Q01581 (HMCS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	520 AA.
Sequence status	Complete.
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	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 process	Cholesterol biosynthesis Cholesterol metabolism Lipid biosynthesis Lipid metabolism Steroid biosynthesis Steroid metabolism Sterol biosynthesis Sterol metabolism
Cellular component	Cytoplasm
Molecular function	Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	brain development Inferred from electronic annotation. Source: Compara cellular lipid metabolic process Traceable author statement. Source: Reactome cellular response to cholesterol Inferred from electronic annotation. Source: Compara cellular response to follicle-stimulating hormone stimulus Inferred from electronic annotation. Source: Compara cholesterol biosynthetic process Traceable author statement. Source: Reactome isoprenoid biosynthetic process Inferred from electronic annotation. Source: InterPro liver development Inferred from electronic annotation. Source: Compara male gonad development Inferred from electronic annotation. Source: Compara response to acid Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to lipoprotein particle stimulus Inferred from electronic annotation. Source: Compara response to low light intensity stimulus Inferred from electronic annotation. Source: Compara response to purine-containing compound Inferred from electronic annotation. Source: Compara response to tellurium ion Inferred from electronic annotation. Source: Compara response to vitamin E Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay. Source: HPA
Molecular_function	drug binding Inferred from electronic annotation. Source: Compara hydroxymethylglutaryl-CoA synthase activity Traceable author statement Ref.2. Source: ProtInc isomerase activity Inferred from electronic annotation. Source: Compara organic acid binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 520

520

Hydroxymethylglutaryl-CoA synthase, cytoplasmic

PRO_0000213747

Sites

Active site

129

1

Amino acid modifications

Modified residue

4

1

Phosphoserine Ref.12

Modified residue

46

1

N6-acetyllysine Ref.9

Modified residue

273

1

N6-acetyllysine Ref.9

Modified residue

476

1

Phosphothreonine Ref.7

Modified residue

495

1

Phosphoserine Ref.7 Ref.8 Ref.10 Ref.12

Experimental info

Mutagenesis

129

1

C → A or S: Loss of activity.

Sequence conflict

248

1

G → A in CAA47061. Ref.1

Sequence conflict

251

1

K → N in CAA47061. Ref.1

Sequence conflict

299

1

E → K in CAA47061. Ref.1

Sequence conflict

364

1

Q → H in CAA47061. Ref.1

Sequence conflict

420

1

P → Q in CAA47061. Ref.1

Sequence conflict

519 – 520

2

EH → VW in CAA47061. Ref.1

Secondary structure

1

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520

Helix Strand Turn

Details...

Beta strand

18 – 25

8

Beta strand

28 – 32

5

Helix

33 – 40

8

Helix

46 – 51

6

Beta strand

55 – 57

3

Helix

65 – 79

15

Helix

84 – 86

3

Beta strand

87 – 93

7

Beta strand

100 – 102

3

Helix

104 – 108

5

Helix

109 – 111

3

Turn

112 – 116

5

Beta strand

124 – 127

4

Helix

128 – 130

3

Helix

131 – 143

13

Beta strand

152 – 161

10

Helix

169 – 171

3

Beta strand

173 – 184

12

Beta strand

186 – 189

4

Beta strand

195 – 198

4

Beta strand

203 – 205

3

Helix

218 – 247

30

Helix

255 – 257

3

Beta strand

259 – 263

5

Helix

268 – 285

18

Helix

289 – 291

3

Helix

293 – 295

3

Helix

299 – 301

3

Helix

306 – 308

3

Helix

313 – 322

10

Helix

324 – 330

7

Helix

333 – 335

3

Helix

336 – 341

6

Helix

345 – 347

3

Helix

348 – 359

12

Helix

362 – 365

4

Beta strand

369 – 376

8

Turn

377 – 379

3

Beta strand

380 – 388

9

Helix

397 – 403

7

Turn

404 – 407

4

Helix

408 – 413

6

Beta strand

415 – 417

3

Helix

420 – 433

14

Beta strand

453 – 458

6

Beta strand

464 – 468

5

Sequences

	Sequence		Length	Mass (Da)
	Q01581 [UniParc]. Last modified October 1, 1996. Version 2. Checksum: C669212BF86CFF9B	FASTA	520	57,294
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"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, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[9]	"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, MASS SPECTROMETRY.
[10]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"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].
[12]	"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, MASS SPECTROMETRY.
+	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.

IPI

IPI00008475.

PIR

S27197.
S45497.

RefSeq

NP_001091742.1. NM_001098272.2.
NP_002121.4. NM_002130.7.

UniGene

Hs.397729.
Hs.741287.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2P8U	X-ray	2.00	A/B	16-470	[»]

ProteinModelPortal

Q01581.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q01581. 2 interactions.

STRING

9606.ENSP00000322706.

PTM databases

PhosphoSite

Q01581.

Polymorphism databases

DMDM

1708239.

Proteomic databases

PaxDb

Q01581.

PeptideAtlas

Q01581.

PRIDE

Q01581.

Protocols and materials databases

DNASU

3157.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000325110; ENSP00000322706; ENSG00000112972.
ENST00000433297; ENSP00000399402; ENSG00000112972.

GeneID

3157.

KEGG

hsa:3157.

UCSC

uc003jnq.4. human.

Organism-specific databases

CTD

3157.

GeneCards

GC05M043326.

HGNC

HGNC:5007. HMGCS1.

HPA

CAB032907.
HPA036913.
HPA036914.

MIM

142940. gene.

neXtProt

NX_Q01581.

PharmGKB

PA29337.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG3425.

HOGENOM

HOG000012351.

HOVERGEN

HBG051912.

InParanoid

Q01581.

KO

K01641.

OMA

RDFTLND.

OrthoDB

EOG4F1X30.

PhylomeDB

Q01581.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000112972-MONOMER.

BRENDA

2.3.3.10. 2681.

Pathway_Interaction_DB

hnf3bpathway. FOXA2 and FOXA3 transcription factor networks.

Reactome

REACT_111217. Metabolism.

SABIO-RK

Q01581.

UniPathway

UPA00058; UER00102.

Gene expression databases

ArrayExpress

Q01581.

Bgee

Q01581.

CleanEx

HS_HMGCS1.

Genevestigator

Q01581.

GermOnline

ENSG00000112972. Homo sapiens.

Family and domain databases

Gene3D

3.40.47.10. 1 hit.

InterPro

IPR000590. 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]

Pfam

PF08540. HMG_CoA_synt_C. 1 hit.
PF01154. HMG_CoA_synt_N. 1 hit.
[Graphical view]

SUPFAM

SSF53901. Thiolase-like. 2 hits.

TIGRFAMs

TIGR01833. HMG-CoA-S_euk. 1 hit.

PROSITE

PS01226. HMG_COA_SYNTHASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

HMGCS1. human.

EvolutionaryTrace

Q01581.

GenomeRNAi

3157.

NextBio

12504.

SOURCE

Search...

Entry information

Entry name

HMCS1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 146 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.