Reviewed, UniProtKB/Swiss-Prot Q01581 (HMCS1_HUMAN)

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) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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.

Ontologies

Keywords
Biological process	Cholesterol biosynthesis Lipid synthesis Steroid biosynthesis Sterol biosynthesis
Cellular component	Cytoplasm
Molecular function	Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome
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	cytosol Ref.2 Inferred from Experiment. Source: Reactome soluble fraction Ref.2 Traceable author statement. Source: ProtInc
Molecular function	hydroxymethylglutaryl-CoA synthase activity Ref.2 Inferred from Experiment. Source: Reactome
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.11

Modified residue

246

1

N6-acetyllysine Ref.11

Modified residue

273

1

N6-acetyllysine Ref.11

Modified residue

321

1

N6-acetyllysine Ref.11

Modified residue

476

1

Phosphothreonine Ref.8

Modified residue

495

1

Phosphoserine Ref.8 Ref.7 Ref.10

Modified residue

516

1

Phosphoserine Ref.10

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)
	Q01581-1 [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: 1358203] [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: 7913309] [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: 14702039] [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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[7]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-495, MASS SPECTROMETRY. Tissue: Epithelium.
[8]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-476 AND SER-495, MASS SPECTROMETRY.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[10]	"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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-495 AND SER-516, MASS SPECTROMETRY. Tissue: T-cell.
[11]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-46; LYS-246; LYS-273 AND LYS-321, MASS SPECTROMETRY.
[12]	"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: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-4, 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.
NP_002121.4.

UniGene

Hs.397729

3D structure databases

PDBe
RCSB PDB
PDBj

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

ModBase

Search...

Protein-protein interaction databases

IntAct

Q01581. 2 interactions.

STRING

Q01581.

PTM databases

PhosphoSite

Q01581.

Proteomic databases

PeptideAtlas

Q01581.

PRIDE

Q01581.

Genome annotation databases

Ensembl

ENST00000325110; ENSP00000322706; ENSG00000112972; Homo sapiens. [Genome view]
ENST00000433297; ENSP00000399402; ENSG00000112972; Homo sapiens. [Genome view]

GeneID

3157.

KEGG

hsa:3157.

NMPDR

fig|9606.3.peg.25212.

UCSC

uc003jnq.2. human.

Organism-specific databases

CTD

3157.

GeneCards

GC05M043326.

H-InvDB

HIX0004843.

HGNC

HGNC:5007. HMGCS1.

MIM

142940. gene.

PharmGKB

PA29337.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG12583.

HOGENOM

HBG578402.

HOVERGEN

Q01581.

InParanoid

Q01581.

OMA

MKASAEL.

OrthoDB

EOG9S4S1K.

PhylomeDB

Q01581.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000112972-MONOMER.

BRENDA

2.3.3.10. 247.

Pathway_Interaction_DB

hnf3bpathway. FOXA2 and FOXA3 transcription factor networks.

Reactome

REACT_602. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpress

Q01581.

Bgee

Q01581.

CleanEx

HS_HMGCS1.

Genevestigator

Q01581.

GermOnline

ENSG00000112972. Homo sapiens.

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.
IPR016039. Thiolase-like.
[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

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:	February 9, 2010
This is version 113 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.