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

Gene ID: 55218, updated on 27-Nov-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, Nov 2024]
Expression
Ubiquitous expression in testis (RPKM 9.7), brain (RPKM 8.0) and 25 other tissues See more
Orthologs
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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

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

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

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

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