HMGCL

Functionⁱ

Key enzyme in ketogenesis (ketone body formation). 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

Catalytic activityⁱ

(S)-3-hydroxy-3-methylglutaryl-CoA = acetyl-CoA + acetoacetate.PROSITE-ProRule annotation2 Publications

Cofactorⁱ

a divalent metal cation1 Publication

Activity regulationⁱ

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

Kineticsⁱ

V_max=
191 µmol/min/mg enzyme
2 Publications
Manual assertion based on experiment inⁱ
- Ref.13
  "Investigation of conserved acidic residues in 3-hydroxy-3-methylglutaryl-CoA lyase: implications for human disease and for functional roles in a family of related proteins."
  Tuinstra R.L., Miziorko H.M.
  J. Biol. Chem. 278:37092-37098(2003) [PubMed] [Europe PMC] [Abstract]
  Cited for: MUTAGENESIS OF GLU-37; ASP-42; GLU-72; ASP-204; HIS-233; GLU-279 AND ASP-280, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVITY REGULATION.
- Ref.14
  "Evaluation of 3-hydroxy-3-methylglutaryl-coenzyme A lyase arginine-41 as a catalytic residue: use of acetyldithio-coenzyme A to monitor product enolization."
  Tuinstra R.L., Wang C.-Z., Mitchell G.A., Miziorko H.M.
  Biochemistry 43:5287-5295(2004) [PubMed] [Europe PMC] [Abstract]
  Cited for: MUTAGENESIS OF ARG-41; ASP-42 AND HIS-233, BIOPHYSICOCHEMICAL PROPERTIES.

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:

3-hydroxymethyl-3-methylglutaryl-CoA lyase, cytoplasmic (HMGCLL1), Hydroxymethylglutaryl-CoA lyase, mitochondrial (HMGCL)

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 key	Position(s)	DescriptionActions	Length
Binding siteⁱ	41	Substrate	1
Metal bindingⁱ	42	Divalent metal cation	1
Metal bindingⁱ	233	Divalent metal cation	1
Metal bindingⁱ	235	Divalent metal cation	1
Active siteⁱ	266	PROSITE-ProRule annotation	1
Metal bindingⁱ	275	Divalent metal cation	1

GO - Molecular functionⁱ

carboxylic acid binding Source: Ensembl
fatty-acyl-CoA binding Source: Ensembl
hydroxymethylglutaryl-CoA lyase activity
Source: UniProtKB
Inferred from direct assayⁱ
magnesium ion binding
Source: UniProtKB
Inferred from direct assayⁱ
- 9200711
manganese ion binding
Source: UniProtKB
Inferred from direct assayⁱ
- 9200711
metal ion binding
Source: UniProtKB
Inferred from direct assayⁱ
- 16330550
protein homodimerization activity
Source: UniProtKB
Inferred from direct assayⁱ
- 12464283
- 8670134
signaling receptor binding
Source: UniProtKB
Inferred from physical interactionⁱ
- 20178365

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

acyl-CoA metabolic process Source: Ensembl
ketone body biosynthetic process
Source: UniProtKB
Inferred from direct assayⁱ
leucine catabolic process
Source: BHF-UCL
Traceable author statementⁱ
- 8027038
lipid metabolic process
Source: BHF-UCL
Inferred from direct assayⁱ
- 8027038
liver development Source: Ensembl
mitochondrion organization Source: Ensembl
protein targeting to peroxisome Source: Reactome
protein tetramerization
Source: UniProtKB
Inferred from direct assayⁱ
- 12464283
response to fatty acid Source: Ensembl
response to nutrient Source: Ensembl
response to starvation Source: Ensembl

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Lyase
Ligand	Metal-binding

Enzyme and pathway databases

BioCycⁱ	MetaCyc:HS04116-MONOMER
BRENDAⁱ	4.1.3.4 2681
Reactomeⁱ	R-HSA-77111 Synthesis of Ketone Bodies R-HSA-9033241 Peroxisomal protein import
SABIO-RKⁱ	P35914
UniPathwayⁱ	UPA00896;UER00863

Chemistry databases

SwissLipidsⁱ	SLP:000001292 [P35914-1]

SwissLipidsⁱ

SLP:000001292 [P35914-1]

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: Hydroxymethylglutaryl-CoA lyase, mitochondrial (EC:4.1.3.4) Short name: HL Short name: HMG-CoA lyase Alternative name(s): 3-hydroxy-3-methylglutarate-CoA lyase
Gene namesⁱ	Name:HMGCL
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640 Componentⁱ: Chromosome 1

Organism-specific databases

EuPathDBⁱ	HostDB:ENSG00000117305.14
Human Gene Nomenclature Database More...HGNCⁱ	HGNC:5005 HMGCL
MIMⁱ	613898 gene
neXtProtⁱ	NX_P35914

Keywords - Cellular componentⁱ

Mitochondrion, Peroxisome

Pathology & Biotechⁱ

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.

Mutagenesis

Feature key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	37	E → D: Normal activity. 1 Publication	1
Mutagenesisⁱ	41	R → M: Reduced activity, and loss of proton exchange. 1 Publication	1
Mutagenesisⁱ	42	D → A or N: Loss of activity, and reduced proton exchange rate. 2 Publications	1
Mutagenesisⁱ	72	E → A: Loss of activity, and reduced affinity for metal cofactor and substrate. 1 Publication	1
Mutagenesisⁱ	204	D → A: Reduced activity, and reduced affinity for metal cofactor and substrate. 1 Publication	1
Mutagenesisⁱ	233	H → A: Loss of activity, and reduced proton exchange rate. 2 Publications	1
Mutagenesisⁱ	266	C → A: Loss of activity.	1
Mutagenesisⁱ	279	E → A: Reduced thermal stability, but normal activity. 1 Publication	1
Mutagenesisⁱ	280	D → A: Normal activity. 1 Publication	1
Mutagenesisⁱ	323	C → S: Abolishes interchain homodimerization. Exhibits no DTT stimulated activity. 2 Publications	1

Keywords - Diseaseⁱ

Disease mutation

Organism-specific databases

DisGeNET More...DisGeNETⁱ	3155
MalaCards human disease database More...MalaCardsⁱ	HMGCL
MIMⁱ	246450 phenotype
Open Targets More...OpenTargetsⁱ	ENSG00000117305
Orphanetⁱ	20 3-hydroxy-3-methylglutaric aciduria
PharmGKBⁱ	PA29336

Chemistry databases

Drug and drug target database More...DrugBankⁱ	DB04594 3-hydroxyglutaric acid

DrugBankⁱ

DB04594 3-hydroxyglutaric acid

Polymorphism and mutation databases

BioMutaⁱ	HMGCL
DMDMⁱ	24418852

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Transit peptideⁱ	1 – 27	MitochondrionAdd BLAST		27
ChainⁱPRO_0000013478	28 – 325	Hydroxymethylglutaryl-CoA lyase, mitochondrialAdd BLAST		298

Amino acid modifications

Feature key	Position(s)	DescriptionActions	Length
Modified residueⁱ	48	N6-acetyllysine; alternateCombined sources	1
Modified residueⁱ	48	N6-succinyllysine; alternateBy similarity	1
Modified residueⁱ	111	N6-acetyllysineBy similarity	1
Modified residueⁱ	137	N6-acetyllysine; alternateBy similarity	1
Modified residueⁱ	137	N6-succinyllysine; alternateBy similarity	1
Modified residueⁱ	179	N6-acetyllysine; alternateBy similarity	1
Modified residueⁱ	179	N6-succinyllysine; alternateBy similarity	1
Disulfide bondⁱ	323	Interchain1 Publication
Modified residueⁱ	324	N6-acetyllysineBy similarity	1

Keywords - PTMⁱ

Acetylation, Disulfide bond

Proteomic databases

EPDⁱ	P35914
PaxDbⁱ	P35914
PeptideAtlas More...PeptideAtlasⁱ	P35914
PRIDEⁱ	P35914
ProteomicsDBⁱ	55164 55165 [P35914-2]

PTM databases

iPTMnetⁱ	P35914
PhosphoSitePlusⁱ	P35914

Expressionⁱ

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

Bgeeⁱ	ENSG00000117305 Expressed in 228 organ(s), highest expression level in right lobe of liver
CleanExⁱ	HS_HMGCL
ExpressionAtlasⁱ	P35914 baseline and differential
Genevisibleⁱ	P35914 HS

Organism-specific databases

Human Protein Atlas More...HPAⁱ	HPA004727

HPAⁱ

HPA004727

Interactionⁱ

Subunit structureⁱ

Homodimer; disulfide-linked. Can also form homotetramers.2 Publications

GO - Molecular functionⁱ

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridⁱ	109398, 24 interactors
IntActⁱ	P35914, 11 interactors
Molecular INTeraction database More...MINTⁱ	P35914
STRINGⁱ	9606.ENSP00000363614

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	34 – 37	Combined sources	4
Turnⁱ	39 – 41	Combined sources	3
Helixⁱ	42 – 45	Combined sources	4
Helixⁱ	53 – 65	Combined sources	13
Beta strandⁱ	69 – 71	Combined sources	3
Turnⁱ	79 – 81	Combined sources	3
Helixⁱ	83 – 85	Combined sources	3
Helixⁱ	88 – 94	Combined sources	7
Helixⁱ	110 – 118	Combined sources	9
Beta strandⁱ	122 – 130	Combined sources	9
Helixⁱ	132 – 139	Combined sources	8
Helixⁱ	143 – 159	Combined sources	17
Beta strandⁱ	163 – 169	Combined sources	7
Turnⁱ	170 – 172	Combined sources	3
Turnⁱ	175 – 177	Combined sources	3
Helixⁱ	182 – 194	Combined sources	13
Beta strandⁱ	198 – 204	Combined sources	7
Helixⁱ	211 – 224	Combined sources	14
Helixⁱ	227 – 229	Combined sources	3
Beta strandⁱ	230 – 235	Combined sources	6
Helixⁱ	241 – 250	Combined sources	10
Beta strandⁱ	255 – 259	Combined sources	5
Helixⁱ	278 – 288	Combined sources	11
Helixⁱ	296 – 309	Combined sources	14
Helixⁱ	317 – 322	Combined sources	6

Show more details

3D structure databases

ProteinModelPortalⁱ	P35914
SMRⁱ	P35914
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	P35914

EvolutionaryTraceⁱ

P35914

Family & Domainsⁱ

Domains and Repeats

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Domainⁱ	33 – 300	Pyruvate carboxyltransferasePROSITE-ProRule annotationAdd BLAST		268

Motif

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Motifⁱ	323 – 325	Microbody targeting signalSequence analysis		3

Sequence similaritiesⁱ

Belongs to the HMG-CoA lyase family.Curated

Keywords - Domainⁱ

Transit peptide

Phylogenomic databases

eggNOGⁱ	KOG2368 Eukaryota COG0119 LUCA
Ensembl GeneTree More...GeneTreeⁱ	ENSGT00390000017690
HOGENOMⁱ	HOG000219757
HOVERGENⁱ	HBG064656
InParanoidⁱ	P35914
KEGG Orthology (KO) More...KOⁱ	K01640
OMAⁱ	FGGCPMA
Database of Orthologous Groups More...OrthoDBⁱ	EOG091G0DA9
PhylomeDBⁱ	P35914
TreeFamⁱ	TF105363

Family and domain databases

Gene3Dⁱ	3.20.20.70, 1 hit
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
PROSITEⁱ	View protein in PROSITE PS01062 HMG_COA_LYASE, 1 hit PS50991 PYR_CT, 1 hit

Sequences (3+)ⁱ

Sequence statusⁱ: Complete.

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

This entry describes 3 isoformsⁱ produced by alternative splicing. Align Add to basket

This entry has 3 described isoforms and 2 potential isoforms that are computationally mapped.ⁱShow all

Isoform 1 (identifier: P35914-1) [UniParc]FASTA Add to basket

This isoform has been chosen as the 'canonical' 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
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

Checksum:ⁱB82B2488A10D6980

GO

Isoform 2 (identifier: P35914-2) [UniParc]FASTA Add to basket

Also known as: HMGCS2delta5,6

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

« Hide

        10         20         30         40         50
MAAMRKALPR RLVGLASLRA VSTSSMGTLP KRVKIVEVGP RDGLQNEKNI 
        60         70         80         90        100
VSTPVKIKLI DMLSEAGLSV IETTSFVSPK WVPQMGDHTE VLKGIQKFPG 
       110        120        130        140        150
INYPVLTPNL KGFEAAVTKK FYSMGCYEIS LGDTIGVGTP GIMKDMLSAV 
       160        170        180        190        200
MQEVPLAALA VHCHDTYGQA LANTLMALQM GVSVVDSSVA GLGGCPYAQG 
       210        220        230        240        250
ASGNLATEDL VYMLEGLGIH TGVNLQKLLE AGNFICQALN RKTSSKVAQA 

TCKL

Note: The transcript is not translated, but would result in a catalytically impaired product if it was.

Show »

Length:254

Mass (Da):26,910

Checksum:ⁱFAD9D90A1A62F3AD

GO

Isoform 3 (identifier: P35914-3) [UniParc]FASTA Add 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.

« Hide

        10         20         30         40         50
MAAMRKALPR RLVGLASLRA VSTSSMGTLP KRVKIVEVGP RDGLQNEKNI 
        60         70         80         90        100
VSTPVKIKLI DMLSEAGLSV IETTSFVSPK WVPQMGDHTE VLKGIQKFPG 
       110        120        130        140        150
INYPVLTPNL KGFEAAMGVS VVDSSVAGLG GCPYAQGASG NLATEDLVYM 
       160        170        180        190 
LEGLGIHTGV NLQKLLEAGN FICQALNRKT SSKVAQATCK L

Note: Very low expression. The transcript is not translated, but would result in a catalytically inactive product if it was.

Show »

Length:191

Mass (Da):20,222

Checksum:ⁱD5540BECDB75D854

GO

Computationally mapped potential isoform sequencesⁱ

There are 2 potential isoforms mapped to this entry.BLAST Align Show all Add to basket

	Entry	Entry name		Protein names	Gene names	Length	Annotation
	H0Y2L7	H0Y2L7_HUMAN		Hydroxymethylglutaryl-CoA lyase, mi... Hydroxymethylglutaryl-CoA lyase, mitochondrial	HMGCL	182	Annotation score:
	D6REN8	D6REN8_HUMAN		Hydroxymethylglutaryl-CoA lyase, mi... Hydroxymethylglutaryl-CoA lyase, mitochondrial	HMGCL	77	Annotation score:

Experimental Info

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Sequence conflictⁱ	243	A → T in AAA92733 (PubMed:8440722).Curated		1

Natural variant

Feature key	Position(s)	DescriptionActions	Length
Natural variantⁱVAR_058440	37	E → K in HMGCLD; activity lower than 5% respect to the wild-type. 1 Publication	1
Natural variantⁱVAR_003744	41	R → Q in HMGCLD; loss of activity and of proton exchange. 2 PublicationsCorresponds to variant dbSNP:rs121964997EnsemblClinVar.	1
Natural variantⁱVAR_003745	42	D → E in HMGCLD; reduced activity. 1 Publication	1
Natural variantⁱVAR_003746	42	D → G in HMGCLD; loss of activity. 2 Publications	1
Natural variantⁱVAR_003747	42	D → H in HMGCLD; loss of activity. 1 Publication	1
Natural variantⁱVAR_058441	48	K → N in HMGCLD; abolishes almost all enzymatic activity. 1 Publication	1
Natural variantⁱVAR_003748	70	V → L in HMGCLD. Corresponds to variant dbSNP:rs121964996EnsemblClinVar.	1
Natural variantⁱVAR_058442	75	S → R in HMGCLD. 1 Publication	1
Natural variantⁱVAR_058443	142	S → F in HMGCLD; activity lower than 5% respect to the wild-type. 1 Publication	1
Natural variantⁱVAR_065453	165	R → Q in HMGCLD. 1 PublicationCorresponds to variant dbSNP:rs199587895EnsemblClinVar.	1
Natural variantⁱVAR_058444	174	C → Y in HMGCLD; activity lower than 5% respect to the wild-type. 1 PublicationCorresponds to variant dbSNP:rs765475941Ensembl.	1
Natural variantⁱVAR_058445	192	F → S in HMGCLD; activity lower than 5% respect to the wild-type. 1 Publication	1
Natural variantⁱVAR_058446	200	I → F in HMGCLD; activity lower than 5% respect to the wild-type. 1 Publication	1
Natural variantⁱVAR_058447	201	S → Y in HMGCLD. 1 PublicationCorresponds to variant dbSNP:rs760106433EnsemblClinVar.	1
Natural variantⁱVAR_058448	203	G → E in HMGCLD; complete loss of activity. 1 Publication	1
Natural variantⁱVAR_058449	204	D → N in HMGCLD. 1 Publication	1
Natural variantⁱVAR_003749	233	H → R in HMGCLD; loss of activity. 3 PublicationsCorresponds to variant dbSNP:rs727503963EnsemblClinVar.	1
Natural variantⁱVAR_058450	263	L → P in HMGCLD. 1 Publication	1
Natural variantⁱVAR_014202	279	E → K in HMGCLD. 1 PublicationCorresponds to variant dbSNP:rs121964998EnsemblClinVar.	1

Alternative sequence

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Alternative sequenceⁱVSP_047444	117 – 187	Missing in isoform 2 and isoform 3. 2 PublicationsAdd BLAST		71
Alternative sequenceⁱVSP_043788	188 – 250	Missing in isoform 3. 1 PublicationAdd BLAST		63

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
The Consensus CDS (CCDS) project More...CCDSⁱ	CCDS243.1 [P35914-1] CCDS53279.1 [P35914-2]
PIRⁱ	A45470
NCBI Reference Sequences More...RefSeqⁱ	NP_000182.2, NM_000191.2 [P35914-1] NP_001159531.1, NM_001166059.1 [P35914-2]
UniGeneⁱ	Hs.533444

Genome annotation databases

Ensemblⁱ	ENST00000374490; ENSP00000363614; ENSG00000117305 [P35914-1] ENST00000436439; ENSP00000389281; ENSG00000117305 [P35914-2]
GeneIDⁱ	3155
KEGGⁱ	hsa:3155
UCSC genome browser More...UCSCⁱ	uc001bib.4 human [P35914-1]

Keywords - Coding sequence diversityⁱ

Alternative splicing

Similar proteinsⁱ

100% Identity
90% Identity
50% Identity

Protein	Similar proteins		Species	Score	Length	Source
P35914	3-hydroxymethyl-3-methylglutaryl-CoA lyase		PANPA		325	UniRef100_P35914
3-hydroxymethyl-3-methylglutaryl-Coenzyme A lyase (Hydroxymethylglutaricaciduria), isoform CRA_b		HUMAN		300
UPI000065CA71		HUMAN		298

Protein	Similar proteins		Species	Score	Length	Source
P35914	Hydroxymethylglutaryl-CoA lyase, mitochondrial		PONAB		325	UniRef90_P35914
Hydroxymethylglutaryl-CoA lyase, mitochondrial		MACFA		325
3-hydroxymethyl-3-methylglutaryl-CoA lyase		PANPA		325
3-hydroxymethyl-3-methylglutaryl-Coenzyme A lyase (Hydroxymethylglutaricaciduria), isoform CRA_b		HUMAN		300
3-hydroxymethyl-3-methylglutaryl-CoA lyase		AOTNA		374
+43
P35914-2	3-hydroxymethyl-3-methylglutaryl-CoA lyase		PANTR		254	UniRef90_A0A2I3RNF9
3-hydroxymethyl-3-methylglutaryl-CoA lyase		SAIBB		254
3-hydroxymethyl-3-methylglutaryl-CoA lyase		PROCO		254
3-hydroxymethyl-3-methylglutaryl-CoA lyase		CALJA		254
3-hydroxymethyl-3-methylglutaryl-CoA lyase		MACMU		254
+16

Protein	Similar proteins		Species	Score	Length	Source
P35914	Hydroxymethylglutaryl-CoA lyase, mitochondrial		PONAB		325	UniRef50_P35914
Hydroxymethylglutaryl-CoA lyase, mitochondrial		MACFA		325
3-hydroxymethyl-3-methylglutaryl-CoA lyase, cytoplasmic		RAT		343
3-hydroxymethyl-3-methylglutaryl-CoA lyase, cytoplasmic		MOUSE		343
3-hydroxymethyl-3-methylglutaryl-CoA lyase		PANPA		325
+202
P35914-2	hydroxymethylglutaryl-CoA lyase, mitochondrial isoform X4		TURTR		262	UniRef50_A0A2U4BLN6
3-hydroxymethyl-3-methylglutaryl-CoA lyase		PANPA		254
3-hydroxymethyl-3-methylglutaryl-CoA lyase		PAPAN		254
3-hydroxymethyl-3-methylglutaryl-CoA lyase		MANLE		254
3-hydroxymethyl-3-methylglutaryl-CoA lyase		COLAP		254
+22

Entry informationⁱ

Entry nameⁱ	HMGCL_HUMAN
Accessionⁱ	P35914Primary (citable) accession number: P35914 Secondary accession number(s): B4DUP4 , B7UCC6, D3Y5K7, Q6IBC0, Q96FP8
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	June 1, 1994
	Last sequence update:	October 25, 2002
	Last modified:	September 12, 2018
	This is version 179 of the entry and version 2 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Chordata Protein Annotation Program
Disclaimer	Any 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.

Miscellaneousⁱ

Keywords - Technical termⁱ

3D-structure, Complete proteome, Reference proteome

UniProtKB

UniParc

Help

UniRef

Proteomes

Annotation systems

Supporting data

UniProtKB - P35914 (HMGCL_HUMAN)

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Hydroxymethylglutaryl-CoA lyase, mitochondrial

Select a section on the left to see content.

<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

<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

<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

Sites

<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

Enzyme and pathway databases

Chemistry databases

<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

Organism-specific databases

<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

Peroxisome

Mitochondrion

Cytosol

Mitochondrion

Peroxisome

Keywords - Cellular componenti

<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

Mutagenesis

Keywords - Diseasei

Organism-specific databases

Chemistry databases

Polymorphism and mutation databases

<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

Amino acid modifications

Keywords - PTMi

Proteomic databases

PTM databases

<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

Gene expression databases

Organism-specific databases

<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

GO - Molecular functioni

Protein-protein interaction databases

<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

3D structure databases

Miscellaneous databases

<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

Motif

<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

Phylogenomic databases

Family and domain databases

Computationally mapped potential isoform sequencesi

Experimental Info

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

<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 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

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Functionⁱ

Kineticsⁱ

Pathwayⁱ: (S)-3-hydroxy-3-methylglutaryl-CoA degradation

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

Keywords - Diseaseⁱ

PTM / Processingⁱ

Keywords - PTMⁱ

Expressionⁱ

Interactionⁱ

GO - Molecular functionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Keywords - Domainⁱ

Computationally mapped potential isoform sequencesⁱ

Keywords - Coding sequence diversityⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ