AEN_HUMAN
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 03-AUG-2022, entry version 160.
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};
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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. [Q8WTP8-1]
DR RefSeq; XP_011520207.1; XM_011521905.2. [Q8WTP8-1]
DR RefSeq; XP_016877978.1; XM_017022489.1. [Q8WTP8-1]
DR AlphaFoldDB; Q8WTP8; -.
DR SMR; Q8WTP8; -.
DR BioGRID; 122292; 45.
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; Q8WTP8; -.
DR PeptideAtlas; Q8WTP8; -.
DR PRIDE; Q8WTP8; -.
DR ProteomicsDB; 74578; -. [Q8WTP8-1]
DR ProteomicsDB; 74579; -. [Q8WTP8-2]
DR Antibodypedia; 28501; 86 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 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; LCPSFTI; -.
DR OrthoDB; 1562214at2759; -.
DR PhylomeDB; Q8WTP8; -.
DR TreeFam; TF354340; -.
DR PathwayCommons; Q8WTP8; -.
DR SignaLink; Q8WTP8; -.
DR BioGRID-ORCS; 64782; 11 hits in 1079 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 adenohypophysis and 138 other tissues.
DR ExpressionAtlas; Q8WTP8; baseline and differential.
DR Genevisible; Q8WTP8; HS.
DR GO; GO:0031965; C:nuclear membrane; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
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; -; 1.
DR InterPro; IPR013520; Exonuclease_RNaseT/DNA_pol3.
DR InterPro; IPR012337; RNaseH-like_sf.
DR InterPro; IPR036397; RNaseH_sf.
DR Pfam; PF00929; RNase_T; 1.
DR SMART; SM00479; EXOIII; 1.
DR SUPFAM; SSF53098; SSF53098; 1.
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
