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Q8WTP8

- AEN_HUMAN

UniProt

Q8WTP8 - AEN_HUMAN

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Protein

Apoptosis-enhancing nuclease

Gene
AEN, ISG20L1, SBBI58
Organism
Homo sapiens (Human)
Status
Reviewed - 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: Chromosome 15

Organism-specific databases

HGNCiHGNC:25722. AEN.

Subcellular locationi

Nucleus. Nucleusnucleolus
Note: Localized predomintly in the nucleolus. Translocates from the nucleolus to the nucleoplasm upon apoptosis induction.2 Publications

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.

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

ArrayExpressiQ8WTP8.
BgeeiQ8WTP8.
CleanExiHS_AEN.
GenevestigatoriQ8WTP8.

Organism-specific databases

HPAiHPA048599.

Interactioni

Protein-protein interaction databases

BioGridi122292. 2 interactions.
STRINGi9606.ENSP00000331944.

Structurei

3D structure databases

ProteinModelPortaliQ8WTP8.
SMRiQ8WTP8. Positions 111-270.

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.

Phylogenomic databases

eggNOGiCOG0847.
HOGENOMiHOG000182422.
HOVERGENiHBG100435.
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. Align

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

MVPREAPESA QCLCPSLTIP NAKDVLRKRH KRRSRQHQRF MARKALLQEQ    50
GLLSMPPEPG SSPLPTPFGA ATATEAASSG KQCLRAGSGS APCSRRPAPG 100
KASGPLPSKC VAIDCEMVGT GPRGRVSELA RCSIVSYHGN VLYDKYIRPE 150
MPIADYRTRW SGITRQHMRK AVPFQVAQKE ILKLLKGKVV VGHALHNDFQ 200
ALKYVHPRSQ TRDTTYVPNF LSEPGLHTRA RVSLKDLALQ LLHKKIQVGQ 250
HGHSSVEDAT TAMELYRLVE VQWEQQEARS LWTCPEDREP DSSTDMEQYM 300
EDQYWPDDLA HGSRGGAREA QDRRN 325
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.
The sequence BAB14091.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

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. VSP_032132Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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]
ENST00000379231; ENSP00000368533; ENSG00000181026. [Q8WTP8-2]
GeneIDi64782.
KEGGihsa:64782.
UCSCiuc002bmt.2. human. [Q8WTP8-1]

Polymorphism databases

DMDMi296434390.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
CCDSi CCDS10344.1. [Q8WTP8-1 ]
RefSeqi NP_073604.3. NM_022767.3. [Q8WTP8-1 ]
XP_005255023.1. XM_005254966.1. [Q8WTP8-1 ]
XP_005255024.1. XM_005254967.1. [Q8WTP8-1 ]
UniGenei Hs.436102.

3D structure databases

ProteinModelPortali Q8WTP8.
SMRi Q8WTP8. Positions 111-270.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 122292. 2 interactions.
STRINGi 9606.ENSP00000331944.

PTM databases

PhosphoSitei Q8WTP8.

Polymorphism databases

DMDMi 296434390.

Proteomic databases

MaxQBi Q8WTP8.
PaxDbi Q8WTP8.
PRIDEi Q8WTP8.

Protocols and materials databases

DNASUi 64782.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000332810 ; ENSP00000331944 ; ENSG00000181026 . [Q8WTP8-1 ]
ENST00000379231 ; ENSP00000368533 ; ENSG00000181026 . [Q8WTP8-2 ]
GeneIDi 64782.
KEGGi hsa:64782.
UCSCi uc002bmt.2. human. [Q8WTP8-1 ]

Organism-specific databases

CTDi 64782.
GeneCardsi GC15P089164.
H-InvDB HIX0012556.
HGNCi HGNC:25722. AEN.
HPAi HPA048599.
MIMi 610177. gene.
neXtProti NX_Q8WTP8.
PharmGKBi PA162375720.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0847.
HOGENOMi HOG000182422.
HOVERGENi HBG100435.
KOi K18340.
OMAi HKRKSRQ.
OrthoDBi EOG7WHHB0.
PhylomeDBi Q8WTP8.
TreeFami TF354340.

Miscellaneous databases

GenomeRNAii 64782.
NextBioi 66818.
PROi Q8WTP8.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q8WTP8.
Bgeei Q8WTP8.
CleanExi HS_AEN.
Genevestigatori Q8WTP8.

Family and domain databases

Gene3Di 3.30.420.10. 1 hit.
InterProi IPR006055. Exonuclease.
IPR013520. Exonuclease_RNaseT/DNA_pol3.
IPR012337. RNaseH-like_dom.
[Graphical view ]
Pfami PF00929. RNase_T. 1 hit.
[Graphical view ]
SMARTi SM00479. EXOIII. 1 hit.
[Graphical view ]
SUPFAMi SSF53098. SSF53098. 1 hit.
ProtoNeti Search...

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: September 3, 2014
This is version 104 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

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