| UniProt ID | ISG15_HUMAN | |
|---|---|---|
| UniProt AC | P05161 | |
| Protein Name | Ubiquitin-like protein ISG15 | |
| Gene Name | ISG15 | |
| Organism | Homo sapiens (Human). | |
| Sequence Length | 165 | |
| Subcellular Localization | Cytoplasm . Secreted . Exists in three distinct states: free within the cell, released into the extracellular space, or conjugated to target proteins. | |
| Protein Description | 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. Its target proteins include IFIT1, MX1/MxA, PPM1B, UBE2L6, UBA7, CHMP5, CHMP2A, CHMP4B and CHMP6. Can also isgylate: EIF2AK2/PKR which results in its activation, DDX58/RIG-I which inhibits its function in antiviral signaling response, EIF4E2 which enhances its cap structure-binding activity and translation-inhibition activity, UBE2N and UBE2E1 which negatively regulates their activity, IRF3 which inhibits its ubiquitination and degradation and FLNB which prevents its ability to interact with the upstream activators of the JNK cascade therby inhibiting IFNA-induced JNK signaling. Exhibits antiviral activity towards both DNA and RNA viruses, including influenza A, HIV-1 and Ebola virus. Restricts HIV-1 and ebola virus via disruption of viral budding. Inhibits the ubiquitination of HIV-1 Gag and host TSG101 and disrupts their interaction, thereby preventing assembly and release of virions from infected cells. Inhibits Ebola virus budding mediated by the VP40 protein by disrupting ubiquitin ligase activity of NEDD4 and its ability to ubiquitinate VP40. ISGylates influenza A virus NS1 protein which causes a loss of function of the protein and the inhibition of virus replication. The secreted form of ISG15 can: induce natural killer cell proliferation, act as a chemotactic factor for neutrophils and act as a IFN-gamma-inducing cytokine playing an essential role in antimycobacterial immunity.. | |
| Protein Sequence | MGWDLTVKMLAGNEFQVSLSSSMSVSELKAQITQKIGVHAFQQRLAVHPSGVALQDRVPLASQGLGPGSTVLLVVDKCDEPLSILVRNNKGRSSTYEVRLTQTVAHLKQQVSGLEGVQDDLFWLTFEGKPLEDQLPLGEYGLKPLSTVFMNLRLRGGGTEPGGRS | |
| Overview of Protein Modification Sites with Functional and Structural Information | ||
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* ASA = Accessible Surface Area
| Locations | Modification | Substrate Peptides & Secondary Structure |
ASA (%) | Reference | Orthologous Protein Cluster |
|---|---|---|---|---|---|
| 6 | Phosphorylation | --MGWDLTVKMLAGN --CCCEEEEEEECCC | 18.66 | 26670566 | |
| 18 | Phosphorylation | AGNEFQVSLSSSMSV CCCEEEEEECCCCCH | 16.26 | 26670566 | |
| 20 | Phosphorylation | NEFQVSLSSSMSVSE CEEEEEECCCCCHHH | 16.92 | 26670566 | |
| 21 | Phosphorylation | EFQVSLSSSMSVSEL EEEEEECCCCCHHHH | 35.04 | 26670566 | |
| 22 | Phosphorylation | FQVSLSSSMSVSELK EEEEECCCCCHHHHH | 16.23 | 26670566 | |
| 24 | Phosphorylation | VSLSSSMSVSELKAQ EEECCCCCHHHHHHH | 25.17 | 26670566 | |
| 26 | Phosphorylation | LSSSMSVSELKAQIT ECCCCCHHHHHHHHH | 29.88 | 20068231 | |
| 29 | Ubiquitination | SMSVSELKAQITQKI CCCHHHHHHHHHHHH | 33.91 | 29967540 | |
| 33 | Phosphorylation | SELKAQITQKIGVHA HHHHHHHHHHHCHHH | 16.24 | 26670566 | |
| 35 | Ubiquitination | LKAQITQKIGVHAFQ HHHHHHHHHCHHHHH | 32.55 | 21906983 | |
| 50 | Phosphorylation | QRLAVHPSGVALQDR HHEEECCCCCCCCCC | 30.90 | 23312004 | |
| 78 | S-nitrosocysteine | VLLVVDKCDEPLSIL EEEEEECCCCCEEEE | 6.57 | - | |
| 78 | S-nitrosylation | VLLVVDKCDEPLSIL EEEEEECCCCCEEEE | 6.57 | 18606809 | |
| 93 | Phosphorylation | VRNNKGRSSTYEVRL EECCCCCCCEEEEEH | 35.38 | 23403867 | |
| 94 | Phosphorylation | RNNKGRSSTYEVRLT ECCCCCCCEEEEEHH | 33.38 | 23403867 | |
| 95 | Phosphorylation | NNKGRSSTYEVRLTQ CCCCCCCEEEEEHHH | 25.58 | 23403867 | |
| 96 | Phosphorylation | NKGRSSTYEVRLTQT CCCCCCEEEEEHHHH | 17.86 | 23403867 |
| Modified Location | Modified Residue | Modification | Type of Upstream Proteins | Gene Name of Upstream Proteins | UniProt AC of Upstream Proteins | Sources |
|---|---|---|---|---|---|---|
Oops, there are no upstream regulatory protein records of ISG15_HUMAN !! | ||||||
| Modified Location | Modified Residue | Modification | Function | Reference | ||
|---|---|---|---|---|---|---|
Oops, there are no descriptions of PTM sites of ISG15_HUMAN !! | ||||||
* Distance = the distance between SAP position and PTM sites.
| Modified Location | Modification | Variant Position (Distance <= 10) |
Residue Change | SAP | Related Disease | Reference |
|---|---|---|---|---|---|---|
Oops, there are no SNP-PTM records of ISG15_HUMAN !! | ||||||
| Kegg Disease | ||||||
|---|---|---|---|---|---|---|
| There are no disease associations of PTM sites. | ||||||
| OMIM Disease | ||||||
| 616126 | Immunodeficiency 38, with basal ganglia calcification (IMD38) | |||||
| Kegg Drug | ||||||
| There are no disease associations of PTM sites. | ||||||
| DrugBank | ||||||
| There are no disease associations of PTM sites. | ||||||
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