ID EXO5_HUMAN Reviewed; 373 AA. AC Q9H790; D3DPV4; Q5SWM7; Q5SWM8; Q5SWM9; Q5SWN0; Q5SWN1; Q8WTW9; DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 1. DT 24-JAN-2024, entry version 138. DE RecName: Full=Exonuclease V; DE Short=Exo V; DE Short=hExo5; DE EC=3.1.-.-; DE AltName: Full=Defects in morphology protein 1 homolog; GN Name=EXO5; Synonyms=C1orf176, DEM1; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Coronary artery; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-172. RC TISSUE=Ovary; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, COFACTOR, INTERACTION RP WITH THE REPLICATION PROTEIN A (RPA) COMPLEX, MUTAGENESIS OF GLU-196; RP CYS-343 AND CYS-346, AND CHARACTERIZATION OF VARIANTS ASN-115 AND VAL-172. RX PubMed=23095756; DOI=10.1074/jbc.m112.422444; RA Sparks J.L., Kumar R., Singh M., Wold M.S., Pandita T.K., Burgers P.M.; RT "Human exonuclease 5 is a novel sliding exonuclease required for genome RT stability."; RL J. Biol. Chem. 287:42773-42783(2012). CC -!- FUNCTION: Single-stranded DNA (ssDNA) bidirectional exonuclease CC involved in DNA repair. Probably involved in DNA repair following CC ultraviolet (UV) irradiation and interstrand cross-links (ICLs) damage. CC Has both 5'-3' and 3'-5' exonuclease activities with a strong CC preference for 5'-ends. Acts as a sliding exonuclease that loads at CC ssDNA ends and then slides along the ssDNA prior to cutting; however CC the sliding and the 3'-5' exonuclease activities are abolished upon CC binding to the replication protein A (RPA) complex that enforces 5'- CC directionality activity. {ECO:0000269|PubMed:23095756}. CC -!- COFACTOR: CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; CC Evidence={ECO:0000269|PubMed:23095756}; CC Note=Binds 1 [4Fe-4S] cluster. {ECO:0000269|PubMed:23095756}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:P38289}; CC -!- SUBUNIT: Monomer; monomeric form has weak exonuclease activity. CC Homodimer; homodimeric form is unsure but has much higher exonuclease CC activity, suggesting that it could homodimerize upon DNA-binding. CC Interacts with the replication protein A (RPA) complex. CC {ECO:0000269|PubMed:23095756}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23095756}. Cytoplasm, CC cytosol {ECO:0000269|PubMed:23095756}. Note=Localizes to repair foci in CC response to DNA damage. CC -!- SIMILARITY: Belongs to the EXO5 family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK024797; BAB15008.1; -; mRNA. DR EMBL; AL603839; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471059; EAX07210.1; -; Genomic_DNA. DR EMBL; CH471059; EAX07211.1; -; Genomic_DNA. DR EMBL; CH471059; EAX07212.1; -; Genomic_DNA. DR EMBL; CH471059; EAX07213.1; -; Genomic_DNA. DR EMBL; CH471059; EAX07214.1; -; Genomic_DNA. DR EMBL; BC021969; AAH21969.1; -; mRNA. DR CCDS; CCDS453.1; -. DR RefSeq; NP_001333875.1; NM_001346946.1. DR RefSeq; NP_001333876.1; NM_001346947.1. DR RefSeq; NP_001333877.1; NM_001346948.1. DR RefSeq; NP_001333878.1; NM_001346949.1. DR RefSeq; NP_001333879.1; NM_001346950.1. DR RefSeq; NP_001333880.1; NM_001346951.1. DR RefSeq; NP_001333881.1; NM_001346952.1. DR RefSeq; NP_001333882.1; NM_001346953.1. DR RefSeq; NP_001333883.1; NM_001346954.1. DR RefSeq; NP_001333884.1; NM_001346955.1. DR RefSeq; NP_001333885.1; NM_001346956.1. DR RefSeq; NP_073611.1; NM_022774.2. DR RefSeq; XP_016857588.1; XM_017002099.1. DR RefSeq; XP_016857591.1; XM_017002102.1. DR PDB; 7LW7; X-ray; 2.50 A; A=31-373. DR PDB; 7LW8; X-ray; 2.88 A; A=31-373. DR PDB; 7LW9; X-ray; 2.71 A; A=31-373. DR PDB; 7LWA; X-ray; 2.85 A; A=31-373. DR PDBsum; 7LW7; -. DR PDBsum; 7LW8; -. DR PDBsum; 7LW9; -. DR PDBsum; 7LWA; -. DR AlphaFoldDB; Q9H790; -. DR SMR; Q9H790; -. DR BioGRID; 122299; 4. DR STRING; 9606.ENSP00000361788; -. DR iPTMnet; Q9H790; -. DR PhosphoSitePlus; Q9H790; -. DR BioMuta; EXO5; -. DR DMDM; 74752706; -. DR MassIVE; Q9H790; -. DR MaxQB; Q9H790; -. DR PaxDb; 9606-ENSP00000361788; -. DR PeptideAtlas; Q9H790; -. DR ProteomicsDB; 81089; -. DR Antibodypedia; 32100; 99 antibodies from 19 providers. DR DNASU; 64789; -. DR Ensembl; ENST00000296380.9; ENSP00000296380.4; ENSG00000164002.12. DR Ensembl; ENST00000358527.6; ENSP00000351328.2; ENSG00000164002.12. DR Ensembl; ENST00000372703.1; ENSP00000361788.1; ENSG00000164002.12. DR Ensembl; ENST00000415550.6; ENSP00000413565.2; ENSG00000164002.12. DR Ensembl; ENST00000418186.2; ENSP00000391240.2; ENSG00000164002.12. DR Ensembl; ENST00000419161.2; ENSP00000392115.2; ENSG00000164002.12. DR Ensembl; ENST00000420209.2; ENSP00000398437.2; ENSG00000164002.12. DR Ensembl; ENST00000432259.6; ENSP00000416857.2; ENSG00000164002.12. DR Ensembl; ENST00000443729.6; ENSP00000409715.2; ENSG00000164002.12. DR Ensembl; ENST00000682383.1; ENSP00000508270.1; ENSG00000164002.12. DR GeneID; 64789; -. DR KEGG; hsa:64789; -. DR MANE-Select; ENST00000415550.6; ENSP00000413565.2; NM_001346953.2; NP_001333882.1. DR UCSC; uc001cfp.4; human. DR AGR; HGNC:26115; -. DR CTD; 64789; -. DR DisGeNET; 64789; -. DR GeneCards; EXO5; -. DR HGNC; HGNC:26115; EXO5. DR HPA; ENSG00000164002; Low tissue specificity. DR MIM; 618601; gene. DR neXtProt; NX_Q9H790; -. DR OpenTargets; ENSG00000164002; -. DR PharmGKB; PA164718736; -. DR VEuPathDB; HostDB:ENSG00000164002; -. DR eggNOG; KOG4760; Eukaryota. DR GeneTree; ENSGT00390000015205; -. DR HOGENOM; CLU_013225_0_2_1; -. DR InParanoid; Q9H790; -. DR OMA; CPDKPLG; -. DR OrthoDB; 1111955at2759; -. DR PhylomeDB; Q9H790; -. DR TreeFam; TF332529; -. DR PathwayCommons; Q9H790; -. DR BioGRID-ORCS; 64789; 17 hits in 1162 CRISPR screens. DR GenomeRNAi; 64789; -. DR Pharos; Q9H790; Tbio. DR PRO; PR:Q9H790; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q9H790; Protein. DR Bgee; ENSG00000164002; Expressed in secondary oocyte and 123 other cell types or tissues. DR ExpressionAtlas; Q9H790; baseline and differential. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IDA:UniProtKB. DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0008310; F:single-stranded DNA 3'-5' DNA exonuclease activity; TAS:UniProtKB. DR GO; GO:0045145; F:single-stranded DNA 5'-3' DNA exonuclease activity; IDA:UniProtKB. DR GO; GO:0036297; P:interstrand cross-link repair; IMP:UniProtKB. DR Gene3D; 3.90.320.10; -; 1. DR InterPro; IPR019190; EXOV. DR InterPro; IPR011604; PDDEXK-like_dom_sf. DR PANTHER; PTHR14464; EXONUCLEASE V; 1. DR PANTHER; PTHR14464:SF4; EXONUCLEASE V; 1. DR Pfam; PF09810; Exo5; 2. DR Genevisible; Q9H790; HS. PE 1: Evidence at protein level; KW 3D-structure; 4Fe-4S; Cytoplasm; DNA damage; DNA repair; DNA-binding; KW Exonuclease; Hydrolase; Iron; Iron-sulfur; Magnesium; Metal-binding; KW Nuclease; Nucleus; Reference proteome. FT CHAIN 1..373 FT /note="Exonuclease V" FT /id="PRO_0000307320" FT BINDING 92 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT BINDING 343 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT BINDING 346 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT BINDING 352 FT /ligand="[4Fe-4S] cluster" FT /ligand_id="ChEBI:CHEBI:49883" FT VARIANT 115 FT /note="D -> N (does not affect exonuclease activity; FT dbSNP:rs1134586)" FT /evidence="ECO:0000269|PubMed:23095756" FT /id="VAR_035407" FT VARIANT 172 FT /note="G -> V (does not affect exonuclease activity; FT dbSNP:rs11208299)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:23095756" FT /id="VAR_035408" FT MUTAGEN 196 FT /note="E->A: Nearly abolishes exonuclease activity." FT /evidence="ECO:0000269|PubMed:23095756" FT MUTAGEN 343 FT /note="C->A: Abolishes iron-sulfur-binding and affects FT exonuclease activity; when associated with A-346." FT /evidence="ECO:0000269|PubMed:23095756" FT MUTAGEN 346 FT /note="C->A: Abolishes iron-sulfur-binding and affects FT exonuclease activity; when associated with A-343." FT /evidence="ECO:0000269|PubMed:23095756" FT HELIX 72..75 FT /evidence="ECO:0007829|PDB:7LW7" FT STRAND 79..82 FT /evidence="ECO:0007829|PDB:7LW7" FT HELIX 83..91 FT /evidence="ECO:0007829|PDB:7LW7" FT HELIX 93..101 FT /evidence="ECO:0007829|PDB:7LW7" FT HELIX 122..128 FT /evidence="ECO:0007829|PDB:7LW7" FT HELIX 139..160 FT /evidence="ECO:0007829|PDB:7LW7" FT STRAND 161..172 FT /evidence="ECO:0007829|PDB:7LW7" FT STRAND 175..186 FT /evidence="ECO:0007829|PDB:7LW7" FT STRAND 192..202 FT /evidence="ECO:0007829|PDB:7LW7" FT HELIX 208..229 FT /evidence="ECO:0007829|PDB:7LW7" FT HELIX 235..242 FT /evidence="ECO:0007829|PDB:7LW7" FT STRAND 246..248 FT /evidence="ECO:0007829|PDB:7LW7" FT HELIX 252..259 FT /evidence="ECO:0007829|PDB:7LW7" FT TURN 260..262 FT /evidence="ECO:0007829|PDB:7LW7" FT HELIX 268..281 FT /evidence="ECO:0007829|PDB:7LW7" FT STRAND 289..296 FT /evidence="ECO:0007829|PDB:7LW7" FT TURN 297..299 FT /evidence="ECO:0007829|PDB:7LW7" FT STRAND 302..307 FT /evidence="ECO:0007829|PDB:7LW7" FT HELIX 312..326 FT /evidence="ECO:0007829|PDB:7LW7" FT HELIX 337..345 FT /evidence="ECO:0007829|PDB:7LW7" FT TURN 347..351 FT /evidence="ECO:0007829|PDB:7LW7" FT HELIX 353..356 FT /evidence="ECO:0007829|PDB:7LW7" SQ SEQUENCE 373 AA; 41816 MW; EAFB31099EA40FAD CRC64; MAETREEETV SAEASGFSDL SDSEFLEFLD LEDAQESKAL VNMPGPSSES LGKDDKPISL QNWKRGLDIL SPMERFHLKY LYVTDLATQN WCELQTAYGK ELPGFLAPEK AAVLDTGASI HLARELELHD LVTVPVTTKE DAWAIKFLNI LLLIPTLQSE GHIREFPVFG EGEGVLLVGV IDELHYTAKG ELELAELKTR RRPMLPLEAQ KKKDCFQVSL YKYIFDAMVQ GKVTPASLIH HTKLCLEKPL GPSVLRHAQQ GGFSVKSLGD LMELVFLSLT LSDLPVIDIL KIEYIHQETA TVLGTEIVAF KEKEVRAKVQ HYMAYWMGHR EPQGVDVEEA WKCRTCTYAD ICEWRKGSGV LSSTLAPQVK KAK //