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HMDH2_DICDI
ID   HMDH2_DICDI             Reviewed;         526 AA.
AC   P34136; Q551D5;
DT   01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT   04-DEC-2007, sequence version 2.
DT   25-MAY-2022, entry version 142.
DE   RecName: Full=3-hydroxy-3-methylglutaryl-coenzyme A reductase 2;
DE            Short=HMG-CoA reductase 2;
DE            EC=1.1.1.34;
GN   Name=hmgB; ORFNames=DDB_G0276615;
OS   Dictyostelium discoideum (Slime mold).
OC   Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC   Dictyosteliaceae; Dictyostelium.
OX   NCBI_TaxID=44689;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=AX4;
RX   PubMed=12097910; DOI=10.1038/nature00847;
RA   Gloeckner G., Eichinger L., Szafranski K., Pachebat J.A., Bankier A.T.,
RA   Dear P.H., Lehmann R., Baumgart C., Parra G., Abril J.F., Guigo R.,
RA   Kumpf K., Tunggal B., Cox E.C., Quail M.A., Platzer M., Rosenthal A.,
RA   Noegel A.A.;
RT   "Sequence and analysis of chromosome 2 of Dictyostelium discoideum.";
RL   Nature 418:79-85(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=AX4;
RX   PubMed=15875012; DOI=10.1038/nature03481;
RA   Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA   Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA   Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA   Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA   Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA   Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA   Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA   Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA   Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA   Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA   Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA   Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA   Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA   Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA   Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA   Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA   Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT   "The genome of the social amoeba Dictyostelium discoideum.";
RL   Nature 435:43-57(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 46-526.
RC   STRAIN=AX3;
RA   De Lozanne A.;
RT   "The dictyostelium HMGCoA reductase genes.";
RL   Submitted (JUN-1993) to the EMBL/GenBank/DDBJ databases.
CC   -!- FUNCTION: This transmembrane glycoprotein is involved in the control of
CC       cholesterol biosynthesis. It is the rate-limiting enzyme of the sterol
CC       biosynthesis.
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:0000255|PROSITE-ProRule:PRU10003};
CC   -!- PATHWAY: Metabolic intermediate biosynthesis; (R)-mevalonate
CC       biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
CC   -!- SIMILARITY: Belongs to the HMG-CoA reductase family. {ECO:0000305}.
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DR   EMBL; AAFI02000016; EAL69120.1; -; Genomic_DNA.
DR   EMBL; L19350; AAA33215.1; -; mRNA.
DR   RefSeq; XP_643058.1; XM_637966.1.
DR   AlphaFoldDB; P34136; -.
DR   SMR; P34136; -.
DR   STRING; 44689.DDB0215357; -.
DR   PaxDb; P34136; -.
DR   EnsemblProtists; EAL69120; EAL69120; DDB_G0276615.
DR   GeneID; 8620599; -.
DR   KEGG; ddi:DDB_G0276615; -.
DR   dictyBase; DDB_G0276615; hmgB.
DR   eggNOG; KOG2480; Eukaryota.
DR   HOGENOM; CLU_001734_2_0_1; -.
DR   InParanoid; P34136; -.
DR   OMA; DDKMTRA; -.
DR   PhylomeDB; P34136; -.
DR   UniPathway; UPA00058; UER00103.
DR   PRO; PR:P34136; -.
DR   Proteomes; UP000002195; Chromosome 2.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR   GO; GO:0005778; C:peroxisomal membrane; IBA:GO_Central.
DR   GO; GO:0004420; F:hydroxymethylglutaryl-CoA reductase (NADPH) activity; IBA:GO_Central.
DR   GO; GO:0006695; P:cholesterol biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0015936; P:coenzyme A metabolic process; IEA:InterPro.
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   PANTHER; PTHR10572; PTHR10572; 1.
DR   Pfam; PF00368; HMG-CoA_red; 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; PS01192; HMG_COA_REDUCTASE_3; 1.
DR   PROSITE; PS50065; HMG_COA_REDUCTASE_4; 1.
PE   2: Evidence at transcript level;
KW   Cholesterol biosynthesis; Cholesterol metabolism; Lipid biosynthesis;
KW   Lipid metabolism; NADP; Oxidoreductase; Reference proteome;
KW   Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW   Sterol metabolism.
FT   CHAIN           1..526
FT                   /note="3-hydroxy-3-methylglutaryl-coenzyme A reductase 2"
FT                   /id="PRO_0000114428"
FT   REGION          503..526
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        510..526
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        193
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        325
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        401
FT                   /note="Charge relay system"
FT                   /evidence="ECO:0000250"
FT   ACT_SITE        499
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10003"
SQ   SEQUENCE   526 AA;  56160 MW;  5C95CCBB7180EC92 CRC64;
     MIRIGSNLIK QSIKNTNKSG ISRFFTTGSN NSTNYKPESC VKEEPKGKSV NVEDLKDQEI
     IALVDKGEIQ PHNLETRLPN NFQRAVHIRR KLLARDLQKE HQRALHAQAV VAAAEKAATS
     GEDPSSIQPV VPPTSNLDFE GSLTNLPVDH FDYTKVLGAC CENVIGYIPI PVGVAGPILL
     DGKLVSIPMA TTEGCLVAST HRGAKAITKS GGAKTVLLQS GMTRAPVCRL PSSIRAGELK
     QWIENQENFY QVASAFNSTS RFARLKSIKV VIAGRLVYLR FKSSTGDAMG MNMVSKGVEK
     ALEVITEYFP EMEVLSLSGN VCTDKKPSSI NWLEGRGKSV VAEAVISGDI VRDVLKTTVE
     ALVSLNIDKN LIGSAMAGSI GGFNAHASNI VTALYIATGQ DPAQNVESSN CITLMESING
     GKDLYISVTM PSIEVGTVGG GTHLPAQSAC LDLLKIRGAN LERPGANSEQ LARVVAAAVL
     SGELSLMSAL AAGHLVRSHL KHNRKTEAPA PQADTISMTH NLPHSD
 
 
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