Reviewed, UniProtKB/Swiss-Prot P54869 (HMCS2_MOUSE)

Names and origin

Protein names

Recommended name:
    Hydroxymethylglutaryl-CoA synthase, mitochondrial
      Short name=HMG-CoA synthase
    EC=2.3.3.10
Alternative name(s):
    3-hydroxy-3-methylglutaryl coenzyme A synthase

Gene names

Name:

Hmgcs2

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	508 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	This enzyme condenses acetyl-CoA with acetoacetyl-CoA to form HMG-CoA, which is the substrate for HMG-CoA reductase.
Catalytic activity	Acetyl-CoA + H2O + acetoacetyl-CoA = (S)-3-hydroxy-3-methylglutaryl-CoA + CoA.
Pathway	Metabolic intermediate biosynthesis; (R)-mevalonate biosynthesis; (R)-mevalonate from acetyl-CoA: step 2/3.
Subcellular location	Mitochondrion.
Tissue specificity	Liver and kidney.
Post-translational modification	Acetylation of Lys-427 is observed in liver mitochondria from fasted mice but not from fed mice.
Sequence similarities	Belongs to the HMG-CoA synthase family.

Ontologies

Keywords
Biological process	Cholesterol biosynthesis Lipid synthesis Steroid biosynthesis Sterol biosynthesis
Cellular component	Mitochondrion
Domain	Transit peptide
Molecular function	Transferase
PTM	Acetylation Phosphoprotein
Gene Ontology (GO)
Biological process	cholesterol biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW isoprenoid biosynthetic process Inferred from electronic annotation. Source: InterPro
Cellular component	mitochondrial inner membrane Inferred from direct assay. Source: MGI
Molecular function	hydroxymethylglutaryl-CoA synthase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 37	37	Mitochondrion Probable
	Chain	38 – 508	471	Hydroxymethylglutaryl-CoA synthase, mitochondrial		PRO_0000013484
Sites
	Active site	166	1	Potential
Amino acid modifications
	Modified residue	83	1	N6-acetyllysine Ref.4
	Modified residue	427	1	N6-acetyllysine Ref.4
	Modified residue	433	1	Phosphoserine Ref.5
	Modified residue	437	1	N6-acetyllysine Ref.4
Experimental info
	Sequence conflict	29 – 31	3	LSA → EFR Ref.2
	Sequence conflict	394	1	L → I in BAB23657. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P54869-1 [UniParc]. Last modified March 15, 2005. Version 2. Checksum: 5A20ACE918FF4758	FASTA	508	56,823
	10 20 30 40 50 60 MQRLLAPARR VLQVKRAMQE TSLTPAHLLS AAQQRFSTIP PAPLAKTDTW PKDVGILALE 70 80 90 100 110 120 VYFPAQYVDQ TDLEKFNNVE AGKYTVGLGQ TRMGFCSVQE DINSLCLTVV QRLMERTKLP 130 140 150 160 170 180 WDAVGRLEVG TETIIDKSKA VKTVLMELFQ DSGNTDIEGI DTTNACYGGT ASLFNAANWM 190 200 210 220 230 240 ESSYWDGRYA LVVCGDIAVY PSGNARPTGG AGAVAMLIGP KAPLVLEQGL RGTHMENAYD 250 260 270 280 290 300 FYKPNLASEY PLVDGKLSIQ CYLRALDRCY AAYRKKIQNQ WKQAGNNQPF TLDDVQYMIF 310 320 330 340 350 360 HTPFCKMVQK SLARLMFNDF LSSSSDKQNN LYKGLEAFRG LKLEETYTNK DVDKALLKAS 370 380 390 400 410 420 LDMFNQKTKA SLYLSTNNGN MYTSSLYGCL ASLLSHHSAQ ELAGSRIGAF SYGSGLAASF 430 440 450 460 470 480 FSFRVSKDAS PGSPLEKLVS SVSDLPKRLD SRRRMSPEEF TEIMNQREQF YHKVNFSPPG 490 500 DTSNLFPGTW YLERVDEMHR RKYARCPV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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(2005) [PubMed: 16141072] [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(2004) [PubMed: 15489334] [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(1994) [PubMed: 7851882] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 29-508. Strain: CHS. Tissue: Liver.
[4]	"Substrate and functional diversity of lysine acetylation revealed by a proteomics survey." Kim S.C., Sprung R., Chen Y., Xu Y., Ball H., Pei J., Cheng T., Kho Y., Xiao H., Xiao L., Grishin N.V., White M., Yang X.-J., Zhao Y. Mol. Cell 23:607-618(2006) [PubMed: 16916647] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-83; LYS-427 AND LYS-437, MASS SPECTROMETRY. Tissue: Liver.
[5]	"Mitochondrial phosphoproteome revealed by an improved IMAC method and MS/MS/MS." Lee J., Xu Y., Chen Y., Sprung R., Kim S.C., Xie S., Zhao Y. Mol. Cell. Proteomics 6:669-676(2007) [PubMed: 17208939] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-433, MASS SPECTROMETRY. Tissue: Liver.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
IPI	IPI00420718.
PIR	B55729.
RefSeq	NP_032282.2.
UniGene	Mm.289131
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	P54869.
PTM databases
PhosphoSite	P54869.
2-D gel databases
SWISS-2DPAGE	P54869.
REPRODUCTION-2DPAGE	P54869.
Proteomic databases
PRIDE	P54869.
Genome annotation databases
Ensembl	ENSMUST00000090746; ENSMUSP00000088249; ENSMUSG00000027875; Mus musculus. [Genome view] ENSMUST00000120541; ENSMUSP00000113296; ENSMUSG00000027875; Mus musculus. [Genome view]
GeneID	15360.
KEGG	mmu:15360.
UCSC	uc008qpr.1. mouse.
Organism-specific databases
CTD	15360.
MGI	MGI:101939. Hmgcs2.
Phylogenomic databases
HOGENOM	P54869.
HOVERGEN	P54869.
OMA	GKYSTEQ.
Enzyme and pathway databases
BRENDA	2.3.3.10. 244.
Gene expression databases
ArrayExpress	P54869.
Bgee	P54869.
CleanEx	MM_HMGCS2.
Genevestigator	P54869.
GermOnline	ENSMUSG00000027875. Mus musculus.
Family and domain databases
InterPro	IPR000590. HMG_CoA_synt_AS. IPR013746. HMG_CoA_synt_C. IPR013528. HMG_CoA_synth_N. IPR010122. HMG_CoA_synthase_euk. [Graphical view]
Pfam	PF08540. HMG_CoA_synt_C. 1 hit. PF01154. HMG_CoA_synt_N. 1 hit. [Graphical view]
TIGRFAMs	TIGR01833. HMG-CoA-S_euk. 1 hit.
PROSITE	PS01226. HMG_COA_SYNTHASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	287976.
SOURCE	Search...

Entry information

Entry name

HMCS2_MOUSE

Accession

Primary (citable) accession number: P54869
Secondary accession number(s): Q64740, Q9DBK1, Q9DBM4

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	March 15, 2005
Last modified:	November 3, 2009
This is version 84 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)