Reviewed, UniProtKB/Swiss-Prot Q8WTP8 (AEN_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	325 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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.5 Ref.6
Subcellular location	Nucleus. Nucleus › nucleolus. Note: Localized predomintly in the nucleolus. Translocates from the nucleolus to the nucleoplasm upon apoptosis induction. Ref.5 Ref.6
Induction	Up-regulated by p53 in response to ionizing radiation and DNA-damaging agents such as adriamycin. Phosphorylation of p53 at 'Ser-15' is required for effective induction. Ref.5 Ref.6
Sequence similarities	Contains 1 exonuclease domain.

Ontologies

Keywords
Biological process	Apoptosis DNA damage
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Molecular function	Exonuclease Hydrolase Nuclease
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	DNA damage response, signal transduction by p53 class mediator resulting in induction of apoptosis Ref.6 Inferred from direct assay. Source: UniProtKB apoptosis Inferred from electronic annotation. Source: UniProtKB-KW response to ionizing radiation Ref.5 Inferred from direct assay. Source: UniProtKB
Cellular component	nucleolus Ref.6 Inferred from direct assay. Source: UniProtKB nucleoplasm Ref.5 Ref.6 Inferred from direct assay. Source: UniProtKB
Molecular function	exonuclease activity Ref.5 Ref.6 Inferred from direct assay. Source: UniProtKB nucleic acid binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 325	325	Apoptosis-enhancing nuclease		PRO_0000324088
Regions
	Domain	110 – 266	157	Exonuclease
	Motif	27 – 35	9	Nucleolar localization signal
	Motif	165 – 188	24	Nuclear localization signal Ref.6
Natural variations
	Alternative sequence	304 – 325	22	YWPDD…QDRRN → STQYWALKQKSEKQDSGLNS GAFV in isoform 2.		VSP_032132
	Natural variant	15	1	P → L: dbSNP rs3743477.		VAR_039651
	Natural variant	88	1	S → C: dbSNP rs8026929.		VAR_039652
	Natural variant	140	1	D → N: dbSNP rs8027765.		VAR_039653
Experimental info
	Mutagenesis	114	1	D → A: Abolishes exonuclease activity; when associated with A-116 and A-258. Ref.6
	Mutagenesis	116	1	E → A: Abolishes exonuclease activity; when associated with A-114 and A-258. Ref.6
	Mutagenesis	258	1	D → A: Abolishes exonuclease activity; when associated with A-114 and A-116. Ref.6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2002. Version 1. Checksum: FCD45034F2501788	FASTA	325	36,351
	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 RCSIVSYHGD 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
	Isoform 2. Checksum: BD3EFA45E04AB1DE	FASTA	327	36,497
	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 RCSIVSYHGD 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 EDQSTQYWAL KQKSEKQDSG LNSGAFV

References

	« Hide 'large scale' referencesShow '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).
[2]	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 Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Colon and Muscle.
[4]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 106-325 (ISOFORM 1).
[5]	"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: 16171785] [Abstract] Cited for: FUNCTION, INDUCTION, SUBCELLULAR LOCATION.
[6]	"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: 18264133] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INDUCTION, NUCLEAR LOCALIZATION SIGNAL, NUCLEOLAR LOCALIZATION SIGNAL, MUTAGENESIS OF ASP-114; GLU-116 AND ASP-258.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF327352 mRNA. Translation: AAL56012.1. 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.
IPI	IPI00074083. IPI00141525.
RefSeq	NP_073604.3.
UniGene	Hs.436102
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q8WTP8.
Proteomic databases
PRIDE	Q8WTP8.
Genome annotation databases
Ensembl	ENST00000332810; ENSP00000331944; ENSG00000181026; Homo sapiens. [Genome view]
GeneID	64782.
KEGG	hsa:64782.
UCSC	uc002bmt.1. human.
Organism-specific databases
CTD	64782.
GeneCards	GC15P086967.
HGNC	HGNC:25722. AEN.
MIM	610177. gene.
PharmGKB	PA142671649.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q8WTP8.
Gene expression databases
ArrayExpress	Q8WTP8.
Bgee	Q8WTP8.
CleanEx	HS_AEN.
Genevestigator	Q8WTP8.
Family and domain databases
InterPro	IPR006055. Exonuclease. IPR013520. Exonuclease_RNaseT/DNA_pol3. IPR012337. PolynucTfrase_RNaseH_fold. [Graphical view]
Pfam	PF00929. Exonuc_X-T. 1 hit. [Graphical view]
SMART	SM00479. EXOIII. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	66818.
SOURCE	Search...

Entry information

Entry name

AEN_HUMAN

Accession

Primary (citable) accession number: Q8WTP8
Secondary accession number(s): Q9BSA5, Q9H9X7

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 18, 2008
Last sequence update:	March 1, 2002
Last modified:	November 24, 2009
This is version 65 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.