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Protein

Apoptosis-enhancing nuclease

Gene

AEN

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

GO - Molecular functioni

  1. exonuclease activity Source: UniProtKB
  2. nucleic acid binding Source: InterPro

GO - Biological processi

  1. intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: UniProtKB
  2. nucleic acid phosphodiester bond hydrolysis Source: GOC
  3. response to ionizing radiation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Exonuclease, Hydrolase, Nuclease

Keywords - Biological processi

Apoptosis, DNA damage

Names & Taxonomyi

Protein namesi
Recommended name:
Apoptosis-enhancing nuclease (EC:3.1.-.-)
Alternative name(s):
Interferon-stimulated 20 kDa exonuclease-like 1
Gene namesi
Name:AEN
Synonyms:ISG20L1
ORF Names:SBBI58
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:25722. AEN.

Subcellular locationi

  1. Nucleus
  2. Nucleusnucleolus

  3. Note: Localized predomintly in the nucleolus. Translocates from the nucleolus to the nucleoplasm upon apoptosis induction.

GO - Cellular componenti

  1. nuclear membrane Source: HPA
  2. nucleolus Source: UniProtKB
  3. nucleoplasm Source: UniProtKB
  4. nucleus Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi114 – 1141D → A: Abolishes exonuclease activity; when associated with A-116 and A-258. 1 Publication
Mutagenesisi116 – 1161E → A: Abolishes exonuclease activity; when associated with A-114 and A-258. 1 Publication
Mutagenesisi258 – 2581D → A: Abolishes exonuclease activity; when associated with A-114 and A-116. 1 Publication

Organism-specific databases

PharmGKBiPA162375720.

Polymorphism and mutation databases

BioMutaiAEN.
DMDMi296434390.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 325325Apoptosis-enhancing nucleasePRO_0000324088Add
BLAST

Proteomic databases

MaxQBiQ8WTP8.
PaxDbiQ8WTP8.
PRIDEiQ8WTP8.

PTM databases

PhosphoSiteiQ8WTP8.

Expressioni

Inductioni

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.2 Publications

Gene expression databases

BgeeiQ8WTP8.
CleanExiHS_AEN.
ExpressionAtlasiQ8WTP8. baseline and differential.
GenevestigatoriQ8WTP8.

Organism-specific databases

HPAiHPA048599.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
AAMPC9JG973EBI-8637627,EBI-10176499
AESQ081173EBI-8637627,EBI-717810
EMDP504023EBI-8637627,EBI-489887
EXOSC8Q96B263EBI-8637627,EBI-371922
GNPTABQ3T9063EBI-8637627,EBI-1104907
HOMEZQ8IX15-33EBI-8637627,EBI-10172004
IKZF1Q134223EBI-8637627,EBI-745305
KHDRBS2Q5VWX13EBI-8637627,EBI-742808
KRT40Q6A1623EBI-8637627,EBI-10171697
KRTAP10-5P603703EBI-8637627,EBI-10172150
KRTAP10-7P604093EBI-8637627,EBI-10172290
KRTAP10-8P604103EBI-8637627,EBI-10171774
LZTS2Q9BRK43EBI-8637627,EBI-741037
MBNL1Q86VM63EBI-8637627,EBI-10225084
MID2Q9UJV3-23EBI-8637627,EBI-10172526
MTUS2Q5JR593EBI-8637627,EBI-742948
PDE4DIPQ5VU433EBI-8637627,EBI-1105124
PHC2Q8IXK03EBI-8637627,EBI-713786
RALYLQ86SE53EBI-8637627,EBI-741520
RBMY1A1P0DJD33EBI-8637627,EBI-8638511
RBMY1JQ154153EBI-8637627,EBI-8642021
RPGRIP1Q96KN73EBI-8637627,EBI-1050213
SSX2IPQ9Y2D83EBI-8637627,EBI-2212028
TRIM27P143733EBI-8637627,EBI-719493
TRIM41Q8WV443EBI-8637627,EBI-725997
ZBTB43O432983EBI-8637627,EBI-740718
ZBTB8AQ96BR93EBI-8637627,EBI-742740
ZFP64Q9NPA53EBI-8637627,EBI-711679
ZFP64Q9NTW73EBI-8637627,EBI-745730
ZNF317Q96PQ63EBI-8637627,EBI-1210473
ZNF473Q8WTR73EBI-8637627,EBI-751409

Protein-protein interaction databases

BioGridi122292. 34 interactions.
IntActiQ8WTP8. 31 interactions.
STRINGi9606.ENSP00000331944.

Structurei

3D structure databases

ProteinModelPortaliQ8WTP8.
SMRiQ8WTP8. Positions 111-270.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini110 – 266157ExonucleaseAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi27 – 359Nucleolar localization signal
Motifi165 – 18824Nuclear localization signal1 PublicationAdd
BLAST

Sequence similaritiesi

Contains 1 exonuclease domain.Curated

Phylogenomic databases

eggNOGiCOG0847.
GeneTreeiENSGT00520000055542.
HOGENOMiHOG000182422.
HOVERGENiHBG100435.
InParanoidiQ8WTP8.
KOiK18340.
OMAiHKRKSRQ.
OrthoDBiEOG7WHHB0.
PhylomeDBiQ8WTP8.
TreeFamiTF354340.

Family and domain databases

Gene3Di3.30.420.10. 1 hit.
InterProiIPR006055. Exonuclease.
IPR013520. Exonuclease_RNaseT/DNA_pol3.
IPR012337. RNaseH-like_dom.
[Graphical view]
PfamiPF00929. RNase_T. 1 hit.
[Graphical view]
SMARTiSM00479. EXOIII. 1 hit.
[Graphical view]
SUPFAMiSSF53098. SSF53098. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8WTP8-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MVPREAPESA QCLCPSLTIP NAKDVLRKRH KRRSRQHQRF MARKALLQEQ
60 70 80 90 100
GLLSMPPEPG SSPLPTPFGA ATATEAASSG KQCLRAGSGS APCSRRPAPG
110 120 130 140 150
KASGPLPSKC VAIDCEMVGT GPRGRVSELA RCSIVSYHGN VLYDKYIRPE
160 170 180 190 200
MPIADYRTRW SGITRQHMRK AVPFQVAQKE ILKLLKGKVV VGHALHNDFQ
210 220 230 240 250
ALKYVHPRSQ TRDTTYVPNF LSEPGLHTRA RVSLKDLALQ LLHKKIQVGQ
260 270 280 290 300
HGHSSVEDAT TAMELYRLVE VQWEQQEARS LWTCPEDREP DSSTDMEQYM
310 320
EDQYWPDDLA HGSRGGAREA QDRRN
Length:325
Mass (Da):36,350
Last modified:May 18, 2010 - v2
Checksum:iF230BA301CB4FD88
GO
Isoform 2 (identifier: Q8WTP8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     304-325: YWPDDLAHGSRGGAREAQDRRN → STQYWALKQKSEKQDSGLNSGAFV

Show »
Length:327
Mass (Da):36,496
Checksum:i31DEF4A10A4E5F3A
GO

Sequence cautioni

The sequence AAH14407.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAB14091.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti15 – 151P → L.
Corresponds to variant rs3743477 [ dbSNP | Ensembl ].
VAR_039651
Natural varianti88 – 881S → C.
Corresponds to variant rs8026929 [ dbSNP | Ensembl ].
VAR_039652
Natural varianti140 – 1401N → D.4 Publications
Corresponds to variant rs8027765 [ dbSNP | Ensembl ].
VAR_039653

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei304 – 32522YWPDD…QDRRN → STQYWALKQKSEKQDSGLNS GAFV in isoform 2. 1 PublicationVSP_032132Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF327352 mRNA. Translation: AAL56012.1.
AC013489 Genomic DNA. No translation available.
CH471101 Genomic DNA. Translation: EAX02009.1.
BC005164 mRNA. Translation: AAH05164.1.
BC014407 mRNA. Translation: AAH14407.1. Different initiation.
BC020988 mRNA. Translation: AAH20988.1.
AK022546 mRNA. Translation: BAB14091.1. Different initiation.
CCDSiCCDS10344.1. [Q8WTP8-1]
RefSeqiNP_073604.3. NM_022767.3. [Q8WTP8-1]
XP_005255023.1. XM_005254966.1. [Q8WTP8-1]
XP_005255024.1. XM_005254967.1. [Q8WTP8-1]
UniGeneiHs.436102.

Genome annotation databases

EnsembliENST00000332810; ENSP00000331944; ENSG00000181026. [Q8WTP8-1]
GeneIDi64782.
KEGGihsa:64782.
UCSCiuc002bmt.2. human. [Q8WTP8-1]

Polymorphism and mutation databases

BioMutaiAEN.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF327352 mRNA. Translation: AAL56012.1.
AC013489 Genomic DNA. No translation available.
CH471101 Genomic DNA. Translation: EAX02009.1.
BC005164 mRNA. Translation: AAH05164.1.
BC014407 mRNA. Translation: AAH14407.1. Different initiation.
BC020988 mRNA. Translation: AAH20988.1.
AK022546 mRNA. Translation: BAB14091.1. Different initiation.
CCDSiCCDS10344.1. [Q8WTP8-1]
RefSeqiNP_073604.3. NM_022767.3. [Q8WTP8-1]
XP_005255023.1. XM_005254966.1. [Q8WTP8-1]
XP_005255024.1. XM_005254967.1. [Q8WTP8-1]
UniGeneiHs.436102.

3D structure databases

ProteinModelPortaliQ8WTP8.
SMRiQ8WTP8. Positions 111-270.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122292. 34 interactions.
IntActiQ8WTP8. 31 interactions.
STRINGi9606.ENSP00000331944.

PTM databases

PhosphoSiteiQ8WTP8.

Polymorphism and mutation databases

BioMutaiAEN.
DMDMi296434390.

Proteomic databases

MaxQBiQ8WTP8.
PaxDbiQ8WTP8.
PRIDEiQ8WTP8.

Protocols and materials databases

DNASUi64782.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000332810; ENSP00000331944; ENSG00000181026. [Q8WTP8-1]
GeneIDi64782.
KEGGihsa:64782.
UCSCiuc002bmt.2. human. [Q8WTP8-1]

Organism-specific databases

CTDi64782.
GeneCardsiGC15P089164.
H-InvDBHIX0012556.
HGNCiHGNC:25722. AEN.
HPAiHPA048599.
MIMi610177. gene.
neXtProtiNX_Q8WTP8.
PharmGKBiPA162375720.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0847.
GeneTreeiENSGT00520000055542.
HOGENOMiHOG000182422.
HOVERGENiHBG100435.
InParanoidiQ8WTP8.
KOiK18340.
OMAiHKRKSRQ.
OrthoDBiEOG7WHHB0.
PhylomeDBiQ8WTP8.
TreeFamiTF354340.

Miscellaneous databases

GenomeRNAii64782.
NextBioi66818.
PROiQ8WTP8.
SOURCEiSearch...

Gene expression databases

BgeeiQ8WTP8.
CleanExiHS_AEN.
ExpressionAtlasiQ8WTP8. baseline and differential.
GenevestigatoriQ8WTP8.

Family and domain databases

Gene3Di3.30.420.10. 1 hit.
InterProiIPR006055. Exonuclease.
IPR013520. Exonuclease_RNaseT/DNA_pol3.
IPR012337. RNaseH-like_dom.
[Graphical view]
PfamiPF00929. RNase_T. 1 hit.
[Graphical view]
SMARTiSM00479. EXOIII. 1 hit.
[Graphical view]
SUPFAMiSSF53098. SSF53098. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Zhang W., Li N., Wan T., Chen T., Zhang J., Cao X.
    Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ASP-140.
  2. "Analysis of the DNA sequence and duplication history of human chromosome 15."
    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.
    Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT ASP-140.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT ASP-140.
    Tissue: Colon and Muscle.
  5. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    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.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 106-325 (ISOFORM 1), VARIANT ASP-140.
  6. "Identification of a novel ionizing radiation-induced nuclease, AEN, and its functional characterization in apoptosis."
    Lee J.-H., Koh Y.A., Cho C.-K., Lee S.J., Lee Y.-S., Bae S.
    Biochem. Biophys. Res. Commun. 337:39-47(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION, SUBCELLULAR LOCATION.
  7. "p53 target gene AEN is a nuclear exonuclease required for p53-dependent apoptosis."
    Kawase T., Ichikawa H., Ohta T., Nozaki N., Tashiro F., Ohki R., Taya Y.
    Oncogene 27:3797-3810(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INDUCTION, NUCLEAR LOCALIZATION SIGNAL, NUCLEOLAR LOCALIZATION SIGNAL, MUTAGENESIS OF ASP-114; GLU-116 AND ASP-258.

Entry informationi

Entry nameiAEN_HUMAN
AccessioniPrimary (citable) accession number: Q8WTP8
Secondary accession number(s): C9J571, Q9BSA5, Q9H9X7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: May 18, 2010
Last modified: April 29, 2015
This is version 109 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.