ISG20_HUMAN
ID ISG20_HUMAN Reviewed; 181 AA.
AC Q96AZ6; O00441; O00586;
DT 04-JAN-2005, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Interferon-stimulated gene 20 kDa protein;
DE EC=3.1.13.1;
DE AltName: Full=Estrogen-regulated transcript 45 protein;
DE AltName: Full=Promyelocytic leukemia nuclear body-associated protein ISG20;
GN Name=ISG20; Synonyms=HEM45;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE
RP SPECIFICITY, IDENTIFICATION IN PML NB COMPLEX, AND INDUCTION.
RX PubMed=9235947; DOI=10.1074/jbc.272.31.19457;
RA Gongora C., David G., Pintard L., Tissot C., Hua T.D., Dejean A.,
RA Mechti N.;
RT "Molecular cloning of a new interferon-induced PML nuclear bodies-
RT associated protein.";
RL J. Biol. Chem. 272:19457-19463(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=9569007; DOI=10.1016/s0960-0760(97)00140-4;
RA Pentecost B.T.;
RT "Expression and estrogen regulation of the HEM45 mRNA in human tumor lines
RT and in the rat uterus.";
RL J. Steroid Biochem. Mol. Biol. 64:25-33(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=B-cell, and Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=11401564; DOI=10.1021/bi010141t;
RA Nguyen L.H., Espert L., Mechti N., Wilson D.M. III;
RT "The human interferon- and estrogen-regulated ISG20/HEM45 gene product
RT degrades single-stranded RNA and DNA in vitro.";
RL Biochemistry 40:7174-7179(2001).
RN [7]
RP FUNCTION.
RX PubMed=12594219; DOI=10.1074/jbc.m209628200;
RA Espert L., Degols G., Gongora C., Blondel D., Williams B.R.,
RA Silverman R.H., Mechti N.;
RT "ISG20, a new interferon-induced RNase specific for single-stranded RNA,
RT defines an alternative antiviral pathway against RNA genomic viruses.";
RL J. Biol. Chem. 278:16151-16158(2003).
RN [8]
RP FUNCTION.
RX PubMed=16033969; DOI=10.1099/vir.0.81074-0;
RA Espert L., Degols G., Lin Y.L., Vincent T., Benkirane M., Mechti N.;
RT "Interferon-induced exonuclease ISG20 exhibits an antiviral activity
RT against human immunodeficiency virus type 1.";
RL J. Gen. Virol. 86:2221-2229(2005).
RN [9]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH SMN COMPLEX AND SNRNAS.
RX PubMed=16514659; DOI=10.1002/jcb.20869;
RA Espert L., Eldin P., Gongora C., Bayard B., Harper F., Chelbi-Alix M.K.,
RA Bertrand E., Degols G., Mechti N.;
RT "The exonuclease ISG20 mainly localizes in the nucleolus and the Cajal
RT (Coiled) bodies and is associated with nuclear SMN protein-containing
RT complexes.";
RL J. Cell. Biochem. 98:1320-1333(2006).
RN [10]
RP REVIEW ON FUNCTION.
RX PubMed=17445960; DOI=10.1016/j.biochi.2007.03.006;
RA Degols G., Eldin P., Mechti N.;
RT "ISG20, an actor of the innate immune response.";
RL Biochimie 89:831-835(2007).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [12]
RP FUNCTION IN HCV; HAV AND YFV RESTRICTION, AND SUBCELLULAR LOCATION.
RX PubMed=21036379; DOI=10.1016/j.virol.2010.10.008;
RA Zhou Z., Wang N., Woodson S.E., Dong Q., Wang J., Liang Y., Rijnbrand R.,
RA Wei L., Nichols J.E., Guo J.T., Holbrook M.R., Lemon S.M., Li K.;
RT "Antiviral activities of ISG20 in positive-strand RNA virus infections.";
RL Virology 409:175-188(2011).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH UMP, COFACTOR, AND
RP MANGANESE-BINDING SITES.
RX PubMed=15527770; DOI=10.1016/j.febslet.2004.09.074;
RA Horio T., Murai M., Inoue T., Hamasaki T., Tanaka T., Ohgi T.;
RT "Crystal structure of human ISG20, an interferon-induced antiviral
RT ribonuclease.";
RL FEBS Lett. 577:111-116(2004).
CC -!- FUNCTION: Interferon-induced antiviral exoribonuclease that acts on
CC single-stranded RNA and also has minor activity towards single-stranded
CC DNA. Exhibits antiviral activity against RNA viruses including
CC hepatitis C virus (HCV), hepatitis A virus (HAV) and yellow fever virus
CC (YFV) in an exonuclease-dependent manner. May also play additional
CC roles in the maturation of snRNAs and rRNAs, and in ribosome
CC biogenesis. {ECO:0000269|PubMed:11401564, ECO:0000269|PubMed:12594219,
CC ECO:0000269|PubMed:16033969, ECO:0000269|PubMed:21036379}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Exonucleolytic cleavage in the 3'- to 5'-direction to yield
CC nucleoside 5'-phosphates.; EC=3.1.13.1;
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:15527770};
CC Note=Binds 2 manganese ions per subunit. {ECO:0000269|PubMed:15527770};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.0.;
CC -!- SUBUNIT: Associates with PML and SP100 in the PML NB complex.
CC Associates with survival motor neuron protein (SMN)-containing
CC macromolecular nuclear complexes and U1 and U2 snRNAs and U3 snoRNA.
CC {ECO:0000269|PubMed:15527770, ECO:0000269|PubMed:9235947}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Nucleus, nucleolus. Cytoplasm. Nucleus,
CC Cajal body.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96AZ6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96AZ6-2; Sequence=VSP_012429, VSP_012430;
CC -!- TISSUE SPECIFICITY: Highly expressed in peripheral blood leukocytes,
CC spleen, thymus, colon and lung. Up regulated by E2 in estrogen
CC receptor-positive breast cancer lines. {ECO:0000269|PubMed:9235947,
CC ECO:0000269|PubMed:9569007}.
CC -!- INDUCTION: Induced by interferons alpha and beta. Weaker induction was
CC seen with interferon gamma. Increased expression was seen at the
CC transcriptional level. {ECO:0000269|PubMed:9235947}.
CC -!- SIMILARITY: Belongs to the exonuclease superfamily. {ECO:0000305}.
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DR EMBL; X89773; CAA61915.2; -; mRNA.
DR EMBL; U88964; AAB53416.1; -; mRNA.
DR EMBL; BT006952; AAP35598.1; -; mRNA.
DR EMBL; CR456942; CAG33223.1; -; mRNA.
DR EMBL; BC007922; AAH07922.1; -; mRNA.
DR EMBL; BC016341; AAH16341.1; -; mRNA.
DR CCDS; CCDS10345.1; -. [Q96AZ6-1]
DR RefSeq; NP_001290162.1; NM_001303233.1. [Q96AZ6-1]
DR RefSeq; NP_001290163.1; NM_001303234.1. [Q96AZ6-1]
DR RefSeq; NP_001290165.1; NM_001303236.1.
DR RefSeq; NP_002192.2; NM_002201.5. [Q96AZ6-1]
DR RefSeq; XP_005254956.1; XM_005254899.2. [Q96AZ6-1]
DR RefSeq; XP_006720551.1; XM_006720488.3. [Q96AZ6-1]
DR PDB; 1WLJ; X-ray; 1.90 A; A=1-181.
DR PDBsum; 1WLJ; -.
DR AlphaFoldDB; Q96AZ6; -.
DR SMR; Q96AZ6; -.
DR BioGRID; 109876; 14.
DR IntAct; Q96AZ6; 10.
DR STRING; 9606.ENSP00000306565; -.
DR DrugBank; DB03685; Uridine monophosphate.
DR iPTMnet; Q96AZ6; -.
DR PhosphoSitePlus; Q96AZ6; -.
DR BioMuta; ISG20; -.
DR DMDM; 57012967; -.
DR EPD; Q96AZ6; -.
DR jPOST; Q96AZ6; -.
DR MassIVE; Q96AZ6; -.
DR MaxQB; Q96AZ6; -.
DR PaxDb; Q96AZ6; -.
DR PeptideAtlas; Q96AZ6; -.
DR PRIDE; Q96AZ6; -.
DR ProteomicsDB; 76025; -. [Q96AZ6-1]
DR ProteomicsDB; 76026; -. [Q96AZ6-2]
DR Antibodypedia; 15665; 356 antibodies from 27 providers.
DR DNASU; 3669; -.
DR Ensembl; ENST00000306072.10; ENSP00000306565.5; ENSG00000172183.16. [Q96AZ6-1]
DR Ensembl; ENST00000379224.10; ENSP00000368526.6; ENSG00000172183.16. [Q96AZ6-1]
DR Ensembl; ENST00000560741.5; ENSP00000453638.1; ENSG00000172183.16. [Q96AZ6-1]
DR GeneID; 3669; -.
DR KEGG; hsa:3669; -.
DR MANE-Select; ENST00000306072.10; ENSP00000306565.5; NM_002201.6; NP_002192.2.
DR UCSC; uc002bmv.2; human. [Q96AZ6-1]
DR CTD; 3669; -.
DR DisGeNET; 3669; -.
DR GeneCards; ISG20; -.
DR HGNC; HGNC:6130; ISG20.
DR HPA; ENSG00000172183; Tissue enhanced (lymphoid).
DR MIM; 604533; gene.
DR neXtProt; NX_Q96AZ6; -.
DR OpenTargets; ENSG00000172183; -.
DR PharmGKB; PA29930; -.
DR VEuPathDB; HostDB:ENSG00000172183; -.
DR eggNOG; KOG2249; Eukaryota.
DR GeneTree; ENSGT00940000160781; -.
DR HOGENOM; CLU_022453_3_1_1; -.
DR InParanoid; Q96AZ6; -.
DR OMA; LSHPRRY; -.
DR OrthoDB; 1562214at2759; -.
DR PhylomeDB; Q96AZ6; -.
DR TreeFam; TF354340; -.
DR PathwayCommons; Q96AZ6; -.
DR Reactome; R-HSA-909733; Interferon alpha/beta signaling.
DR SignaLink; Q96AZ6; -.
DR BioGRID-ORCS; 3669; 11 hits in 1078 CRISPR screens.
DR ChiTaRS; ISG20; human.
DR EvolutionaryTrace; Q96AZ6; -.
DR GeneWiki; ISG20; -.
DR GenomeRNAi; 3669; -.
DR Pharos; Q96AZ6; Tbio.
DR PRO; PR:Q96AZ6; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q96AZ6; protein.
DR Bgee; ENSG00000172183; Expressed in spleen and 155 other tissues.
DR ExpressionAtlas; Q96AZ6; baseline and differential.
DR Genevisible; Q96AZ6; HS.
DR GO; GO:0015030; C:Cajal body; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016605; C:PML body; IDA:UniProtKB.
DR GO; GO:0000175; F:3'-5'-exoribonuclease activity; IDA:UniProtKB.
DR GO; GO:0004527; F:exonuclease activity; IMP:UniProtKB.
DR GO; GO:0008859; F:exoribonuclease II activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008310; F:single-stranded DNA 3'-5' exodeoxyribonuclease activity; IDA:UniProtKB.
DR GO; GO:0030619; F:U1 snRNA binding; IDA:UniProtKB.
DR GO; GO:0030620; F:U2 snRNA binding; IDA:UniProtKB.
DR GO; GO:0034511; F:U3 snoRNA binding; IDA:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IMP:UniProtKB.
DR GO; GO:0000738; P:DNA catabolic process, exonucleolytic; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0045071; P:negative regulation of viral genome replication; IMP:UniProtKB.
DR GO; GO:0009615; P:response to virus; IDA:UniProtKB.
DR GO; GO:0006401; P:RNA catabolic process; IDA:UniProtKB.
DR GO; GO:0006364; P:rRNA processing; IEA:UniProtKB-KW.
DR Gene3D; 3.30.420.10; -; 1.
DR InterPro; IPR013520; Exonuclease_RNaseT/DNA_pol3.
DR InterPro; IPR012337; RNaseH-like_sf.
DR InterPro; IPR036397; RNaseH_sf.
DR Pfam; PF00929; RNase_T; 1.
DR SMART; SM00479; EXOIII; 1.
DR SUPFAM; SSF53098; SSF53098; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Antiviral defense; Cytoplasm;
KW Exonuclease; Hydrolase; Immunity; Innate immunity; Manganese;
KW Metal-binding; Nuclease; Nucleus; Reference proteome; RNA-binding;
KW rRNA processing.
FT CHAIN 1..181
FT /note="Interferon-stimulated gene 20 kDa protein"
FT /id="PRO_0000084243"
FT BINDING 11
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT BINDING 13
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT BINDING 90
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT BINDING 93
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT BINDING 154
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT VAR_SEQ 77..86
FT /note="ILQLLKGKLV -> VPFPSSPTAA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_012429"
FT VAR_SEQ 87..181
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_012430"
FT STRAND 7..17
FT /evidence="ECO:0007829|PDB:1WLJ"
FT TURN 18..21
FT /evidence="ECO:0007829|PDB:1WLJ"
FT STRAND 22..31
FT /evidence="ECO:0007829|PDB:1WLJ"
FT STRAND 37..44
FT /evidence="ECO:0007829|PDB:1WLJ"
FT STRAND 49..51
FT /evidence="ECO:0007829|PDB:1WLJ"
FT HELIX 54..57
FT /evidence="ECO:0007829|PDB:1WLJ"
FT HELIX 61..64
FT /evidence="ECO:0007829|PDB:1WLJ"
FT HELIX 70..81
FT /evidence="ECO:0007829|PDB:1WLJ"
FT STRAND 84..90
FT /evidence="ECO:0007829|PDB:1WLJ"
FT HELIX 91..97
FT /evidence="ECO:0007829|PDB:1WLJ"
FT STRAND 106..109
FT /evidence="ECO:0007829|PDB:1WLJ"
FT HELIX 110..112
FT /evidence="ECO:0007829|PDB:1WLJ"
FT HELIX 114..120
FT /evidence="ECO:0007829|PDB:1WLJ"
FT HELIX 130..137
FT /evidence="ECO:0007829|PDB:1WLJ"
FT HELIX 151..171
FT /evidence="ECO:0007829|PDB:1WLJ"
SQ SEQUENCE 181 AA; 20363 MW; 24519CB52CEA5581 CRC64;
MAGSREVVAM DCEMVGLGPH RESGLARCSL VNVHGAVLYD KFIRPEGEIT DYRTRVSGVT
PQHMVGATPF AVARLEILQL LKGKLVVGHD LKHDFQALKE DMSGYTIYDT STDRLLWREA
KLDHCRRVSL RVLSERLLHK SIQNSLLGHS SVEDARATME LYQISQRIRA RRGLPRLAVS
D
