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    DDI2 DNA damage inducible 1 homolog 2 [ Homo sapiens (human) ]

    Gene ID: 84301, updated on 2-Nov-2024

    Summary

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    Official Symbol
    DDI2provided by HGNC
    Official Full Name
    DNA damage inducible 1 homolog 2provided by HGNC
    Primary source
    HGNC:HGNC:24578
    See related
    Ensembl:ENSG00000197312 MIM:620871; AllianceGenome:HGNC:24578
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Summary
    Enables aspartic-type endopeptidase activity; identical protein binding activity; and ubiquitin binding activity. Involved in several processes, including cellular response to hydroxyurea; regulation of DNA stability; and regulation of protein stability. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Nov 2024]
    Expression
    Ubiquitous expression in esophagus (RPKM 7.7), kidney (RPKM 5.8) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See DDI2 in Genome Data Viewer
    Location:
    1p36.21
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (15617458..15669044)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (15062171..15113775)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (15943953..15995539)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene RNA, U7 small nuclear 179 pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 309 Neighboring gene CD24 molecule pseudogene 1 Neighboring gene MPRA-validated peak82 silencer Neighboring gene regulator of solute carriers 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:16005129-16005676 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:16006379-16006879 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 310 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 311 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 312 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 240 Neighboring gene pleckstrin homology and RUN domain containing M2 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 241 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 242 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 243 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 244 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:16051023-16051299 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:16051819-16052339 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:16061087-16061852 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:16061853-16062619 Neighboring gene SLC25A34 and TMEM82 antisense RNA 1 Neighboring gene solute carrier family 25 member 34

    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. Proteolytic activation of angiomotin by DDI2 promotes angiogenesis. Wang Y, et al. EMBO J, 2023 Aug 1. PMID 37350545, Free PMC Article
    2. The aspartyl protease DDI2 drives adaptation to proteasome inhibition in multiple myeloma. Op M, et al. Cell Death Dis, 2022 May 19. PMID 35589686, Free PMC Article
    3. DDI2 promotes tumor metastasis and resists antineoplastic drugs-induced apoptosis in colorectal cancer. Lei L, et al. Apoptosis, 2023 Apr. PMID 36520320
    4. Human DNA-Damage-Inducible 2 Protein Is Structurally and Functionally Distinct from Its Yeast Ortholog. Sivá M, et al. Sci Rep, 2016 Jul 27. PMID 27461074, Free PMC Article
    5. DDI2 Is a Ubiquitin-Directed Endoprotease Responsible for Cleavage of Transcription Factor NRF1. Dirac-Svejstrup AB, et al. Mol Cell, 2020 Jul 16. PMID 32521225, Free PMC Article

    See all (47) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. UBE4A catalyzes NRF1 ubiquitination and facilitates DDI2-mediated NRF1 cleavage.
      Title: UBE4A catalyzes NRF1 ubiquitination and facilitates DDI2-mediated NRF1 cleavage.
    2. The aspartyl protease DDI2 drives adaptation to proteasome inhibition in multiple myeloma.
      Title: The aspartyl protease DDI2 drives adaptation to proteasome inhibition in multiple myeloma.
    3. Multiple myeloma cells depend on the DDI2/NRF1-mediated proteasome stress response for survival.
      Title: Multiple myeloma cells depend on the DDI2/NRF1-mediated proteasome stress response for survival.
    4. DDI2 Is a Ubiquitin-Directed Endoprotease Responsible for Cleavage of Transcription Factor NRF1.
      Title: DDI2 Is a Ubiquitin-Directed Endoprotease Responsible for Cleavage of Transcription Factor NRF1.
    5. the 3D structures of the human Ddi2 UBL and RVP domains were solved and identified a new helical domain that extends on either side of the Rretroviral protease-like dimer.
      Title: Human DNA-Damage-Inducible 2 Protein Is Structurally and Functionally Distinct from Its Yeast Ortholog.
    6. Here the authors show that the aspartyl protease DNA-damage inducible 1 homolog 2 (DDI2) is required to cleave and activate Nrf1.
      Title: The aspartyl protease DDI2 activates Nrf1 to compensate for proteasome dysfunction.
    7. 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

    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

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Homology

    Clone Names

    • MGC14844

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables aspartic-type endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables identical protein binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables ubiquitin binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in cellular response to hydroxyurea IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in proteasomal protein catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in protein processing IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein processing IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of DNA stability IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of protein stability IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in chromosome IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  

    General protein information

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    Preferred Names
    protein DDI1 homolog 2
    Names
    DDI1, DNA-damage inducible 1, homolog 2
    DNA-damage inducible protein 2 (DDI2)
    NP_115717.3

    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_032341.5 → NP_115717.3  protein DDI1 homolog 2

      See identical proteins and their annotated locations for NP_115717.3

      Status: VALIDATED

      Source sequence(s)
      AK057374, AK293006, AL121992, AL598343, BC006011
      Consensus CDS
      CCDS30607.1
      UniProtKB/Swiss-Prot
      A8KAE1, Q5TDH0, Q7RTZ0, Q9BRT1
      UniProtKB/TrEMBL
      A0AA34QVV2
      Related
      ENSP00000417748.1, ENST00000480945.6
      Conserved Domains (2) summary
      cd05479
      Location:221 → 343
      RP_DDI; retropepsin-like domain of DNA damage inducible protein
      cd01796
      Location:1 → 76
      Ubl_Ddi1_like; ubiquitin-like (Ubl) domain found in the eukaryotic Ddi1 family

    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
      15617458..15669044
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      15062171..15113775
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q5TDH0.1 GenPept UniProtKB/Swiss-Prot:Q5TDH0

    Gene LinkOut

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

    Chemical Information
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