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Protein

Diphthine methyl ester synthase

Gene

DPH5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

S-adenosyl-L-methionine-dependent methyltransferase that 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 four successive methylation reactions represent the second step of diphthamide biosynthesis.By similarity1 Publication

Catalytic activityi

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].By similarity

Pathwayi: peptidyl-diphthamide biosynthesis

This protein is involved in the pathway peptidyl-diphthamide biosynthesis, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway peptidyl-diphthamide biosynthesis and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei9S-adenosyl-L-methionine; via carbonyl oxygenBy similarity1
Binding sitei84S-adenosyl-L-methionine; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei87S-adenosyl-L-methionine; via carbonyl oxygenBy similarity1
Binding sitei163S-adenosyl-L-methionine; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei225S-adenosyl-L-methionine; via amide nitrogen and carbonyl oxygenBy similarity1
Binding sitei250S-adenosyl-L-methionine; via carbonyl oxygenBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionMethyltransferase, Transferase
LigandS-adenosyl-L-methionine

Enzyme and pathway databases

ReactomeiR-HSA-5358493 Synthesis of diphthamide-EEF2
UniPathwayi
UPA00559

Names & Taxonomyi

Protein namesi
Recommended name:
Diphthine methyl ester synthase (EC:2.1.1.314)
Alternative name(s):
Diphthamide biosynthesis methyltransferase
Gene namesi
Name:DPH5
ORF Names:AD-018, CGI-30, HSPC143, NPD015
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000117543.19
HGNCiHGNC:24270 DPH5
MIMi611075 gene
neXtProtiNX_Q9H2P9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Organism-specific databases

OpenTargetsiENSG00000117543
PharmGKBiPA142671956

Chemistry databases

DrugBankiDB01752 S-Adenosyl-L-Homocysteine

Polymorphism and mutation databases

BioMutaiDPH5
DMDMi46397414

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001561331 – 285Diphthine methyl ester synthaseAdd BLAST285

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei171PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9H2P9
MaxQBiQ9H2P9
PaxDbiQ9H2P9
PeptideAtlasiQ9H2P9
PRIDEiQ9H2P9
ProteomicsDBi80572
80573 [Q9H2P9-2]
80574 [Q9H2P9-3]
80575 [Q9H2P9-4]
80576 [Q9H2P9-5]
80577 [Q9H2P9-6]

PTM databases

iPTMnetiQ9H2P9
PhosphoSitePlusiQ9H2P9

Expressioni

Gene expression databases

BgeeiENSG00000117543 Expressed in 227 organ(s), highest expression level in testis
CleanExiHS_DPH5
ExpressionAtlasiQ9H2P9 baseline and differential
GenevisibleiQ9H2P9 HS

Organism-specific databases

HPAiHPA046439
HPA076234

Interactioni

Protein-protein interaction databases

BioGridi119637, 13 interactors
STRINGi9606.ENSP00000359127

Structurei

3D structure databases

ProteinModelPortaliQ9H2P9
SMRiQ9H2P9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni112 – 113S-adenosyl-L-methionine bindingBy similarity2

Sequence similaritiesi

Belongs to the diphthine synthase family.Curated

Phylogenomic databases

eggNOGiKOG3123 Eukaryota
COG1798 LUCA
GeneTreeiENSGT00390000010568
HOGENOMiHOG000205302
HOVERGENiHBG044879
InParanoidiQ9H2P9
KOiK00586
OMAiLQNYRFG
OrthoDBiEOG091G0EKA
PhylomeDBiQ9H2P9
TreeFamiTF105603

Family and domain databases

CDDicd11647 Diphthine_synthase, 1 hit
Gene3Di3.30.950.10, 1 hit
3.40.1010.10, 1 hit
HAMAPiMF_01084 Diphthine_synth, 1 hit
InterProiView protein in InterPro
IPR000878 4pyrrol_Mease
IPR035996 4pyrrol_Methylase_sf
IPR014777 4pyrrole_Mease_sub1
IPR014776 4pyrrole_Mease_sub2
IPR004551 Dphthn_synthase
PANTHERiPTHR10882:SF0 PTHR10882:SF0, 1 hit
PfamiView protein in Pfam
PF00590 TP_methylase, 1 hit
PIRSFiPIRSF036432 Diphthine_synth, 1 hit
SUPFAMiSSF53790 SSF53790, 1 hit
TIGRFAMsiTIGR00522 dph5, 1 hit

Sequences (6+)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 6 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9H2P9-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MLYLIGLGLG DAKDITVKGL EVVRRCSRVY LEAYTSVLTV GKEALEEFYG
60 70 80 90 100
RKLVVADREE VEQEADNILK DADISDVAFL VVGDPFGATT HSDLVLRATK
110 120 130 140 150
LGIPYRVIHN ASIMNAVGCC GLQLYKFGET VSIVFWTDTW RPESFFDKVK
160 170 180 190 200
KNRQNGMHTL CLLDIKVKEQ SLENLIKGRK IYEPPRYMSV NQAAQQLLEI
210 220 230 240 250
VQNQRIRGEE PAVTEETLCV GLARVGADDQ KIAAGTLRQM CTVDLGEPLH
260 270 280
SLIITGGSIH PMEMEMLSLF SIPENSSESQ SINGL
Length:285
Mass (Da):31,651
Last modified:October 10, 2003 - v2
Checksum:i1348631C25BC624E
GO
Isoform 2 (identifier: Q9H2P9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     85-137: PFGATTHSDLVLRATKLGIPYRVIHNASIMNAVGCCGLQLYKFGETVSIVFWT → HL

Note: No experimental confirmation available.
Show »
Length:234
Mass (Da):26,122
Checksum:iCAA1ABE0A11AF714
GO
Isoform 3 (identifier: Q9H2P9-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     88-143: ATTHSDLVLRATKLGIPYRVIHNASIMNAVGCCGLQLYKFGETVSIVFWTDTWRPE → HLETR

Note: No experimental confirmation available.
Show »
Length:234
Mass (Da):26,025
Checksum:i86A9E6761145DFBA
GO
Isoform 4 (identifier: Q9H2P9-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     117-141: VGCCGLQLYKFGETVSIVFWTDTWR → EAAGGYRYISLERQVLLVFGQTLGG

Note: No experimental confirmation available.
Show »
Length:285
Mass (Da):31,440
Checksum:i2784D835EB96EFC2
GO
Isoform 5 (identifier: Q9H2P9-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     134-137: VFWT → MLISVMLHSLWLVIHL

Note: No experimental confirmation available.
Show »
Length:297
Mass (Da):33,005
Checksum:iE0D27EEEF0B9849D
GO
Isoform 6 (identifier: Q9H2P9-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     212-212: Missing.

Note: No experimental confirmation available.
Show »
Length:284
Mass (Da):31,580
Checksum:i862A9762E32AA574
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q96DC6Q96DC6_HUMAN
DPH5 homolog (S. cerevisiae), isofo...
DPH5 hCG_32849
46Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti107V → G in AAG44563 (Ref. 4) Curated1
Sequence conflicti285L → FEHRYFHCLM in AAF67485 (PubMed:10931946).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00850885 – 137PFGAT…IVFWT → HL in isoform 2. 1 PublicationAdd BLAST53
Alternative sequenceiVSP_00850988 – 143ATTHS…TWRPE → HLETR in isoform 3. 1 PublicationAdd BLAST56
Alternative sequenceiVSP_008510117 – 141VGCCG…TDTWR → EAAGGYRYISLERQVLLVFG QTLGG in isoform 4. 1 PublicationAdd BLAST25
Alternative sequenceiVSP_008511134 – 137VFWT → MLISVMLHSLWLVIHL in isoform 5. 1 Publication4
Alternative sequenceiVSP_043444212Missing in isoform 6. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF132964 mRNA Translation: AAD27739.1
AF157319 mRNA Translation: AAF67485.1
AF161492 mRNA Translation: AAF29107.1
AF248965 mRNA Translation: AAG44563.1
AK289351 mRNA Translation: BAF82040.1
AC093157 Genomic DNA No translation available.
CH471097 Genomic DNA Translation: EAW72933.1
CH471097 Genomic DNA Translation: EAW72937.1
CH471097 Genomic DNA Translation: EAW72938.1
CH471097 Genomic DNA Translation: EAW72940.1
BC053857 mRNA Translation: AAH53857.1
CCDSiCCDS41358.1 [Q9H2P9-1]
CCDS41359.1 [Q9H2P9-6]
RefSeqiNP_001070862.1, NM_001077394.1 [Q9H2P9-1]
NP_001070863.1, NM_001077395.1 [Q9H2P9-6]
NP_057042.2, NM_015958.2 [Q9H2P9-1]
XP_016856949.1, XM_017001460.1 [Q9H2P9-1]
UniGeneiHs.440776

Genome annotation databases

EnsembliENST00000342173; ENSP00000339630; ENSG00000117543 [Q9H2P9-6]
ENST00000370109; ENSP00000359127; ENSG00000117543 [Q9H2P9-1]
ENST00000488176; ENSP00000418282; ENSG00000117543 [Q9H2P9-1]
GeneIDi51611
KEGGihsa:51611
UCSCiuc001dtr.4 human [Q9H2P9-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF132964 mRNA Translation: AAD27739.1
AF157319 mRNA Translation: AAF67485.1
AF161492 mRNA Translation: AAF29107.1
AF248965 mRNA Translation: AAG44563.1
AK289351 mRNA Translation: BAF82040.1
AC093157 Genomic DNA No translation available.
CH471097 Genomic DNA Translation: EAW72933.1
CH471097 Genomic DNA Translation: EAW72937.1
CH471097 Genomic DNA Translation: EAW72938.1
CH471097 Genomic DNA Translation: EAW72940.1
BC053857 mRNA Translation: AAH53857.1
CCDSiCCDS41358.1 [Q9H2P9-1]
CCDS41359.1 [Q9H2P9-6]
RefSeqiNP_001070862.1, NM_001077394.1 [Q9H2P9-1]
NP_001070863.1, NM_001077395.1 [Q9H2P9-6]
NP_057042.2, NM_015958.2 [Q9H2P9-1]
XP_016856949.1, XM_017001460.1 [Q9H2P9-1]
UniGeneiHs.440776

3D structure databases

ProteinModelPortaliQ9H2P9
SMRiQ9H2P9
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119637, 13 interactors
STRINGi9606.ENSP00000359127

Chemistry databases

DrugBankiDB01752 S-Adenosyl-L-Homocysteine

PTM databases

iPTMnetiQ9H2P9
PhosphoSitePlusiQ9H2P9

Polymorphism and mutation databases

BioMutaiDPH5
DMDMi46397414

Proteomic databases

EPDiQ9H2P9
MaxQBiQ9H2P9
PaxDbiQ9H2P9
PeptideAtlasiQ9H2P9
PRIDEiQ9H2P9
ProteomicsDBi80572
80573 [Q9H2P9-2]
80574 [Q9H2P9-3]
80575 [Q9H2P9-4]
80576 [Q9H2P9-5]
80577 [Q9H2P9-6]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000342173; ENSP00000339630; ENSG00000117543 [Q9H2P9-6]
ENST00000370109; ENSP00000359127; ENSG00000117543 [Q9H2P9-1]
ENST00000488176; ENSP00000418282; ENSG00000117543 [Q9H2P9-1]
GeneIDi51611
KEGGihsa:51611
UCSCiuc001dtr.4 human [Q9H2P9-1]

Organism-specific databases

CTDi51611
EuPathDBiHostDB:ENSG00000117543.19
GeneCardsiDPH5
H-InvDBiHIX0023161
HGNCiHGNC:24270 DPH5
HPAiHPA046439
HPA076234
MIMi611075 gene
neXtProtiNX_Q9H2P9
OpenTargetsiENSG00000117543
PharmGKBiPA142671956
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3123 Eukaryota
COG1798 LUCA
GeneTreeiENSGT00390000010568
HOGENOMiHOG000205302
HOVERGENiHBG044879
InParanoidiQ9H2P9
KOiK00586
OMAiLQNYRFG
OrthoDBiEOG091G0EKA
PhylomeDBiQ9H2P9
TreeFamiTF105603

Enzyme and pathway databases

UniPathwayi
UPA00559

ReactomeiR-HSA-5358493 Synthesis of diphthamide-EEF2

Miscellaneous databases

ChiTaRSiDPH5 human
GeneWikiiDPH5
GenomeRNAii51611
PROiPR:Q9H2P9
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000117543 Expressed in 227 organ(s), highest expression level in testis
CleanExiHS_DPH5
ExpressionAtlasiQ9H2P9 baseline and differential
GenevisibleiQ9H2P9 HS

Family and domain databases

CDDicd11647 Diphthine_synthase, 1 hit
Gene3Di3.30.950.10, 1 hit
3.40.1010.10, 1 hit
HAMAPiMF_01084 Diphthine_synth, 1 hit
InterProiView protein in InterPro
IPR000878 4pyrrol_Mease
IPR035996 4pyrrol_Methylase_sf
IPR014777 4pyrrole_Mease_sub1
IPR014776 4pyrrole_Mease_sub2
IPR004551 Dphthn_synthase
PANTHERiPTHR10882:SF0 PTHR10882:SF0, 1 hit
PfamiView protein in Pfam
PF00590 TP_methylase, 1 hit
PIRSFiPIRSF036432 Diphthine_synth, 1 hit
SUPFAMiSSF53790 SSF53790, 1 hit
TIGRFAMsiTIGR00522 dph5, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiDPH5_HUMAN
AccessioniPrimary (citable) accession number: Q9H2P9
Secondary accession number(s): A8JZY6
, D3DT62, Q9P017, Q9P0I4, Q9Y319
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 10, 2003
Last sequence update: October 10, 2003
Last modified: November 7, 2018
This is version 133 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PATHWAY comments
    Index of metabolic and biosynthesis pathways
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Main funding by: National Institutes of Health

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