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Protein

Hydroxymethylglutaryl-CoA synthase, mitochondrial

Gene

Hmgcs2

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

Functioni

This enzyme condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is the substrate for HMG-CoA reductase.

Catalytic activityi

Acetyl-CoA + H2O + acetoacetyl-CoA = (S)-3-hydroxy-3-methylglutaryl-CoA + CoA.PROSITE-ProRule annotation

Pathwayi

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei80 – 801SubstrateBy similarity
Active sitei132 – 1321Proton donor/acceptorPROSITE-ProRule annotation
Active sitei166 – 1661Acyl-thioester intermediatePROSITE-ProRule annotation
Binding sitei204 – 2041SubstrateBy similarity
Binding sitei258 – 2581SubstrateBy similarity
Active sitei301 – 3011Proton donor/acceptorPROSITE-ProRule annotation
Binding sitei380 – 3801SubstrateBy similarity

GO - Molecular functioni

  1. hydroxymethylglutaryl-CoA synthase activity Source: UniProtKB-EC

GO - Biological processi

  1. cholesterol biosynthetic process Source: UniProtKB-KW
  2. isoprenoid biosynthetic process Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Transferase

Keywords - Biological processi

Cholesterol biosynthesis, Cholesterol metabolism, Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis, Steroid metabolism, Sterol biosynthesis, Sterol metabolism

Enzyme and pathway databases

BRENDAi2.3.3.10. 3474.
ReactomeiREACT_272139. PPARA activates gene expression.
REACT_286913. Synthesis of Ketone Bodies.
UniPathwayiUPA00058; UER00102.

Names & Taxonomyi

Protein namesi
Recommended name:
Hydroxymethylglutaryl-CoA synthase, mitochondrial (EC:2.3.3.10)
Short name:
HMG-CoA synthase
Alternative name(s):
3-hydroxy-3-methylglutaryl coenzyme A synthase
Gene namesi
Name:Hmgcs2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 3

Organism-specific databases

MGIiMGI:101939. Hmgcs2.

Subcellular locationi

GO - Cellular componenti

  1. mitochondrial inner membrane Source: MGI
  2. mitochondrion Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 3737MitochondrionCuratedAdd
BLAST
Chaini38 – 508471Hydroxymethylglutaryl-CoA synthase, mitochondrialPRO_0000013484Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei52 – 521N6-succinyllysine1 Publication
Modified residuei83 – 831N6-acetyllysine; alternate1 Publication
Modified residuei83 – 831N6-succinyllysine; alternate1 Publication
Modified residuei118 – 1181N6-acetyllysine; alternate1 Publication
Modified residuei118 – 1181N6-succinyllysine; alternate1 Publication
Modified residuei221 – 2211N6-succinyllysine1 Publication
Modified residuei243 – 2431N6-acetyllysine1 Publication
Modified residuei256 – 2561N6-acetyllysine; alternate1 Publication
Modified residuei256 – 2561N6-succinyllysine; alternate1 Publication
Modified residuei306 – 3061N6-acetyllysine1 Publication
Modified residuei310 – 3101N6-acetyllysine; alternate1 Publication
Modified residuei310 – 3101N6-succinyllysine; alternate1 Publication
Modified residuei327 – 3271N6-acetyllysine; alternate1 Publication
Modified residuei327 – 3271N6-succinyllysine; alternate1 Publication
Modified residuei333 – 3331N6-succinyllysine1 Publication
Modified residuei342 – 3421N6-acetyllysine; alternate1 Publication
Modified residuei342 – 3421N6-succinyllysine; alternate1 Publication
Modified residuei350 – 3501N6-acetyllysine; alternate1 Publication
Modified residuei350 – 3501N6-succinyllysine; alternate1 Publication
Modified residuei354 – 3541N6-acetyllysine; alternate1 Publication
Modified residuei354 – 3541N6-succinyllysine; alternate1 Publication
Modified residuei358 – 3581N6-acetyllysine; alternate1 Publication
Modified residuei358 – 3581N6-succinyllysine; alternate1 Publication
Modified residuei427 – 4271N6-acetyllysine1 Publication
Modified residuei433 – 4331PhosphoserineBy similarity
Modified residuei437 – 4371N6-acetyllysine1 Publication
Modified residuei440 – 4401PhosphoserineBy similarity
Modified residuei447 – 4471N6-acetyllysine; alternate1 Publication
Modified residuei447 – 4471N6-succinyllysine; alternate1 Publication
Modified residuei473 – 4731N6-acetyllysine; alternate1 Publication
Modified residuei473 – 4731N6-succinyllysine; alternate1 Publication

Post-translational modificationi

Acetylation of Lys-427 is observed in liver mitochondria from fasted mice but not from fed mice.

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP54869.
PaxDbiP54869.
PRIDEiP54869.

2D gel databases

REPRODUCTION-2DPAGEP54869.
SWISS-2DPAGEP54869.

PTM databases

PhosphoSiteiP54869.

Expressioni

Tissue specificityi

Liver and kidney.

Gene expression databases

BgeeiP54869.
CleanExiMM_HMGCS2.
GenevestigatoriP54869.

Interactioni

Subunit structurei

Homodimer.By similarity

Protein-protein interaction databases

IntActiP54869. 1 interaction.
MINTiMINT-1859685.

Structurei

3D structure databases

ProteinModelPortaliP54869.
SMRiP54869. Positions 51-508.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the HMG-CoA synthase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG3425.
GeneTreeiENSGT00390000006096.
HOGENOMiHOG000012351.
HOVERGENiHBG051912.
InParanoidiP54869.
KOiK01641.
OMAiACFGLTA.
OrthoDBiEOG741Z1W.
PhylomeDBiP54869.
TreeFamiTF105361.

Family and domain databases

Gene3Di3.40.47.10. 1 hit.
InterProiIPR000590. HMG_CoA_synt_AS.
IPR013746. HMG_CoA_synt_C_dom.
IPR013528. HMG_CoA_synth_N.
IPR010122. HMG_CoA_synthase_euk.
IPR016039. Thiolase-like.
IPR016038. Thiolase-like_subgr.
[Graphical view]
PfamiPF08540. HMG_CoA_synt_C. 1 hit.
PF01154. HMG_CoA_synt_N. 1 hit.
[Graphical view]
SUPFAMiSSF53901. SSF53901. 3 hits.
TIGRFAMsiTIGR01833. HMG-CoA-S_euk. 1 hit.
PROSITEiPS01226. HMG_COA_SYNTHASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P54869-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQRLLAPARR VLQVKRAMQE TSLTPAHLLS AAQQRFSTIP PAPLAKTDTW
60 70 80 90 100
PKDVGILALE VYFPAQYVDQ TDLEKFNNVE AGKYTVGLGQ TRMGFCSVQE
110 120 130 140 150
DINSLCLTVV QRLMERTKLP WDAVGRLEVG TETIIDKSKA VKTVLMELFQ
160 170 180 190 200
DSGNTDIEGI DTTNACYGGT ASLFNAANWM ESSYWDGRYA LVVCGDIAVY
210 220 230 240 250
PSGNARPTGG AGAVAMLIGP KAPLVLEQGL RGTHMENAYD FYKPNLASEY
260 270 280 290 300
PLVDGKLSIQ CYLRALDRCY AAYRKKIQNQ WKQAGNNQPF TLDDVQYMIF
310 320 330 340 350
HTPFCKMVQK SLARLMFNDF LSSSSDKQNN LYKGLEAFRG LKLEETYTNK
360 370 380 390 400
DVDKALLKAS LDMFNQKTKA SLYLSTNNGN MYTSSLYGCL ASLLSHHSAQ
410 420 430 440 450
ELAGSRIGAF SYGSGLAASF FSFRVSKDAS PGSPLEKLVS SVSDLPKRLD
460 470 480 490 500
SRRRMSPEEF TEIMNQREQF YHKVNFSPPG DTSNLFPGTW YLERVDEMHR

RKYARCPV
Length:508
Mass (Da):56,823
Last modified:March 15, 2005 - v2
Checksum:i5A20ACE918FF4758
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti29 – 313LSA → EFR (PubMed:15489334).Curated
Sequence conflicti394 – 3941L → I in BAB23657 (PubMed:16141072).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK004865 mRNA. Translation: BAB23626.1.
AK004902 mRNA. Translation: BAB23657.1.
BC014714 mRNA. Translation: AAH14714.1.
BC024744 mRNA. Translation: AAH24744.1.
U12790 Genomic DNA. Translation: AAA92675.1.
U12791 Genomic DNA. Translation: AAA92676.1.
CCDSiCCDS17662.1.
PIRiB55729.
RefSeqiNP_032282.2. NM_008256.4.
UniGeneiMm.289131.

Genome annotation databases

EnsembliENSMUST00000090746; ENSMUSP00000088249; ENSMUSG00000027875.
ENSMUST00000120541; ENSMUSP00000113296; ENSMUSG00000027875.
GeneIDi15360.
KEGGimmu:15360.
UCSCiuc008qpr.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK004865 mRNA. Translation: BAB23626.1.
AK004902 mRNA. Translation: BAB23657.1.
BC014714 mRNA. Translation: AAH14714.1.
BC024744 mRNA. Translation: AAH24744.1.
U12790 Genomic DNA. Translation: AAA92675.1.
U12791 Genomic DNA. Translation: AAA92676.1.
CCDSiCCDS17662.1.
PIRiB55729.
RefSeqiNP_032282.2. NM_008256.4.
UniGeneiMm.289131.

3D structure databases

ProteinModelPortaliP54869.
SMRiP54869. Positions 51-508.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP54869. 1 interaction.
MINTiMINT-1859685.

PTM databases

PhosphoSiteiP54869.

2D gel databases

REPRODUCTION-2DPAGEP54869.
SWISS-2DPAGEP54869.

Proteomic databases

MaxQBiP54869.
PaxDbiP54869.
PRIDEiP54869.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000090746; ENSMUSP00000088249; ENSMUSG00000027875.
ENSMUST00000120541; ENSMUSP00000113296; ENSMUSG00000027875.
GeneIDi15360.
KEGGimmu:15360.
UCSCiuc008qpr.2. mouse.

Organism-specific databases

CTDi3158.
MGIiMGI:101939. Hmgcs2.

Phylogenomic databases

eggNOGiCOG3425.
GeneTreeiENSGT00390000006096.
HOGENOMiHOG000012351.
HOVERGENiHBG051912.
InParanoidiP54869.
KOiK01641.
OMAiACFGLTA.
OrthoDBiEOG741Z1W.
PhylomeDBiP54869.
TreeFamiTF105361.

Enzyme and pathway databases

UniPathwayiUPA00058; UER00102.
BRENDAi2.3.3.10. 3474.
ReactomeiREACT_272139. PPARA activates gene expression.
REACT_286913. Synthesis of Ketone Bodies.

Miscellaneous databases

NextBioi287976.
PROiP54869.
SOURCEiSearch...

Gene expression databases

BgeeiP54869.
CleanExiMM_HMGCS2.
GenevestigatoriP54869.

Family and domain databases

Gene3Di3.40.47.10. 1 hit.
InterProiIPR000590. HMG_CoA_synt_AS.
IPR013746. HMG_CoA_synt_C_dom.
IPR013528. HMG_CoA_synth_N.
IPR010122. HMG_CoA_synthase_euk.
IPR016039. Thiolase-like.
IPR016038. Thiolase-like_subgr.
[Graphical view]
PfamiPF08540. HMG_CoA_synt_C. 1 hit.
PF01154. HMG_CoA_synt_N. 1 hit.
[Graphical view]
SUPFAMiSSF53901. SSF53901. 3 hits.
TIGRFAMsiTIGR01833. HMG-CoA-S_euk. 1 hit.
PROSITEiPS01226. HMG_COA_SYNTHASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "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(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Liver.
  2. "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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: FVB/N.
    Tissue: Colon and Liver.
  3. "Human mitochondrial HMG CoA synthase: liver cDNA and partial genomic cloning, chromosome mapping to 1p12-p13, and possible role in vertebrate evolution."
    Boukaftane Y., Duncan A., Wang S., Labuda D., Robert M.-F., Sarrazin J., Schappert K.T., Mitchell G.A.
    Genomics 23:552-559(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 29-508.
    Strain: CHS.
    Tissue: Liver.
  4. "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(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUCCINYLATION [LARGE SCALE ANALYSIS] AT LYS-52; LYS-83; LYS-118; LYS-221; LYS-256; LYS-310; LYS-327; LYS-333; LYS-342; LYS-350; LYS-354; LYS-358; LYS-447 AND LYS-473, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  5. "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(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-83; LYS-118; LYS-243; LYS-256; LYS-306; LYS-310; LYS-327; LYS-342; LYS-350; LYS-354; LYS-358; LYS-427; LYS-437; LYS-447 AND LYS-473, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

Entry informationi

Entry nameiHMCS2_MOUSE
AccessioniPrimary (citable) accession number: P54869
Secondary accession number(s): Q64740, Q9DBK1, Q9DBM4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: March 15, 2005
Last modified: April 1, 2015
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

External Data

Dasty 3

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 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.