LOCUS       NM_001193360            5009 bp    mRNA    linear   PRI 21-SEP-2024
DEFINITION  Homo sapiens exonuclease 3'-5' domain containing 2 (EXD2),
            transcript variant 1, mRNA.
ACCESSION   NM_001193360
VERSION     NM_001193360.2
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 5009)
  AUTHORS   Morgenstern,M., Peikert,C.D., Lubbert,P., Suppanz,I., Klemm,C.,
            Alka,O., Steiert,C., Naumenko,N., Schendzielorz,A., Melchionda,L.,
            Muhlhauser,W.W.D., Knapp,B., Busch,J.D., Stiller,S.B.,
            Dannenmaier,S., Lindau,C., Licheva,M., Eickhorst,C., Galbusera,R.,
            Zerbes,R.M., Ryan,M.T., Kraft,C., Kozjak-Pavlovic,V., Drepper,F.,
            Dennerlein,S., Oeljeklaus,S., Pfanner,N., Wiedemann,N. and
            Warscheid,B.
  TITLE     Quantitative high-confidence human mitochondrial proteome and its
            dynamics in cellular context
  JOURNAL   Cell Metab 33 (12), 2464-2483 (2021)
   PUBMED   34800366
REFERENCE   2  (bases 1 to 5009)
  AUTHORS   Nieminuszczy,J., Broderick,R., Bellani,M.A., Smethurst,E.,
            Schwab,R.A., Cherdyntseva,V., Evmorfopoulou,T., Lin,Y.L.,
            Minczuk,M., Pasero,P., Gagos,S., Seidman,M.M. and Niedzwiedz,W.
  TITLE     EXD2 Protects Stressed Replication Forks and Is Required for Cell
            Viability in the Absence of BRCA1/2
  JOURNAL   Mol Cell 75 (3), 605-619 (2019)
   PUBMED   31255466
  REMARK    GeneRIF: 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.
REFERENCE   3  (bases 1 to 5009)
  AUTHORS   Park,J., Lee,S.Y., Jeong,H., Kang,M.G., Van Haute,L., Minczuk,M.,
            Seo,J.K., Jun,Y., Myung,K., Rhee,H.W. and Lee,C.
  TITLE     The structure of human EXD2 reveals a chimeric 3' to 5' exonuclease
            domain that discriminates substrates via metal coordination
  JOURNAL   Nucleic Acids Res 47 (13), 7078-7093 (2019)
   PUBMED   31127291
  REMARK    GeneRIF: 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.
REFERENCE   4  (bases 1 to 5009)
  AUTHORS   Hensen,F., Moretton,A., van Esveld,S., Farge,G. and Spelbrink,J.N.
  TITLE     The mitochondrial outer-membrane location of the EXD2 exonuclease
            contradicts its direct role in nuclear DNA repair
  JOURNAL   Sci Rep 8 (1), 5368 (2018)
   PUBMED   29599527
  REMARK    GeneRIF: 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.
            Publication Status: Online-Only
REFERENCE   5  (bases 1 to 5009)
  AUTHORS   Zid,B.M. and Kapahi,P.
  TITLE     Exonuclease EXD2 in mitochondrial translation
  JOURNAL   Nat Cell Biol 20 (2), 120-122 (2018)
   PUBMED   29371705
REFERENCE   6  (bases 1 to 5009)
  AUTHORS   Broderick,R., Nieminuszczy,J., Baddock,H.T., Deshpande,R.,
            Gileadi,O., Paull,T.T., McHugh,P.J. and Niedzwiedz,W.
  TITLE     EXD2 promotes homologous recombination by facilitating DNA end
            resection
  JOURNAL   Nat Cell Biol 18 (3), 271-280 (2016)
   PUBMED   26807646
  REMARK    GeneRIF: establish that EXD2 stimulates both short- and long-range
            DSB resection
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            DB087350.1, AK001600.1, BX647767.1, AU143711.1 and AL359317.3.
            
            On Aug 13, 2020 this sequence version replaced NM_001193360.1.
            
            Transcript Variant: This variant (1) represents the predominant
            transcript and encodes the longer isoform (1). Variants 1-4 encode
            the same isoform.
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            ##Evidence-Data-START##
            Transcript exon combination :: SRR14038192.531893.1,
                                           SRR18074967.3461374.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000685843.1/ ENSP00000510642.1
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression, longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: complete on the 3' end.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-532               DB087350.1         22-553
            533-2594            AK001600.1         18-2079
            2595-3349           BX647767.1         2482-3236
            3350-3457           AU143711.1         402-509
            3458-5009           AL359317.3         117991-119542
FEATURES             Location/Qualifiers
     source          1..5009
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="14"
                     /map="14q24.1"
     gene            1..5009
                     /gene="EXD2"
                     /gene_synonym="C14orf114; EXDL2"
                     /note="exonuclease 3'-5' domain containing 2"
                     /db_xref="GeneID:55218"
                     /db_xref="HGNC:HGNC:20217"
                     /db_xref="MIM:616940"
     exon            1..94
                     /gene="EXD2"
                     /gene_synonym="C14orf114; EXDL2"
                     /inference="alignment:Splign:2.1.0"
     exon            95..178
                     /gene="EXD2"
                     /gene_synonym="C14orf114; EXDL2"
                     /inference="alignment:Splign:2.1.0"
     exon            179..558
                     /gene="EXD2"
                     /gene_synonym="C14orf114; EXDL2"
                     /inference="alignment:Splign:2.1.0"
     CDS             226..2091
                     /gene="EXD2"
                     /gene_synonym="C14orf114; EXDL2"
                     /EC_number="3.1.11.1"
                     /note="isoform 1 is encoded by transcript variant 1;
                     exonuclease 3'-5' domain-like 2; exonuclease 3'-5'
                     domain-containing protein 2; 3'-5' exoribonuclease EXD2;
                     exonuclease 3'-5' domain-like-containing protein 2"
                     /codon_start=1
                     /product="exonuclease 3'-5' domain-containing protein 2
                     isoform 1"
                     /protein_id="NP_001180289.1"
                     /db_xref="CCDS:CCDS53902.1"
                     /db_xref="GeneID:55218"
                     /db_xref="HGNC:HGNC:20217"
                     /db_xref="MIM:616940"
                     /translation="MSRQNLVALTVTTLLGVAVGGFVLWKGIQRRRRSKTSPVTQQPQ
                     QKVLGSRELPPPEDDQLHSSAPRSSWKERILKAKVVTVSQEAEWDQIEPLLRSELEDF
                     PVLGIDCEWVNLEGKASPLSLLQMASPSGLCVLVRLPKLICGGKTLPRTLLDILADGT
                     ILKVGVGCSEDASKLLQDYGLVVRGCLDLRYLAMRQRNNLLCNGLSLKSLAETVLNFP
                     LDKSLLLRCSNWDAETLTEDQVIYAARDAQISVALFLHLLGYPFSRNSPGEKNDDHSS
                     WRKVLEKCQGVVDIPFRSKGMSRLGEEVNGEATESQQKPRNKKSKMDGMVPGNHQGRD
                     PRKHKRKPLGVGYSARKSPLYDNCFLHAPDGQPLCTCDRRKAQWYLDKGIGELVSEEP
                     FVVKLRFEPAGRPESPGDYYLMVKENLCVVCGKRDSYIRKNVIPHEYRKHFPIEMKDH
                     NSHDVLLLCTSCHAISNYYDNHLKQQLAKEFQAPIGSEEGLRLLEDPERRQVRSGARA
                     LLNAESLPTQRKEELLQALREFYNTDVVTEEMLQEAASLETRISNENYVPHGLKVVQC
                     HSQGGLRSLMQLESRWRQHFLDSMQPKHLPQQWSVDHNHQKLLRKFGEDLPIQLS"
     exon            559..815
                     /gene="EXD2"
                     /gene_synonym="C14orf114; EXDL2"
                     /inference="alignment:Splign:2.1.0"
     exon            816..942
                     /gene="EXD2"
                     /gene_synonym="C14orf114; EXDL2"
                     /inference="alignment:Splign:2.1.0"
     exon            943..1274
                     /gene="EXD2"
                     /gene_synonym="C14orf114; EXDL2"
                     /inference="alignment:Splign:2.1.0"
     exon            1275..1381
                     /gene="EXD2"
                     /gene_synonym="C14orf114; EXDL2"
                     /inference="alignment:Splign:2.1.0"
     exon            1382..1517
                     /gene="EXD2"
                     /gene_synonym="C14orf114; EXDL2"
                     /inference="alignment:Splign:2.1.0"
     exon            1518..1874
                     /gene="EXD2"
                     /gene_synonym="C14orf114; EXDL2"
                     /inference="alignment:Splign:2.1.0"
     exon            1875..5009
                     /gene="EXD2"
                     /gene_synonym="C14orf114; EXDL2"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3327..3332
                     /regulatory_class="polyA_signal_sequence"
                     /gene="EXD2"
                     /gene_synonym="C14orf114; EXDL2"
                     /note="hexamer: AATAAA"
     polyA_site      3349
                     /gene="EXD2"
                     /gene_synonym="C14orf114; EXDL2"
                     /note="major polyA site"
     regulatory      4601..4606
                     /regulatory_class="polyA_signal_sequence"
                     /gene="EXD2"
                     /gene_synonym="C14orf114; EXDL2"
                     /note="hexamer: GATAAA"
     polyA_site      4620
                     /gene="EXD2"
                     /gene_synonym="C14orf114; EXDL2"
     regulatory      4988..4993
                     /regulatory_class="polyA_signal_sequence"
                     /gene="EXD2"
                     /gene_synonym="C14orf114; EXDL2"
                     /note="hexamer: AATAAA"
     polyA_site      5009
                     /gene="EXD2"
                     /gene_synonym="C14orf114; EXDL2"
ORIGIN      
        1 agtgaatccg ggtgggtgcg cgcaggcggc cgcacaggtt ccaggtcttt aacgtgagcc
       61 cgctgcaggt gtgcggccca gtccgagaca gcagatgagg agactgtcct tcctgtttcg
      121 cagatgagga aactgaggct tagagaagtt tggcaaattg gctaagttcc tacagctaat
      181 tgtgggatta gtgatatgct tttctaaaga gtagaaaagt cgaagatgtc tagacagaac
      241 ttagtggctt tgacagtgac tacccttctg ggtgtggctg taggggggtt tgtcctctgg
      301 aaaggcatcc agcgccgccg aaggagtaaa acgagtcctg tgacccaaca gccacagcag
      361 aaagtgctgg gcagtagaga gctgccccct ccagaagatg atcagctgca ctccagtgcc
      421 cccagatcct cgtggaagga acggatcctt aaagcaaagg tggtgacggt gtctcaggag
      481 gcagagtggg atcaaatcga gcccttgctt agaagtgaat tagaagattt tccagtactt
      541 ggaattgact gtgagtgggt aaatttggaa ggcaaagcca gccctctgtc acttctacaa
      601 atggcctccc caagtggcct gtgtgtcttg gttcgcctgc ccaagctaat ctgtggagga
      661 aaaacactac caagaacgtt attggatatt ttggcagatg gcaccatttt gaaagttgga
      721 gtgggatgct cagaagatgc cagcaagctt ctgcaggatt atggcctcgt tgttaggggg
      781 tgcctggacc tccgatacct agccatgcgg cagagaaaca atttgctctg taatgggctt
      841 agcctgaagt ccctcgctga gactgttttg aactttcccc ttgacaagtc ccttctactt
      901 cgttgcagca actgggatgc tgagactctc acagaggacc aggtaattta tgctgccagg
      961 gatgcccaga tttcagtggc tctctttctt catcttcttg gatacccttt ctctaggaat
     1021 tcacctggag aaaaaaacga tgaccacagt agctggagaa aagtcttgga aaaatgccag
     1081 ggtgtggtcg acatcccatt tcgaagcaaa ggaatgagca gattgggaga agaggttaat
     1141 ggggaagcaa cagaatctca gcagaagcca agaaataaga agtctaagat ggatgggatg
     1201 gtgccaggca accaccaagg gagagacccc agaaaacata aaagaaagcc tctgggggtg
     1261 ggctattctg ccagaaaatc acctctttat gataactgct ttctccatgc tcctgatgga
     1321 cagcccctct gcacttgtga tagaagaaaa gctcagtggt acctggacaa aggcattggt
     1381 gagctggtga gtgaagagcc ctttgtggtg aagctacggt ttgaacctgc aggaaggccc
     1441 gaatctcctg gagactatta cttgatggtt aaagagaacc tgtgtgtagt gtgtggcaag
     1501 agagactcct acattcggaa gaacgtgatt ccacatgagt accggaagca cttccccatc
     1561 gagatgaagg accacaactc ccacgatgtg ctgctgctct gcacctcctg ccatgccatt
     1621 tccaactact atgacaacca tctgaagcag cagctggcca aggagttcca ggcccccatc
     1681 ggctctgagg agggcttgcg cctgctggaa gatcctgagc gccggcaggt gcgttctggg
     1741 gccagggccc tgctcaacgc ggagagcctg cctactcagc gaaaggagga gctgctgcaa
     1801 gcactcagag agttttataa cacagacgtg gtcacagagg agatgcttca agaggctgcc
     1861 agcctggaga ccagaatctc caatgaaaac tatgttcctc acgggctgaa ggtggtgcag
     1921 tgtcacagcc agggtggcct gcgctccctc atgcagctgg agagccgctg gcgtcagcac
     1981 ttcctggact ccatgcagcc caagcacctg ccccagcagt ggtcagtgga ccacaaccat
     2041 cagaagctgc tccggaaatt cggggaagat cttcccatcc agctgtcttg atagctgctt
     2101 tcctcccagt taggacaagt gggaagctgg agccaaggtt gaagagtcac ctcttcccat
     2161 tttagtacat cattaattgt caaagcctgt gtgacacaac tcagaatact aacctagact
     2221 aatcccagga tgcttctgct ggagcaaaga tattgtttga aggagagttt atggttttgg
     2281 attttaaacg ggcagggtct tttttcctct catttttgtg gacaagagag gccttcgcct
     2341 ttatttttac tctccctctt ctgctgtccc tgtgcagagg aaaaatgaag aattctccca
     2401 gaagtgactt gtcaagactt aaaaaaaatg tttttaatgc atttcttcct tgtctagtgc
     2461 ctcggtttat ctctaacagg ggctgtccag tatatcggtc ctgttaggag gggagaaaaa
     2521 gttcttccaa aggctggaga agtgaacaag gagtcaaatt tattttccca attcaacttc
     2581 ataattatca tttctttggc ttcatgctct cccgtaactc atgtggttgg gatccatccc
     2641 atctgggtca cttcagtcta cttcacgtac ttgaaaaggc tttcctttac acttccagga
     2701 ccaaacagca acttcctgcc acacacttcc accctatcac tgggagaaat ccttttctgg
     2761 acatgagcct ttgacctggg tggggcagaa agaaccacaa actccatctc ccaatagaac
     2821 tttgaaattc actcagcttt tcctttcatg ctgtttgttg cctgcttgtt gcactcctcc
     2881 tgccccagaa ctgcaagatt tttagcttca cccctttctg agagtaatgt tatcttttat
     2941 cagaatcagt atcagttccc ctgtattctg tgcttcatcg aatttgcaag actgacctct
     3001 tttaagcatt taattcactc ccagagtcat ctggtcaggt tgcaatatga ggacttctct
     3061 gtctcctctg aagcctggga cactgagctt acttaataca ttagatgttc aaaagaggag
     3121 cgttgtttca tctttcaaaa tgttaggcca ttactttgag tataaaatcg acttattaat
     3181 gattagtaat ttttctaaag tattgggaaa actttcttat tttataagat cttaacaagc
     3241 ttaaaaaaga attttatgac cagaatccaa caagagctct attttggaat tgtgcccaag
     3301 ttggtgatgt ttactctaaa attaataata aaactacttg taagcacaag gctcactgga
     3361 tgtaaatgta aaacttcgcg actttataaa actggcattc ctaggggagg ggctatttat
     3421 cctacaggtc cctgcctcct ggcagtgcca tggtatgtgt gcatggatat accagacaca
     3481 gtcaccatcg gccatcagta gcagcccatg aacccacgtg cacatcctgc atcttgctct
     3541 tctgaccctt cattcccact tgtcttcagg caggcatttc tgggatctaa actagaaatc
     3601 cttgaaaaca aatagtacca gccactttga ggaatgtgca ttcactgtag tgggttatta
     3661 tggggtctct gcctcctggc tgtgttatgc ggagcccagg agtggaggag agccgtggaa
     3721 atagacaggg agaggctggt acttgggttg tggtaatagt caggcttgcc acaagagggc
     3781 actcatagat ttgtttttat attcattctt gagaaaaaag caactggtta ctgaacgtaa
     3841 ctcatgactt atgtttcaaa ttttgcatag ctgattttaa gtcattttga tagctttgca
     3901 agaaaaattt ttcctttgaa acaagggagt agggctgttt cattttcttt ccttctaatc
     3961 ctcatgccaa gaggtgagaa acacttaagg tcatttaagg tgctagggaa agggttttcc
     4021 catggagctt tctgtgaggc gcagtaaaat agagccagca gcaaagtaga ggaaaaagcc
     4081 agactgcgtc acacaagatt tctcatcctt ttcaggagag agtcactgtg tagatttgaa
     4141 tcttttttct ttgagtctgc tttgaacttt agcaggcttt tcctaagact gacaattgtc
     4201 gtcttaaatc agagatttga gggtagactt attttatggc aaatgtctat ttttctgata
     4261 taaaagtaac aatgctcatt acagaagaat ctaaacaaag aataaaaatt agccatcttc
     4321 tctccatcta aaacagagct aaactttgct gatatgttta tgaatttcct ttcagtatta
     4381 aaaagtgcat ataaggtgta tatttacaca aaattgaagg tcatacatag atacaggttg
     4441 gtatcctaac tttaccctct cactgattaa catggtatca cgagtaactt cctatgtttt
     4501 taaatctttg aaaatagatt tctagtggtt ctaccttatc catccccaca ctgttgaaaa
     4561 ttttggttgt ttcagatact tttattatca atgatgatgt gataaagttt cttgtatata
     4621 tctctttggc tctatctttg gtaatttctt aagaatggaa tcttagaatt ggactgtgaa
     4681 gagggggatt cacattgctg gggctaagta caaattgaca tcacctttta ggaatgaaat
     4741 gcttctcttt gaccctttag ctccagtgtc ccagcatagt cactgggctt cataggagta
     4801 gcagtgagag gacagtgtca cagcaagggc ctctctgcat gctccctgat cattgtgttt
     4861 gcaggttcag catttcttct tgagtccttc ccttcttcca accttattgc ctcatttccc
     4921 ccttgtagtc aatgtttttt ggaaacactg tttattttaa aataaaaatg taaaaaaaag
     4981 gtaaaaaaat aaaattttaa attttaaaa
//
