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Q8WTP8 (AEN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Apoptosis-enhancing nuclease

EC=3.1.-.-
Alternative name(s):
Interferon-stimulated 20 kDa exonuclease-like 1
Gene names
Name:AEN
Synonyms:ISG20L1
ORF Names:SBBI58
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length325 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.6 Ref.7

Subcellular location

Nucleus. Nucleusnucleolus. Note: Localized predomintly in the nucleolus. Translocates from the nucleolus to the nucleoplasm upon apoptosis induction. Ref.6 Ref.7

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. Ref.6 Ref.7

Sequence similarities

Contains 1 exonuclease domain.

Sequence caution

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

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

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8WTP8-1)

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.
Isoform 2 (identifier: Q8WTP8-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 325325Apoptosis-enhancing nuclease
PRO_0000324088

Regions

Domain110 – 266157Exonuclease
Motif27 – 359Nucleolar localization signal
Motif165 – 18824Nuclear localization signal Ref.7

Natural variations

Alternative sequence304 – 32522YWPDD…QDRRN → STQYWALKQKSEKQDSGLNS GAFV in isoform 2.
VSP_032132
Natural variant151P → L.
Corresponds to variant rs3743477 [ dbSNP | Ensembl ].
VAR_039651
Natural variant881S → C.
Corresponds to variant rs8026929 [ dbSNP | Ensembl ].
VAR_039652
Natural variant1401N → D. Ref.1 Ref.3 Ref.4 Ref.5
Corresponds to variant rs8027765 [ dbSNP | Ensembl ].
VAR_039653

Experimental info

Mutagenesis1141D → A: Abolishes exonuclease activity; when associated with A-116 and A-258. Ref.7
Mutagenesis1161E → A: Abolishes exonuclease activity; when associated with A-114 and A-258. Ref.7
Mutagenesis2581D → A: Abolishes exonuclease activity; when associated with A-114 and A-116. Ref.7

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 18, 2010. Version 2.
Checksum: F230BA301CB4FD88

FASTA32536,350
        10         20         30         40         50         60 
MVPREAPESA QCLCPSLTIP NAKDVLRKRH KRRSRQHQRF MARKALLQEQ GLLSMPPEPG 

        70         80         90        100        110        120 
SSPLPTPFGA ATATEAASSG KQCLRAGSGS APCSRRPAPG KASGPLPSKC VAIDCEMVGT 

       130        140        150        160        170        180 
GPRGRVSELA RCSIVSYHGN VLYDKYIRPE MPIADYRTRW SGITRQHMRK AVPFQVAQKE 

       190        200        210        220        230        240 
ILKLLKGKVV VGHALHNDFQ ALKYVHPRSQ TRDTTYVPNF LSEPGLHTRA RVSLKDLALQ 

       250        260        270        280        290        300 
LLHKKIQVGQ HGHSSVEDAT TAMELYRLVE VQWEQQEARS LWTCPEDREP DSSTDMEQYM 

       310        320 
EDQYWPDDLA HGSRGGAREA QDRRN 

« Hide

Isoform 2 [UniParc].

Checksum: 31DEF4A10A4E5F3A
Show »

FASTA32736,496

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]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. expand/collapse author list , 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
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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS10344.1. [Q8WTP8-1]
RefSeqNP_073604.3. NM_022767.3. [Q8WTP8-1]
XP_005255023.1. XM_005254966.1. [Q8WTP8-1]
XP_005255024.1. XM_005254967.1. [Q8WTP8-1]
UniGeneHs.436102.

3D structure databases

ProteinModelPortalQ8WTP8.
SMRQ8WTP8. Positions 111-270.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122292. 2 interactions.
STRING9606.ENSP00000331944.

PTM databases

PhosphoSiteQ8WTP8.

Polymorphism databases

DMDM296434390.

Proteomic databases

MaxQBQ8WTP8.
PaxDbQ8WTP8.
PRIDEQ8WTP8.

Protocols and materials databases

DNASU64782.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000332810; ENSP00000331944; ENSG00000181026. [Q8WTP8-1]
ENST00000379231; ENSP00000368533; ENSG00000181026. [Q8WTP8-2]
GeneID64782.
KEGGhsa:64782.
UCSCuc002bmt.2. human. [Q8WTP8-1]

Organism-specific databases

CTD64782.
GeneCardsGC15P089164.
H-InvDBHIX0012556.
HGNCHGNC:25722. AEN.
HPAHPA048599.
MIM610177. gene.
neXtProtNX_Q8WTP8.
PharmGKBPA162375720.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0847.
HOGENOMHOG000182422.
HOVERGENHBG100435.
OMAHKRKSRQ.
OrthoDBEOG7WHHB0.
PhylomeDBQ8WTP8.
TreeFamTF354340.

Gene expression databases

ArrayExpressQ8WTP8.
BgeeQ8WTP8.
CleanExHS_AEN.
GenevestigatorQ8WTP8.

Family and domain databases

Gene3D3.30.420.10. 1 hit.
InterProIPR006055. Exonuclease.
IPR013520. Exonuclease_RNaseT/DNA_pol3.
IPR012337. RNaseH-like_dom.
[Graphical view]
PfamPF00929. RNase_T. 1 hit.
[Graphical view]
SMARTSM00479. EXOIII. 1 hit.
[Graphical view]
SUPFAMSSF53098. SSF53098. 1 hit.
ProtoNetSearch...

Other

GenomeRNAi64782.
NextBio66818.
PROQ8WTP8.
SOURCESearch...

Entry information

Entry nameAEN_HUMAN
AccessionPrimary (citable) accession number: Q8WTP8
Secondary accession number(s): C9J571, Q9BSA5, Q9H9X7
Entry history
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: May 18, 2010
Last modified: July 9, 2014
This is version 103 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM