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Apoptosis-enhancing nuclease (EC 3.1.-.-) (Interferon-stimulated 20 kDa exonuclease-like 1)

 AEN_HUMAN               Reviewed;         325 AA.
Q8WTP8; C9J571; Q9BSA5; Q9H9X7;
18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
18-MAY-2010, sequence version 2.
12-SEP-2018, entry version 136.
RecName: Full=Apoptosis-enhancing nuclease;
EC=3.1.-.-;
AltName: Full=Interferon-stimulated 20 kDa exonuclease-like 1;
Name=AEN; Synonyms=ISG20L1; ORFNames=SBBI58;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
ASP-140.
Zhang W., Li N., Wan T., Chen T., Zhang J., Cao X.;
Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=16572171; DOI=10.1038/nature04601;
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R.,
Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G.,
Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A.,
Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W.,
Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X.,
Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K.,
Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S.,
Nusbaum C.;
"Analysis of the DNA sequence and duplication history of human
chromosome 15.";
Nature 440:671-675(2006).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASP-140.
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
ASP-140.
TISSUE=Colon, and Muscle;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 106-325 (ISOFORM 1), AND
VARIANT ASP-140.
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[6]
FUNCTION, INDUCTION, AND SUBCELLULAR LOCATION.
PubMed=16171785; DOI=10.1016/j.bbrc.2005.08.264;
Lee J.-H., Koh Y.A., Cho C.-K., Lee S.J., Lee Y.-S., Bae S.;
"Identification of a novel ionizing radiation-induced nuclease, AEN,
and its functional characterization in apoptosis.";
Biochem. Biophys. Res. Commun. 337:39-47(2005).
[7]
FUNCTION, SUBCELLULAR LOCATION, INDUCTION, NUCLEAR LOCALIZATION
SIGNAL, NUCLEOLAR LOCALIZATION SIGNAL, AND MUTAGENESIS OF ASP-114;
GLU-116 AND ASP-258.
PubMed=18264133; DOI=10.1038/onc.2008.32;
Kawase T., Ichikawa H., Ohta T., Nozaki N., Tashiro F., Ohki R.,
Taya Y.;
"p53 target gene AEN is a nuclear exonuclease required for p53-
dependent apoptosis.";
Oncogene 27:3797-3810(2008).
-!- FUNCTION: Exonuclease with activity against single- and double-
stranded DNA and RNA. Mediates p53-induced apoptosis. When induced
by p53 following DNA damage, digests double-stranded DNA to form
single-stranded DNA and amplifies DNA damage signals, leading to
enhancement of apoptosis. {ECO:0000269|PubMed:16171785,
ECO:0000269|PubMed:18264133}.
-!- INTERACTION:
C9JG97:AAMP; NbExp=3; IntAct=EBI-8637627, EBI-10176499;
Q08117:AES; NbExp=3; IntAct=EBI-8637627, EBI-717810;
P50402:EMD; NbExp=3; IntAct=EBI-8637627, EBI-489887;
Q96B26:EXOSC8; NbExp=3; IntAct=EBI-8637627, EBI-371922;
Q3T906:GNPTAB; NbExp=3; IntAct=EBI-8637627, EBI-1104907;
Q8IX15-3:HOMEZ; NbExp=3; IntAct=EBI-8637627, EBI-10172004;
Q13422:IKZF1; NbExp=3; IntAct=EBI-8637627, EBI-745305;
Q5VWX1:KHDRBS2; NbExp=3; IntAct=EBI-8637627, EBI-742808;
Q6A162:KRT40; NbExp=3; IntAct=EBI-8637627, EBI-10171697;
P60370:KRTAP10-5; NbExp=3; IntAct=EBI-8637627, EBI-10172150;
P60409:KRTAP10-7; NbExp=3; IntAct=EBI-8637627, EBI-10172290;
P60410:KRTAP10-8; NbExp=3; IntAct=EBI-8637627, EBI-10171774;
Q9BRK4:LZTS2; NbExp=3; IntAct=EBI-8637627, EBI-741037;
Q86VM6:MBNL1; NbExp=3; IntAct=EBI-8637627, EBI-10225084;
Q9UJV3-2:MID2; NbExp=3; IntAct=EBI-8637627, EBI-10172526;
Q5JR59:MTUS2; NbExp=3; IntAct=EBI-8637627, EBI-742948;
Q5VU43:PDE4DIP; NbExp=3; IntAct=EBI-8637627, EBI-1105124;
Q8IXK0:PHC2; NbExp=3; IntAct=EBI-8637627, EBI-713786;
Q86SE5:RALYL; NbExp=3; IntAct=EBI-8637627, EBI-741520;
P0DJD3:RBMY1A1; NbExp=3; IntAct=EBI-8637627, EBI-8638511;
Q15415:RBMY1J; NbExp=3; IntAct=EBI-8637627, EBI-8642021;
Q96KN7:RPGRIP1; NbExp=3; IntAct=EBI-8637627, EBI-1050213;
Q9Y2D8:SSX2IP; NbExp=3; IntAct=EBI-8637627, EBI-2212028;
P14373:TRIM27; NbExp=3; IntAct=EBI-8637627, EBI-719493;
Q8WV44:TRIM41; NbExp=3; IntAct=EBI-8637627, EBI-725997;
O43298:ZBTB43; NbExp=3; IntAct=EBI-8637627, EBI-740718;
Q96BR9:ZBTB8A; NbExp=3; IntAct=EBI-8637627, EBI-742740;
Q9NPA5:ZFP64; NbExp=3; IntAct=EBI-8637627, EBI-711679;
Q9NTW7:ZFP64; NbExp=3; IntAct=EBI-8637627, EBI-745730;
Q96PQ6:ZNF317; NbExp=3; IntAct=EBI-8637627, EBI-1210473;
Q8WTR7:ZNF473; NbExp=3; IntAct=EBI-8637627, EBI-751409;
-!- SUBCELLULAR LOCATION: Nucleus. Nucleus, nucleolus. Note=Localized
predomintly in the nucleolus. Translocates from the nucleolus to
the nucleoplasm upon apoptosis induction.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1;
IsoId=Q8WTP8-1; Sequence=Displayed;
Name=2;
IsoId=Q8WTP8-2; Sequence=VSP_032132;
-!- INDUCTION: Up-regulated by p53/TP53 in response to ionizing
radiation and DNA-damaging agents such as adriamycin.
Phosphorylation of p53/TP53 at 'Ser-15' is required for effective
induction. {ECO:0000269|PubMed:16171785,
ECO:0000269|PubMed:18264133}.
-!- SEQUENCE CAUTION:
Sequence=AAH14407.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
Sequence=BAB14091.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
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EMBL; AF327352; AAL56012.1; -; mRNA.
EMBL; AC013489; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH471101; EAX02009.1; -; Genomic_DNA.
EMBL; BC005164; AAH05164.1; -; mRNA.
EMBL; BC014407; AAH14407.1; ALT_INIT; mRNA.
EMBL; BC020988; AAH20988.1; -; mRNA.
EMBL; AK022546; BAB14091.1; ALT_INIT; mRNA.
CCDS; CCDS10344.1; -. [Q8WTP8-1]
RefSeq; NP_073604.3; NM_022767.3. [Q8WTP8-1]
RefSeq; XP_005255023.1; XM_005254966.1. [Q8WTP8-1]
RefSeq; XP_005255024.1; XM_005254967.1. [Q8WTP8-1]
RefSeq; XP_011520207.1; XM_011521905.2. [Q8WTP8-1]
RefSeq; XP_016877978.1; XM_017022489.1. [Q8WTP8-1]
UniGene; Hs.436102; -.
ProteinModelPortal; Q8WTP8; -.
SMR; Q8WTP8; -.
BioGrid; 122292; 37.
IntAct; Q8WTP8; 36.
MINT; Q8WTP8; -.
STRING; 9606.ENSP00000331944; -.
iPTMnet; Q8WTP8; -.
PhosphoSitePlus; Q8WTP8; -.
BioMuta; AEN; -.
DMDM; 296434390; -.
EPD; Q8WTP8; -.
MaxQB; Q8WTP8; -.
PaxDb; Q8WTP8; -.
PeptideAtlas; Q8WTP8; -.
PRIDE; Q8WTP8; -.
ProteomicsDB; 74578; -.
ProteomicsDB; 74579; -. [Q8WTP8-2]
DNASU; 64782; -.
Ensembl; ENST00000332810; ENSP00000331944; ENSG00000181026. [Q8WTP8-1]
GeneID; 64782; -.
KEGG; hsa:64782; -.
UCSC; uc002bmt.3; human. [Q8WTP8-1]
CTD; 64782; -.
DisGeNET; 64782; -.
EuPathDB; HostDB:ENSG00000181026.14; -.
GeneCards; AEN; -.
H-InvDB; HIX0012556; -.
HGNC; HGNC:25722; AEN.
HPA; HPA048599; -.
MIM; 610177; gene.
neXtProt; NX_Q8WTP8; -.
OpenTargets; ENSG00000181026; -.
PharmGKB; PA162375720; -.
eggNOG; KOG2249; Eukaryota.
eggNOG; COG0847; LUCA.
GeneTree; ENSGT00520000055542; -.
HOGENOM; HOG000182422; -.
HOVERGEN; HBG100435; -.
InParanoid; Q8WTP8; -.
KO; K18340; -.
OMA; QRFMARK; -.
OrthoDB; EOG091G0BHZ; -.
PhylomeDB; Q8WTP8; -.
TreeFam; TF354340; -.
ChiTaRS; AEN; human.
GenomeRNAi; 64782; -.
PRO; PR:Q8WTP8; -.
Proteomes; UP000005640; Chromosome 15.
Bgee; ENSG00000181026; Expressed in 183 organ(s), highest expression level in adenohypophysis.
CleanEx; HS_AEN; -.
ExpressionAtlas; Q8WTP8; baseline and differential.
Genevisible; Q8WTP8; HS.
GO; GO:0031965; C:nuclear membrane; IDA:HPA.
GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
GO; GO:0005634; C:nucleus; IDA:HPA.
GO; GO:0004527; F:exonuclease activity; IDA:UniProtKB.
GO; GO:0003676; F:nucleic acid binding; IEA:InterPro.
GO; GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IDA:UniProtKB.
GO; GO:0010212; P:response to ionizing radiation; IDA:UniProtKB.
Gene3D; 3.30.420.10; -; 1.
InterPro; IPR013520; Exonuclease_RNaseT/DNA_pol3.
InterPro; IPR012337; RNaseH-like_sf.
InterPro; IPR036397; RNaseH_sf.
Pfam; PF00929; RNase_T; 1.
SMART; SM00479; EXOIII; 1.
SUPFAM; SSF53098; SSF53098; 1.
1: Evidence at protein level;
Alternative splicing; Apoptosis; Complete proteome; DNA damage;
Exonuclease; Hydrolase; Nuclease; Nucleus; Polymorphism;
Reference proteome.
CHAIN 1 325 Apoptosis-enhancing nuclease.
/FTId=PRO_0000324088.
DOMAIN 110 266 Exonuclease.
MOTIF 27 35 Nucleolar localization signal.
MOTIF 165 188 Nuclear localization signal.
{ECO:0000269|PubMed:18264133}.
VAR_SEQ 304 325 YWPDDLAHGSRGGAREAQDRRN -> STQYWALKQKSEKQD
SGLNSGAFV (in isoform 2).
{ECO:0000303|PubMed:15489334}.
/FTId=VSP_032132.
VARIANT 15 15 P -> L (in dbSNP:rs3743477).
/FTId=VAR_039651.
VARIANT 88 88 S -> C (in dbSNP:rs8026929).
/FTId=VAR_039652.
VARIANT 140 140 N -> D (in dbSNP:rs8027765).
{ECO:0000269|PubMed:14702039,
ECO:0000269|PubMed:15489334,
ECO:0000269|Ref.1, ECO:0000269|Ref.3}.
/FTId=VAR_039653.
MUTAGEN 114 114 D->A: Abolishes exonuclease activity;
when associated with A-116 and A-258.
{ECO:0000269|PubMed:18264133}.
MUTAGEN 116 116 E->A: Abolishes exonuclease activity;
when associated with A-114 and A-258.
{ECO:0000269|PubMed:18264133}.
MUTAGEN 258 258 D->A: Abolishes exonuclease activity;
when associated with A-114 and A-116.
{ECO:0000269|PubMed:18264133}.
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


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