ID AEN_HUMAN Reviewed; 325 AA. AC Q8WTP8; C9J571; Q9BSA5; Q9H9X7; DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 2. DT 27-MAR-2024, entry version 169. DE RecName: Full=Apoptosis-enhancing nuclease; DE EC=3.1.-.-; DE AltName: Full=Interferon-stimulated 20 kDa exonuclease-like 1; GN Name=AEN; Synonyms=ISG20L1; ORFNames=SBBI58; 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] (ISOFORM 1), AND VARIANT ASP-140. RA Zhang W., Li N., Wan T., Chen T., Zhang J., Cao X.; RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16572171; DOI=10.1038/nature04601; RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S., RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human chromosome RT 15."; RL Nature 440:671-675(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASP-140. 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT RP ASP-140. RC TISSUE=Colon, and Muscle; 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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 106-325 (ISOFORM 1), AND VARIANT RP ASP-140. 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 [6] RP FUNCTION, INDUCTION, AND SUBCELLULAR LOCATION. RX PubMed=16171785; DOI=10.1016/j.bbrc.2005.08.264; RA Lee J.-H., Koh Y.A., Cho C.-K., Lee S.J., Lee Y.-S., Bae S.; RT "Identification of a novel ionizing radiation-induced nuclease, AEN, and RT its functional characterization in apoptosis."; RL Biochem. Biophys. Res. Commun. 337:39-47(2005). RN [7] RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, NUCLEAR LOCALIZATION SIGNAL, RP NUCLEOLAR LOCALIZATION SIGNAL, AND MUTAGENESIS OF ASP-114; GLU-116 AND RP ASP-258. RX PubMed=18264133; DOI=10.1038/onc.2008.32; RA Kawase T., Ichikawa H., Ohta T., Nozaki N., Tashiro F., Ohki R., Taya Y.; RT "p53 target gene AEN is a nuclear exonuclease required for p53-dependent RT apoptosis."; RL Oncogene 27:3797-3810(2008). CC -!- FUNCTION: Exonuclease with activity against single- and double-stranded CC DNA and RNA. Mediates p53-induced apoptosis. When induced by p53 CC following DNA damage, digests double-stranded DNA to form single- CC stranded DNA and amplifies DNA damage signals, leading to enhancement CC of apoptosis. {ECO:0000269|PubMed:16171785, CC ECO:0000269|PubMed:18264133}. CC -!- INTERACTION: CC Q8WTP8; C9JG97: AAMP; NbExp=3; IntAct=EBI-8637627, EBI-10176499; CC Q8WTP8; P50402: EMD; NbExp=3; IntAct=EBI-8637627, EBI-489887; CC Q8WTP8; Q96B26: EXOSC8; NbExp=3; IntAct=EBI-8637627, EBI-371922; CC Q8WTP8; Q3T906: GNPTAB; NbExp=3; IntAct=EBI-8637627, EBI-1104907; CC Q8WTP8; Q8IX15-3: HOMEZ; NbExp=3; IntAct=EBI-8637627, EBI-10172004; CC Q8WTP8; Q13422: IKZF1; NbExp=3; IntAct=EBI-8637627, EBI-745305; CC Q8WTP8; Q5VWX1: KHDRBS2; NbExp=3; IntAct=EBI-8637627, EBI-742808; CC Q8WTP8; Q6A162: KRT40; NbExp=3; IntAct=EBI-8637627, EBI-10171697; CC Q8WTP8; P60370: KRTAP10-5; NbExp=3; IntAct=EBI-8637627, EBI-10172150; CC Q8WTP8; P60409: KRTAP10-7; NbExp=3; IntAct=EBI-8637627, EBI-10172290; CC Q8WTP8; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-8637627, EBI-10171774; CC Q8WTP8; Q9BRK4: LZTS2; NbExp=3; IntAct=EBI-8637627, EBI-741037; CC Q8WTP8; Q86VM6: MBNL1; NbExp=3; IntAct=EBI-8637627, EBI-10225084; CC Q8WTP8; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-8637627, EBI-10172526; CC Q8WTP8; Q5JR59: MTUS2; NbExp=3; IntAct=EBI-8637627, EBI-742948; CC Q8WTP8; Q5VU43: PDE4DIP; NbExp=3; IntAct=EBI-8637627, EBI-1105124; CC Q8WTP8; Q8IXK0: PHC2; NbExp=3; IntAct=EBI-8637627, EBI-713786; CC Q8WTP8; Q86SE5: RALYL; NbExp=3; IntAct=EBI-8637627, EBI-741520; CC Q8WTP8; P0DJD3: RBMY1A1; NbExp=3; IntAct=EBI-8637627, EBI-8638511; CC Q8WTP8; Q15415: RBMY1J; NbExp=3; IntAct=EBI-8637627, EBI-8642021; CC Q8WTP8; Q96KN7: RPGRIP1; NbExp=3; IntAct=EBI-8637627, EBI-1050213; CC Q8WTP8; Q9Y2D8: SSX2IP; NbExp=3; IntAct=EBI-8637627, EBI-2212028; CC Q8WTP8; Q08117: TLE5; NbExp=3; IntAct=EBI-8637627, EBI-717810; CC Q8WTP8; P14373: TRIM27; NbExp=3; IntAct=EBI-8637627, EBI-719493; CC Q8WTP8; Q8WV44: TRIM41; NbExp=3; IntAct=EBI-8637627, EBI-725997; CC Q8WTP8; O43298: ZBTB43; NbExp=3; IntAct=EBI-8637627, EBI-740718; CC Q8WTP8; Q96BR9: ZBTB8A; NbExp=3; IntAct=EBI-8637627, EBI-742740; CC Q8WTP8; Q9NTW7: ZFP64; NbExp=7; IntAct=EBI-8637627, EBI-711679; CC Q8WTP8; Q96PQ6: ZNF317; NbExp=4; IntAct=EBI-8637627, EBI-1210473; CC Q8WTP8; Q8WTR7: ZNF473; NbExp=5; IntAct=EBI-8637627, EBI-751409; CC Q8WTP8-2; Q13685: AAMP; NbExp=4; IntAct=EBI-12119298, EBI-727274; CC Q8WTP8-2; P54257: HAP1; NbExp=3; IntAct=EBI-12119298, EBI-712814; CC Q8WTP8-2; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-12119298, EBI-2556193; CC Q8WTP8-2; Q9BRK4: LZTS2; NbExp=3; IntAct=EBI-12119298, EBI-741037; CC Q8WTP8-2; Q5T7P8-2: SYT6; NbExp=3; IntAct=EBI-12119298, EBI-10246152; CC Q8WTP8-2; Q9H9D4: ZNF408; NbExp=3; IntAct=EBI-12119298, EBI-347633; CC -!- SUBCELLULAR LOCATION: Nucleus. Nucleus, nucleolus. Note=Localized CC predomintly in the nucleolus. Translocates from the nucleolus to the CC nucleoplasm upon apoptosis induction. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q8WTP8-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8WTP8-2; Sequence=VSP_032132; CC -!- INDUCTION: Up-regulated by p53/TP53 in response to ionizing radiation CC and DNA-damaging agents such as adriamycin. Phosphorylation of p53/TP53 CC at 'Ser-15' is required for effective induction. CC {ECO:0000269|PubMed:16171785, ECO:0000269|PubMed:18264133}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH14407.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAB14091.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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; AF327352; AAL56012.1; -; mRNA. DR EMBL; AC013489; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471101; EAX02009.1; -; Genomic_DNA. DR EMBL; BC005164; AAH05164.1; -; mRNA. DR EMBL; BC014407; AAH14407.1; ALT_INIT; mRNA. DR EMBL; BC020988; AAH20988.1; -; mRNA. DR EMBL; AK022546; BAB14091.1; ALT_INIT; mRNA. DR CCDS; CCDS10344.1; -. [Q8WTP8-1] DR RefSeq; NP_073604.3; NM_022767.3. [Q8WTP8-1] DR RefSeq; XP_005255023.1; XM_005254966.1. [Q8WTP8-1] DR RefSeq; XP_005255024.1; XM_005254967.1. DR RefSeq; XP_011520207.1; XM_011521905.2. DR RefSeq; XP_016877978.1; XM_017022489.1. [Q8WTP8-1] DR AlphaFoldDB; Q8WTP8; -. DR SMR; Q8WTP8; -. DR BioGRID; 122292; 48. DR IntAct; Q8WTP8; 41. DR MINT; Q8WTP8; -. DR STRING; 9606.ENSP00000331944; -. DR iPTMnet; Q8WTP8; -. DR PhosphoSitePlus; Q8WTP8; -. DR BioMuta; AEN; -. DR DMDM; 296434390; -. DR CPTAC; CPTAC-2613; -. DR EPD; Q8WTP8; -. DR jPOST; Q8WTP8; -. DR MassIVE; Q8WTP8; -. DR MaxQB; Q8WTP8; -. DR PaxDb; 9606-ENSP00000331944; -. DR PeptideAtlas; Q8WTP8; -. DR ProteomicsDB; 74578; -. [Q8WTP8-1] DR ProteomicsDB; 74579; -. [Q8WTP8-2] DR Pumba; Q8WTP8; -. DR Antibodypedia; 28501; 92 antibodies from 20 providers. DR DNASU; 64782; -. DR Ensembl; ENST00000332810.4; ENSP00000331944.3; ENSG00000181026.15. [Q8WTP8-1] DR GeneID; 64782; -. DR KEGG; hsa:64782; -. DR MANE-Select; ENST00000332810.4; ENSP00000331944.3; NM_022767.4; NP_073604.3. DR UCSC; uc002bmt.3; human. [Q8WTP8-1] DR AGR; HGNC:25722; -. DR CTD; 64782; -. DR DisGeNET; 64782; -. DR GeneCards; AEN; -. DR HGNC; HGNC:25722; AEN. DR HPA; ENSG00000181026; Low tissue specificity. DR MIM; 610177; gene. DR neXtProt; NX_Q8WTP8; -. DR OpenTargets; ENSG00000181026; -. DR PharmGKB; PA162375720; -. DR VEuPathDB; HostDB:ENSG00000181026; -. DR eggNOG; KOG2249; Eukaryota. DR GeneTree; ENSGT00940000161660; -. DR HOGENOM; CLU_022453_0_0_1; -. DR InParanoid; Q8WTP8; -. DR OMA; TDTEQYM; -. DR OrthoDB; 5479236at2759; -. DR PhylomeDB; Q8WTP8; -. DR TreeFam; TF354340; -. DR PathwayCommons; Q8WTP8; -. DR SignaLink; Q8WTP8; -. DR BioGRID-ORCS; 64782; 12 hits in 1156 CRISPR screens. DR ChiTaRS; AEN; human. DR GenomeRNAi; 64782; -. DR Pharos; Q8WTP8; Tbio. DR PRO; PR:Q8WTP8; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; Q8WTP8; Protein. DR Bgee; ENSG00000181026; Expressed in primordial germ cell in gonad and 139 other cell types or tissues. DR ExpressionAtlas; Q8WTP8; baseline and differential. DR GO; GO:0031965; C:nuclear membrane; IDA:HPA. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0004529; F:DNA exonuclease activity; IDA:UniProtKB. DR GO; GO:0004527; F:exonuclease activity; IDA:UniProtKB. DR GO; GO:0003676; F:nucleic acid binding; IEA:InterPro. DR GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IDA:UniProtKB. DR GO; GO:0010212; P:response to ionizing radiation; IDA:UniProtKB. DR Gene3D; 3.30.420.10; Ribonuclease H-like superfamily/Ribonuclease H; 1. DR InterPro; IPR013520; Exonuclease_RNaseT/DNA_pol3. DR InterPro; IPR047021; REXO1/3/4-like. DR InterPro; IPR012337; RNaseH-like_sf. DR InterPro; IPR036397; RNaseH_sf. DR PANTHER; PTHR12801:SF57; APOPTOSIS-ENHANCING NUCLEASE; 1. DR PANTHER; PTHR12801; RNA EXONUCLEASE REXO1 / RECO3 FAMILY MEMBER-RELATED; 1. DR Pfam; PF00929; RNase_T; 1. DR SMART; SM00479; EXOIII; 1. DR SUPFAM; SSF53098; Ribonuclease H-like; 1. DR Genevisible; Q8WTP8; HS. PE 1: Evidence at protein level; KW Alternative splicing; Apoptosis; DNA damage; Exonuclease; Hydrolase; KW Nuclease; Nucleus; Reference proteome. FT CHAIN 1..325 FT /note="Apoptosis-enhancing nuclease" FT /id="PRO_0000324088" FT DOMAIN 110..266 FT /note="Exonuclease" FT REGION 85..105 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 281..325 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 27..35 FT /note="Nucleolar localization signal" FT MOTIF 165..188 FT /note="Nuclear localization signal" FT /evidence="ECO:0000269|PubMed:18264133" FT COMPBIAS 281..295 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 304..325 FT /note="YWPDDLAHGSRGGAREAQDRRN -> STQYWALKQKSEKQDSGLNSGAFV FT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_032132" FT VARIANT 15 FT /note="P -> L (in dbSNP:rs3743477)" FT /id="VAR_039651" FT VARIANT 88 FT /note="S -> C (in dbSNP:rs8026929)" FT /id="VAR_039652" FT VARIANT 140 FT /note="N -> D (in dbSNP:rs8027765)" FT /evidence="ECO:0000269|PubMed:14702039, FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.1, FT ECO:0000269|Ref.3" FT /id="VAR_039653" FT MUTAGEN 114 FT /note="D->A: Abolishes exonuclease activity; when FT associated with A-116 and A-258." FT /evidence="ECO:0000269|PubMed:18264133" FT MUTAGEN 116 FT /note="E->A: Abolishes exonuclease activity; when FT associated with A-114 and A-258." FT /evidence="ECO:0000269|PubMed:18264133" FT MUTAGEN 258 FT /note="D->A: Abolishes exonuclease activity; when FT associated with A-114 and A-116." FT /evidence="ECO:0000269|PubMed:18264133" SQ SEQUENCE 325 AA; 36350 MW; F230BA301CB4FD88 CRC64; MVPREAPESA QCLCPSLTIP NAKDVLRKRH KRRSRQHQRF MARKALLQEQ GLLSMPPEPG SSPLPTPFGA ATATEAASSG KQCLRAGSGS APCSRRPAPG KASGPLPSKC VAIDCEMVGT GPRGRVSELA RCSIVSYHGN VLYDKYIRPE MPIADYRTRW SGITRQHMRK AVPFQVAQKE ILKLLKGKVV VGHALHNDFQ ALKYVHPRSQ TRDTTYVPNF LSEPGLHTRA RVSLKDLALQ LLHKKIQVGQ HGHSSVEDAT TAMELYRLVE VQWEQQEARS LWTCPEDREP DSSTDMEQYM EDQYWPDDLA HGSRGGAREA QDRRN //