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Conserved domains on  [gi|767904610|ref|XP_011539872|]
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diphthine methyl ester synthase isoform X4 [Homo sapiens]

Protein Classification

SAM-dependent methyltransferase( domain architecture ID 148)

SAM-dependent methyltransferase catalyzes the methylation of one or more specific substrates using S-adenosyl-L-methionine (SAM or AdoMet) as the methyl donor; belongs to the tetrapyrrole methylase family

CATH:  3.40.1010.10|3.30.950.10
EC:  2.1.1.-
Gene Ontology:  GO:1904047|GO:0008168
PubMed:  16225687
SCOP:  4000056

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
TP_methylase super family cl00304
S-AdoMet-dependent tetrapyrrole methylases; This superfamily uses S-AdoMet ...
 1-159 3.78e-92

S-AdoMet-dependent tetrapyrrole methylases; This superfamily uses S-AdoMet (S-adenosyl-L-methionine or SAM) in the methylation of diverse substrates. Most members catalyze various methylation steps in cobalamin (vitamin B12) biosynthesis. There are two distinct cobalamin biosynthetic pathways in bacteria. The aerobic pathway requires oxygen, and cobalt is inserted late in the pathway; the anaerobic pathway does not require oxygen, and cobalt insertion is the first committed step towards cobalamin synthesis. The enzymes involved in the aerobic pathway are prefixed Cob and those of the anaerobic pathway Cbi. Most of the enzymes are shared by both pathways and a few enzymes are pathway-specific. Diphthine synthase and ribosomal RNA small subunit methyltransferase I (RsmI) are two superfamily members that are not involved in cobalamin biosynthesis. Diphthine synthase participates in the posttranslational modification of a specific histidine residue in elongation factor 2 (EF-2) of eukaryotes and archaea to diphthamide. RsmI catalyzes the 2-O-methylation of the ribose of cytidine 1402 (C1402) in 16S rRNA. Other superfamily members not involved in cobalamin biosynthesis include the N-terminal tetrapyrrole methylase domain of Bacillus subtilis YabN whose specific function is unknown, and Omphalotus olearius omphalotin methyltransferase which catalyzes the automethylation of its own C-terminus; this C terminus is subsequently released and macrocyclized to give Omphalotin A, a potent nematicide.


The actual alignment was detected with superfamily member PTZ00175:

Pssm-ID: 444820  Cd Length: 270  Bit Score: 269.14  E-value: 3.78e-92
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904610   1 MNAVGCCGLQLYKFGETVSIVFWTDTWRPESFFDKVKKNRQNGMHTLCLLDIKVKEQSLENLIKGRKIYEPPRYMSVNQA 80
Cdd:PTZ00175 116 MNAIGCTGLQLYRFGETVSIPFFTETWKPDSFYDKIKANRDNGLHTLCLLDIKVKERSVENLMKGRKIYEPPRYMTINQA 195

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767904610  81 AQQLLEIVQNQRirgeEPAVTEETLCVGLARVGADDQKIAAGTLRQMCTVDLGEPLHSLIITGGSIHPMEMEMLSLFSI 159
Cdd:PTZ00175 196 IEQLLEVEEKKG----GGVIAEDTLVVGVARVGSDDQQIVSGTLEDLLDVDFGPPLHSLVICAPTLHDIEEEFFELYRI 270
 
Name Accession Description Interval E-value
PTZ00175 PTZ00175
diphthine synthase; Provisional
 1-159 3.78e-92

diphthine synthase; Provisional


Pssm-ID: 185500  Cd Length: 270  Bit Score: 269.14  E-value: 3.78e-92
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904610   1 MNAVGCCGLQLYKFGETVSIVFWTDTWRPESFFDKVKKNRQNGMHTLCLLDIKVKEQSLENLIKGRKIYEPPRYMSVNQA 80
Cdd:PTZ00175 116 MNAIGCTGLQLYRFGETVSIPFFTETWKPDSFYDKIKANRDNGLHTLCLLDIKVKERSVENLMKGRKIYEPPRYMTINQA 195

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767904610  81 AQQLLEIVQNQRirgeEPAVTEETLCVGLARVGADDQKIAAGTLRQMCTVDLGEPLHSLIITGGSIHPMEMEMLSLFSI 159
Cdd:PTZ00175 196 IEQLLEVEEKKG----GGVIAEDTLVVGVARVGSDDQQIVSGTLEDLLDVDFGPPLHSLVICAPTLHDIEEEFFELYRI 270
DHP5_DphB cd11647
diphthine methyl ester synthase and diphthine synthase; Eukaryotic diphthine methyl ester ...
 1-143 1.33e-64

diphthine methyl ester synthase and diphthine synthase; Eukaryotic diphthine methyl ester synthase (DHP5) and archaeal diphthamide synthase (DphB) participate in the second step of the biosynthetic pathway of diphthamide. The eukaryotic enzyme catalyzes four methylations of the modified target histidine residue in translation elongation factor 2 (EF-2), to form an intermediate called diphthine methyl ester; the archaeal enzyme, catalyzes only 3 methylations, producing diphthine. Diphtheria toxin ADP-ribosylates diphthamide leading to inhibition of protein synthesis in the eukaryotic host cells.


Pssm-ID: 381174  Cd Length: 241  Bit Score: 198.02  E-value: 1.33e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904610   1 MNAVGCC-GLQLYKFGETVSIVFWTDTWRPESFFDKVKKNRQNGMHTLCLLDIKVkeqslenlikgrkiyEPPRYMSVNQ 79
Cdd:cd11647  115 LSAAGSTsGLQLYKFGRTVTIPFPEENYKPESPYDVIKENLKRGLHTLLLLDIKV---------------EEGRFMTINE 179

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767904610  80 AAQQLLEIVQNQRirgeEPAVTEETLCVGLARVGADDQKIAAGTLRQMCTVDLGEPLHSLIITG 143
Cdd:cd11647  180 AIEILLEIEEKRK----EGVITEDTLVVGLARLGSDDQKIVAGTLKELLKEDFGPPPHSLIIPG 239
DPH5 COG1798
Diphthamide biosynthesis methyltransferase [Translation, ribosomal structure and biogenesis];
3-158 5.28e-48

Diphthamide biosynthesis methyltransferase [Translation, ribosomal structure and biogenesis];


Pssm-ID: 441403  Cd Length: 255  Bit Score: 156.12  E-value: 5.28e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904610   3 AVGCCGLQLYKFGETVSIVFWTDTWRPESFFDKVKKNRQNGMHTLCLLDIKVKEQslenlikgrkiyeppRYMSVNQAAQ 82
Cdd:COG1798  118 AIGLTGLQNYKFGKTVTIPFPYEGFVPTSPYDTIKENLERGLHTLVLLDIKADKN---------------RYMTANEALE 182

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767904610  83 QLLEIVQNQRirgeEPAVTEETLCVGLARVGADDQKIAAGTLRQMCTVDLGEPLHSLIITgGSIHPMEMEMLSLFS 158
Cdd:COG1798  183 LLLEIEKKRR----EGVISDDTLAVVVARAGSPDPKIVAGKLSELANYDFGEPPHSLIIP-GRLHFMEAEALKALA 253
dph5 TIGR00522
diphthine synthase; Alternate name: diphthamide biosynthesis S-adenosylmethionine-dependent ...
 1-158 5.31e-44

diphthine synthase; Alternate name: diphthamide biosynthesis S-adenosylmethionine-dependent methyltransferase. This protein participates in the modification of a specific His of elongation factor 2 of eukarotes and Archaea to diphthamide. The protein was characterized in Saccharomyces cerevisiae and designated DPH5. [Protein fate, Protein modification and repair]


Pssm-ID: 273117  Cd Length: 257  Bit Score: 146.11  E-value: 5.31e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904610    1 MNAV-GCCGLQLYKFGETVSIVFWTDTWRPESFFDKVKKNRQNGMHTLCLLDIKVKEqslenlikgrkiyepPRYMSVNQ 79
Cdd:TIGR00522 115 SSAVcGLTGLQLYKFGKTATIVFFTDNYRPQTPYNVIKENRKIGLHTLVLLDIHPKE---------------NRAMTIGE 179

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767904610   80 AAQQLLEIvQNQRirgEEPAVTEETLCVGLARVGADDQKIAAGTLRQMCTVDLGEPLHSLIITGGSIHPMEMEMLSLFS 158
Cdd:TIGR00522 180 GLENLLEE-EEKR---KTGAITPDTYAVVIARAGSGKPVVKCDKIENLKNYDFGEPLHCLVVLAKTLHFMEFEYLREFA 254
 
Name Accession Description Interval E-value
PTZ00175 PTZ00175
diphthine synthase; Provisional
 1-159 3.78e-92

diphthine synthase; Provisional


Pssm-ID: 185500  Cd Length: 270  Bit Score: 269.14  E-value: 3.78e-92
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904610   1 MNAVGCCGLQLYKFGETVSIVFWTDTWRPESFFDKVKKNRQNGMHTLCLLDIKVKEQSLENLIKGRKIYEPPRYMSVNQA 80
Cdd:PTZ00175 116 MNAIGCTGLQLYRFGETVSIPFFTETWKPDSFYDKIKANRDNGLHTLCLLDIKVKERSVENLMKGRKIYEPPRYMTINQA 195

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767904610  81 AQQLLEIVQNQRirgeEPAVTEETLCVGLARVGADDQKIAAGTLRQMCTVDLGEPLHSLIITGGSIHPMEMEMLSLFSI 159
Cdd:PTZ00175 196 IEQLLEVEEKKG----GGVIAEDTLVVGVARVGSDDQQIVSGTLEDLLDVDFGPPLHSLVICAPTLHDIEEEFFELYRI 270
DHP5_DphB cd11647
diphthine methyl ester synthase and diphthine synthase; Eukaryotic diphthine methyl ester ...
 1-143 1.33e-64

diphthine methyl ester synthase and diphthine synthase; Eukaryotic diphthine methyl ester synthase (DHP5) and archaeal diphthamide synthase (DphB) participate in the second step of the biosynthetic pathway of diphthamide. The eukaryotic enzyme catalyzes four methylations of the modified target histidine residue in translation elongation factor 2 (EF-2), to form an intermediate called diphthine methyl ester; the archaeal enzyme, catalyzes only 3 methylations, producing diphthine. Diphtheria toxin ADP-ribosylates diphthamide leading to inhibition of protein synthesis in the eukaryotic host cells.


Pssm-ID: 381174  Cd Length: 241  Bit Score: 198.02  E-value: 1.33e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904610   1 MNAVGCC-GLQLYKFGETVSIVFWTDTWRPESFFDKVKKNRQNGMHTLCLLDIKVkeqslenlikgrkiyEPPRYMSVNQ 79
Cdd:cd11647  115 LSAAGSTsGLQLYKFGRTVTIPFPEENYKPESPYDVIKENLKRGLHTLLLLDIKV---------------EEGRFMTINE 179

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767904610  80 AAQQLLEIVQNQRirgeEPAVTEETLCVGLARVGADDQKIAAGTLRQMCTVDLGEPLHSLIITG 143
Cdd:cd11647  180 AIEILLEIEEKRK----EGVITEDTLVVGLARLGSDDQKIVAGTLKELLKEDFGPPPHSLIIPG 239
DPH5 COG1798
Diphthamide biosynthesis methyltransferase [Translation, ribosomal structure and biogenesis];
3-158 5.28e-48

Diphthamide biosynthesis methyltransferase [Translation, ribosomal structure and biogenesis];


Pssm-ID: 441403  Cd Length: 255  Bit Score: 156.12  E-value: 5.28e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904610   3 AVGCCGLQLYKFGETVSIVFWTDTWRPESFFDKVKKNRQNGMHTLCLLDIKVKEQslenlikgrkiyeppRYMSVNQAAQ 82
Cdd:COG1798  118 AIGLTGLQNYKFGKTVTIPFPYEGFVPTSPYDTIKENLERGLHTLVLLDIKADKN---------------RYMTANEALE 182

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767904610  83 QLLEIVQNQRirgeEPAVTEETLCVGLARVGADDQKIAAGTLRQMCTVDLGEPLHSLIITgGSIHPMEMEMLSLFS 158
Cdd:COG1798  183 LLLEIEKKRR----EGVISDDTLAVVVARAGSPDPKIVAGKLSELANYDFGEPPHSLIIP-GRLHFMEAEALKALA 253
dph5 TIGR00522
diphthine synthase; Alternate name: diphthamide biosynthesis S-adenosylmethionine-dependent ...
 1-158 5.31e-44

diphthine synthase; Alternate name: diphthamide biosynthesis S-adenosylmethionine-dependent methyltransferase. This protein participates in the modification of a specific His of elongation factor 2 of eukarotes and Archaea to diphthamide. The protein was characterized in Saccharomyces cerevisiae and designated DPH5. [Protein fate, Protein modification and repair]


Pssm-ID: 273117  Cd Length: 257  Bit Score: 146.11  E-value: 5.31e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767904610    1 MNAV-GCCGLQLYKFGETVSIVFWTDTWRPESFFDKVKKNRQNGMHTLCLLDIKVKEqslenlikgrkiyepPRYMSVNQ 79
Cdd:TIGR00522 115 SSAVcGLTGLQLYKFGKTATIVFFTDNYRPQTPYNVIKENRKIGLHTLVLLDIHPKE---------------NRAMTIGE 179

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767904610   80 AAQQLLEIvQNQRirgEEPAVTEETLCVGLARVGADDQKIAAGTLRQMCTVDLGEPLHSLIITGGSIHPMEMEMLSLFS 158
Cdd:TIGR00522 180 GLENLLEE-EEKR---KTGAITPDTYAVVIARAGSGKPVVKCDKIENLKNYDFGEPLHCLVVLAKTLHFMEFEYLREFA 254
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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