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Protein

Interferon-stimulated gene 20 kDa protein

Gene

ISG20

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Interferon-induced antiviral exoribonuclease that acts on single-stranded RNA and also has minor activity towards single-stranded DNA. Exhibits antiviral activity against RNA viruses including hepatitis C virus (HCV), hepatitis A virus (HAV) and yellow fever virus (YFV) in an exonuclease-dependent manner. May also play additional roles in the maturation of snRNAs and rRNAs, and in ribosome biogenesis.4 Publications

Catalytic activityi

Exonucleolytic cleavage in the 3'- to 5'-direction to yield nucleoside 5'-phosphates.

Cofactori

Mn2+1 PublicationNote: Binds 2 manganese ions per subunit.1 Publication

pH dependencei

Optimum pH is 7.0.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi11 – 111Manganese 1
Metal bindingi13 – 131Manganese 1
Metal bindingi90 – 901Manganese 2
Metal bindingi93 – 931Manganese 2
Metal bindingi154 – 1541Manganese 1

GO - Molecular functioni

  • 3'-5'-exoribonuclease activity Source: UniProtKB
  • exonuclease activity Source: UniProtKB
  • exoribonuclease II activity Source: UniProtKB-EC
  • metal ion binding Source: UniProtKB-KW
  • single-stranded DNA 3'-5' exodeoxyribonuclease activity Source: UniProtKB
  • U1 snRNA binding Source: UniProtKB
  • U2 snRNA binding Source: UniProtKB
  • U3 snoRNA binding Source: UniProtKB

GO - Biological processi

  • cell proliferation Source: ProtInc
  • cytokine-mediated signaling pathway Source: Reactome
  • defense response to virus Source: UniProtKB
  • DNA catabolic process, exonucleolytic Source: UniProtKB
  • negative regulation of viral genome replication Source: UniProtKB
  • response to virus Source: UniProtKB
  • RNA catabolic process Source: UniProtKB
  • RNA phosphodiester bond hydrolysis, exonucleolytic Source: GOC
  • rRNA processing Source: UniProtKB-KW
  • type I interferon signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Exonuclease, Hydrolase, Nuclease

Keywords - Biological processi

Antiviral defense, Immunity, Innate immunity, rRNA processing

Keywords - Ligandi

Manganese, Metal-binding, RNA-binding

Enzyme and pathway databases

ReactomeiR-HSA-909733. Interferon alpha/beta signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Interferon-stimulated gene 20 kDa protein (EC:3.1.13.1)
Alternative name(s):
Estrogen-regulated transcript 45 protein
Promyelocytic leukemia nuclear body-associated protein ISG20
Gene namesi
Name:ISG20
Synonyms:HEM45
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:6130. ISG20.

Subcellular locationi

GO - Cellular componenti

  • Cajal body Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • nucleolus Source: UniProtKB
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • PML body Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA29930.

Polymorphism and mutation databases

BioMutaiISG20.
DMDMi57012967.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 181181Interferon-stimulated gene 20 kDa proteinPRO_0000084243Add
BLAST

Proteomic databases

EPDiQ96AZ6.
MaxQBiQ96AZ6.
PaxDbiQ96AZ6.
PRIDEiQ96AZ6.

PTM databases

iPTMnetiQ96AZ6.
PhosphoSiteiQ96AZ6.

Expressioni

Tissue specificityi

Highly expressed in peripheral blood leukocytes, spleen, thymus, colon and lung. Up regulated by E2 in estrogen receptor-positive breast cancer lines.2 Publications

Inductioni

Induced by interferons alpha and beta. Weaker induction was seen with interferon gamma. Increased expression was seen at the transcriptional level.1 Publication

Gene expression databases

BgeeiQ96AZ6.
CleanExiHS_ISG20.
ExpressionAtlasiQ96AZ6. baseline and differential.
GenevisibleiQ96AZ6. HS.

Interactioni

Subunit structurei

Associates with PML and SP100 in the PML NB complex. Associates with survival motor neuron protein (SMN)-containing macromolecular nuclear complexes and U1 and U2 snRNAs and U3 snoRNA.2 Publications

Protein-protein interaction databases

BioGridi109876. 10 interactions.
MINTiMINT-4714850.
STRINGi9606.ENSP00000306565.

Structurei

Secondary structure

1
181
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi7 – 1711Combined sources
Turni18 – 214Combined sources
Beta strandi22 – 3110Combined sources
Beta strandi37 – 448Combined sources
Beta strandi49 – 513Combined sources
Helixi54 – 574Combined sources
Helixi61 – 644Combined sources
Helixi70 – 8112Combined sources
Beta strandi84 – 907Combined sources
Helixi91 – 977Combined sources
Beta strandi106 – 1094Combined sources
Helixi110 – 1123Combined sources
Helixi114 – 1207Combined sources
Helixi130 – 1378Combined sources
Helixi151 – 17121Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1WLJX-ray1.90A1-181[»]
ProteinModelPortaliQ96AZ6.
SMRiQ96AZ6. Positions 6-178.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96AZ6.

Family & Domainsi

Sequence similaritiesi

Belongs to the exonuclease superfamily.Curated

Phylogenomic databases

eggNOGiKOG2249. Eukaryota.
COG0847. LUCA.
GeneTreeiENSGT00520000055542.
HOGENOMiHOG000182422.
HOVERGENiHBG052149.
InParanoidiQ96AZ6.
KOiK12579.
OMAiARCSLVD.
OrthoDBiEOG7WHHB0.
PhylomeDBiQ96AZ6.
TreeFamiTF354340.

Family and domain databases

Gene3Di3.30.420.10. 1 hit.
InterProiIPR013520. 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. AlignAdd to basket

Isoform 1 (identifier: Q96AZ6-1) [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

        10         20         30         40         50
MAGSREVVAM DCEMVGLGPH RESGLARCSL VNVHGAVLYD KFIRPEGEIT
60 70 80 90 100
DYRTRVSGVT PQHMVGATPF AVARLEILQL LKGKLVVGHD LKHDFQALKE
110 120 130 140 150
DMSGYTIYDT STDRLLWREA KLDHCRRVSL RVLSERLLHK SIQNSLLGHS
160 170 180
SVEDARATME LYQISQRIRA RRGLPRLAVS D
Length:181
Mass (Da):20,363
Last modified:January 4, 2005 - v2
Checksum:i24519CB52CEA5581
GO
Isoform 2 (identifier: Q96AZ6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     77-86: ILQLLKGKLV → VPFPSSPTAA
     87-181: Missing.

Note: No experimental confirmation available.
Show »
Length:86
Mass (Da):9,199
Checksum:iE8FF51046D16A6F1
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei77 – 8610ILQLLKGKLV → VPFPSSPTAA in isoform 2. 1 PublicationVSP_012429
Alternative sequencei87 – 18195Missing in isoform 2. 1 PublicationVSP_012430Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X89773 mRNA. Translation: CAA61915.2.
U88964 mRNA. Translation: AAB53416.1.
BT006952 mRNA. Translation: AAP35598.1.
CR456942 mRNA. Translation: CAG33223.1.
BC007922 mRNA. Translation: AAH07922.1.
BC016341 mRNA. Translation: AAH16341.1.
CCDSiCCDS10345.1. [Q96AZ6-1]
RefSeqiNP_001290162.1. NM_001303233.1. [Q96AZ6-1]
NP_001290163.1. NM_001303234.1. [Q96AZ6-1]
NP_001290165.1. NM_001303236.1.
NP_002192.2. NM_002201.5. [Q96AZ6-1]
XP_005254956.1. XM_005254899.1. [Q96AZ6-1]
XP_006720551.1. XM_006720488.2. [Q96AZ6-1]
UniGeneiHs.459265.

Genome annotation databases

EnsembliENST00000306072; ENSP00000306565; ENSG00000172183. [Q96AZ6-1]
ENST00000560741; ENSP00000453638; ENSG00000172183. [Q96AZ6-1]
GeneIDi3669.
KEGGihsa:3669.
UCSCiuc002bmv.2. human. [Q96AZ6-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X89773 mRNA. Translation: CAA61915.2.
U88964 mRNA. Translation: AAB53416.1.
BT006952 mRNA. Translation: AAP35598.1.
CR456942 mRNA. Translation: CAG33223.1.
BC007922 mRNA. Translation: AAH07922.1.
BC016341 mRNA. Translation: AAH16341.1.
CCDSiCCDS10345.1. [Q96AZ6-1]
RefSeqiNP_001290162.1. NM_001303233.1. [Q96AZ6-1]
NP_001290163.1. NM_001303234.1. [Q96AZ6-1]
NP_001290165.1. NM_001303236.1.
NP_002192.2. NM_002201.5. [Q96AZ6-1]
XP_005254956.1. XM_005254899.1. [Q96AZ6-1]
XP_006720551.1. XM_006720488.2. [Q96AZ6-1]
UniGeneiHs.459265.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1WLJX-ray1.90A1-181[»]
ProteinModelPortaliQ96AZ6.
SMRiQ96AZ6. Positions 6-178.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109876. 10 interactions.
MINTiMINT-4714850.
STRINGi9606.ENSP00000306565.

PTM databases

iPTMnetiQ96AZ6.
PhosphoSiteiQ96AZ6.

Polymorphism and mutation databases

BioMutaiISG20.
DMDMi57012967.

Proteomic databases

EPDiQ96AZ6.
MaxQBiQ96AZ6.
PaxDbiQ96AZ6.
PRIDEiQ96AZ6.

Protocols and materials databases

DNASUi3669.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000306072; ENSP00000306565; ENSG00000172183. [Q96AZ6-1]
ENST00000560741; ENSP00000453638; ENSG00000172183. [Q96AZ6-1]
GeneIDi3669.
KEGGihsa:3669.
UCSCiuc002bmv.2. human. [Q96AZ6-1]

Organism-specific databases

CTDi3669.
GeneCardsiISG20.
HGNCiHGNC:6130. ISG20.
MIMi604533. gene.
neXtProtiNX_Q96AZ6.
PharmGKBiPA29930.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2249. Eukaryota.
COG0847. LUCA.
GeneTreeiENSGT00520000055542.
HOGENOMiHOG000182422.
HOVERGENiHBG052149.
InParanoidiQ96AZ6.
KOiK12579.
OMAiARCSLVD.
OrthoDBiEOG7WHHB0.
PhylomeDBiQ96AZ6.
TreeFamiTF354340.

Enzyme and pathway databases

ReactomeiR-HSA-909733. Interferon alpha/beta signaling.

Miscellaneous databases

ChiTaRSiISG20. human.
EvolutionaryTraceiQ96AZ6.
GeneWikiiISG20.
GenomeRNAii3669.
NextBioi14359.
PROiQ96AZ6.
SOURCEiSearch...

Gene expression databases

BgeeiQ96AZ6.
CleanExiHS_ISG20.
ExpressionAtlasiQ96AZ6. baseline and differential.
GenevisibleiQ96AZ6. HS.

Family and domain databases

Gene3Di3.30.420.10. 1 hit.
InterProiIPR013520. 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.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning of a new interferon-induced PML nuclear bodies-associated protein."
    Gongora C., David G., Pintard L., Tissot C., Hua T.D., Dejean A., Mechti N.
    J. Biol. Chem. 272:19457-19463(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE SPECIFICITY, IDENTIFICATION IN PML NB COMPLEX, INDUCTION.
  2. "Expression and estrogen regulation of the HEM45 mRNA in human tumor lines and in the rat uterus."
    Pentecost B.T.
    J. Steroid Biochem. Mol. Biol. 64:25-33(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
  3. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  4. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  5. "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).
    Tissue: B-cell and Brain.
  6. "The human interferon- and estrogen-regulated ISG20/HEM45 gene product degrades single-stranded RNA and DNA in vitro."
    Nguyen L.H., Espert L., Mechti N., Wilson D.M. III
    Biochemistry 40:7174-7179(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, ENZYME REGULATION.
  7. "ISG20, a new interferon-induced RNase specific for single-stranded RNA, defines an alternative antiviral pathway against RNA genomic viruses."
    Espert L., Degols G., Gongora C., Blondel D., Williams B.R., Silverman R.H., Mechti N.
    J. Biol. Chem. 278:16151-16158(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. "Interferon-induced exonuclease ISG20 exhibits an antiviral activity against human immunodeficiency virus type 1."
    Espert L., Degols G., Lin Y.L., Vincent T., Benkirane M., Mechti N.
    J. Gen. Virol. 86:2221-2229(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "The exonuclease ISG20 mainly localizes in the nucleolus and the Cajal (Coiled) bodies and is associated with nuclear SMN protein-containing complexes."
    Espert L., Eldin P., Gongora C., Bayard B., Harper F., Chelbi-Alix M.K., Bertrand E., Degols G., Mechti N.
    J. Cell. Biochem. 98:1320-1333(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH SMN COMPLEX AND SNRNAS.
  10. "ISG20, an actor of the innate immune response."
    Degols G., Eldin P., Mechti N.
    Biochimie 89:831-835(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW ON FUNCTION.
  11. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  12. Cited for: FUNCTION IN HCV; HAV AND YFV RESTRICTION, SUBCELLULAR LOCATION.
  13. "Crystal structure of human ISG20, an interferon-induced antiviral ribonuclease."
    Horio T., Murai M., Inoue T., Hamasaki T., Tanaka T., Ohgi T.
    FEBS Lett. 577:111-116(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH UMP, COFACTOR, MANGANESE-BINDING SITES.

Entry informationi

Entry nameiISG20_HUMAN
AccessioniPrimary (citable) accession number: Q96AZ6
Secondary accession number(s): O00441, O00586
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 4, 2005
Last sequence update: January 4, 2005
Last modified: March 16, 2016
This is version 119 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.