HMDH_SCHPO
ID HMDH_SCHPO Reviewed; 1053 AA.
AC Q10283; O74425;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2000, sequence version 2.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase {ECO:0000303|PubMed:8896278};
DE Short=HMG-CoA reductase {ECO:0000303|PubMed:8896278};
DE EC=1.1.1.34 {ECO:0000305|PubMed:8896278};
GN Name=hmg1 {ECO:0000303|PubMed:8896278}; Synonyms=its12;
GN ORFNames=SPCC162.09c;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RX PubMed=8896278;
RX DOI=10.1002/(sici)1097-0061(19960915)12:11<1107::aid-yea992>3.0.co;2-e;
RA Lum P.Y., Edwards S., Wright R.;
RT "Molecular, functional and evolutionary characterization of the gene
RT encoding HMG-CoA reductase in the fission yeast, Schizosaccharomyces
RT pombe.";
RL Yeast 12:1107-1124(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1024 AND THR-1028, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=18257517; DOI=10.1021/pr7006335;
RA Wilson-Grady J.T., Villen J., Gygi S.P.;
RT "Phosphoproteome analysis of fission yeast.";
RL J. Proteome Res. 7:1088-1097(2008).
RN [4]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=19486165; DOI=10.1111/j.1365-2443.2009.01308.x;
RA Fang Y., Imagawa K., Zhou X., Kita A., Sugiura R., Jaiseng W., Kuno T.;
RT "Pleiotropic phenotypes caused by an opal nonsense mutation in an essential
RT gene encoding HMG-CoA reductase in fission yeast.";
RL Genes Cells 14:759-771(2009).
CC -!- FUNCTION: Part of the first module of ergosterol biosynthesis pathway
CC that includes the early steps of the pathway, conserved across all
CC eukaryotes, and which results in the formation of mevalonate from
CC acetyl-coenzyme A (acetyl-CoA) (PubMed:8896278, PubMed:19486165). Hmg1
CC catalyzes the reduction of hydroxymethylglutaryl-CoA (HMG-CoA) to
CC mevalonate (PubMed:8896278, PubMed:19486165). The first module starts
CC with the action of the cytosolic acetyl-CoA acetyltransferase eg10 that
CC catalyzes the formation of acetoacetyl-CoA. The hydroxymethylglutaryl-
CC CoA synthases erg13 then condenses acetyl-CoA with acetoacetyl-CoA to
CC form HMG-CoA. The rate-limiting step of the early module is the
CC reduction to mevalonate by the 3-hydroxy-3-methylglutaryl-coenzyme A
CC (HMG-CoA) reductases hcs1 (Probable). {ECO:0000269|PubMed:19486165,
CC ECO:0000269|PubMed:8896278, ECO:0000305}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(R)-mevalonate + CoA + 2 NADP(+) = (3S)-hydroxy-3-
CC methylglutaryl-CoA + 2 H(+) + 2 NADPH; Xref=Rhea:RHEA:15989,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:36464, ChEBI:CHEBI:43074,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.1.1.34;
CC Evidence={ECO:0000305|PubMed:8896278};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:15991;
CC Evidence={ECO:0000305|PubMed:8896278};
CC -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
CC {ECO:0000305|PubMed:8896278}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:19486165}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:19486165}. Nucleus envelope
CC {ECO:0000269|PubMed:19486165}.
CC -!- SIMILARITY: Belongs to the HMG-CoA reductase family. {ECO:0000305}.
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DR EMBL; L76979; AAB39277.1; -; Genomic_DNA.
DR EMBL; CU329672; CAA19589.1; -; Genomic_DNA.
DR PIR; S72194; S72194.
DR RefSeq; NP_588235.1; NM_001023225.2.
DR AlphaFoldDB; Q10283; -.
DR SMR; Q10283; -.
DR BioGRID; 275573; 10.
DR STRING; 4896.SPCC162.09c.1; -.
DR BindingDB; Q10283; -.
DR ChEMBL; CHEMBL1163121; -.
DR DrugCentral; Q10283; -.
DR iPTMnet; Q10283; -.
DR MaxQB; Q10283; -.
DR PaxDb; Q10283; -.
DR PRIDE; Q10283; -.
DR EnsemblFungi; SPCC162.09c.1; SPCC162.09c.1:pep; SPCC162.09c.
DR GeneID; 2538999; -.
DR KEGG; spo:SPCC162.09c; -.
DR PomBase; SPCC162.09c; hmg1.
DR VEuPathDB; FungiDB:SPCC162.09c; -.
DR eggNOG; KOG2480; Eukaryota.
DR HOGENOM; CLU_001734_0_0_1; -.
DR InParanoid; Q10283; -.
DR OMA; ILFFDCV; -.
DR PhylomeDB; Q10283; -.
DR Reactome; R-SPO-191273; Cholesterol biosynthesis.
DR UniPathway; UPA00058; UER00103.
DR PRO; PR:Q10283; -.
DR Proteomes; UP000002485; Chromosome III.
DR GO; GO:0005783; C:endoplasmic reticulum; HDA:PomBase.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005635; C:nuclear envelope; IDA:PomBase.
DR GO; GO:0031965; C:nuclear membrane; ISS:PomBase.
DR GO; GO:0042175; C:nuclear outer membrane-endoplasmic reticulum membrane network; IDA:PomBase.
DR GO; GO:0005778; C:peroxisomal membrane; IBA:GO_Central.
DR GO; GO:0004420; F:hydroxymethylglutaryl-CoA reductase (NADPH) activity; IDA:PomBase.
DR GO; GO:0015936; P:coenzyme A metabolic process; IEA:InterPro.
DR GO; GO:0006696; P:ergosterol biosynthetic process; IBA:GO_Central.
DR GO; GO:0010142; P:farnesyl diphosphate biosynthetic process, mevalonate pathway; ISS:PomBase.
DR GO; GO:0019287; P:isopentenyl diphosphate biosynthetic process, mevalonate pathway; IMP:PomBase.
DR GO; GO:0008299; P:isoprenoid biosynthetic process; IBA:GO_Central.
DR GO; GO:0016126; P:sterol biosynthetic process; IBA:GO_Central.
DR CDD; cd00643; HMG-CoA_reductase_classI; 1.
DR Gene3D; 1.10.3270.10; -; 1.
DR Gene3D; 3.30.70.420; -; 1.
DR Gene3D; 3.90.770.10; -; 1.
DR InterPro; IPR002202; HMG_CoA_Rdtase.
DR InterPro; IPR023074; HMG_CoA_Rdtase_cat_sf.
DR InterPro; IPR023076; HMG_CoA_Rdtase_CS.
DR InterPro; IPR004554; HMG_CoA_Rdtase_eu_arc.
DR InterPro; IPR023282; HMG_CoA_Rdtase_N.
DR InterPro; IPR009023; HMG_CoA_Rdtase_NAD(P)-bd_sf.
DR InterPro; IPR009029; HMG_CoA_Rdtase_sub-bd_dom_sf.
DR InterPro; IPR000731; SSD.
DR PANTHER; PTHR10572; PTHR10572; 1.
DR Pfam; PF00368; HMG-CoA_red; 1.
DR Pfam; PF12349; Sterol-sensing; 1.
DR PRINTS; PR00071; HMGCOARDTASE.
DR SUPFAM; SSF55035; SSF55035; 1.
DR SUPFAM; SSF56542; SSF56542; 1.
DR TIGRFAMs; TIGR00533; HMG_CoA_R_NADP; 1.
DR PROSITE; PS00066; HMG_COA_REDUCTASE_1; 1.
DR PROSITE; PS00318; HMG_COA_REDUCTASE_2; 1.
DR PROSITE; PS50065; HMG_COA_REDUCTASE_4; 1.
DR PROSITE; PS50156; SSD; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Glycoprotein; Lipid biosynthesis; Lipid metabolism;
KW Membrane; NADP; Nucleus; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..1053
FT /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase"
FT /id="PRO_0000114455"
FT TOPO_DOM 1..8
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT TRANSMEM 9..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..203
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT TRANSMEM 204..224
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 225..232
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT TRANSMEM 233..253
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 254..258
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT TRANSMEM 259..279
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 280..320
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT TRANSMEM 321..341
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 342..362
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 363..417
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT TRANSMEM 418..438
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 439..526
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT TRANSMEM 527..547
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 548..1053
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT DOMAIN 204..365
FT /note="SSD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00199"
FT REGION 1028..1053
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 712
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 846
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 922
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT ACT_SITE 1018
FT /note="Proton donor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10003"
FT BINDING 718..724
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 779..781
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 806..814
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 875..877
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 1017..1018
FT /ligand="CoA"
FT /ligand_id="ChEBI:CHEBI:57287"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT BINDING 1022..1023
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:P04035"
FT MOD_RES 1024
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18257517"
FT MOD_RES 1028
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18257517"
FT CARBOHYD 137
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 518
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 751
FT /note="N -> D (in Ref. 1; AAB39277)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1053 AA; 114877 MW; 33E5C2365222D238 CRC64;
MIYKLAARYP IQVIAIVGIL VSMAYFSFLE ALTQEDFPVL IRALKRFGIL DGFPNTRLPN
EMILKLSSVQ GEDASVWEQI PAAELGGEGF VDFDITQWYY PANAKVDVAQ LVEPYRNDCI
FHDASGACHF FFKEVGNWTV SSIALPSNLA NPPIDYFLDS SSTVIQRILP AIREHGISWS
WLLQLIARTW MNTLKIASQA SKTELLIVGT AYACMLISIV SLYLKMRRLG SKFWLFFSVL
LSTLFSVQFA MTLVRASGVR ISLVSLIESL PFLINVVALD KAAELTRQVI TRCSVSDSHS
PMHEDIAKAC RNAAPPILRH FSFGIVVLAI FSYCNFGIKQ FFLFAAVMIY DLLLLFSFFV
AILTLKLEMR RYNAKDDVRK VLIEEGLSES TARHVADGND SSATTSAGSR YFKVRYGTKI
ILFIFIAFNL FELCSIPFKH YAATSAAAAR LIPLVRSQYP DFKSQRLLDD GVFDDVLSAI
SSMSNIESPS VRLLPAVFYG AELSSTSFLS TIHSFINNWS HYISASFLSK WIVCALSLSI
AVNVFLLNAA RLNSIKEEPE KKVVEKVVEV VKYIPSSNSS SIDDIQKDEI AQESVVRSLE
ECITLYNNGQ ISTLNDEEVV QLTLAKKIPL YALERVLKDV TRAVVIRRTV VSRSSRTKTL
ESSNCPVYHY DYSRVLNACC ENVIGYMPLP LGVAGPLIID GKPFYIPMAT TEGALVASTM
RGCKAINAGG GAVTVLTRDQ MSRGPCVAFP NLTRAGRAKI WLDSPEGQEV MKKAFNSTSR
FARLQHIKTA LAGTRLFIRF CTSTGDAMGM NMISKGVEHA LVVMSNDAGF DDMQVISVSG
NYCTDKKPAA INWIDGRGKS VIAEAIIPGD AVKSVLKTTV EDLVKLNVDK NLIGSAMAGS
VGGFNAHAAN IVTAVYLATG QDPAQNVESS NCITLMDNVD GNLQLSVSMP SIEVGTIGGG
TVLEPQGAML DLLGVRGAHM TSPGDNSRQL ARVVAAAVMA GELSLCSALA SGHLVKSHIG
LNRSALNTPA MDSSAKKPAT DALKSVNSRV PGR
