Q8WTP8 (AEN_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	325 AA.
Sequence status	Complete.
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.6 Ref.7
Subcellular location	Nucleus. Nucleus › nucleolus. 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.

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 Reference proteome
Gene Ontology (GO)
Biological_process	intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Inferred from direct assay Ref.7. Source: UniProtKB response to ionizing radiation Inferred from direct assay Ref.6. Source: UniProtKB
Cellular_component	nucleolus Inferred from direct assay Ref.7. Source: UniProtKB nucleoplasm Inferred from direct assay Ref.6Ref.7. Source: UniProtKB
Molecular_function	exonuclease activity Inferred from direct assay Ref.6Ref.7. 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.7
Natural variations
	Alternative sequence	304 – 325	22	YWPDD…QDRRN → STQYWALKQKSEKQDSGLNS GAFV in isoform 2.		VSP_032132
	Natural variant	15	1	P → L. Corresponds to variant rs3743477 [ dbSNP | Ensembl ].		VAR_039651
	Natural variant	88	1	S → C. Corresponds to variant rs8026929 [ dbSNP | Ensembl ].		VAR_039652
	Natural variant	140	1	N → D. Ref.1 Ref.3 Ref.4 Ref.5 Corresponds to variant rs8027765 [ dbSNP | Ensembl ].		VAR_039653
Experimental info
	Mutagenesis	114	1	D → A: Abolishes exonuclease activity; when associated with A-116 and A-258. Ref.7
	Mutagenesis	116	1	E → A: Abolishes exonuclease activity; when associated with A-114 and A-258. Ref.7
	Mutagenesis	258	1	D → A: Abolishes exonuclease activity; when associated with A-114 and A-116. Ref.7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 18, 2010. Version 2. Checksum: F230BA301CB4FD88	FASTA	325	36,350
	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
	Isoform 2 [UniParc]. Checksum: 31DEF4A10A4E5F3A	FASTA	327	36,496
	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 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), 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]	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], 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.
+	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.
IPI	IPI00074083. IPI00141525.
RefSeq	NP_073604.3. NM_022767.3.
UniGene	Hs.436102.
3D structure databases
ProteinModelPortal	Q8WTP8.
SMR	Q8WTP8. Positions 111-270.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000331944.
PTM databases
PhosphoSite	Q8WTP8.
Polymorphism databases
DMDM	296434390.
Proteomic databases
PaxDb	Q8WTP8.
PRIDE	Q8WTP8.
Protocols and materials databases
DNASU	64782.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000332810; ENSP00000331944; ENSG00000181026. ENST00000379231; ENSP00000368533; ENSG00000181026.
GeneID	64782.
KEGG	hsa:64782.
UCSC	uc002bmt.2. human.
Organism-specific databases
CTD	64782.
GeneCards	GC15P089164.
H-InvDB	HIX0012556.
HGNC	HGNC:25722. AEN.
HPA	HPA048599.
MIM	610177. gene.
neXtProt	NX_Q8WTP8.
PharmGKB	PA162375720.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0847.
HOGENOM	HOG000182422.
HOVERGEN	HBG100435.
OMA	HKRKSRQ.
OrthoDB	EOG4P8FJM.
PhylomeDB	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. RNaseH-like_dom. [Graphical view]
Pfam	PF00929. RNase_T. 1 hit. [Graphical view]
SMART	SM00479. EXOIII. 1 hit. [Graphical view]
SUPFAM	SSF53098. RNaseH_fold. 1 hit.
ProtoNet	Search...
Other
GenomeRNAi	64782.
NextBio	66818.
SOURCE	Search...

Entry information

Entry name

AEN_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 94 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.