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Q8WTP8

- AEN_HUMAN

UniProt

Q8WTP8 - AEN_HUMAN

Protein

Apoptosis-enhancing nuclease

Gene

AEN

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 105 (01 Oct 2014)
      Sequence version 2 (18 May 2010)
      Previous versions | rss
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    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

    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.

    GO - Cellular componenti

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

    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.
    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.
    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. 1 PublicationVSP_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]
    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 ]
    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

    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: October 1, 2014
    This is version 105 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