3-hydroxy-3-methylglutaryl-coenzyme A reductase 2 (P12684)

Identification

Name

3-hydroxy-3-methylglutaryl-coenzyme A reductase 2

Synonyms

HMG-CoA reductase 2

Gene Name

HMG2

Enzyme Class

1.1.1.34

Biological Properties

General Function

Involved in hydroxymethylglutaryl-CoA reductase (NADPH) activity

Specific Function

This transmembrane glycoprotein is involved in the control of cholesterol biosynthesis. It is the rate-limiting enzyme of the sterol biosynthesis

Cellular Location

Endoplasmic reticulum membrane; Multi-pass membrane protein

SMPDB Pathways

Cholesterol biosynthesis and metabolism CE(10:0)	PW002545
Cholesterol biosynthesis and metabolism CE(12:0)	PW002548
Cholesterol biosynthesis and metabolism CE(14:0)	PW002544
Cholesterol biosynthesis and metabolism CE(16:0)	PW002550
Cholesterol biosynthesis and metabolism CE(18:0)	PW002551

KEGG Pathways

Terpenoid backbone biosynthesis

ec00900

SMPDB Reactions

3-Hydroxy-3-methylglutaryl-CoA + NADPH → (R)-Mevalonic acid + NADP + Coenzyme A

KEGG Reactions

NADP + (R)-Mevalonic acid + Coenzyme A ↔ 3-Hydroxy-3-methylglutaryl-CoA + hydron + NADPH

Metabolites

YMDB ID	Name	View
YMDB00045	Coenzyme A	Show
YMDB00310	22b-Hydroxycholesterol	Show
YMDB00426	NADPH	Show
YMDB00427	NADP	Show
YMDB00707	(R)-Mevalonic acid	Show
YMDB00708	3-Hydroxy-3-methylglutaryl-CoA	Show
YMDB00862	hydron	Show
YMDB01039	(R)-Mevalonate	Show

GO Classification

Component
cell part
membrane part
intrinsic to membrane
integral to membrane
Function
nucleotide binding
oxidoreductase activity
cofactor binding
oxidoreductase activity, acting on CH-OH group of donors
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
catalytic activity
NADP or NADPH binding
coenzyme binding
hydroxymethylglutaryl-CoA reductase (NADPH) activity
binding
Process
coenzyme A metabolic process
primary metabolic process
oxidation reduction
cofactor metabolic process
coenzyme metabolic process
metabolic process
lipid metabolic process
cellular lipid metabolic process
isoprenoid metabolic process
cellular metabolic process
isoprenoid biosynthetic process

Gene Properties

Chromosome Location

chromosome 12

Locus

YLR450W

Gene Sequence

>3138 bp ATGTCACTTCCCTTAAAAACGATAGTACATTTGGTAAAGCCCTTTGCTTGCACTGCTAGG TTTAGTGCGAGATACCCAATCCACGTCATTGTTGTTGCTGTTTTATTGAGTGCCGCTGCT TATCTATCCGTGACACAATCTTACCTTAACGAATGGAAGCTGGACTCTAATCAGTATTCT ACATACTTAAGCATAAAGCCGGATGAGTTGTTTGAAAAATGCACACACTACTATAGGTCT CCTGTGTCTGATACATGGAAGTTACTCAGCTCTAAAGAAGCCGCCGATATTTATACCCCT TTTCATTATTATTTGTCTACCATAAGTTTTCAAAGTAAGGACAATTCAACGACTTTGCCT TCCCTTGATGACGTTATTTACAGTGTTGACCATACCAGGTACTTATTAAGTGAAGAGCCA AAGATACCAACTGAACTAGTGTCTGAAAACGGAACGAAATGGAGATTGAGAAACAACAGC AATTTTATTTTGGACCTGCATAATATTTACCGAAATATGGTGAAGCAATTTTCTAACAAA ACGAGCGAATTTGATCAGTTCGATTTGTTTATCATCCTAGCTGCTTACCTTACTCTTTTT TATACTCTCTGTTGCCTGTTTAATGACATGAGGAAAATCGGATCAAAGTTTTGGTTAAGC TTTTCTGCTCTTTCAAACTCTGCATGCGCATTATATTTATCGCTGTACACAACTCACAGT TTATTGAAGAAACCGGCTTCCTTATTAAGTTTGGTCATTGGACTACCATTTATCGTAGTA ATTATTGGCTTTAAGCATAAAGTTCGACTTGCGGCATTCTCGCTACAAAAATTCCACAGA ATTAGTATTGACAAGAAAATAACGGTAAGCAACATTATTTATGAGGCTATGTTTCAAGAA GGTGCCTACTTAATCCGCGACTACTTATTTTATATTAGCTCCTTCATTGGATGTGCTATT TATGCTAGACATCTTCCCGGATTGGTCAATTTCTGTATTTTGTCTACATTTATGCTAGTT TTCGACTTGCTTTTGTCTGCTACTTTTTATTCTGCCATTTTATCAATGAAGCTGGAAATT AACATCATTCACAGATCAACCGTCATCAGACAGACTTTGGAAGAGGACGGAGTTGTCCCA ACTACAGCAGATATTATATATAAGGATGAAACTGCCTCAGAACCACATTTTTTGAGATCT AACGTGGCTATCATTCTGGGAAAAGCATCAGTTATTGGTCTTTTGCTTCTGATCAACCTT TATGTTTTCACAGATAAGTTAAATGCTACAATACTAAACACGGTATATTTTGACTCTACA ATTTACTCGTTACCAAATTTTATCAATTATAAAGATATTGGCAATCTCAGCAATCAAGTG ATCATTTCCGTGTTGCCAAAGCAATATTATACTCCGCTGAAAAAATACCATCAGATCGAA GATTCTGTTCTACTTATCATTGATTCCGTTAGCAATGCTATTCGGGACCAATTTATCAGC AAGTTACTTTTTTTTGCATTTGCAGTTAGTATTTCCATCAATGTCTACTTACTGAATGCT GCAAAAATTCACACAGGATACATGAACTTCCAACCACAATCAAATAAGATCGATGATCTT GTTGTTCAGCAAAAATCGGCAACGATTGAGTTTTCAGAAACTCGAAGTATGCCTGCTTCT TCTGGCCTAGAAACTCCAGTGACCGCGAAAGATATAATTATCTCTGAAGAAATCCAGAAT AACGAATGCGTCTATGCTTTGAGTTCCCAGGACGAGCCTATCCGTCCTTTATCGAATTTA GTGGAACTTATGGAGAAAGAACAATTAAAGAACATGAATAATACTGAGGTTTCGAATCTT GTCGTCAACGGTAAACTGCCATTATATTCCTTAGAGAAAAAATTAGAGGACACAACTCGT GCGGTTTTAGTTAGGAGAAAGGCACTTTCAACTTTGGCTGAATCGCCAATTTTAGTTTCC GAAAAATTGCCCTTCAGAAATTATGATTATGATCGCGTTTTTGGAGCTTGCTGTGAAAAT GTCATCGGCTATATGCCAATACCAGTTGGTGTAATTGGTCCATTAATTATTGATGGAACA TCTTATCACATACCAATGGCAACCACGGAAGGTTGTTTAGTGGCTTCAGCTATGCGTGGT TGCAAAGCCATCAATGCTGGTGGTGGTGCAACAACTGTTTTAACCAAAGATGGTATGACT AGAGGCCCAGTCGTTCGTTTCCCTACTTTAATAAGATCTGGTGCCTGCAAGATATGGTTA GACTCGGAAGAGGGACAAAATTCAATTAAAAAAGCTTTTAATTCTACATCAAGGTTTGCA CGTTTGCAACATATTCAAACCTGTCTAGCAGGCGATTTGCTTTTTATGAGATTTCGGACA ACTACCGGTGACGCAATGGGTATGAACATGATATCGAAAGGTGTCGAATACTCTTTGAAA CAAATGGTAGAAGAATATGGTTGGGAAGATATGGAAGTTGTCTCCGTATCTGGTAACTAT TGTACTGATAAGAAACCTGCCGCAATCAATTGGATTGAAGGTCGTGGTAAAAGTGTCGTA GCTGAAGCTACTATTCCTGGTGATGTCGTAAAAAGTGTTTTAAAGAGCGATGTTTCCGCT TTAGTTGAATTAAATATATCCAAGAACTTGGTTGGATCCGCAATGGCTGGATCTGTTGGT GGTTTCAACGCGCACGCAGCTAATTTGGTCACTGCACTTTTCTTGGCATTAGGCCAAGAT CCTGCGCAGAACGTCGAAAGTTCCAACTGTATAACTTTGATGAAGGAAGTTGATGGTGAT TTAAGGATCTCTGTTTCCATGCCATCTATTGAAGTTGGTACGATTGGCGGGGGTACTGTT CTGGAGCCTCAGGGCGCCATGCTTGATCTTCTCGGCGTTCGTGGTCCTCACCCCACTGAA CCTGGAGCAAATGCTAGGCAATTAGCTAGAATAATCGCGTGTGCTGTCTTGGCTGGTGAA CTGTCTCTGTGCTCCGCACTTGCTGCCGGTCACCTGGTACAAAGCCATATGACTCACAAC CGTAAAACAAACAAAGCCAATGAACTGCCACAACCAAGTAACAAAGGGCCCCCCTGTAAA ACCTCAGCATTATTATAA

Protein Properties

Pfam Domain Function

HMG-CoA_red (PF00368 )

Protein Residues

1045

Protein Molecular Weight

115691.0

Protein Theoretical pI

7.62

Signalling Regions

None

Transmembrane Regions

27-53
186-210
241-265
299-323
331-356
397-421
498-523

Protein Sequence

>3-hydroxy-3-methylglutaryl-coenzyme A reductase 2 MSLPLKTIVHLVKPFACTARFSARYPIHVIVVAVLLSAAAYLSVTQSYLNEWKLDSNQYS TYLSIKPDELFEKCTHYYRSPVSDTWKLLSSKEAADIYTPFHYYLSTISFQSKDNSTTLP SLDDVIYSVDHTRYLLSEEPKIPTELVSENGTKWRLRNNSNFILDLHNIYRNMVKQFSNK TSEFDQFDLFIILAAYLTLFYTLCCLFNDMRKIGSKFWLSFSALSNSACALYLSLYTTHS LLKKPASLLSLVIGLPFIVVIIGFKHKVRLAAFSLQKFHRISIDKKITVSNIIYEAMFQE GAYLIRDYLFYISSFIGCAIYARHLPGLVNFCILSTFMLVFDLLLSATFYSAILSMKLEI NIIHRSTVIRQTLEEDGVVPTTADIIYKDETASEPHFLRSNVAIILGKASVIGLLLLINL YVFTDKLNATILNTVYFDSTIYSLPNFINYKDIGNLSNQVIISVLPKQYYTPLKKYHQIE DSVLLIIDSVSNAIRDQFISKLLFFAFAVSISINVYLLNAAKIHTGYMNFQPQSNKIDDL VVQQKSATIEFSETRSMPASSGLETPVTAKDIIISEEIQNNECVYALSSQDEPIRPLSNL VELMEKEQLKNMNNTEVSNLVVNGKLPLYSLEKKLEDTTRAVLVRRKALSTLAESPILVS EKLPFRNYDYDRVFGACCENVIGYMPIPVGVIGPLIIDGTSYHIPMATTEGCLVASAMRG CKAINAGGGATTVLTKDGMTRGPVVRFPTLIRSGACKIWLDSEEGQNSIKKAFNSTSRFA RLQHIQTCLAGDLLFMRFRTTTGDAMGMNMISKGVEYSLKQMVEEYGWEDMEVVSVSGNY CTDKKPAAINWIEGRGKSVVAEATIPGDVVKSVLKSDVSALVELNISKNLVGSAMAGSVG GFNAHAANLVTALFLALGQDPAQNVESSNCITLMKEVDGDLRISVSMPSIEVGTIGGGTV LEPQGAMLDLLGVRGPHPTEPGANARQLARIIACAVLAGELSLCSALAAGHLVQSHMTHN RKTNKANELPQPSNKGPPCKTSALL

References

External Links

Resource	Link
Saccharomyces Genome Database	HMG2
Uniprot ID	P12684
Uniprot Name	HMDH2_YEAST
GenBank Gene ID	M22255
Genebank Protein ID	171688

General Reference

Basson, M. E., Thorsness, M., Finer-Moore, J., Stroud, R. M., Rine, J. (1988). "Structural and functional conservation between yeast and human 3-hydroxy-3-methylglutaryl coenzyme A reductases, the rate-limiting enzyme of sterol biosynthesis." Mol Cell Biol 8:3797-3808.3065625
Johnston, M., Hillier, L., Riles, L., Albermann, K., Andre, B., Ansorge, W., Benes, V., Bruckner, M., Delius, H., Dubois, E., Dusterhoft, A., Entian, K. D., Floeth, M., Goffeau, A., Hebling, U., Heumann, K., Heuss-Neitzel, D., Hilbert, H., Hilger, F., Kleine, K., Kotter, P., Louis, E. J., Messenguy, F., Mewes, H. W., Hoheisel, J. D., et, a. l. .. (1997). "The nucleotide sequence of Saccharomyces cerevisiae chromosome XII." Nature 387:87-90.9169871
Basson, M. E., Thorsness, M., Rine, J. (1986). "Saccharomyces cerevisiae contains two functional genes encoding 3-hydroxy-3-methylglutaryl-coenzyme A reductase." Proc Natl Acad Sci U S A 83:5563-5567.3526336
Ghaemmaghami, S., Huh, W. K., Bower, K., Howson, R. W., Belle, A., Dephoure, N., O'Shea, E. K., Weissman, J. S. (2003). "Global analysis of protein expression in yeast." Nature 425:737-741.14562106
Kim, H., Melen, K., Osterberg, M., von Heijne, G. (2006). "A global topology map of the Saccharomyces cerevisiae membrane proteome." Proc Natl Acad Sci U S A 103:11142-11147.16847258
Li, X., Gerber, S. A., Rudner, A. D., Beausoleil, S. A., Haas, W., Villen, J., Elias, J. E., Gygi, S. P. (2007). "Large-scale phosphorylation analysis of alpha-factor-arrested Saccharomyces cerevisiae." J Proteome Res 6:1190-1197.17330950
Albuquerque, C. P., Smolka, M. B., Payne, S. H., Bafna, V., Eng, J., Zhou, H. (2008). "A multidimensional chromatography technology for in-depth phosphoproteome analysis." Mol Cell Proteomics 7:1389-1396.18407956