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Protein

Hydroxymethylglutaryl-CoA lyase, mitochondrial

Gene

Hmgcl

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 (By similarity).By similarity

Catalytic activityi

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

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-hydroxymethyl-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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei41 – 411SubstrateBy similarity
Metal bindingi42 – 421Divalent metal cationBy similarity
Metal bindingi233 – 2331Divalent metal cationBy similarity
Metal bindingi235 – 2351Divalent metal cationBy similarity
Active sitei266 – 2661PROSITE-ProRule annotation
Metal bindingi275 – 2751Divalent metal cationBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Ligandi

Metal-binding

Enzyme and pathway databases

ReactomeiR-MMU-77111. Synthesis of Ketone Bodies.
UniPathwayiUPA00896; UER00863.

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:96158. Hmgcl.

Subcellular locationi

  • Mitochondrion matrix 1 Publication
  • Peroxisome 1 Publication

  • Note: Unprocessed form is peroxisomal.

GO - Cellular componenti

  • mitochondrial inner membrane Source: MGI
  • mitochondrial matrix Source: UniProtKB-SubCell
  • mitochondrion Source: MGI
  • peroxisome Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion, Peroxisome

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 2727MitochondrionBy similarityAdd
BLAST
Chaini28 – 325298Hydroxymethylglutaryl-CoA lyase, mitochondrialPRO_0000013480Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei48 – 481N6-acetyllysine; alternateCombined sources
Modified residuei48 – 481N6-succinyllysine; alternateCombined sources
Modified residuei111 – 1111N6-acetyllysineCombined sources
Modified residuei137 – 1371N6-acetyllysine; alternateCombined sources
Modified residuei137 – 1371N6-succinyllysine; alternateCombined sources
Modified residuei179 – 1791N6-acetyllysine; alternateCombined sources
Modified residuei179 – 1791N6-succinyllysine; alternateCombined sources
Disulfide bondi323 – 323InterchainBy similarity
Modified residuei324 – 3241N6-acetyllysineCombined sources

Keywords - PTMi

Acetylation, Disulfide bond

Proteomic databases

EPDiP38060.
MaxQBiP38060.
PaxDbiP38060.
PeptideAtlasiP38060.
PRIDEiP38060.

PTM databases

iPTMnetiP38060.
PhosphoSiteiP38060.
SwissPalmiP38060.

Expressioni

Gene expression databases

BgeeiP38060.
CleanExiMM_HMGCL.
GenevisibleiP38060. MM.

Interactioni

Subunit structurei

Homodimer; disulfide-linked. Can also form homotetramers.By similarity

GO - Molecular functioni

Protein-protein interaction databases

IntActiP38060. 1 interaction.
MINTiMINT-1840478.
STRINGi10090.ENSMUSP00000030432.

Structurei

3D structure databases

ProteinModelPortaliP38060.
SMRiP38060. Positions 28-323.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi323 – 3253Microbody targeting signalSequence analysis

Sequence similaritiesi

Belongs to the HMG-CoA lyase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG2368. Eukaryota.
COG0119. LUCA.
GeneTreeiENSGT00390000017690.
HOGENOMiHOG000219757.
HOVERGENiHBG064656.
InParanoidiP38060.
KOiK01640.
OMAiEAFAQKN.
OrthoDBiEOG73Z2TR.
TreeFamiTF105363.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
InterProiIPR013785. Aldolase_TIM.
IPR030020. HL.
IPR000138. HMG_CoA_lyase_AS.
IPR000891. PYR_CT.
[Graphical view]
PANTHERiPTHR10277:SF35. PTHR10277:SF35. 1 hit.
PfamiPF00682. HMGL-like. 1 hit.
[Graphical view]
PROSITEiPS01062. HMG_COA_LYASE. 1 hit.
PS50991. PYR_CT. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P38060-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASVRKAFPR RLVGLTSLRA VSTSSMGTLP KQVKIVEVGP RDGLQNEKSI
60 70 80 90 100
VPTPVKIRLI DMLSEAGLPV IEATSFVSPK WVPQMADHSD VLKGIQKFPG
110 120 130 140 150
INYPVLTPNM KGFEEAVAAG AKEVSVFGAV SELFTRKNAN CSIEESFQRF
160 170 180 190 200
AGVMQAAQAA SISVRGYVSC ALGCPYEGKV SPAKVAEVAK KLYSMGCYEI
210 220 230 240 250
SLGDTIGVGT PGLMKDMLTA VMHEVPVTAL AVHCHDTYGQ ALANTLVALQ
260 270 280 290 300
MGVSVVDSSV AGLGGCPYAK GASGNLATED LVYMLNGLGI HTGVNLQKLL
310 320
EAGDFICQAL NRKTSSKVAQ ATCKL
Length:325
Mass (Da):34,239
Last modified:July 27, 2011 - v2
Checksum:iE6A85659EBA1D87F
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti62 – 632ML → IV in AAB03107 (PubMed:8617516).Curated
Sequence conflicti80 – 801K → N in AAB27965 (PubMed:8102917).Curated
Sequence conflicti231 – 2311A → G in AAB27965 (PubMed:8102917).Curated
Sequence conflicti238 – 2381Y → I in AAB27965 (PubMed:8102917).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S65036 mRNA. Translation: AAB27965.1.
U49878
, U49870, U49871, U49872, U49873, U49874, U49875, U49876, U49877 Genomic DNA. Translation: AAB03107.1.
AK132035 mRNA. Translation: BAE20956.1.
AK145251 mRNA. Translation: BAE26328.1.
AK154033 mRNA. Translation: BAE32329.1.
AL672076 Genomic DNA. Translation: CAM15901.1.
CH466552 Genomic DNA. Translation: EDL29963.1.
BC025440 mRNA. Translation: AAH25440.1.
CCDSiCCDS18795.1.
RefSeqiNP_032280.2. NM_008254.2.
UniGeneiMm.482102.

Genome annotation databases

EnsembliENSMUST00000030432; ENSMUSP00000030432; ENSMUSG00000028672.
GeneIDi15356.
KEGGimmu:15356.
UCSCiuc012dnc.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S65036 mRNA. Translation: AAB27965.1.
U49878
, U49870, U49871, U49872, U49873, U49874, U49875, U49876, U49877 Genomic DNA. Translation: AAB03107.1.
AK132035 mRNA. Translation: BAE20956.1.
AK145251 mRNA. Translation: BAE26328.1.
AK154033 mRNA. Translation: BAE32329.1.
AL672076 Genomic DNA. Translation: CAM15901.1.
CH466552 Genomic DNA. Translation: EDL29963.1.
BC025440 mRNA. Translation: AAH25440.1.
CCDSiCCDS18795.1.
RefSeqiNP_032280.2. NM_008254.2.
UniGeneiMm.482102.

3D structure databases

ProteinModelPortaliP38060.
SMRiP38060. Positions 28-323.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP38060. 1 interaction.
MINTiMINT-1840478.
STRINGi10090.ENSMUSP00000030432.

PTM databases

iPTMnetiP38060.
PhosphoSiteiP38060.
SwissPalmiP38060.

Proteomic databases

EPDiP38060.
MaxQBiP38060.
PaxDbiP38060.
PeptideAtlasiP38060.
PRIDEiP38060.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000030432; ENSMUSP00000030432; ENSMUSG00000028672.
GeneIDi15356.
KEGGimmu:15356.
UCSCiuc012dnc.1. mouse.

Organism-specific databases

CTDi3155.
MGIiMGI:96158. Hmgcl.

Phylogenomic databases

eggNOGiKOG2368. Eukaryota.
COG0119. LUCA.
GeneTreeiENSGT00390000017690.
HOGENOMiHOG000219757.
HOVERGENiHBG064656.
InParanoidiP38060.
KOiK01640.
OMAiEAFAQKN.
OrthoDBiEOG73Z2TR.
TreeFamiTF105363.

Enzyme and pathway databases

UniPathwayiUPA00896; UER00863.
ReactomeiR-MMU-77111. Synthesis of Ketone Bodies.

Miscellaneous databases

PROiP38060.
SOURCEiSearch...

Gene expression databases

BgeeiP38060.
CleanExiMM_HMGCL.
GenevisibleiP38060. MM.

Family and domain databases

Gene3Di3.20.20.70. 1 hit.
InterProiIPR013785. Aldolase_TIM.
IPR030020. HL.
IPR000138. HMG_CoA_lyase_AS.
IPR000891. PYR_CT.
[Graphical view]
PANTHERiPTHR10277:SF35. PTHR10277:SF35. 1 hit.
PfamiPF00682. HMGL-like. 1 hit.
[Graphical view]
PROSITEiPS01062. HMG_COA_LYASE. 1 hit.
PS50991. PYR_CT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "3-hydroxy-3-methylglutaryl coenzyme A lyase (HL): cloning and characterization of a mouse liver HL cDNA and subchromosomal mapping of the human and mouse HL genes."
    Wang S., Nadeau J.H., Duncan A., Robert M.-F., Fontaine G., Schappert K., Johnson K.R., Zietkiewicz E., Hruz P., Miziorko H.
    Mamm. Genome 4:382-387(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Liver.
  2. "3-hydroxy-3-methylglutaryl CoA lyase (HL): mouse and human HL gene (HMGCL) cloning and detection of large gene deletions in two unrelated HL-deficient patients."
    Wang S.P., Robert M.-F., Gibson K.M., Wanders R.J.A., Mitchell G.A.
    Genomics 33:99-104(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: 129.
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J and NOD.
    Tissue: Hippocampus, Mammary gland and Thymus.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  5. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
    Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Liver.
  7. "3-Hydroxy-3-methylglutaryl-CoA lyase is present in mouse and human liver peroxisomes."
    Ashmarina L.I., Rusnak N., Miziorko H.M., Mitchell G.A.
    J. Biol. Chem. 269:31929-31932(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas, Spleen and Testis.
  9. "SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
    Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
    Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-48, SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-48; LYS-137 AND LYS-179, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Embryonic fibroblast and Liver.
  10. "Label-free quantitative proteomics of the lysine acetylome in mitochondria identifies substrates of SIRT3 in metabolic pathways."
    Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B., Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.
    Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-48; LYS-111; LYS-137; LYS-179 AND LYS-324, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiHMGCL_MOUSE
AccessioniPrimary (citable) accession number: P38060
Secondary accession number(s): Q8QZS6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: July 27, 2011
Last modified: July 6, 2016
This is version 127 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.