DPH5_MOUSE
ID DPH5_MOUSE Reviewed; 281 AA.
AC Q9CWQ0; Q6PAC5;
DT 10-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Diphthine methyl ester synthase;
DE EC=2.1.1.314;
DE AltName: Full=Diphthamide biosynthesis methyltransferase;
GN Name=Dph5;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryonic stem cell;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Olfactory epithelium;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION.
RX PubMed=15485916; DOI=10.1128/mcb.24.21.9487-9497.2004;
RA Liu S., Milne G.T., Kuremsky J.G., Fink G.R., Leppla S.H.;
RT "Identification of the proteins required for biosynthesis of diphthamide,
RT the target of bacterial ADP-ribosylating toxins on translation elongation
RT factor 2.";
RL Mol. Cell. Biol. 24:9487-9497(2004).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Liver, Pancreas, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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:0000250|UniProtKB:P32469, ECO:0000269|PubMed:15485916}.
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:0000250|UniProtKB:P32469};
CC -!- PATHWAY: Protein modification; peptidyl-diphthamide biosynthesis.
CC -!- SIMILARITY: Belongs to the diphthine synthase family. {ECO:0000305}.
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DR EMBL; AK010475; BAB26968.1; -; mRNA.
DR EMBL; AC131113; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466532; EDL12395.1; -; Genomic_DNA.
DR EMBL; BC060372; AAH60372.1; -; mRNA.
DR CCDS; CCDS17782.1; -.
DR RefSeq; NP_081469.2; NM_027193.2.
DR AlphaFoldDB; Q9CWQ0; -.
DR SMR; Q9CWQ0; -.
DR STRING; 10090.ENSMUSP00000043730; -.
DR PhosphoSitePlus; Q9CWQ0; -.
DR EPD; Q9CWQ0; -.
DR MaxQB; Q9CWQ0; -.
DR PaxDb; Q9CWQ0; -.
DR PeptideAtlas; Q9CWQ0; -.
DR PRIDE; Q9CWQ0; -.
DR ProteomicsDB; 277382; -.
DR Antibodypedia; 33698; 31 antibodies from 9 providers.
DR DNASU; 69740; -.
DR Ensembl; ENSMUST00000043342; ENSMUSP00000043730; ENSMUSG00000033554.
DR Ensembl; ENSMUST00000189799; ENSMUSP00000140958; ENSMUSG00000033554.
DR GeneID; 69740; -.
DR KEGG; mmu:69740; -.
DR UCSC; uc008rbs.1; mouse.
DR CTD; 51611; -.
DR MGI; MGI:1916990; Dph5.
DR VEuPathDB; HostDB:ENSMUSG00000033554; -.
DR eggNOG; KOG3123; Eukaryota.
DR GeneTree; ENSGT00390000010568; -.
DR HOGENOM; CLU_066040_1_0_1; -.
DR InParanoid; Q9CWQ0; -.
DR OMA; TAGDPMV; -.
DR OrthoDB; 1018517at2759; -.
DR PhylomeDB; Q9CWQ0; -.
DR TreeFam; TF105603; -.
DR Reactome; R-MMU-5358493; Synthesis of diphthamide-EEF2.
DR UniPathway; UPA00559; -.
DR BioGRID-ORCS; 69740; 29 hits in 74 CRISPR screens.
DR ChiTaRS; Dph5; mouse.
DR PRO; PR:Q9CWQ0; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9CWQ0; protein.
DR Bgee; ENSMUSG00000033554; Expressed in paneth cell and 231 other tissues.
DR ExpressionAtlas; Q9CWQ0; baseline and differential.
DR Genevisible; Q9CWQ0; MM.
DR GO; GO:0004164; F:diphthine synthase activity; ISO:MGI.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0017183; P:peptidyl-diphthamide biosynthetic process from peptidyl-histidine; ISS:UniProtKB.
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 Methyltransferase; Phosphoprotein; Reference proteome;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..281
FT /note="Diphthine methyl ester synthase"
FT /id="PRO_0000156134"
FT BINDING 9
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 84
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 87
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 112..113
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 163
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 225
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 250
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT MOD_RES 171
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H2P9"
FT CONFLICT 16
FT /note="T -> K (in Ref. 1; BAB26968)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 281 AA; 31218 MW; 28AEC5E6ABBC3C1F CRC64;
MLYLIGLGLG DAKDITVKGL EVVRRCSRVY LEAYTSVLTV GKEALEEFYG RKLILADREE
VEQEADNIFK DADVSDVAFL VVGDPFGATT HSDLILRATK LGIPYQVIHN ASIMNAVGCC
GLQLYRFGET VSIVFWTDTW RPESFFDKVK RNRANGMHTL CLLDIKVKEQ SLENLIRGRK
IYEPPRYMSV NQAAQQLLEI VQNHRARGEE PAITEETLCV GLARVGAEDQ KIAAGTLQQM
CTVSLGEPLH SLVITGGNLH PLEMEMLSLF SIPESQSTDG L
