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    EXD2 exonuclease 3'-5' domain containing 2 [ Homo sapiens (human) ]

    Gene ID: 55218, updated on 9-Dec-2024

    Summary

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    Official Symbol
    EXD2provided by HGNC
    Official Full Name
    exonuclease 3'-5' domain containing 2provided by HGNC
    Primary source
    HGNC:HGNC:20217
    See related
    Ensembl:ENSG00000081177 MIM:616940; AllianceGenome:HGNC:20217
    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
    Also known as
    EXDL2; C14orf114
    Summary
    Enables 3'-5' exonuclease activity; metal ion binding activity; and protein homodimerization activity. Involved in DNA double-strand break processing; double-strand break repair via homologous recombination; and replication fork processing. Located in intermediate filament cytoskeleton; mitochondrial outer membrane; and site of DNA damage. [provided by Alliance of Genome Resources, Dec 2024]
    Expression
    Ubiquitous expression in testis (RPKM 9.7), brain (RPKM 8.0) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See EXD2 in Genome Data Viewer
    Location:
    14q24.1
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (69191498..69244018)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (63404602..63457085)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (69658215..69710735)

    Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:69504114-69504810 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:69504811-69505508 Neighboring gene ribosomal protein S29 pseudogene 1 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:69515530-69516030 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr14:69521614-69522813 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr14:69522944-69523511 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8632 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8633 Neighboring gene DDB1 and CUL4 associated factor 5 Neighboring gene Sharpr-MPRA regulatory region 2739 Neighboring gene DEAD-box helicase 18 pseudogene 1 Neighboring gene Sharpr-MPRA regulatory region 12367 Neighboring gene Sharpr-MPRA regulatory region 6895 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5876 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5877 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5878 Neighboring gene GALNT16 and EXD2 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5879 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr14:69705439-69706063 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5880 Neighboring gene polypeptide N-acetylgalactosaminyltransferase 16 Neighboring gene uncharacterized LOC105370549 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:69800956-69801456 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:69801457-69801957 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr14:69815418-69815918 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8634 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8635 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8636 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:69864016-69864524 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:69864525-69865032 Neighboring gene ERH mRNA splicing and mitosis factor

    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. Exonuclease EXD2 in mitochondrial translation. Zid BM, et al. Nat Cell Biol, 2018 Feb. PMID 29371705
    2. The mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repair. Hensen F, et al. Sci Rep, 2018 Mar 29. PMID 29599527, Free PMC Article
    3. The structure of human EXD2 reveals a chimeric 3' to 5' exonuclease domain that discriminates substrates via metal coordination. Park J, et al. Nucleic Acids Res, 2019 Jul 26. PMID 31127291, Free PMC Article
    4. EXD2 Protects Stressed Replication Forks and Is Required for Cell Viability in the Absence of BRCA1/2. Nieminuszczy J, et al. Mol Cell, 2019 Aug 8. PMID 31255466, Free PMC Article
    5. EXD2 promotes homologous recombination by facilitating DNA end resection. Broderick R, et al. Nat Cell Biol, 2016 Mar. PMID 26807646, Free PMC Article

    See all (52) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. EXD2 deficiency leads to fork collapse, hypersensitivity to replication inhibitors, and genomic instability. Impeding fork regression by inactivation of SMARCAL1 or removal of RECQ1's inhibition in EXD2(-/-) cells restores efficient fork restart and genome stability. Moreover, purified EXD2 efficiently processes substrates mimicking regressed forks.
      Title: EXD2 Protects Stressed Replication Forks and Is Required for Cell Viability in the Absence of BRCA1/2.
    2. EXD2 is anchored to the mitochondrial outer membrane through a conserved N-terminal transmembrane domain, while the C-terminal region is cytosolic. Crystal structures of the exonuclease domain in complex with Mn2+/Mg2+ revealed a domain-swapped dimer in which the central alpha5-alpha7 helices are mutually crossed over, resulting in chimeric active sites.
      Title: The structure of human EXD2 reveals a chimeric 3' to 5' exonuclease domain that discriminates substrates via metal coordination.
    3. EXD2 re-locates to the nucleus following double-strand breaks and thus is unlikely to have a direct role in nuclear DNA repair. Knockdown or overexpression of EXD2 affects the cellular distribution of mitochondria.
      Title: The mitochondrial outer-membrane location of the EXD2 exonuclease contradicts its direct role in nuclear DNA repair.
    4. establish that EXD2 stimulates both short- and long-range DSB resection
      Title: EXD2 promotes homologous recombination by facilitating DNA end resection.
    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)

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ10738, DKFZp781A0133, DKFZp781L15100

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables 3'-5' exonuclease activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables 3'-5' exonuclease activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables 3'-5' exonuclease activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables 3'-5'-DNA exonuclease activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables 3'-5'-RNA exonuclease activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables magnesium ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables manganese ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables nucleic acid binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables single-stranded DNA 3'-5' DNA exonuclease activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in DNA double-strand break processing IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in double-strand break repair IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in double-strand break repair via homologous recombination IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in nucleic acid metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in replication fork processing IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in intermediate filament cytoskeleton IDA
    Inferred from Direct Assay
    more info
    		  
    located_in mitochondrial matrix IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in mitochondrial outer membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion HTP PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in site of DNA damage IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    exonuclease 3'-5' domain-containing protein 2
    Names
    3'-5' exoribonuclease EXD2
    exonuclease 3'-5' domain-like 2
    exonuclease 3'-5' domain-like-containing protein 2
    NP_001180289.1
    NP_001180290.1
    NP_001180291.1
    NP_001180292.1
    NP_060669.1
    XP_005267874.1
    XP_011535210.1
    XP_016876910.1
    XP_054232277.1
    XP_054232278.1
    XP_054232279.1

    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_001193360.2 → NP_001180289.1  exonuclease 3'-5' domain-containing protein 2 isoform 1

      See identical proteins and their annotated locations for NP_001180289.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (1) represents the predominant transcript and encodes the longer isoform (1). Variants 1-4 encode the same isoform.
      Source sequence(s)
      AK001600, AL359317, AU143711, BX647767, DB087350
      Consensus CDS
      CCDS53902.1
      UniProtKB/Swiss-Prot
      B4DIH6, G5E947, Q6AWB6, Q8N3D3, Q9NVH0
      Related
      ENSP00000510642.1, ENST00000685843.1
      Conserved Domains (1) summary
      cd06141
      Location:82 → 258
      WRN_exo; DEDDy 3'-5' exonuclease domain of WRN and similar proteins

    2. NM_001193361.2 → NP_001180290.1  exonuclease 3'-5' domain-containing protein 2 isoform 1

      See identical proteins and their annotated locations for NP_001180290.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (2) is missing a 5' non-coding exon compared to variant 1. Variants 1-4 encode the same isoform (1).
      Source sequence(s)
      AK001600, AL359317, AU143711, BX647767, DB087350
      Consensus CDS
      CCDS53902.1
      UniProtKB/Swiss-Prot
      B4DIH6, G5E947, Q6AWB6, Q8N3D3, Q9NVH0
      Related
      ENSP00000387331.3, ENST00000409018.7
      Conserved Domains (1) summary
      cd06141
      Location:82 → 258
      WRN_exo; DEDDy 3'-5' exonuclease domain of WRN and similar proteins

    3. NM_001193362.2 → NP_001180291.1  exonuclease 3'-5' domain-containing protein 2 isoform 1

      See identical proteins and their annotated locations for NP_001180291.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (3) uses an alternate 5' terminal non-coding exon compared to variant 1. Variants 1-4 encode the same isoform (1).
      Source sequence(s)
      AK001600, AK292563, AL359317, AU143711, BX161412, BX647767
      Consensus CDS
      CCDS53902.1
      UniProtKB/Swiss-Prot
      B4DIH6, G5E947, Q6AWB6, Q8N3D3, Q9NVH0
      Conserved Domains (1) summary
      cd06141
      Location:82 → 258
      WRN_exo; DEDDy 3'-5' exonuclease domain of WRN and similar proteins

    4. NM_001193363.2 → NP_001180292.1  exonuclease 3'-5' domain-containing protein 2 isoform 1

      See identical proteins and their annotated locations for NP_001180292.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (4) uses an alternate 5' terminal non-coding exon, and is missing another 5' non-coding exon compared to variant 1. Variants 1-4 encode the same isoform (1).
      Source sequence(s)
      AK001600, AK292563, AK295601, AL359317, AU143711, BX647767, DC369956
      Consensus CDS
      CCDS53902.1
      UniProtKB/Swiss-Prot
      B4DIH6, G5E947, Q6AWB6, Q8N3D3, Q9NVH0
      Related
      ENSP00000313140.5, ENST00000312994.9
      Conserved Domains (1) summary
      cd06141
      Location:82 → 258
      WRN_exo; DEDDy 3'-5' exonuclease domain of WRN and similar proteins

    5. NM_018199.4 → NP_060669.1  exonuclease 3'-5' domain-containing protein 2 isoform 2

      See identical proteins and their annotated locations for NP_060669.1

      Status: VALIDATED

      Description
      Transcript Variant: This variant (5) is missing 2 internal exons compared to variant 1. This results in translation initiation from an in-frame downstream AUG and a shorter isoform (2) compared to isoform 1.
      Source sequence(s)
      AK001600, AL359317, AL834434, AU143711, BX647767, DB087350
      Consensus CDS
      CCDS9793.1
      UniProtKB/TrEMBL
      B3KP95
      Related
      ENSP00000386762.1, ENST00000409675.5
      Conserved Domains (2) summary
      cd06141
      Location:1 → 133
      WRN_exo; DEDDy 3'-5' exonuclease domain of WRN and similar proteins
      pfam14239
      Location:238 → 283
      RRXRR; RRXRR protein

    RNA

    1. NR_034164.2 RNA Sequence

      Status: VALIDATED

      Description
      Transcript Variant: This variant (6) contains an additional internal exon compared to variant 1. It is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AK001600, AL359317, AU143711, BX161412, BX647767, DB087350

    2. NR_034165.2 RNA Sequence

      Status: VALIDATED

      Description
      Transcript Variant: This variant (7) contains an alternate 5' terminal exon, and an additional internal exon compared to variant 1. It is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).
      Source sequence(s)
      AK001600, AK292563, AL359317, AU143711, BX161412, BX647767

    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_000014.9 Reference GRCh38.p14 Primary Assembly

      Range
      69191498..69244018
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017021421.3 → XP_016876910.1  exonuclease 3'-5' domain-containing protein 2 isoform X1

      UniProtKB/TrEMBL
      B3KP95
      Related
      ENSP00000386915.1, ENST00000409014.5
      Conserved Domains (2) summary
      cd06141
      Location:1 → 133
      WRN_exo; DEDDy 3'-5' exonuclease domain of WRN and similar proteins
      pfam14239
      Location:238 → 283
      RRXRR; RRXRR protein

    2. XM_011536908.4 → XP_011535210.1  exonuclease 3'-5' domain-containing protein 2 isoform X1

      See identical proteins and their annotated locations for XP_011535210.1

      UniProtKB/TrEMBL
      B3KP95
      Related
      ENSP00000386839.1, ENST00000409242.5
      Conserved Domains (2) summary
      cd06141
      Location:1 → 133
      WRN_exo; DEDDy 3'-5' exonuclease domain of WRN and similar proteins
      pfam14239
      Location:238 → 283
      RRXRR; RRXRR protein

    3. XM_005267817.5 → XP_005267874.1  exonuclease 3'-5' domain-containing protein 2 isoform X1

      See identical proteins and their annotated locations for XP_005267874.1

      UniProtKB/TrEMBL
      B3KP95
      Conserved Domains (2) summary
      cd06141
      Location:1 → 133
      WRN_exo; DEDDy 3'-5' exonuclease domain of WRN and similar proteins
      pfam14239
      Location:238 → 283
      RRXRR; RRXRR protein

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060938.1 Alternate T2T-CHM13v2.0

      Range
      63404602..63457085
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054376303.1 → XP_054232278.1  exonuclease 3'-5' domain-containing protein 2 isoform X1

      UniProtKB/TrEMBL
      A8K948

    2. XM_054376302.1 → XP_054232277.1  exonuclease 3'-5' domain-containing protein 2 isoform X1

      UniProtKB/TrEMBL
      A8K948

    3. XM_054376304.1 → XP_054232279.1  exonuclease 3'-5' domain-containing protein 2 isoform X1

      UniProtKB/TrEMBL
      A8K948
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9NVH0.2 GenPept UniProtKB/Swiss-Prot:Q9NVH0

    Gene LinkOut

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

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