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 24-JAN-2024, entry version 134. 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). RN [7] RP MUTAGENESIS OF HIS-260, AND DEVELOPMENTAL STAGE. RX PubMed=35482014; DOI=10.1016/j.gim.2022.03.014; RG Undiagnosed Diseases Network; RA Shankar S.P., Grimsrud K., Lanoue L., Egense A., Willis B., Hoerberg J., RA AlAbdi L., Mayer K., Uetkuer K., Monaghan K.G., Krier J., Stoler J., RA Alnemer M., Shankar P.R., Schaffrath R., Alkuraya F.S., Brinkmann U., RA Eriksson L.A., Lloyd K., Rauen K.A.; RT "A novel DPH5-related diphthamide-deficiency syndrome causing embryonic RT lethality or profound neurodevelopmental disorder."; RL Genet. Med. 24:1567-1582(2022). RN [8] RP ERRATUM OF PUBMED:35482014. RX PubMed=36205747; DOI=10.1016/j.gim.2022.07.021; RG Undiagnosed Diseases Network; RA Shankar S.P., Grimsrud K., Lanoue L., Egense A., Willis B., Hoerberg J., RA AlAbdi L., Mayer K., Uetkuer K., Monaghan K.G., Krier J., Stoler J., RA Alnemer M., Shankar P.R., Schaffrath R., Alkuraya F.S., Brinkmann U., RA Eriksson L.A., Lloyd K., Rauen K.A.; RL Genet. Med. 24:2207-2207(2022). 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 -!- DEVELOPMENTAL STAGE: The protein is expressed in embryos at 18.5 dpc. CC {ECO:0000269|PubMed:35482014}. CC -!- SIMILARITY: Belongs to the diphthine synthase family. {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; 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 SwissPalm; Q9CWQ0; -. DR EPD; Q9CWQ0; -. DR MaxQB; Q9CWQ0; -. DR PaxDb; 10090-ENSMUSP00000043730; -. DR PeptideAtlas; Q9CWQ0; -. DR ProteomicsDB; 277382; -. DR Pumba; Q9CWQ0; -. DR Antibodypedia; 33698; 35 antibodies from 9 providers. DR DNASU; 69740; -. DR Ensembl; ENSMUST00000043342.10; ENSMUSP00000043730.10; ENSMUSG00000033554.18. DR Ensembl; ENSMUST00000189799.7; ENSMUSP00000140958.2; ENSMUSG00000033554.18. DR GeneID; 69740; -. DR KEGG; mmu:69740; -. DR UCSC; uc008rbs.1; mouse. DR AGR; MGI:1916990; -. 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; 1093496at2759; -. 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 79 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 234 other cell types or tissues. DR ExpressionAtlas; Q9CWQ0; baseline and differential. DR GO; GO:0004164; F:diphthine synthase activity; ISO:MGI. DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW. DR GO; GO:0017183; P:protein histidyl modification to diphthamide; ISS:UniProtKB. DR CDD; cd11647; DHP5_DphB; 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 NCBIfam; TIGR00522; dph5; 1. DR PANTHER; PTHR10882:SF0; DIPHTHINE METHYL ESTER SYNTHASE; 1. DR PANTHER; PTHR10882; DIPHTHINE SYNTHASE; 1. DR Pfam; PF00590; TP_methylase; 1. DR PIRSF; PIRSF036432; Diphthine_synth; 1. DR SUPFAM; SSF53790; Tetrapyrrole methylase; 1. DR Genevisible; Q9CWQ0; MM. 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 MUTAGEN 260 FT /note="H->R: Most homozygous embryos are non-viable and FT show craniofacial, ophthalmologic, cardiac, visceral, and FT hemopoietic abnormalities." FT /evidence="ECO:0000269|PubMed:35482014" 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 //