3-hydroxy-3-methylglutaryl-coenzyme A reductase 1 (P12683)

Identification

Name

3-hydroxy-3-methylglutaryl-coenzyme A reductase 1

Synonyms

HMG-CoA reductase 1

Gene Name

HMG1

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

Gene Properties

Chromosome Location

chromosome 13

Locus

YML075C

Gene Sequence

>3165 bp ATGCCGCCGCTATTCAAGGGACTGAAACAGATGGCAAAGCCAATTGCCTATGTTTCAAGA TTTTCGGCGAAACGACCAATTCATATAATACTTTTTTCTCTAATCATATCCGCATTCGCT TATCTATCCGTCATTCAGTATTACTTCAATGGTTGGCAACTAGATTCAAATAGTGTTTTT GAAACTGCTCCAAATAAAGACTCCAACACTCTATTTCAAGAATGTTCCCATTACTACAGA GATTCCTCTCTAGATGGTTGGGTATCAATCACCGCGCATGAAGCTAGTGAGTTACCAGCC CCACACCATTACTATCTATTAAACCTGAACTTCAATAGTCCTAATGAAACTGACTCCATT CCAGAACTAGCTAACACGGTTTTTGAGAAAGATAATACAAAATATATTCTGCAAGAAGAT CTCAGTGTTTCCAAAGAAATTTCTTCTACTGATGGAACGAAATGGAGGTTAAGAAGTGAC AGAAAAAGTCTTTTCGACGTAAAGACGTTAGCATATTCTCTCTACGATGTATTTTCAGAA AATGTAACCCAAGCAGACCCGTTTGACGTCCTTATTATGGTTACTGCCTACCTAATGATG TTCTACACCATATTCGGCCTCTTCAATGACATGAGGAAGACCGGGTCAAATTTTTGGTTG AGCGCCTCTACAGTGGTCAATTCTGCATCATCACTTTTCTTAGCATTGTATGTCACCCAA TGTATTCTAGGCAAAGAAGTTTCCGCATTAACTCTTTTTGAAGGTTTGCCTTTCATTGTA GTTGTTGTTGGTTTCAAGCACAAAATCAAGATTGCCCAGTATGCCCTGGAGAAATTTGAA AGAGTCGGTTTATCTAAAAGGATTACTACCGATGAAATCGTTTTTGAATCCGTGAGCGAA GAGGGTGGTCGTTTGATTCAAGACCATTTGCTTTGTATTTTTGCCTTTATCGGATGCTCT ATGTATGCTCACCAATTGAAGACTTTGACAAACTTCTGCATATTATCAGCATTTATCCTA ATTTTTGAATTGATTTTAACTCCTACATTTTATTCTGCTATCTTAGCGCTTAGACTGGAA ATGAATGTTATCCACAGATCTACTATTATCAAGCAAACATTAGAAGAAGACGGTGTTGTT CCATCTACAGCAAGAATCATTTCTAAAGCAGAAAAGAAATCCGTATCTTCTTTCTTAAAT CTCAGTGTGGTTGTCATTATCATGAAACTCTCTGTCATACTGTTGTTTGTCTTCATCAAC TTTTATAACTTTGGTGCAAATTGGGTCAATGATGCCTTCAATTCATTGTACTTCGATAAG GAACGTGTTTCTCTACCAGATTTTATTACCTCGAATGCCTCTGAAAACTTTAAAGAGCAA GCTATTGTTAGTGTCACCCCATTATTATATTACAAACCCATTAAGTCCTACCAACGCATT GAGGATATGGTTCTTCTATTGCTTCGTAATGTCAGTGTTGCCATTCGTGATAGGTTCGTC AGTAAATTAGTTCTTTCCGCCTTAGTATGCAGTGCTGTCATCAATGTGTATTTATTGAAT GCTGCTAGAATTCATACCAGTTATACTGCAGACCAATTGGTGAAAACTGAAGTCACCAAG AAGTCTTTTACTGCTCCTGTACAAAAGGCTTCTACACCAGTTTTAACCAATAAAACAGTC ATTTCTGGATCGAAAGTCAAAAGTTTATCATCTGCGCAATCGAGCTCATCAGGACCTTCA TCATCTAGTGAGGAAGATGATTCCCGCGATATTGAAAGCTTGGATAAGAAAATACGTCCT TTAGAAGAATTAGAAGCATTATTAAGTAGTGGAAATACAAAACAATTGAAGAACAAAGAG GTCGCTGCCTTGGTTATTCACGGTAAGTTACCTTTGTACGCTTTGGAGAAAAAATTAGGT GATACTACGAGAGCGGTTGCGGTACGTAGGAAGGCTCTTTCAATTTTGGCAGAAGCTCCT GTATTAGCATCTGATCGTTTACCATATAAAAATTATGACTACGACCGCGTATTTGGCGCT TGTTGTGAAAATGTTATAGGTTACATGCCTTTGCCCGTTGGTGTTATAGGCCCCTTGGTT ATCGATGGTACATCTTATCATATACCAATGGCAACTACAGAGGGTTGTTTGGTAGCTTCT GCCATGCGTGGCTGTAAGGCAATCAATGCTGGCGGTGGTGCAACAACTGTTTTAACTAAG GATGGTATGACAAGAGGCCCAGTAGTCCGTTTCCCAACTTTGAAAAGATCTGGTGCCTGT AAGATATGGTTAGACTCAGAAGAGGGACAAAACGCAATTAAAAAAGCTTTTAACTCTACA TCAAGATTTGCACGTCTGCAACATATTCAAACTTGTCTAGCAGGAGATTTACTCTTCATG AGATTTAGAACAACTACTGGTGACGCAATGGGTATGAATATGATTTCTAAAGGTGTCGAA TACTCATTAAAGCAAATGGTAGAAGAGTATGGCTGGGAAGATATGGAGGTTGTCTCCGTT TCTGGTAACTACTGTACCGACAAAAAACCAGCTGCCATCAACTGGATCGAAGGTCGTGGT AAGAGTGTCGTCGCAGAAGCTACTATTCCTGGTGATGTTGTCAGAAAAGTGTTAAAAAGT GATGTTTCCGCATTGGTTGAGTTGAACATTGCTAAGAATTTGGTTGGATCTGCAATGGCT GGGTCTGTTGGTGGATTTAACGCACATGCAGCTAATTTAGTGACAGCTGTTTTCTTGGCA TTAGGACAAGATCCTGCACAAAATGTTGAAAGTTCCAACTGTATAACATTGATGAAAGAA GTGGACGGTGATTTGAGAATTTCCGTATCCATGCCATCCATCGAAGTAGGTACCATCGGT GGTGGTACTGTTCTAGAACCACAAGGTGCCATGTTGGACTTATTAGGTGTAAGAGGCCCG CATGCTACCGCTCCTGGTACCAACGCACGTCAATTAGCAAGAATAGTTGCCTGTGCCGTC TTGGCAGGTGAATTATCCTTATGTGCTGCCCTAGCAGCCGGCCATTTGGTTCAAAGTCAT ATGACCCACAACAGGAAACCTGCTGAACCAACAAAACCTAACAATTTGGACGCCACTGAT ATAAATCGTTTGAAAGATGGGTCCGTCACCTGCATTAAATCCTAA

Protein Properties

Pfam Domain Function

HMG-CoA_red (PF00368 )

Protein Residues

1054

Protein Molecular Weight

115624.0

Protein Theoretical pI

8.09

Signalling Regions

None

Transmembrane Regions

27-53
187-211
242-266
300-324
332-357
398-422
499-524

Protein Sequence

>3-hydroxy-3-methylglutaryl-coenzyme A reductase 1 MPPLFKGLKQMAKPIAYVSRFSAKRPIHIILFSLIISAFAYLSVIQYYFNGWQLDSNSVF ETAPNKDSNTLFQECSHYYRDSSLDGWVSITAHEASELPAPHHYYLLNLNFNSPNETDSI PELANTVFEKDNTKYILQEDLSVSKEISSTDGTKWRLRSDRKSLFDVKTLAYSLYDVFSE NVTQADPFDVLIMVTAYLMMFYTIFGLFNDMRKTGSNFWLSASTVVNSASSLFLALYVTQ CILGKEVSALTLFEGLPFIVVVVGFKHKIKIAQYALEKFERVGLSKRITTDEIVFESVSE EGGRLIQDHLLCIFAFIGCSMYAHQLKTLTNFCILSAFILIFELILTPTFYSAILALRLE MNVIHRSTIIKQTLEEDGVVPSTARIISKAEKKSVSSFLNLSVVVIIMKLSVILLFVFIN FYNFGANWVNDAFNSLYFDKERVSLPDFITSNASENFKEQAIVSVTPLLYYKPIKSYQRI EDMVLLLLRNVSVAIRDRFVSKLVLSALVCSAVINVYLLNAARIHTSYTADQLVKTEVTK KSFTAPVQKASTPVLTNKTVISGSKVKSLSSAQSSSSGPSSSSEEDDSRDIESLDKKIRP LEELEALLSSGNTKQLKNKEVAALVIHGKLPLYALEKKLGDTTRAVAVRRKALSILAEAP VLASDRLPYKNYDYDRVFGACCENVIGYMPLPVGVIGPLVIDGTSYHIPMATTEGCLVAS AMRGCKAINAGGGATTVLTKDGMTRGPVVRFPTLKRSGACKIWLDSEEGQNAIKKAFNST SRFARLQHIQTCLAGDLLFMRFRTTTGDAMGMNMISKGVEYSLKQMVEEYGWEDMEVVSV SGNYCTDKKPAAINWIEGRGKSVVAEATIPGDVVRKVLKSDVSALVELNIAKNLVGSAMA GSVGGFNAHAANLVTAVFLALGQDPAQNVESSNCITLMKEVDGDLRISVSMPSIEVGTIG GGTVLEPQGAMLDLLGVRGPHATAPGTNARQLARIVACAVLAGELSLCAALAAGHLVQSH MTHNRKPAEPTKPNNLDATDINRLKDGSVTCIKS

References

External Links

Resource	Link
Saccharomyces Genome Database	HMG1
Uniprot ID	P12683
Uniprot Name	HMDH1_YEAST
GenBank Gene ID	M22002
Genebank Protein ID	171686

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
Bowman, S., Churcher, C., Badcock, K., Brown, D., Chillingworth, T., Connor, R., Dedman, K., Devlin, K., Gentles, S., Hamlin, N., Hunt, S., Jagels, K., Lye, G., Moule, S., Odell, C., Pearson, D., Rajandream, M., Rice, P., Skelton, J., Walsh, S., Whitehead, S., Barrell, B. (1997). "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII." Nature 387:90-93.9169872
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
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
Smolka, M. B., Albuquerque, C. P., Chen, S. H., Zhou, H. (2007). "Proteome-wide identification of in vivo targets of DNA damage checkpoint kinases." Proc Natl Acad Sci U S A 104:10364-10369.17563356
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