DPH7_YEAST
ID DPH7_YEAST Reviewed; 387 AA.
AC P38332; D6VQP2;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1994, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Diphthine methyltransferase;
DE EC=3.1.1.97 {ECO:0000269|PubMed:24739148};
DE AltName: Full=Diphthamide biosynthesis protein 7;
DE AltName: Full=Endosomal recycling protein 1;
DE AltName: Full=Regulator of rDNA transcription protein 2;
GN Name=RRT2; Synonyms=DPH7, ERE1; OrderedLocusNames=YBR246W;
GN ORFNames=YBR1634;
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 [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7813418; DOI=10.1002/j.1460-2075.1994.tb06923.x;
RA Feldmann H., Aigle M., Aljinovic G., Andre B., Baclet M.C., Barthe C.,
RA Baur A., Becam A.-M., Biteau N., Boles E., Brandt T., Brendel M.,
RA Brueckner M., Bussereau F., Christiansen C., Contreras R., Crouzet M.,
RA Cziepluch C., Demolis N., Delaveau T., Doignon F., Domdey H.,
RA Duesterhus S., Dubois E., Dujon B., El Bakkoury M., Entian K.-D.,
RA Feuermann M., Fiers W., Fobo G.M., Fritz C., Gassenhuber J., Glansdorff N.,
RA Goffeau A., Grivell L.A., de Haan M., Hein C., Herbert C.J.,
RA Hollenberg C.P., Holmstroem K., Jacq C., Jacquet M., Jauniaux J.-C.,
RA Jonniaux J.-L., Kallesoee T., Kiesau P., Kirchrath L., Koetter P.,
RA Korol S., Liebl S., Logghe M., Lohan A.J.E., Louis E.J., Li Z.Y.,
RA Maat M.J., Mallet L., Mannhaupt G., Messenguy F., Miosga T., Molemans F.,
RA Mueller S., Nasr F., Obermaier B., Perea J., Pierard A., Piravandi E.,
RA Pohl F.M., Pohl T.M., Potier S., Proft M., Purnelle B., Ramezani Rad M.,
RA Rieger M., Rose M., Schaaff-Gerstenschlaeger I., Scherens B.,
RA Schwarzlose C., Skala J., Slonimski P.P., Smits P.H.M., Souciet J.-L.,
RA Steensma H.Y., Stucka R., Urrestarazu L.A., van der Aart Q.J.M.,
RA Van Dyck L., Vassarotti A., Vetter I., Vierendeels F., Vissers S.,
RA Wagner G., de Wergifosse P., Wolfe K.H., Zagulski M., Zimmermann F.K.,
RA Mewes H.-W., Kleine K.;
RT "Complete DNA sequence of yeast chromosome II.";
RL EMBO J. 13:5795-5809(1994).
RN [2]
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 [3]
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 [4]
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 [5]
RP GENE NAME, AND FUNCTION.
RX PubMed=19270272; DOI=10.1534/genetics.108.100313;
RA Hontz R.D., Niederer R.O., Johnson J.M., Smith J.S.;
RT "Genetic identification of factors that modulate ribosomal DNA
RT transcription in Saccharomyces cerevisiae.";
RL Genetics 182:105-119(2009).
RN [6]
RP FUNCTION.
RX PubMed=19965467; DOI=10.1126/science.1178955;
RA Carette J.E., Guimaraes C.P., Varadarajan M., Park A.S., Wuethrich I.,
RA Godarova A., Kotecki M., Cochran B.H., Spooner E., Ploegh H.L.,
RA Brummelkamp T.R.;
RT "Haploid genetic screens in human cells identify host factors used by
RT pathogens.";
RL Science 326:1231-1235(2009).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH CAN1 AND RRT10.
RX PubMed=21880895; DOI=10.1091/mbc.e11-05-0440;
RA Shi Y., Stefan C.J., Rue S.M., Teis D., Emr S.D.;
RT "Two novel WD40 domain-containing proteins, Ere1 and Ere2, function in the
RT retromer-mediated endosomal recycling pathway.";
RL Mol. Biol. Cell 22:4093-4107(2011).
RN [8]
RP FUNCTION.
RX PubMed=22188241; DOI=10.1021/ja208870a;
RA Su X., Chen W., Lee W., Jiang H., Zhang S., Lin H.;
RT "YBR246W is required for the third step of diphthamide biosynthesis.";
RL J. Am. Chem. Soc. 134:773-776(2012).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23468660; DOI=10.1371/journal.pgen.1003334;
RA Uthman S., Bar C., Scheidt V., Liu S., ten Have S., Giorgini F.,
RA Stark M.J., Schaffrath R.;
RT "The amidation step of diphthamide biosynthesis in yeast requires DPH6, a
RT gene identified through mining the DPH1-DPH5 interaction network.";
RL PLoS Genet. 9:E1003334-E1003334(2013).
RN [10]
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: Catalyzes the demethylation of diphthine methyl ester to form
CC diphthine, an intermediate in diphthamide biosynthesis, a post-
CC translational modification of histidine which occurs in translation
CC elongation factor 2 (EFT1 and EFT2). Also plays a role in the
CC regulation of the retromer complex and is required for the recycling
CC from endosomes of plasma membrane proteins like CAN1 and MUP1.
CC Identified in a screen for mutants with decreased levels of rDNA
CC transcription. {ECO:0000269|PubMed:19270272,
CC ECO:0000269|PubMed:19965467, ECO:0000269|PubMed:21880895,
CC ECO:0000269|PubMed:22188241, ECO:0000269|PubMed:23468660,
CC ECO:0000269|PubMed:24739148}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=diphthine methyl ester-[translation elongation factor 2] + H2O
CC = diphthine-[translation elongation factor 2] + H(+) + methanol;
CC Xref=Rhea:RHEA:42656, Rhea:RHEA-COMP:10172, Rhea:RHEA-COMP:10173,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:17790,
CC ChEBI:CHEBI:79005, ChEBI:CHEBI:82696; EC=3.1.1.97;
CC Evidence={ECO:0000269|PubMed:24739148};
CC -!- PATHWAY: Protein modification; peptidyl-diphthamide biosynthesis.
CC -!- SUBUNIT: Interacts with CAN1 and RTT10. {ECO:0000269|PubMed:21880895}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21880895}. Endosome
CC {ECO:0000269|PubMed:21880895}. Note=Recruited to endosomes in cells in
CC which increased recycling of internalized plasma membrane proteins
CC occurs.
CC -!- DISRUPTION PHENOTYPE: Accumulates diphthine, the last intermediate in
CC the diphthamide biosynthesis pathway. Increases the interaction of DPH5
CC with elongation factor 2. {ECO:0000269|PubMed:23468660}.
CC -!- MISCELLANEOUS: Present with 2640 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the DPH7 family. {ECO:0000305}.
CC -!- CAUTION: Was originally (PubMed:19965467) thought to be required for
CC the first step of diphthamide biosynthesis but further studies
CC (PubMed:22188241, PubMed:23468660) clearly suggest that it is involved
CC in the third step of diphthamide biosynthesis.
CC {ECO:0000305|PubMed:19965467, ECO:0000305|PubMed:22188241,
CC ECO:0000305|PubMed:23468660}.
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DR EMBL; Z36115; CAA85209.1; -; Genomic_DNA.
DR EMBL; AY692624; AAT92643.1; -; Genomic_DNA.
DR EMBL; BK006936; DAA07362.1; -; Genomic_DNA.
DR PIR; S46123; S46123.
DR RefSeq; NP_009805.1; NM_001178594.1.
DR AlphaFoldDB; P38332; -.
DR BioGRID; 32941; 118.
DR DIP; DIP-4948N; -.
DR IntAct; P38332; 2.
DR STRING; 4932.YBR246W; -.
DR MaxQB; P38332; -.
DR PaxDb; P38332; -.
DR PRIDE; P38332; -.
DR EnsemblFungi; YBR246W_mRNA; YBR246W; YBR246W.
DR GeneID; 852548; -.
DR KEGG; sce:YBR246W; -.
DR SGD; S000000450; RRT2.
DR VEuPathDB; FungiDB:YBR246W; -.
DR eggNOG; KOG0280; Eukaryota.
DR HOGENOM; CLU_036100_2_0_1; -.
DR InParanoid; P38332; -.
DR OMA; HESMCYG; -.
DR BioCyc; MetaCyc:MON-18824; -.
DR BioCyc; YEAST:MON-18824; -.
DR BRENDA; 3.1.1.97; 984.
DR UniPathway; UPA00559; -.
DR PRO; PR:P38332; -.
DR Proteomes; UP000002311; Chromosome II.
DR RNAct; P38332; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005768; C:endosome; IDA:SGD.
DR GO; GO:0061685; F:diphthine methylesterase activity; IDA:SGD.
DR GO; GO:0051723; F:protein methylesterase activity; EXP:Reactome.
DR GO; GO:0032456; P:endocytic recycling; IMP:SGD.
DR GO; GO:0017183; P:peptidyl-diphthamide biosynthetic process from peptidyl-histidine; IMP:SGD.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR SMART; SM00320; WD40; 4.
DR SUPFAM; SSF50978; SSF50978; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Endosome; Hydrolase; Reference proteome; Repeat; WD repeat.
FT CHAIN 1..387
FT /note="Diphthine methyltransferase"
FT /id="PRO_0000202523"
FT REPEAT 62..102
FT /note="WD 1"
FT REPEAT 119..159
FT /note="WD 2"
FT REPEAT 195..237
FT /note="WD 3"
FT REPEAT 241..286
FT /note="WD 4"
FT REPEAT 357..387
FT /note="WD 5"
SQ SEQUENCE 387 AA; 43308 MW; 97CAFD285BC11456 CRC64;
MDSIQESDVL NAVKTKLPPC CLRIFRNKII LVGTYDLDKS TGYRSGSLDV FTMDLKLLCS
NNTYGAILDL KLSPFDDTLI CTAHSTGNIM LWRIRCTDKD DFQSNELDIH AIANLQLFEK
DVLIASCHFS PLDCKKLLVT NTAGEAATID IRTLSVQFTA SAIAQAYSKL DKIDYEVQGA
TEKVIHVESG QFLKPHELEC WTAEFGSLQP FQDVVFTGGD DSRIMAHDLR SKEFIWSNNR
IHDAGVVSIK CSQPNFRNNK PTSIITGSYD DNIRSLDLRM MGESIFPGAN VPTVNKLACD
LGGGVWRFVE SPIDQEQSHH NGSDRLLVCC MYNGAKVVTM NDNSDEYFQI QHYLKKGHDS
MCYGGDWSNS LIATCSFYDN SLQTWIV
