Human Gene DPH5 (uc001dtt.2) Description and Page Index
  Description: Homo sapiens diphthamide biosynthesis 5 (DPH5), transcript variant 1, mRNA.
RefSeq Summary (NM_001077394): This gene encodes a component of the diphthamide synthesis pathway. Diphthamide is a post-translationally modified histidine residue found only on translation elongation factor 2. It is conserved from archaebacteria to humans, and is targeted by diphtheria toxin and Pseudomonas exotoxin A to halt cellular protein synthesis. The yeast and Chinese hamster homologs of this protein catalyze the trimethylation of the histidine residue on elongation factor 2, resulting in a diphthine moiety that is subsequently amidated to yield diphthamide. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008].
Transcript (Including UTRs)
   Position: hg19 chr1:101,455,180-101,491,362 Size: 36,183 Total Exon Count: 8 Strand: -
Coding Region
   Position: hg19 chr1:101,455,964-101,490,999 Size: 35,036 Coding Exon Count: 7 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsCTDGene Alleles
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr1:101,455,180-101,491,362)mRNA (may differ from genome)Protein (285 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaBioGPS
CGAPEnsemblEntrez GeneExonPrimerGeneCardsGeneNetwork
PubMedReactomeStanford SOURCETreefamUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Diphthine synthase; EC=; AltName: Full=Diphthamide biosynthesis methyltransferase;
FUNCTION: S-adenosyl-L-methionine-dependent methyltransferase that catalyzes the trimethylation of the amino group of the modified target histidine residue in translation elongation factor 2 (EF- 2), to form an intermediate called diphthine. The three successive methylation reactions represent the second step of diphthamide biosynthesis (By similarity).
CATALYTIC ACTIVITY: 3 S-adenosyl-L-methionine + 2-(3-carboxy-3- aminopropyl)-L-histidine = 3 S-adenosyl-L-homocysteine + 2-(3- carboxy-3-(trimethylammonio)propyl)-L-histidine.
PATHWAY: Protein modification; peptidyl-diphthamide biosynthesis.
SIMILARITY: Belongs to the diphthine synthase family.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): DPH5
CDC HuGE Published Literature: DPH5
Positive Disease Associations: Heart Rate , Perphenazine
Related Studies:
  1. Heart Rate
    , , . [PubMed 0]
  2. Perphenazine
    D E Adkins et al. Molecular psychiatry 2011, Genomewide pharmacogenomic study of metabolic side effects to antipsychotic drugs., Molecular psychiatry. [PubMed 20195266]

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
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-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 12.14 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 222.72 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -50.00165-0.303 Picture PostScript Text
3' UTR -208.91784-0.266 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000878 - 4pyrrol_Mease
IPR014777 - 4pyrrole_Mease_sub1
IPR014776 - 4pyrrole_Mease_sub2
IPR004551 - Dphthn_synthase

Pfam Domains:
PF00590 - Tetrapyrrole (Corrin/Porphyrin) Methylases

SCOP Domains:
53790 - Tetrapyrrole methylase

ModBase Predicted Comparative 3D Structure on Q9H2P9
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserGenome BrowserGenome BrowserNo ortholog
Gene DetailsGene Details Gene DetailsGene Details 
Gene SorterGene Sorter Gene SorterGene Sorter 
 Protein SequenceProtein SequenceProtein SequenceProtein Sequence 

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0004164 diphthine synthase activity
GO:0008168 methyltransferase activity
GO:0016740 transferase activity

Biological Process:
GO:0008152 metabolic process
GO:0017183 peptidyl-diphthamide biosynthetic process from peptidyl-histidine
GO:0032259 methylation

Cellular Component:
GO:0005575 cellular_component
GO:0005829 cytosol

-  Descriptions from all associated GenBank mRNAs
  AK125485 - Homo sapiens cDNA FLJ43496 fis, clone PEBLM2001465, highly similar to Probable diphthine synthase (EC
AK289351 - Homo sapiens cDNA FLJ76983 complete cds, highly similar to Homo sapiens DPH5 homolog (S. cerevisiae), mRNA.
AF132964 - Homo sapiens CGI-30 protein mRNA, complete cds.
JD551169 - Sequence 532193 from Patent EP1572962.
JD486849 - Sequence 467873 from Patent EP1572962.
BC009620 - Homo sapiens DPH5 homolog (S. cerevisiae), mRNA (cDNA clone IMAGE:3893940), complete cds.
BC003660 - Homo sapiens DPH5 homolog (S. cerevisiae), mRNA (cDNA clone IMAGE:2988502), **** WARNING: chimeric clone ****.
BC053857 - Homo sapiens DPH5 homolog (S. cerevisiae), mRNA (cDNA clone MGC:61450 IMAGE:5503038), complete cds.
AF248965 - Homo sapiens NPD015 mRNA, complete cds.
AK225469 - Homo sapiens mRNA for Probable diphthine synthase variant, clone: HSI07462.
AK225707 - Homo sapiens mRNA for Probable diphthine synthase variant, clone: TMS02611.
AF161492 - Homo sapiens HSPC143 mRNA, complete cds.
BC034669 - Homo sapiens DPH5 homolog (S. cerevisiae), mRNA (cDNA clone IMAGE:5189198), with apparent retained intron.
AK225951 - Homo sapiens mRNA for Probable diphthine synthase variant, clone: FCC115A08.
JD402253 - Sequence 383277 from Patent EP1572962.
AK298181 - Homo sapiens cDNA FLJ60749 complete cds, moderately similar to Homo sapiens DPH5 homolog (DPH5), mRNA.
JD548784 - Sequence 529808 from Patent EP1572962.
AF157319 - Homo sapiens AD-018 protein mRNA, complete cds.
KJ902607 - Synthetic construct Homo sapiens clone ccsbBroadEn_12001 DPH5 gene, encodes complete protein.
AB590970 - Synthetic construct DNA, clone: pFN21AE1778, Homo sapiens DPH5 gene for DPH5 homolog, without stop codon, in Flexi system.
JD358386 - Sequence 339410 from Patent EP1572962.
DL491572 - Novel nucleic acids.
DL490173 - Novel nucleic acids.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q9H2P9 (Reactome details) participates in the following event(s):

R-HSA-5358484 DPH5 transfers four methyl groups from AdoMet to aminocarboxypropyl EEF2
R-HSA-5358493 Synthesis of diphthamide-EEF2
R-HSA-163841 Gamma carboxylation, hypusine formation and arylsulfatase activation
R-HSA-597592 Post-translational protein modification
R-HSA-392499 Metabolism of proteins

-  Other Names for This Gene
  Alternate Gene Symbols: A8JZY6, AD-018, CGI-30, D3DT62, DPH5_HUMAN, HSPC143, NM_001077394, NPD015, NP_057042, Q9H2P9, Q9P017, Q9P0I4, Q9Y319
UCSC ID: uc001dtt.2
RefSeq Accession: NM_001077394
Protein: Q9H2P9 (aka DPH5_HUMAN)
CCDS: CCDS41358.1, CCDS41359.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_001077394.1
exon count: 8CDS single in 3' UTR: no RNA size: 1828
ORF size: 858CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1916.00frame shift in genome: no % Coverage: 98.85
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.