UniProtKB - O02741 (ISG15_BOVIN)
Ubiquitin-like protein ISG15
ISG15
Functioni
Ubiquitin-like protein which plays a key role in the innate immune response to viral infection either via its conjugation to a target protein (ISGylation) or via its action as a free or unconjugated protein. ISGylation involves a cascade of enzymatic reactions involving E1, E2, and E3 enzymes which catalyze the conjugation of ISG15 to a lysine residue in the target protein. Exhibits antiviral activity towards both DNA and RNA viruses. The secreted form of ISG15 can: induce natural killer cell proliferation, augment lymphokine-activated-killer (LAK) activity, induce dendritic cell maturation, act as a chemotactic factor for neutrophils and act as a IFN-gamma-inducing cytokine playing an essential role in antimycobacterial immunity (By similarity).
The secreted form acts through the integrin ITGAL/ITGB2 receptor to initiate activation of SRC family tyrosine kinases including LYN, HCK and FGR which leads to secretion of IFNG and IL10; the interaction is mediated by ITGAL (By similarity).
In response to IFN-tau secreted by the conceptus, may ligate to and regulate proteins involved in the release of prostaglandin F2-alpha (PGF), and thus prevent lysis of the corpus luteum and maintain the pregnancy (PubMed:9546718).
By similarity1 PublicationSites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 150 | Interacts with activating enzymeBy similarity | 1 |
GO - Molecular functioni
- integrin binding Source: UniProtKB
- protein tag Source: GO_Central
- structural constituent of ribosome Source: GO_Central
- ubiquitin protein ligase binding Source: GO_Central
GO - Biological processi
- defense response to bacterium Source: UniProtKB
- defense response to virus Source: UniProtKB
- integrin-mediated signaling pathway Source: UniProtKB
- ISG15-protein conjugation Source: UniProtKB
- modification-dependent protein catabolic process Source: GO_Central
- negative regulation of protein ubiquitination Source: UniProtKB
- negative regulation of type I interferon-mediated signaling pathway Source: Ensembl
- negative regulation of viral genome replication Source: UniProtKB
- positive regulation of bone mineralization Source: UniProtKB
- positive regulation of erythrocyte differentiation Source: Ensembl
- positive regulation of interferon-beta production Source: Ensembl
- positive regulation of interferon-gamma production Source: UniProtKB
- positive regulation of interleukin-10 production Source: UniProtKB
- positive regulation of protein oligomerization Source: Ensembl
- protein localization to mitochondrion Source: Ensembl
- regulation of interferon-gamma production Source: UniProtKB
- response to type I interferon Source: UniProtKB
Keywordsi
Biological process | Antiviral defense, Ubl conjugation pathway |
Enzyme and pathway databases
Reactomei | R-BTA-1169408, ISG15 antiviral mechanism R-BTA-5656169, Termination of translesion DNA synthesis R-BTA-936440, Negative regulators of DDX58/IFIH1 signaling |
Names & Taxonomyi
Protein namesi | Recommended name: Ubiquitin-like protein ISG15Alternative name(s): Interferon-stimulated gene product 17 Ubiquitin cross-reactive protein Short name: BoUCRP |
Gene namesi | Name:ISG15 Synonyms:G1P2, ISG17, UCRP |
Organismi | Bos taurus (Bovine) |
Taxonomic identifieri | 9913 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Artiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos |
Proteomesi |
|
Organism-specific databases
VEuPathDBi | HostDB:ENSBTAG00000014707 |
VGNCi | VGNC:30293, ISG15 |
Subcellular locationi
Cytosol
- cytosolic small ribosomal subunit Source: GO_Central
Extracellular region or secreted
- extracellular region Source: UniProtKB
Nucleus
- nucleus Source: GO_Central
Other locations
- cytoplasm Source: GO_Central
Keywords - Cellular componenti
Cytoplasm, SecretedPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000114913 | 1 – 154 | Ubiquitin-like protein ISG15Add BLAST | 154 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 78 | S-nitrosocysteineBy similarity | 1 | |
Modified residuei | 143 | S-nitrosocysteineBy similarity | 1 | |
Cross-linki | 154 | Glycyl lysine isopeptide (Gly-Lys) (interchain with K-? in acceptor proteins)PROSITE-ProRule annotation |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, Isopeptide bond, S-nitrosylationProteomic databases
PaxDbi | O02741 |
PRIDEi | O02741 |
Expressioni
Tissue specificityi
Developmental stagei
Inductioni
Gene expression databases
Bgeei | ENSBTAG00000014707, Expressed in placenta and 99 other tissues |
Interactioni
Subunit structurei
Homodimer; disulfide-linked (By similarity).
Interacts with, and is conjugated to its targets by the UBE1L (E1 enzyme) and UBE2E2 (E2 enzyme) (By similarity).
Interacts with NEDD4 (By similarity).
By similarityGO - Molecular functioni
- integrin binding Source: UniProtKB
- ubiquitin protein ligase binding Source: GO_Central
Protein-protein interaction databases
IntActi | O02741, 1 interactor |
STRINGi | 9913.ENSBTAP00000019573 |
Structurei
Secondary structure
3D structure databases
AlphaFoldDBi | O02741 |
SMRi | O02741 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 2 – 78 | Ubiquitin-like 1PROSITE-ProRule annotationAdd BLAST | 77 | |
Domaini | 79 – 154 | Ubiquitin-like 2PROSITE-ProRule annotationAdd BLAST | 76 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 150 – 154 | Involved in the ligation of specific target proteins | 5 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 149 – 154 | LRLRGGBy similarity | 6 |
Domaini
Keywords - Domaini
RepeatPhylogenomic databases
eggNOGi | KOG0001, Eukaryota |
GeneTreei | ENSGT00940000162007 |
HOGENOMi | CLU_010412_4_2_1 |
InParanoidi | O02741 |
OMAi | QCTVFMN |
OrthoDBi | 1367357at2759 |
TreeFami | TF338379 |
Family and domain databases
InterProi | View protein in InterPro IPR000626, Ubiquitin-like_dom IPR029071, Ubiquitin-like_domsf IPR019956, Ubiquitin_dom |
Pfami | View protein in Pfam PF00240, ubiquitin, 2 hits |
PRINTSi | PR00348, UBIQUITIN |
SMARTi | View protein in SMART SM00213, UBQ, 2 hits |
SUPFAMi | SSF54236, SSF54236, 2 hits |
PROSITEi | View protein in PROSITE PS50053, UBIQUITIN_2, 2 hits |
i Sequence
Sequence statusi: Complete.
10 20 30 40 50
MGGDLTVKML GGQEILVPLR DSMTVSELKQ FIAQKINVPA FQQRLAHLDS
60 70 80 90 100
REVLQEGVPL VLQGLRAGST VLLVVQNCIS ILVRNDKGRS SPYEVQLKQT
110 120 130 140 150
VAELKQQVCQ KERVQADQFW LSFEGRPMDD EHPLEEYGLM KGCTVFMNLR
LRGG
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U96014 mRNA Translation: AAB57687.1 AF069133 Genomic DNA Translation: AAD56716.1 BC102318 mRNA Translation: AAI02319.1 |
RefSeqi | NP_776791.1, NM_174366.1 |
Genome annotation databases
Ensembli | ENSBTAT00000019573; ENSBTAP00000019573; ENSBTAG00000014707 |
GeneIDi | 281871 |
KEGGi | bta:281871 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U96014 mRNA Translation: AAB57687.1 AF069133 Genomic DNA Translation: AAD56716.1 BC102318 mRNA Translation: AAI02319.1 |
RefSeqi | NP_776791.1, NM_174366.1 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
6JH1 | X-ray | 3.00 | C/D | 1-154 | [»] | |
AlphaFoldDBi | O02741 | |||||
SMRi | O02741 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
IntActi | O02741, 1 interactor |
STRINGi | 9913.ENSBTAP00000019573 |
Proteomic databases
PaxDbi | O02741 |
PRIDEi | O02741 |
Genome annotation databases
Ensembli | ENSBTAT00000019573; ENSBTAP00000019573; ENSBTAG00000014707 |
GeneIDi | 281871 |
KEGGi | bta:281871 |
Organism-specific databases
CTDi | 9636 |
VEuPathDBi | HostDB:ENSBTAG00000014707 |
VGNCi | VGNC:30293, ISG15 |
Phylogenomic databases
eggNOGi | KOG0001, Eukaryota |
GeneTreei | ENSGT00940000162007 |
HOGENOMi | CLU_010412_4_2_1 |
InParanoidi | O02741 |
OMAi | QCTVFMN |
OrthoDBi | 1367357at2759 |
TreeFami | TF338379 |
Enzyme and pathway databases
Reactomei | R-BTA-1169408, ISG15 antiviral mechanism R-BTA-5656169, Termination of translesion DNA synthesis R-BTA-936440, Negative regulators of DDX58/IFIH1 signaling |
Gene expression databases
Bgeei | ENSBTAG00000014707, Expressed in placenta and 99 other tissues |
Family and domain databases
InterProi | View protein in InterPro IPR000626, Ubiquitin-like_dom IPR029071, Ubiquitin-like_domsf IPR019956, Ubiquitin_dom |
Pfami | View protein in Pfam PF00240, ubiquitin, 2 hits |
PRINTSi | PR00348, UBIQUITIN |
SMARTi | View protein in SMART SM00213, UBQ, 2 hits |
SUPFAMi | SSF54236, SSF54236, 2 hits |
PROSITEi | View protein in PROSITE PS50053, UBIQUITIN_2, 2 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | ISG15_BOVIN | |
Accessioni | O02741Primary (citable) accession number: O02741 Secondary accession number(s): Q3T0N6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | January 23, 2007 | |
Last modified: | May 25, 2022 | |
This is version 144 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- PDB cross-references
Index of Protein Data Bank (PDB) cross-references