DPH5_YEAST
ID DPH5_YEAST Reviewed; 300 AA.
AC P32469; D6VYH6; Q6Q5L4;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Diphthine methyl ester synthase;
DE EC=2.1.1.314 {ECO:0000269|PubMed:24739148};
DE AltName: Full=Diphthamide biosynthesis methyltransferase;
GN Name=DPH5; OrderedLocusNames=YLR172C; ORFNames=L9470.17;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX PubMed=1508200; DOI=10.1128/mcb.12.9.4026-4037.1992;
RA Mattheakis L.C., Shen W.H., Collier R.J.;
RT "DPH5, a methyltransferase gene required for diphthamide biosynthesis in
RT Saccharomyces cerevisiae.";
RL Mol. Cell. Biol. 12:4026-4037(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169871;
RA Johnston M., Hillier L.W., Riles L., Albermann K., Andre B., Ansorge W.,
RA Benes V., Brueckner M., Delius H., Dubois E., Duesterhoeft A.,
RA Entian K.-D., Floeth M., Goffeau A., Hebling U., Heumann K.,
RA Heuss-Neitzel D., Hilbert H., Hilger F., Kleine K., Koetter P., Louis E.J.,
RA Messenguy F., Mewes H.-W., Miosga T., Moestl D., Mueller-Auer S.,
RA Nentwich U., Obermaier B., Piravandi E., Pohl T.M., Portetelle D.,
RA Purnelle B., Rechmann S., Rieger M., Rinke M., Rose M., Scharfe M.,
RA Scherens B., Scholler P., Schwager C., Schwarz S., Underwood A.P.,
RA Urrestarazu L.A., Vandenbol M., Verhasselt P., Vierendeels F., Voet M.,
RA Volckaert G., Voss H., Wambutt R., Wedler E., Wedler H., Zimmermann F.K.,
RA Zollner A., Hani J., Hoheisel J.D.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XII.";
RL Nature 387:87-90(1997).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=17322287; DOI=10.1101/gr.6037607;
RA Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA LaBaer J.;
RT "Approaching a complete repository of sequence-verified protein-encoding
RT clones for Saccharomyces cerevisiae.";
RL Genome Res. 17:536-543(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 228-300.
RC STRAIN=SP1;
RX PubMed=8373805; DOI=10.1016/0167-4781(93)90198-m;
RA Nakai M., Takada T., Endo T.;
RT "Cloning of the YAP19 gene encoding a putative yeast homolog of AP19, the
RT mammalian small chain of the clathrin-assembly proteins.";
RL Biochim. Biophys. Acta 1174:282-284(1993).
RN [6]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [7]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-298, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=ADR376;
RX PubMed=17330950; DOI=10.1021/pr060559j;
RA Li X., Gerber S.A., Rudner A.D., Beausoleil S.A., Haas W., Villen J.,
RA Elias J.E., Gygi S.P.;
RT "Large-scale phosphorylation analysis of alpha-factor-arrested
RT Saccharomyces cerevisiae.";
RL J. Proteome Res. 6:1190-1197(2007).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-172, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [10]
RP DISRUPTION PHENOTYPE.
RX PubMed=18627462; DOI=10.1111/j.1365-2958.2008.06350.x;
RA Baer C., Zabel R., Liu S., Stark M.J., Schaffrath R.;
RT "A versatile partner of eukaryotic protein complexes that is involved in
RT multiple biological processes: Kti11/Dph3.";
RL Mol. Microbiol. 69:1221-1233(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-298, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
RN [12]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=24739148; DOI=10.1021/ja5009272;
RA Lin Z., Su X., Chen W., Ci B., Zhang S., Lin H.;
RT "Dph7 catalyzes a previously unknown demethylation step in diphthamide
RT biosynthesis.";
RL J. Am. Chem. Soc. 136:6179-6182(2014).
CC -!- FUNCTION: S-adenosyl-L-methionine-dependent methyltransferase that
CC catalyzes four methylations of the modified target histidine residue in
CC translation elongation factor 2 (EF-2), to form an intermediate called
CC diphthine methyl ester. The four successive methylation reactions
CC represent the second step of diphthamide biosynthesis.
CC {ECO:0000269|PubMed:1508200, ECO:0000269|PubMed:24739148}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-[(3S)-amino-3-carboxypropyl]-L-histidyl-[translation
CC elongation factor 2] + 4 S-adenosyl-L-methionine = diphthine methyl
CC ester-[translation elongation factor 2] + 3 H(+) + 4 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:42652, Rhea:RHEA-COMP:9749, Rhea:RHEA-
CC COMP:10173, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:73995, ChEBI:CHEBI:79005; EC=2.1.1.314;
CC Evidence={ECO:0000269|PubMed:24739148};
CC -!- PATHWAY: Protein modification; peptidyl-diphthamide biosynthesis.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}.
CC -!- DISRUPTION PHENOTYPE: Resistance to sordarin.
CC {ECO:0000269|PubMed:18627462}.
CC -!- MISCELLANEOUS: 2-[3-carboxy-3-(methylammonio)propyl]-L-histidine and
CC the corresponding dimethyl compound can also act as acceptors.
CC -!- MISCELLANEOUS: Present with 13480 molecules/cell in log phase SD
CC medium. {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the diphthine synthase family. {ECO:0000305}.
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DR EMBL; M83375; AAA34577.1; -; Genomic_DNA.
DR EMBL; U17246; AAB67469.1; -; Genomic_DNA.
DR EMBL; AY557947; AAS56273.1; -; Genomic_DNA.
DR EMBL; X70279; CAA49764.1; -; Genomic_DNA.
DR EMBL; BK006945; DAA09492.1; -; Genomic_DNA.
DR PIR; S30890; S30890.
DR RefSeq; NP_013273.1; NM_001182059.1.
DR AlphaFoldDB; P32469; -.
DR SMR; P32469; -.
DR BioGRID; 31443; 208.
DR DIP; DIP-4237N; -.
DR IntAct; P32469; 7.
DR MINT; P32469; -.
DR STRING; 4932.YLR172C; -.
DR iPTMnet; P32469; -.
DR MaxQB; P32469; -.
DR PaxDb; P32469; -.
DR PRIDE; P32469; -.
DR EnsemblFungi; YLR172C_mRNA; YLR172C; YLR172C.
DR GeneID; 850869; -.
DR KEGG; sce:YLR172C; -.
DR SGD; S000004162; DPH5.
DR VEuPathDB; FungiDB:YLR172C; -.
DR eggNOG; KOG3123; Eukaryota.
DR GeneTree; ENSGT00390000010568; -.
DR HOGENOM; CLU_066040_1_0_1; -.
DR InParanoid; P32469; -.
DR OMA; TAGDPMV; -.
DR BioCyc; MetaCyc:MON-15582; -.
DR BioCyc; YEAST:MON-15582; -.
DR BRENDA; 2.1.1.314; 984.
DR Reactome; R-SCE-5358493; Synthesis of diphthamide-EEF2.
DR UniPathway; UPA00559; -.
DR PRO; PR:P32469; -.
DR Proteomes; UP000002311; Chromosome XII.
DR RNAct; P32469; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0004164; F:diphthine synthase activity; IDA:SGD.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0017183; P:peptidyl-diphthamide biosynthetic process from peptidyl-histidine; IDA:SGD.
DR CDD; cd11647; DHP5_DphB; 1.
DR Gene3D; 3.30.950.10; -; 1.
DR Gene3D; 3.40.1010.10; -; 1.
DR HAMAP; MF_01084; Diphthine_synth; 1.
DR InterPro; IPR000878; 4pyrrol_Mease.
DR InterPro; IPR035996; 4pyrrol_Methylase_sf.
DR InterPro; IPR014777; 4pyrrole_Mease_sub1.
DR InterPro; IPR014776; 4pyrrole_Mease_sub2.
DR InterPro; IPR004551; Dphthn_synthase.
DR PANTHER; PTHR10882; PTHR10882; 1.
DR Pfam; PF00590; TP_methylase; 1.
DR PIRSF; PIRSF036432; Diphthine_synth; 1.
DR SUPFAM; SSF53790; SSF53790; 1.
DR TIGRFAMs; TIGR00522; dph5; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Methyltransferase; Phosphoprotein; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..300
FT /note="Diphthine methyl ester synthase"
FT /id="PRO_0000156147"
FT BINDING 9
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 85
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 88
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 113..114
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 164
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 222
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 247
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT MOD_RES 172
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18407956"
FT MOD_RES 298
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17330950,
FT ECO:0007744|PubMed:19779198"
FT CONFLICT 287
FT /note="P -> L (in Ref. 4; AAS56273)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 300 AA; 33847 MW; 405411F6BF2E6DF9 CRC64;
MLYLIGLGLS YKSDITVRGL EAIKKCSRVY LEHYTSILMA ASQEELESYY GKEIILADRE
LVETGSKQIL NNADKEDVAF LVVGDPFGAT THTDLVLRAK REAIPVEIIH NASVMNAVGA
CGLQLYNFGQ TVSMVFFTDN WRPDSWYDKI WENRKIGLHT LVLLDIKVKE QSIENMARGR
LIYEPPRYMS IAQCCEQLLE IEEKRGTKAY TPDTPAVAIS RLGSSSQSFK SGTISELANY
DSGEPLHSLV ILGRQCHELE LEYLLEFADD KEKFGKDVAN DQEYFKPAAW VPPTEDDSDE
