DPH6_YEAST
ID DPH6_YEAST Reviewed; 685 AA.
AC Q12429; D6VYD7; Q07261;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Diphthine--ammonia ligase;
DE EC=6.3.1.14 {ECO:0000269|PubMed:23169644};
DE AltName: Full=Diphthamide synthase;
DE AltName: Full=Diphthamide synthetase;
GN Name=DPH6; OrderedLocusNames=YLR143W; ORFNames=L3177;
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=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 [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 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 [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 FUNCTION, PATHWAY, AND CATALYTIC ACTIVITY.
RX PubMed=23169644; DOI=10.1073/pnas.1214346109;
RA Su X., Lin Z., Chen W., Jiang H., Zhang S., Lin H.;
RT "Chemogenomic approach identified yeast YLR143W as diphthamide
RT synthetase.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:19983-19987(2012).
RN [6]
RP FUNCTION, INTERACTION WITH ELONGATION FACTOR 2, AND MUTAGENESIS OF GLY-216
RP AND GLU-220.
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 [7]
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLU-220.
RX PubMed=23645155; DOI=10.3390/toxins5050958;
RA Abdel-Fattah W., Scheidt V., Uthman S., Stark M.J., Schaffrath R.;
RT "Insights into diphthamide, key diphtheria toxin effector.";
RL Toxins 5:958-968(2013).
CC -!- FUNCTION: Amidase that catalyzes the last step of diphthamide
CC biosynthesis using ammonium and ATP. Diphthamide biosynthesis consists
CC in the conversion of an L-histidine residue in the translation
CC elongation factor eEF-2 (EFT1 or EFT2) to diphthamide.
CC {ECO:0000269|PubMed:23169644, ECO:0000269|PubMed:23468660}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + diphthine-[translation elongation factor 2] + NH4(+) =
CC AMP + diphosphate + diphthamide-[translation elongation factor 2] +
CC H(+); Xref=Rhea:RHEA:19753, Rhea:RHEA-COMP:10172, Rhea:RHEA-
CC COMP:10174, ChEBI:CHEBI:15378, ChEBI:CHEBI:16692, ChEBI:CHEBI:28938,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:82696,
CC ChEBI:CHEBI:456215; EC=6.3.1.14;
CC Evidence={ECO:0000269|PubMed:23169644};
CC -!- PATHWAY: Protein modification; peptidyl-diphthamide biosynthesis.
CC {ECO:0000269|PubMed:23169644}.
CC -!- SUBUNIT: Interacts with elongation factor 2 (eEF-2; EFT1 or EFT2).
CC {ECO:0000269|PubMed:23468660}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}.
CC -!- DISRUPTION PHENOTYPE: Resistance to sordarin.
CC {ECO:0000269|PubMed:23645155}.
CC -!- MISCELLANEOUS: Present with 2270 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the RutC family.
CC {ECO:0000305}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the Diphthine--
CC ammonia ligase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA62663.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U53881; AAB82389.1; -; Genomic_DNA.
DR EMBL; X91258; CAA62663.1; ALT_FRAME; Genomic_DNA.
DR EMBL; Z73315; CAA97715.1; -; Genomic_DNA.
DR EMBL; BK006945; DAA09453.1; -; Genomic_DNA.
DR PIR; S64985; S64985.
DR RefSeq; NP_013244.1; NM_001182030.1.
DR AlphaFoldDB; Q12429; -.
DR SMR; Q12429; -.
DR BioGRID; 31412; 78.
DR DIP; DIP-2618N; -.
DR IntAct; Q12429; 1.
DR MINT; Q12429; -.
DR STRING; 4932.YLR143W; -.
DR iPTMnet; Q12429; -.
DR MaxQB; Q12429; -.
DR PaxDb; Q12429; -.
DR PRIDE; Q12429; -.
DR EnsemblFungi; YLR143W_mRNA; YLR143W; YLR143W.
DR GeneID; 850835; -.
DR KEGG; sce:YLR143W; -.
DR SGD; S000004133; DPH6.
DR VEuPathDB; FungiDB:YLR143W; -.
DR eggNOG; KOG2316; Eukaryota.
DR eggNOG; KOG2317; Eukaryota.
DR GeneTree; ENSGT00420000029820; -.
DR HOGENOM; CLU_010289_2_1_1; -.
DR InParanoid; Q12429; -.
DR OMA; RNTMHVQ; -.
DR BioCyc; MetaCyc:MON-17855; -.
DR BioCyc; YEAST:MON-17855; -.
DR BRENDA; 6.3.1.14; 984.
DR Reactome; R-SCE-5358493; Synthesis of diphthamide-EEF2.
DR UniPathway; UPA00559; -.
DR PRO; PR:Q12429; -.
DR Proteomes; UP000002311; Chromosome XII.
DR RNAct; Q12429; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0017178; F:diphthine-ammonia ligase activity; IDA:SGD.
DR GO; GO:0017183; P:peptidyl-diphthamide biosynthetic process from peptidyl-histidine; IDA:SGD.
DR CDD; cd01994; Alpha_ANH_like_IV; 1.
DR Gene3D; 3.30.1330.40; -; 2.
DR Gene3D; 3.40.50.620; -; 1.
DR InterPro; IPR002761; Diphthami_syn_dom.
DR InterPro; IPR030662; DPH6/MJ0570.
DR InterPro; IPR014729; Rossmann-like_a/b/a_fold.
DR InterPro; IPR035959; RutC-like_sf.
DR InterPro; IPR006175; YjgF/YER057c/UK114.
DR PANTHER; PTHR12196; PTHR12196; 1.
DR Pfam; PF01902; Diphthami_syn_2; 1.
DR Pfam; PF01042; Ribonuc_L-PSP; 1.
DR SUPFAM; SSF55298; SSF55298; 2.
DR TIGRFAMs; TIGR00290; MJ0570_dom; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Ligase; Nucleotide-binding; Reference proteome.
FT CHAIN 1..685
FT /note="Diphthine--ammonia ligase"
FT /id="PRO_0000262869"
FT MUTAGEN 216
FT /note="G->N: Completely inactivates the enzyme."
FT /evidence="ECO:0000269|PubMed:23468660"
FT MUTAGEN 220
FT /note="E->A,H: Completely inactivates the enzyme.
FT Resistance to sordarin."
FT /evidence="ECO:0000269|PubMed:23468660,
FT ECO:0000269|PubMed:23645155"
SQ SEQUENCE 685 AA; 77941 MW; E3AA0C948A57ADC2 CRC64;
MKFIALISGG KDSFYNIFHC LKNNHELIAL GNIYPKESEE QELDSFMFQT VGHDLIDYYS
KCIGVPLFRR SILRNTSNNV ELNYTATQDD EIEELFELLR TVKDKIPDLE AVSVGAILSS
YQRTRVENVC SRLGLVVLSY LWQRDQAELM GEMCLMSKDV NNVENDTNSG NKFDARIIKV
AAIGLNEKHL GMSLPMMQPV LQKLNQLYQV HICGEGGEFE TMVLDAPFFQ HGYLELIDIV
KCSDGEVHNA RLKVKFQPRN LSKSFLLNQL DQLPVPSIFG NNWQDLTQNL PKQQAKTGEQ
RFENHMSNAL PQTTINKTND KLYISNLQSR KSETVEKQSE DIFTELADIL HSNQIPRNHI
LSASLLIRDM SNFGKINKIY NEFLDLSKYG PLPPSRACVG SKCLPEDCHV QLSVVVDVKN
TGKEKINKNK GGLHVQGRSY WAPCNIGPYS QSTWLNDDAN QVSFISGQIG LVPQSMEILG
TPLTDQIVLA LQHFDTLCET IGAQEKLLMT CYISDESVLD SVIKTWAFYC SNMNHRSDLW
MDKSDDVEKC LVLVKISELP RGAVAEFGGV TCKRLIVDDN DSDKKEREEN DDVSTVFQKL
NLNIEGFHNT TVSAFGYNRN FITGFVDSRE ELELILEKTP KSAQITLYYN PKEIITFHHH
IGYYPVEKLF DYRGKEHRFG LHIRS
