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    DOHH deoxyhypusine hydroxylase [ Homo sapiens (human) ]

    Gene ID: 83475, updated on 14-Nov-2024

    Summary

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    Official Symbol
    DOHHprovided by HGNC
    Official Full Name
    deoxyhypusine hydroxylaseprovided by HGNC
    Primary source
    HGNC:HGNC:28662
    See related
    Ensembl:ENSG00000129932 MIM:611262; AllianceGenome:HGNC:28662
    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
    HLRC1; hDOHH; NEDMVIC
    Summary
    This gene encodes a metalloenzyme that catalyzes the last step in the conversion of lysine to the unique amino acid hypusine in eukaryotic initiation factor 5A. The encoded protein hydroxylates deoxyhypusine to form hypusine in the mature eukaryotic initiation factor 5A protein. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Feb 2009]
    Expression
    Ubiquitous expression in kidney (RPKM 3.6), brain (RPKM 3.1) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See DOHH in Genome Data Viewer
    Location:
    19p13.3
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (3490824..3500674, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (3468995..3478845, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (3490822..3500672, complement)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene small integral membrane protein 24 Neighboring gene uncharacterized LOC105372246 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:3483217-3483755 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9845 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9846 Neighboring gene small integral membrane protein 44 Neighboring gene MPRA-validated peak3248 silencer Neighboring gene uncharacterized LOC105372245 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13735 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13736 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13737 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9847 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13738 Neighboring gene fizzy and cell division cycle 20 related 1 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:3516112-3516938 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:3516939-3517763 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:3518044-3518846 Neighboring gene uncharacterized LOC124904617 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:3520450-3521250 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:3539157-3540009 Neighboring gene melanoma risk locus-associated MPRA allelic enhancer 19:3540539 Neighboring gene melanoma risk locus-associated MPRA allelic enhancer 19:3542983 Neighboring gene tektin bundle interacting protein 1 Neighboring gene major facilitator superfamily domain containing 12

    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. Bi-allelic variants in DOHH, catalyzing the last step of hypusine biosynthesis, are associated with a neurodevelopmental disorder. Ziegler A, et al. Am J Hum Genet, 2022 Aug 4. PMID 35858628, Free PMC Article
    2. Deoxyhypusine hydroxylase as a novel pharmacological target for ischemic stroke via inducing a unique post-translational hypusination modification. Guo Q, et al. Pharmacol Res, 2022 Feb. PMID 35007708
    3. Deoxyhypusine hydroxylase: A novel therapeutic target differentially expressed in short-term vs long-term survivors of glioblastoma. Ofek P, et al. Int J Cancer, 2023 Aug 1. PMID 37141410
    4. Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in Hypusination. Han Z, et al. Structure, 2015 May 5. PMID 25865244
    5. Regulation of expression of deoxyhypusine hydroxylase (DOHH), the enzyme that catalyzes the activation of eIF5A, by miR-331-3p and miR-642-5p in prostate cancer cells. Epis MR, et al. J Biol Chem, 2012 Oct 12. PMID 22908221, Free PMC Article

    See all (29) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Deoxyhypusine hydroxylase: A novel therapeutic target differentially expressed in short-term vs long-term survivors of glioblastoma.
      Title: Deoxyhypusine hydroxylase: A novel therapeutic target differentially expressed in short-term vs long-term survivors of glioblastoma.
    2. Bi-allelic variants in DOHH, catalyzing the last step of hypusine biosynthesis, are associated with a neurodevelopmental disorder.
      Title: Bi-allelic variants in DOHH, catalyzing the last step of hypusine biosynthesis, are associated with a neurodevelopmental disorder.
    3. Deoxyhypusine hydroxylase as a novel pharmacological target for ischemic stroke via inducing a unique post-translational hypusination modification.
      Title: Deoxyhypusine hydroxylase as a novel pharmacological target for ischemic stroke via inducing a unique post-translational hypusination modification.
    4. Data describes 3-D structure of hDOHH in two states, hDOHHperoxo (POX) and a complex of the diiron core with glycerol (GLC) providing an explanation for the extreme longevity of POX and illustrate its substrate specificity for deoxyhypusine-eIF-5A.
      Title: Crystal Structure of the Peroxo-diiron(III) Intermediate of Deoxyhypusine Hydroxylase, an Oxygenase Involved in Hypusination.
    5. Here, we show that PCBP1 and PCBP2 also deliver iron to deoxyhypusine hydroxylase (DOHH), the dinuclear iron enzyme required for hypusine modification of the translation factor eukaryotic initiation factor 5A.
      Title: Iron chaperones PCBP1 and PCBP2 mediate the metallation of the dinuclear iron enzyme deoxyhypusine hydroxylase.
    6. eIF-5A as well as the hypusine-forming enzymes deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase (DOHH) are highly overexpressed in glioblastoma patient sample
      Title: Expression of eukaryotic initiation factor 5A and hypusine forming enzymes in glioblastoma patient samples: implications for new targeted therapies.
    7. a novel role for miR-331-3p and miR-642-5p in the control of prostate cancer cell growth via the regulation of DOHH expression and eIF5A activity.
      Title: Regulation of expression of deoxyhypusine hydroxylase (DOHH), the enzyme that catalyzes the activation of eIF5A, by miR-331-3p and miR-642-5p in prostate cancer cells.
    8. Resonance Raman experiments show that its blue chromophore arises from a (mu-1,2-peroxo)diiron(III) center that forms in the reaction of the reduced enzyme with O2, so the peroxo form of hDOHH is unusually stable.
      Title: Human deoxyhypusine hydroxylase, an enzyme involved in regulating cell growth, activates O2 with a nonheme diiron center.
    9. analysis of the deoxyhypusine hydroxylase-eukaryotic translation initiation factor (eIF5A) interaction
      Title: Specificity of the deoxyhypusine hydroxylase-eukaryotic translation initiation factor (eIF5A) interaction: identification of amino acid residues of the enzyme required for binding of its substrate, deoxyhypusine-containing eIF5A.
    10. The structure and function of DOHH are reported.
      Title: Deoxyhypusine hydroxylase is a Fe(II)-dependent, HEAT-repeat enzyme. Identification of amino acid residues critical for Fe(II) binding and catalysis [corrected].
    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
    Neurodevelopmental disorder with microcephaly, cerebral atrophy, and visual impairment
    MedGen: C5774225 OMIM: 620066 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)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    retropepsin gag-pol HIV-1 PR is identified to have a physical interaction with deoxyhypusine hydroxylase/monooxygenase (DOHH) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed

    Go to the HIV-1, Human Interaction Database

    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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    Homology

    Clone Names

    • MGC4293

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables deoxyhypusine monooxygenase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables deoxyhypusine monooxygenase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables iron ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables iron ion binding IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in peptidyl-lysine modification to peptidyl-hypusine IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    deoxyhypusine hydroxylase
    Names
    HEAT-like (PBS lyase) repeat containing 1
    HEAT-like repeat-containing protein 1
    deoxyhypusine dioxygenase
    deoxyhypusine hydroxylase/monooxygenase
    deoxyhypusine monooxygenase
    NP_001138637.1
    NP_112594.1
    XP_011526643.1
    XP_054178268.1

    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_001145165.2 → NP_001138637.1  deoxyhypusine hydroxylase

      See identical proteins and their annotated locations for NP_001138637.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript. Both variants 1 and 2 encode the same protein.
      Source sequence(s)
      BC002817, BG491509, BU624567
      Consensus CDS
      CCDS12108.1
      UniProtKB/Swiss-Prot
      O75265, Q9BU89
      Related
      ENSP00000398882.1, ENST00000427575.6
      Conserved Domains (2) summary
      COG1413
      Location:45 → 298
      HEAT; HEAT repeat [General function prediction only]
      sd00044
      Location:69 → 100
      HEAT; HEAT repeat [structural motif]

    2. NM_031304.5 → NP_112594.1  deoxyhypusine hydroxylase

      See identical proteins and their annotated locations for NP_112594.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same protein.
      Source sequence(s)
      AC005787, BC002817, BU624567
      Consensus CDS
      CCDS12108.1
      UniProtKB/Swiss-Prot
      O75265, Q9BU89
      Related
      ENSP00000500806.1, ENST00000672935.1
      Conserved Domains (2) summary
      COG1413
      Location:45 → 298
      HEAT; HEAT repeat [General function prediction only]
      sd00044
      Location:69 → 100
      HEAT; HEAT repeat [structural motif]

    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_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      3490824..3500674 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011528341.3 → XP_011526643.1  deoxyhypusine hydroxylase isoform X1

      Conserved Domains (3) summary
      smart00567
      Location:85 → 114
      EZ_HEAT; E-Z type HEAT repeats
      pfam13646
      Location:41 → 114
      HEAT_2; HEAT repeats
      sd00044
      Location:69 → 100
      HEAT; HEAT repeat [structural motif]

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      3468995..3478845 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054322293.1 → XP_054178268.1  deoxyhypusine hydroxylase isoform X1

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9BU89.1 GenPept UniProtKB/Swiss-Prot:Q9BU89

    Gene LinkOut

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

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