EXO5_HUMAN
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 03-AUG-2022, entry version 130.
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}.
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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; 3.
DR STRING; 9606.ENSP00000361788; -.
DR iPTMnet; Q9H790; -.
DR PhosphoSitePlus; Q9H790; -.
DR BioMuta; EXO5; -.
DR DMDM; 74752706; -.
DR MassIVE; Q9H790; -.
DR MaxQB; Q9H790; -.
DR PaxDb; Q9H790; -.
DR PeptideAtlas; Q9H790; -.
DR PRIDE; Q9H790; -.
DR ProteomicsDB; 81089; -.
DR Antibodypedia; 32100; 88 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 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; STQNWCE; -.
DR OrthoDB; 1601909at2759; -.
DR PhylomeDB; Q9H790; -.
DR TreeFam; TF332529; -.
DR PathwayCommons; Q9H790; -.
DR BioGRID-ORCS; 64789; 15 hits in 1082 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 122 other tissues.
DR ExpressionAtlas; Q9H790; baseline and differential.
DR Genevisible; Q9H790; HS.
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' exodeoxyribonuclease activity; TAS:UniProtKB.
DR GO; GO:0045145; F:single-stranded DNA 5'-3' exodeoxyribonuclease 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; PTHR14464; 1.
DR Pfam; PF09810; Exo5; 2.
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
