位置:首页 > 蛋白库 > KIME_RAT
KIME_RAT
ID   KIME_RAT                Reviewed;         395 AA.
AC   P17256;
DT   01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-AUG-1990, sequence version 1.
DT   03-AUG-2022, entry version 164.
DE   RecName: Full=Mevalonate kinase {ECO:0000305};
DE            Short=MK;
DE            EC=2.7.1.36 {ECO:0000269|PubMed:14680942};
GN   Name=Mvk {ECO:0000312|RGD:621295};
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 1-20.
RC   STRAIN=Sprague-Dawley; TISSUE=Liver;
RX   PubMed=2158094; DOI=10.1073/pnas.87.8.2872;
RA   Tanaka R.D., Lee L.Y., Schafer B.L., Kratunis V.J., Mohler W.A.,
RA   Robinson G.W., Mosley S.T.;
RT   "Molecular cloning of mevalonate kinase and regulation of its mRNA levels
RT   in rat liver.";
RL   Proc. Natl. Acad. Sci. U.S.A. 87:2872-2876(1990).
RN   [2]
RP   SUBCELLULAR LOCATION.
RX   PubMed=14730012; DOI=10.1242/jcs.00910;
RA   Hogenboom S., Tuyp J.J., Espeel M., Koster J., Wanders R.J., Waterham H.R.;
RT   "Mevalonate kinase is a cytosolic enzyme in humans.";
RL   J. Cell Sci. 117:631-639(2004).
RN   [3]
RP   SUBCELLULAR LOCATION.
RX   PubMed=1312092; DOI=10.1016/s0021-9258(18)42802-5;
RA   Stamellos K.D., Shackelford J.E., Tanaka R.D., Krisans S.K.;
RT   "Mevalonate kinase is localized in rat liver peroxisomes.";
RL   J. Biol. Chem. 267:5560-5568(1992).
RN   [4]
RP   CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP   MUTAGENESIS OF HIS-20.
RX   PubMed=14680942; DOI=10.1016/s1046-5928(03)00221-3;
RA   Chu X., Li D.;
RT   "Expression, purification, and characterization of His20 mutants of rat
RT   mevalonate kinase.";
RL   Protein Expr. Purif. 32:75-82(2003).
RN   [5] {ECO:0007744|PDB:1KVK}
RP   X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) IN COMPLEX WITH ATP AND MAGNESIUM,
RP   SUBUNIT, AND COFACTOR.
RX   PubMed=11877411; DOI=10.1074/jbc.m200912200;
RA   Fu Z., Wang M., Potter D., Miziorko H.M., Kim J.-J.;
RT   "The structure of a binary complex between a mammalian mevalonate kinase
RT   and ATP: insights into the reaction mechanism and human inherited
RT   disease.";
RL   J. Biol. Chem. 277:18134-18142(2002).
RN   [6] {ECO:0007744|PDB:2R42}
RP   X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) IN COMPLEX WITH THE INHIBITOR
RP   FARNESYL DIPHOSPHATE ANALOG.
RX   PubMed=18302342; DOI=10.1021/bi7024386;
RA   Fu Z., Voynova N.E., Herdendorf T.J., Miziorko H.M., Kim J.J.;
RT   "Biochemical and structural basis for feedback inhibition of mevalonate
RT   kinase and isoprenoid metabolism.";
RL   Biochemistry 47:3715-3724(2008).
CC   -!- FUNCTION: Catalyzes the phosphorylation of mevalonate to mevalonate 5-
CC       phosphate, a key step in isoprenoid and cholesterol biosynthesis.
CC       {ECO:0000250|UniProtKB:Q03426}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(R)-mevalonate + ATP = (R)-5-phosphomevalonate + ADP + H(+);
CC         Xref=Rhea:RHEA:17065, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:36464, ChEBI:CHEBI:58146, ChEBI:CHEBI:456216;
CC         EC=2.7.1.36; Evidence={ECO:0000269|PubMed:14680942};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:11877411};
CC   -!- ACTIVITY REGULATION: Farnesyl pyrophosphate and geranyl pyrophosphate
CC       inhibit mevalonate kinase activity by binding competitively at the ATP-
CC       binding sites. {ECO:0000250|UniProtKB:Q03426}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=34.6 uM for (R,S)-mevalonate {ECO:0000269|PubMed:14680942};
CC         KM=953 uM for ATP {ECO:0000269|PubMed:14680942};
CC         Vmax=38.7 umol/min/mg enzyme with (R,S)-mevalonate as substrate
CC         {ECO:0000269|PubMed:14680942};
CC   -!- PATHWAY: Isoprenoid biosynthesis; isopentenyl diphosphate biosynthesis
CC       via mevalonate pathway; isopentenyl diphosphate from (R)-mevalonate:
CC       step 1/3. {ECO:0000305}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:11877411}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14730012}.
CC       Peroxisome {ECO:0000269|PubMed:1312092}.
CC   -!- MISCELLANEOUS: The authors of PubMed:14730012 identify two forms of Mvk
CC       in rat liver, one form localizes to the cytosol and the other form to
CC       the peroxisome, whereas according to the authors of PubMed:14730012 the
CC       protein is found only in the cytoplasm with no evidence for its
CC       peroxisomal localization.
CC   -!- SIMILARITY: Belongs to the GHMP kinase family. Mevalonate kinase
CC       subfamily. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; M29472; AAA41588.1; -; mRNA.
DR   PIR; A35629; A35629.
DR   RefSeq; NP_112325.1; NM_031063.1.
DR   PDB; 1KVK; X-ray; 2.40 A; A=1-395.
DR   PDB; 2R42; X-ray; 2.40 A; A=1-395.
DR   PDBsum; 1KVK; -.
DR   PDBsum; 2R42; -.
DR   AlphaFoldDB; P17256; -.
DR   SMR; P17256; -.
DR   BioGRID; 249600; 5.
DR   STRING; 10116.ENSRNOP00000064795; -.
DR   BindingDB; P17256; -.
DR   ChEMBL; CHEMBL4274; -.
DR   GuidetoPHARMACOLOGY; 640; -.
DR   MoonProt; P17256; -.
DR   iPTMnet; P17256; -.
DR   PhosphoSitePlus; P17256; -.
DR   PRIDE; P17256; -.
DR   GeneID; 81727; -.
DR   KEGG; rno:81727; -.
DR   CTD; 4598; -.
DR   RGD; 621295; Mvk.
DR   eggNOG; KOG1511; Eukaryota.
DR   InParanoid; P17256; -.
DR   OrthoDB; 1196330at2759; -.
DR   PhylomeDB; P17256; -.
DR   BRENDA; 2.7.1.36; 5301.
DR   Reactome; R-RNO-191273; Cholesterol biosynthesis.
DR   SABIO-RK; P17256; -.
DR   UniPathway; UPA00057; UER00098.
DR   EvolutionaryTrace; P17256; -.
DR   PRO; PR:P17256; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0005829; C:cytosol; IDA:RGD.
DR   GO; GO:0005777; C:peroxisome; IDA:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IDA:RGD.
DR   GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR   GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR   GO; GO:0004496; F:mevalonate kinase activity; IDA:RGD.
DR   GO; GO:0003729; F:mRNA binding; IDA:RGD.
DR   GO; GO:1990825; F:sequence-specific mRNA binding; IDA:CAFA.
DR   GO; GO:0006695; P:cholesterol biosynthetic process; ISO:RGD.
DR   GO; GO:0019287; P:isopentenyl diphosphate biosynthetic process, mevalonate pathway; IDA:RGD.
DR   GO; GO:0008299; P:isoprenoid biosynthetic process; IDA:RGD.
DR   GO; GO:0006720; P:isoprenoid metabolic process; TAS:RGD.
DR   GO; GO:0050728; P:negative regulation of inflammatory response; ISO:RGD.
DR   GO; GO:0017148; P:negative regulation of translation; IDA:RGD.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0045540; P:regulation of cholesterol biosynthetic process; NAS:RGD.
DR   GO; GO:0016125; P:sterol metabolic process; TAS:RGD.
DR   Gene3D; 3.30.230.10; -; 1.
DR   Gene3D; 3.30.70.890; -; 1.
DR   InterPro; IPR013750; GHMP_kinase_C_dom.
DR   InterPro; IPR036554; GHMP_kinase_C_sf.
DR   InterPro; IPR006204; GHMP_kinase_N_dom.
DR   InterPro; IPR006203; GHMP_knse_ATP-bd_CS.
DR   InterPro; IPR006205; Mev_gal_kin.
DR   InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR   InterPro; IPR014721; Ribosomal_S5_D2-typ_fold_subgr.
DR   PANTHER; PTHR43290; PTHR43290; 1.
DR   Pfam; PF08544; GHMP_kinases_C; 1.
DR   Pfam; PF00288; GHMP_kinases_N; 1.
DR   SUPFAM; SSF54211; SSF54211; 1.
DR   SUPFAM; SSF55060; SSF55060; 1.
DR   TIGRFAMs; TIGR00549; mevalon_kin; 1.
DR   PROSITE; PS00627; GHMP_KINASES_ATP; 1.
PE   1: Evidence at protein level;
KW   3D-structure; ATP-binding; Cholesterol biosynthesis;
KW   Cholesterol metabolism; Cytoplasm; Direct protein sequencing; Kinase;
KW   Lipid biosynthesis; Lipid metabolism; Magnesium; Metal-binding;
KW   Nucleotide-binding; Peroxisome; Reference proteome; Steroid biosynthesis;
KW   Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transferase.
FT   CHAIN           1..395
FT                   /note="Mevalonate kinase"
FT                   /id="PRO_0000156659"
FT   ACT_SITE        146
FT                   /note="Proton donor"
FT                   /evidence="ECO:0000250|UniProtKB:Q03426"
FT   ACT_SITE        204
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:Q03426"
FT   BINDING         13
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000269|PubMed:11877411,
FT                   ECO:0007744|PDB:1KVK"
FT   BINDING         55
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000269|PubMed:11877411,
FT                   ECO:0007744|PDB:1KVK"
FT   BINDING         104
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000269|PubMed:11877411,
FT                   ECO:0007744|PDB:1KVK"
FT   BINDING         108
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000269|PubMed:11877411,
FT                   ECO:0007744|PDB:1KVK"
FT   BINDING         135
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000269|PubMed:11877411,
FT                   ECO:0007744|PDB:1KVK"
FT   BINDING         140..146
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000269|PubMed:11877411,
FT                   ECO:0007744|PDB:1KVK, ECO:0007744|PDB:2R42"
FT   BINDING         146
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000269|PubMed:11877411,
FT                   ECO:0007744|PDB:1KVK"
FT   BINDING         193
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /evidence="ECO:0000269|PubMed:11877411,
FT                   ECO:0007744|PDB:1KVK"
FT   MUTAGEN         20
FT                   /note="H->K: Induce significant secondary structural
FT                   change."
FT                   /evidence="ECO:0000269|PubMed:14680942"
FT   MUTAGEN         20
FT                   /note="H->L,Y: Approximately 5-fold decrease in Vmax for
FT                   (R,S)-mevalonate. Approximately 3-fold increase in KM for
FT                   (R,S)-mevalonate."
FT                   /evidence="ECO:0000269|PubMed:14680942"
FT   STRAND          6..17
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   HELIX           21..24
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   STRAND          28..43
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   STRAND          45..53
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   TURN            54..57
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   STRAND          58..63
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   HELIX           64..68
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   HELIX           90..95
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   HELIX           106..120
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   STRAND          123..125
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   STRAND          129..137
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   STRAND          141..143
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   HELIX           145..160
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   HELIX           167..170
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   STRAND          173..175
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   HELIX           179..197
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   HELIX           203..210
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   STRAND          212..219
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   STRAND          221..223
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   STRAND          230..236
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   HELIX           243..256
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   HELIX           258..282
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   HELIX           288..308
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   HELIX           313..324
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   STRAND          328..331
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   STRAND          336..344
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   HELIX           350..362
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   STRAND          366..373
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   STRAND          377..380
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   TURN            382..384
FT                   /evidence="ECO:0007829|PDB:1KVK"
FT   HELIX           387..393
FT                   /evidence="ECO:0007829|PDB:1KVK"
SQ   SEQUENCE   395 AA;  41988 MW;  803D1F44E3C525FC CRC64;
     MLSEVLLVSA PGKVILHGEH AVVHGKVALA VALNLRTFLV LRPQSNGKVS LNLPNVGIKQ
     VWDVATLQLL DTGFLEQGDV PAPTLEQLEK LKKVAGLPRD CVGNEGLSLL AFLYLYLAIC
     RKQRTLPSLD IMVWSELPPG AGLGSSAAYS VCVAAALLTA CEEVTNPLKD RGSIGSWPEE
     DLKSINKWAY EGERVIHGNP SGVDNSVSTW GGALRYQQGK MSSLKRLPAL QILLTNTKVP
     RSTKALVAGV RSRLIKFPEI MAPLLTSIDA ISLECERVLG EMAAAPVPEQ YLVLEELMDM
     NQHHLNALGV GHASLDQLCQ VTAAHGLHSK LTGAGGGGCG ITLLKPGLER AKVEAAKQAL
     TGCGFDCWET SIGAPGVSMH SATSIEDPVR QALGL
 
 
维奥蛋白资源库 - 中文蛋白资源 CopyRight © 2010-2024