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    DPH2 diphthamide biosynthesis 2 [ Homo sapiens (human) ]

    Gene ID: 1802, updated on 28-Oct-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
    mouse all
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    Genomic context

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    See DPH2 in Genome Data Viewer
    Location:
    1p34.1
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (43970010..43973369)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (43841090..43844449)
    RS_2024_09 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 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. 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
    2. Cloning and localization of a human diphthamide biosynthesis-like protein-2 gene, DPH2L2. Schultz DC, et al. Genomics, 1998 Sep 1. PMID 9782084
    3. 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
    4. 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
    5. 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

    See all (33) 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
    part_of 2-(3-amino-3-carboxypropyl)histidine synthase complex ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    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_2024_08

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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