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DPH2 diphthamide biosynthesis 2 [ Homo sapiens (human) ]

Gene ID: 1802, updated on 5-Mar-2024

Summary

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Official Symbol
DPH2provided by HGNC
Official Full Name
diphthamide biosynthesis 2provided by HGNC
Primary source
HGNC:HGNC:3004
See related
Ensembl:ENSG00000132768 MIM:603456; AllianceGenome:HGNC:3004
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
DPH2L2; DEDSSH2
Summary
This gene is one of two human genes similar to the yeast gene dph2. The yeast gene was identified by its ability to complement a diphthamide mutant strain, and thus probably functions in diphthamide biosynthesis. Diphthamide is a post-translationally modified histidine residue present in elongation factor 2 (EF2) that is the target of diphtheria toxin ADP-ribosylation. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]
Expression
Ubiquitous expression in lymph node (RPKM 6.6), appendix (RPKM 6.4) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
1p34.1
Exon count:
6
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (43970010..43973369)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (43841090..43844449)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (44435682..44439041)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC101929609 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 796 Neighboring gene importin 13 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr1:44426574-44427773 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 928 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:44436478-44437024 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr1:44437355-44438554 Neighboring gene uncharacterized LOC124904167 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:44439785-44440618 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:44440619-44441451 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:44443584-44444175 Neighboring gene ATPase H+ transporting V0 subunit b Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:44444176-44444766 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:44444767-44445358 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:44447723-44448312 Neighboring gene beta-1,4-galactosyltransferase 2

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Spin-Regulated Electron Transfer and Exchange-Enhanced Reactivity in Fe(4) S(4) -Mediated Redox Reaction of the Dph2 Enzyme During the Biosynthesis of Diphthamide. Feng J, et al. Angew Chem Int Ed Engl, 2021 Sep 6. PMID 34302311
  2. Diphthamide-deficiency syndrome: a novel human developmental disorder and ribosomopathy. Hawer H, et al. Eur J Hum Genet, 2020 Nov. PMID 32576952, Free PMC Article
  3. Cloning and localization of a human diphthamide biosynthesis-like protein-2 gene, DPH2L2. Schultz DC, et al. Genomics, 1998 Sep 1. PMID 9782084
  4. Loss of diphthamide pre-activates NF-κB and death receptor pathways and renders MCF7 cells hypersensitive to tumor necrosis factor. Stahl S, et al. Proc Natl Acad Sci U S A, 2015 Aug 25. PMID 26261303, Free PMC Article
  5. Mutations in the elongation factor 2 gene which confer resistance to diphtheria toxin and Pseudomonas exotoxin A. Genetic and biochemical analyses. Foley BT, et al. J Biol Chem, 1995 Sep 29. PMID 7559470

See all (31) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. DPH1 and DPH2 variants that confer susceptibility to diphthamide deficiency syndrome in human cells and yeast models.
    Title: DPH1 and DPH2 variants that confer susceptibility to diphthamide deficiency syndrome in human cells and yeast models.
  2. Spin-Regulated Electron Transfer and Exchange-Enhanced Reactivity in Fe4 S4 -Mediated Redox Reaction of the Dph2 Enzyme During the Biosynthesis of Diphthamide.
    Title: Spin-Regulated Electron Transfer and Exchange-Enhanced Reactivity in Fe(4) S(4) -Mediated Redox Reaction of the Dph2 Enzyme During the Biosynthesis of Diphthamide.
  3. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
    Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
Submit: New GeneRIF Correction

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Developmental delay with short stature, dysmorphic facial features, and sparse hair 2
MedGen: C5774223 OMIM: 620062 GeneReviews: Not available
not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables 2-(3-amino-3-carboxypropyl)histidine synthase activity EXP
Inferred from Experiment
more info
 PubMed 
contributes_to 2-(3-amino-3-carboxypropyl)histidine synthase activity ISS
Inferred from Sequence or Structural Similarity
more info
  
enables 4 iron, 4 sulfur cluster binding ISS
Inferred from Sequence or Structural Similarity
more info
  
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in protein histidyl modification to diphthamide IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein histidyl modification to diphthamide IEA
Inferred from Electronic Annotation
more info
  
involved_in protein histidyl modification to diphthamide IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in protein histidyl modification to diphthamide ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in protein histidyl modification to diphthamide TAS
Traceable Author Statement
more info
  
Component Evidence Code Pubs
located_in cytosol TAS
Traceable Author Statement
more info
  
part_of protein-containing complex ISS
Inferred from Sequence or Structural Similarity
more info
  

General protein information

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Preferred Names
2-(3-amino-3-carboxypropyl)histidine synthase subunit 2
Names
DPH2 homolog
DPH2-like 2
S-adenosyl-L-methionine:L-histidine 3-amino-3-carboxypropyltransferase 2
diphthamide biosynthesis protein 2 homolog-like 2
diphthamide biosynthesis-like protein 2
diphtheria toxin resistance protein 2
diptheria toxin resistance protein required for diphthamide biosynthesis-like 2
NP_001034678.1
NP_001306094.1
NP_001306095.1
NP_001306096.1
NP_001306097.1
NP_001306098.1
NP_001306099.1
NP_001306100.1
NP_001375.2
XP_047304023.1
XP_047304026.1
XP_054190773.1
XP_054190774.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001039589.2 → NP_001034678.1  2-(3-amino-3-carboxypropyl)histidine synthase subunit 2 isoform b

    See identical proteins and their annotated locations for NP_001034678.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (b) has the same N- and C-termini but is shorter compared to isoform a.
    Source sequence(s)
    AA252672, AL357079
    Consensus CDS
    CCDS41314.1
    UniProtKB/Swiss-Prot
    Q9BQC3
    Related
    ENSP00000379981.2, ENST00000396758.6
    Conserved Domains (1) summary
    cl19374
    Location:32 → 162
    Diphthamide_syn; Putative diphthamide synthesis protein

  2. NM_001319165.2 → NP_001306094.1  2-(3-amino-3-carboxypropyl)histidine synthase subunit 2 isoform c

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) uses an alternate splice junction in the 5' end compared to variant 1. The resulting isoform (c) is shorter at the N-terminus compared to isoform a. Variants 3 and 6 both encode the same isoform (c).
    Source sequence(s)
    AA252672, AK091303, BQ056213, DA906783
    UniProtKB/TrEMBL
    B3KRB8
    Conserved Domains (1) summary
    TIGR00322
    Location:2 → 292
    diphth2_R; diphthamide biosynthesis enzyme Dph1/Dph2 domain

  3. NM_001319166.2 → NP_001306095.1  2-(3-amino-3-carboxypropyl)histidine synthase subunit 2 isoform d

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) uses an alternate in-frame splice junction compared to variant 1. The resulting isoform (d) has the same N- and C-termini but is shorter compared to isoform a.
    Source sequence(s)
    AA252672, AK091303, AK315506, BG385934
    UniProtKB/Swiss-Prot
    Q9BQC3
    UniProtKB/TrEMBL
    B3KRB8
    Conserved Domains (1) summary
    TIGR00322
    Location:32 → 277
    diphth2_R; diphthamide biosynthesis enzyme Dph1/Dph2 domain

  4. NM_001319167.2 → NP_001306096.1  2-(3-amino-3-carboxypropyl)histidine synthase subunit 2 isoform e

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) uses two alternate splice junctions compared to variant 1. The resulting isoform (e) is shorter at the N-terminus compared to isoform a. Variants 5 and 8 both encode the same isoform (e).
    Source sequence(s)
    AA252672, AK091303, AL357079, BG747150
    UniProtKB/TrEMBL
    H0YCR5
    Conserved Domains (1) summary
    cl19374
    Location:7 → 290
    Diphthamide_syn; Putative diphthamide synthesis protein

  5. NM_001319168.2 → NP_001306097.1  2-(3-amino-3-carboxypropyl)histidine synthase subunit 2 isoform c

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) uses an alternate splice junction in the 5' end compared to variant 1. The resulting isoform (c) is shorter at the N-terminus compared to isoform a. Variants 3 and 6 both encode the same isoform (c).
    Source sequence(s)
    AA252672, AK091303, CX164803
    UniProtKB/TrEMBL
    B3KRB8
    Conserved Domains (1) summary
    TIGR00322
    Location:2 → 292
    diphth2_R; diphthamide biosynthesis enzyme Dph1/Dph2 domain

  6. NM_001319169.2 → NP_001306098.1  2-(3-amino-3-carboxypropyl)histidine synthase subunit 2 isoform f

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) lacks an alternate exon compared to variant 1. The resulting isoform (f) has a shorter and distinct N-terminus compared to isoform a.
    Source sequence(s)
    AA252672, AK091303, AK297933
    UniProtKB/Swiss-Prot
    Q9BQC3
    UniProtKB/TrEMBL
    B3KRB8
    Conserved Domains (1) summary
    cl19374
    Location:65 → 348
    Diphthamide_syn; Putative diphthamide synthesis protein

  7. NM_001319170.2 → NP_001306099.1  2-(3-amino-3-carboxypropyl)histidine synthase subunit 2 isoform e

    Status: REVIEWED

    Description
    Transcript Variant: This variant (8) uses an alternate splice junction compared to variant 1. The resulting isoform (e) is shorter at the N-terminus compared to isoform a. Variants 5 and 8 both encode the same isoform (e).
    Source sequence(s)
    AA252672, AK091303, BG472282, DA906783
    UniProtKB/TrEMBL
    H0YCR5
    Conserved Domains (1) summary
    cl19374
    Location:7 → 290
    Diphthamide_syn; Putative diphthamide synthesis protein

  8. NM_001319171.2 → NP_001306100.1  2-(3-amino-3-carboxypropyl)histidine synthase subunit 2 isoform g

    Status: REVIEWED

    Description
    Transcript Variant: This variant (9) uses an alternate splice junction compared to variant 1. The resulting isoform (g) has a shorter and distinct N-terminus compared to isoform a.
    Source sequence(s)
    AA252672, AK091303, AL357079, BM564151, DA906783
    UniProtKB/TrEMBL
    B3KRB8
    Conserved Domains (1) summary
    cl19374
    Location:52 → 335
    Diphthamide_syn; Putative diphthamide synthesis protein

  9. NM_001384.5 → NP_001375.2  2-(3-amino-3-carboxypropyl)histidine synthase subunit 2 isoform a

    See identical proteins and their annotated locations for NP_001375.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (a).
    Source sequence(s)
    AA252672, AL357079
    Consensus CDS
    CCDS504.1
    UniProtKB/Swiss-Prot
    A8MVC9, B2RDE3, B4DNI8, O60623, Q9BQC3
    Related
    ENSP00000255108.3, ENST00000255108.8
    Conserved Domains (1) summary
    TIGR00322
    Location:32 → 368
    diphth2_R; diphthamide biosynthesis enzyme Dph1/Dph2 domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    43970010..43973369
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047448067.1 → XP_047304023.1  2-(3-amino-3-carboxypropyl)histidine synthase subunit 2 isoform X1

  2. XM_047448070.1 → XP_047304026.1  2-(3-amino-3-carboxypropyl)histidine synthase subunit 2 isoform X1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    43841090..43844449
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054334798.1 → XP_054190773.1  2-(3-amino-3-carboxypropyl)histidine synthase subunit 2 isoform X1

  2. XM_054334799.1 → XP_054190774.1  2-(3-amino-3-carboxypropyl)histidine synthase subunit 2 isoform X1

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_201399.1: Suppressed sequence

    Description
    NM_201399.1: This RefSeq was permanently suppressed because it is a nonsense-mediated decay (NMD) candidate.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9BQC3.1 GenPept UniProtKB/Swiss-Prot:Q9BQC3

Gene LinkOut

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