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

Gene ID: 84301, updated on 30-Mar-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 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; proteolysis; and regulation of DNA stability. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]
Expression
Ubiquitous expression in esophagus (RPKM 7.7), kidney (RPKM 5.8) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
1p36.21
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (15617458..15669044)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (15062171..15113775)
105.20220307 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
  • 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. 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
  2. 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
  3. 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
  4. UBE4A catalyzes NRF1 ubiquitination and facilitates DDI2-mediated NRF1 cleavage. Hu X, et al. Biochim Biophys Acta Gene Regul Mech, 2023 Jun. PMID 37084817
  5. Multiple myeloma cells depend on the DDI2/NRF1-mediated proteasome stress response for survival. Chen T, et al. Blood Adv, 2022 Jan 25. PMID 34649278, Free PMC Article

See all (40) 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_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
    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.

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