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Information on EC 2.1.1.314 - diphthine methyl ester synthase and Organism(s) Homo sapiens and UniProt Accession Q9H2P9

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EC Tree
     2 Transferases
         2.1 Transferring one-carbon groups
             2.1.1 Methyltransferases
                2.1.1.314 diphthine methyl ester synthase
IUBMB Comments
This eukaryotic enzyme is part of the biosynthetic pathway of diphthamide. Different from the archaeal enzyme, which performs only 3 methylations, producing diphthine (cf. EC 2.1.1.98). The relevant histidine of elongation factor 2 is His715 in mammals and His699 in yeast. The order of the 4 methylations is not known.
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Homo sapiens
UNIPROT: Q9H2P9
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The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Synonyms
diphthine methyltransferase, diphthine synthase, Dph5, S-adenosyl-L-methionine:elongation factor 2 methyltransferase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
PATHWAY SOURCE
PATHWAYS
-
-
SYSTEMATIC NAME
IUBMB Comments
S-adenosyl-L-methionine:2-[(3S)-3-carboxy-3-aminopropyl]-L-histidine-[translation elongation factor 2] methyltransferase (diphthine methyl ester-[translation elongation factor 2]-forming)
This eukaryotic enzyme is part of the biosynthetic pathway of diphthamide. Different from the archaeal enzyme, which performs only 3 methylations, producing diphthine (cf. EC 2.1.1.98). The relevant histidine of elongation factor 2 is His715 in mammals and His699 in yeast. The order of the 4 methylations is not known.
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
4 S-adenosyl-L-methionine + 2-[(3S)-3-carboxy-3-aminopropyl]-L-histidine-[translation elongation factor 2]
4 S-adenosyl-L-homocysteine + diphthine methyl ester-[translation elongation factor 2]
show the reaction diagram
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-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
4 S-adenosyl-L-methionine + 2-[(3S)-3-carboxy-3-aminopropyl]-L-histidine-[translation elongation factor 2]
4 S-adenosyl-L-homocysteine + diphthine methyl ester-[translation elongation factor 2]
show the reaction diagram
-
-
-
?
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
malfunction
complete inactivation of DPH1, DPH2, DPH4, and DPH5 generated viable cells without diphthamide. Reduced growth rates are observed for all clones with completely inactivated DPH5. These contain ACP-modified eEF2, which occurs only in DPH5-deficient cells and not in other variants
physiological function
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
DPH5_HUMAN
285
0
31651
Swiss-Prot
other Location (Reliability: 1)
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
D57G
mutant retains activity
delA212
frequently occurring DPH5 isoform retained activity
E60stop
inactive mutant containing intact N-terminus with truncations after amino acid 207
G87R
mutant retains activity
Q170H
mutant retains activity
R207stop
inactive mutant containing intact N-terminus with truncations after amino acid 207
S123C
mutant retains activity
W136stop
inactive mutant containing intact N-terminus with truncations after amino acid 207
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of DPH1 and DPH5 cDNA in DPH deficient MCF7 cells
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Stahl, S.; Da Silva Mateus Seidl, A.; Ducret, A.; Van Geijtenbeek, S.; Michel, S.; Racek, T.; Birzele, F.; Haas, A.; Rueger, R.; Gerg, M.; Niederfellner, G.; Pastan, I.; Brinkmann, U.
Loss of diphthamide pre-activates NF-kappaB and death receptor pathways and renders MCF7 cells hypersensitive to tumor necrosis factor
Proc. Natl. Acad. Sci. USA
112
10732-10737
2015
Homo sapiens (Q9H2P9)
Manually annotated by BRENDA team
Mayer, K.; Schrder, A.; Schnitger, J.; Stahl, S.; Brinkmann, U.
Influence of DPH1 and DPH5 protein variants on the synthesis of diphthamide, the target of ADPRibosylating toxins
Toxins
9
E78
2017
Homo sapiens (Q9H2P9)
Manually annotated by BRENDA team