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Q01581 (HMCS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 155. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hydroxymethylglutaryl-CoA synthase, cytoplasmic

Short name=HMG-CoA synthase
EC=2.3.3.10
Alternative name(s):
3-hydroxy-3-methylglutaryl coenzyme A synthase
Gene names
Name:HMGCS1
Synonyms:HMGCS
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length520 AA.
Sequence statusComplete.
Protein existenceEvidence 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

Cytoplasm.

Sequence similarities

Belongs to the HMG-CoA synthase family.

Sequence caution

The sequence AAH00297.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processCholesterol biosynthesis
Cholesterol metabolism
Lipid biosynthesis
Lipid metabolism
Steroid biosynthesis
Steroid metabolism
Sterol biosynthesis
Sterol metabolism
   Cellular componentCytoplasm
   Molecular functionTransferase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbrain development

Inferred from electronic annotation. Source: Ensembl

cellular lipid metabolic process

Traceable author statement. Source: Reactome

cellular response to cholesterol

Inferred from electronic annotation. Source: Ensembl

cellular response to follicle-stimulating hormone stimulus

Inferred from electronic annotation. Source: Ensembl

cholesterol biosynthetic process

Traceable author statement. Source: Reactome

isoprenoid biosynthetic process

Inferred from electronic annotation. Source: InterPro

lipid metabolic process

Non-traceable author statement Ref.2. Source: ProtInc

liver development

Inferred from electronic annotation. Source: Ensembl

male gonad development

Inferred from electronic annotation. Source: Ensembl

response to acid

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from electronic annotation. Source: Ensembl

response to lipoprotein particle

Inferred from electronic annotation. Source: Ensembl

response to low light intensity stimulus

Inferred from electronic annotation. Source: Ensembl

response to purine-containing compound

Inferred from electronic annotation. Source: Ensembl

response to tellurium ion

Inferred from electronic annotation. Source: Ensembl

response to vitamin E

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytoplasm

Inferred from direct assay. Source: HPA

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay. Source: HPA

plasma membrane

Inferred from direct assay. Source: HPA

   Molecular_functiondrug binding

Inferred from electronic annotation. Source: Ensembl

hydroxymethylglutaryl-CoA synthase activity

Traceable author statement Ref.2. Source: ProtInc

isomerase activity

Inferred from electronic annotation. Source: Ensembl

organic acid binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 520520Hydroxymethylglutaryl-CoA synthase, cytoplasmic
PRO_0000213747

Sites

Active site1291

Amino acid modifications

Modified residue41Phosphoserine Ref.13
Modified residue461N6-acetyllysine Ref.10
Modified residue2731N6-acetyllysine Ref.10
Modified residue4761Phosphothreonine Ref.7
Modified residue4951Phosphoserine Ref.7 Ref.9 Ref.11 Ref.13

Experimental info

Mutagenesis1291C → A or S: Loss of activity.
Sequence conflict2481G → A in CAA47061. Ref.1
Sequence conflict2511K → N in CAA47061. Ref.1
Sequence conflict2991E → K in CAA47061. Ref.1
Sequence conflict3641Q → H in CAA47061. Ref.1
Sequence conflict4201P → Q in CAA47061. Ref.1
Sequence conflict519 – 5202EH → VW in CAA47061. Ref.1

Secondary structure

................................................................................. 520
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q01581 [UniParc].

Last modified October 1, 1996. Version 2.
Checksum: C669212BF86CFF9B

FASTA52057,294
        10         20         30         40         50         60 
MPGSLPLNAE ACWPKDVGIV ALEIYFPSQY VDQAELEKYD GVDAGKYTIG LGQAKMGFCT 

        70         80         90        100        110        120 
DREDINSLCM TVVQNLMERN NLSYDCIGRL EVGTETIIDK SKSVKTNLMQ LFEESGNTDI 

       130        140        150        160        170        180 
EGIDTTNACY GGTAAVFNAV NWIESSSWDG RYALVVAGDI AVYATGNARP TGGVGAVALL 

       190        200        210        220        230        240 
IGPNAPLIFE RGLRGTHMQH AYDFYKPDML SEYPIVDGKL SIQCYLSALD RCYSVYCKKI 

       250        260        270        280        290        300 
HAQWQKEGND KDFTLNDFGF MIFHSPYCKL VQKSLARMLL NDFLNDQNRD KNSIYSGLEA 

       310        320        330        340        350        360 
FGDVKLEDTY FDRDVEKAFM KASSELFSQK TKASLLVSNQ NGNMYTSSVY GSLASVLAQY 

       370        380        390        400        410        420 
SPQQLAGKRI GVFSYGSGLA ATLYSLKVTQ DATPGSALDK ITASLCDLKS RLDSRTGVAP 

       430        440        450        460        470        480 
DVFAENMKLR EDTHHLVNYI PQGSIDSLFE GTWYLVRVDE KHRRTYARRP TPNDDTLDEG 

       490        500        510        520 
VGLVHSNIAT EHIPSPAKKV PRLPATAAEP EAAVISNGEH 

« Hide

References

« Hide 'large scale' references
[1]"Amplification and direct sequencing of a cDNA encoding human cytosolic 3-hydroxy-3-methylglutaryl-coenzyme A synthase."
Russ A.P., Ruzicka V., Maerz W., Appelhans H., Gross W.
Biochim. Biophys. Acta 1132:329-331(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fibroblast.
[2]"Human cytoplasmic 3-hydroxy-3-methylglutaryl coenzyme A synthase: expression, purification, and characterization of recombinant wild-type and Cys129 mutant enzymes."
Rokosz L.L., Boulton D.A., Butkiewicz E.A., Sanyal G., Cueto M.A., Lachance P.A., Hermes J.D.
Arch. Biochem. Biophys. 312:1-13(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, MUTAGENESIS.
Tissue: Fetal adrenal gland.
[3]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Placenta.
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-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].
Tissue: Lung.
[7]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-476 AND SER-495, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-495, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[10]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-46 AND LYS-273, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-495, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4 AND SER-495, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X66435 mRNA. Translation: CAA47061.1.
L25798 mRNA. Translation: AAA62411.1.
BT007302 mRNA. Translation: AAP35966.1.
AK315593 mRNA. Translation: BAG37965.1.
CH471119 Genomic DNA. Translation: EAW56054.1.
BC000297 mRNA. Translation: AAH00297.2. Different initiation.
PIRS27197.
S45497.
RefSeqNP_001091742.1. NM_001098272.2.
NP_002121.4. NM_002130.7.
UniGeneHs.397729.
Hs.741287.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2P8UX-ray2.00A/B16-470[»]
ProteinModelPortalQ01581.
SMRQ01581. Positions 16-470.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109400. 10 interactions.
IntActQ01581. 2 interactions.
STRING9606.ENSP00000322706.

Chemistry

GuidetoPHARMACOLOGY638.

PTM databases

PhosphoSiteQ01581.

Polymorphism databases

DMDM1708239.

Proteomic databases

PaxDbQ01581.
PeptideAtlasQ01581.
PRIDEQ01581.

Protocols and materials databases

DNASU3157.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000325110; ENSP00000322706; ENSG00000112972.
ENST00000433297; ENSP00000399402; ENSG00000112972.
GeneID3157.
KEGGhsa:3157.
UCSCuc003jnq.5. human.

Organism-specific databases

CTD3157.
GeneCardsGC05M043326.
HGNCHGNC:5007. HMGCS1.
HPACAB032907.
HPA036913.
HPA036914.
MIM142940. gene.
neXtProtNX_Q01581.
PharmGKBPA29337.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3425.
HOGENOMHOG000012351.
HOVERGENHBG051912.
InParanoidQ01581.
KOK01641.
OMAVPTCKLV.
OrthoDBEOG741Z1W.
PhylomeDBQ01581.
TreeFamTF105361.

Enzyme and pathway databases

BioCycMetaCyc:ENSG00000112972-MONOMER.
BRENDA2.3.3.10. 2681.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00058; UER00102.

Gene expression databases

ArrayExpressQ01581.
BgeeQ01581.
CleanExHS_HMGCS1.
GenevestigatorQ01581.

Family and domain databases

Gene3D3.40.47.10. 1 hit.
InterProIPR000590. HMG_CoA_synt_AS.
IPR013746. HMG_CoA_synt_C.
IPR013528. HMG_CoA_synth_N.
IPR010122. HMG_CoA_synthase_euk.
IPR016039. Thiolase-like.
IPR016038. Thiolase-like_subgr.
[Graphical view]
PfamPF08540. HMG_CoA_synt_C. 1 hit.
PF01154. HMG_CoA_synt_N. 1 hit.
[Graphical view]
SUPFAMSSF53901. SSF53901. 3 hits.
TIGRFAMsTIGR01833. HMG-CoA-S_euk. 1 hit.
PROSITEPS01226. HMG_COA_SYNTHASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSHMGCS1. human.
EvolutionaryTraceQ01581.
GenomeRNAi3157.
NextBio12504.
PROQ01581.
SOURCESearch...

Entry information

Entry nameHMCS1_HUMAN
AccessionPrimary (citable) accession number: Q01581
Secondary accession number(s): B2RDL8
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1993
Last sequence update: October 1, 1996
Last modified: April 16, 2014
This is version 155 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM