029775at2759
PhylomeDBiP35914
TreeFamiTF105363

Enzyme and pathway databases

UniPathwayiUPA00896;UER00863
BioCyciMetaCyc:HS04116-MONOMER
BRENDAi4.1.3.4 2681
ReactomeiR-HSA-77111 Synthesis of Ketone Bodies
R-HSA-9033241 Peroxisomal protein import
SABIO-RKiP35914

Miscellaneous databases

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

More...ChiTaRSi		HMGCL human
EvolutionaryTraceiP35914

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

More...GenomeRNAii		3155
PharosiP35914 Tbio

Protein Ontology

More...PROi		PR:P35914
RNActiP35914 protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000117305 Expressed in 228 organ(s), highest expression level in right lobe of liver
ExpressionAtlasiP35914 baseline and differential
GenevisibleiP35914 HS

Family and domain databases

Gene3Di3.20.20.70, 1 hit
InterProiView protein in InterPro
IPR013785 Aldolase_TIM
IPR000138 HMG_CoA_lyase_AS
IPR000891 PYR_CT
PfamiView protein in Pfam
PF00682 HMGL-like, 1 hit
PROSITEiView protein in PROSITE
PS01062 HMG_COA_LYASE, 1 hit
PS50991 PYR_CT, 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 nameiHMGCL_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: P35914
Secondary accession number(s): B4DUP4
, B7UCC6, D3Y5K7, Q6IBC0, Q96FP8
<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_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: October 25, 2002
Last modified: December 11, 2019
This is version 189 of the entry and version 2 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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