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UniProtKB - P05161 (ISG15_HUMAN)

Entry version 228 (25 May 2022)
Sequence version 5 (23 Jan 2007)
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Protein

Ubiquitin-like protein ISG15

Gene

ISG15

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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 (PubMed:33727702).

Its target proteins include IFIT1, MX1/MxA, PPM1B, UBE2L6, UBA7, CHMP5, CHMP2A, CHMP4B and CHMP6. Isgylation of the viral sensor IFIH1/MDA5 promotes IFIH1/MDA5 oligomerization and triggers activation of innate immunity against a range of viruses, including coronaviruses, flaviviruses and picornaviruses (PubMed:33727702).

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 thereby 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. 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 (PubMed:29100055).

21 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei153Interacts with activating enzymeBy similarity1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Biological processAntiviral defense, Host-virus interaction, Immunity, Innate immunity, Ubl conjugation pathway

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		P05161

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-1169408, ISG15 antiviral mechanism
R-HSA-168276, NS1 Mediated Effects on Host Pathways
R-HSA-168928, DDX58/IFIH1-mediated induction of interferon-alpha/beta
R-HSA-5656169, Termination of translesion DNA synthesis
R-HSA-909733, Interferon alpha/beta signaling
R-HSA-936440, Negative regulators of DDX58/IFIH1 signaling

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		P05161

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Ubiquitin-like protein ISG15
Alternative name(s):
Interferon-induced 15 kDa protein
Interferon-induced 17 kDa protein
Short name:
IP17
Ubiquitin cross-reactive protein
Short name:
hUCRP
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:ISG15Imported
Synonyms:G1P2, UCRP
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 1

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:4053, ISG15

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		147571, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P05161

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000187608

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Keywords - Cellular componenti

Cytoplasm, Secreted

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Immunodeficiency 38, with basal ganglia calcification (IMD38)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA primary immunodeficiency predisposing individuals to severe clinical disease upon infection with weakly virulent mycobacteria, including Mycobacterium bovis Bacille Calmette-Guerin (BCG) vaccines. Patients are also susceptible to Salmonella and Mycobacterium tuberculosis infections. Affected individuals have intracranial calcification.
Related information in OMIM

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi44R → A: Does not affect ISG15 signaling, interaction with ITGAL or activation of SRC family tyrosine kinases. 1 Publication1
Mutagenesisi83S → A: Does not affect ISG15 signaling, interaction with ITGAL or activation of SRC family tyrosine kinases. 1 Publication1
Mutagenesisi96Y → L: Reduces ISG15 signaling. Strongly reduces ISG15 signaling and abolishes interaction with ITGAL and activation of SRC family tyrosine kinases; when associated with D-102. 1 Publication1
Mutagenesisi99R → A: Strongly reduces ISG15 signaling and abolishes interaction with ITGAL. 1 Publication1
Mutagenesisi101T → A: Strongly reduces ISG15 signaling and abolishes interaction with ITGAL and activation of SRC family tyrosine kinases. 1 Publication1
Mutagenesisi102Q → D: Reduces ISG15 signaling. Strongly reduces ISG15 signaling and abolishes interaction with ITGAL and activation of SRC family tyrosine kinases; when associated with L-96. 1 Publication1
Mutagenesisi103T → A: Strongly reduces ISG15 signaling and abolishes interaction with ITGAL. 1 Publication1

Organism-specific databases

DisGeNET

More...DisGeNETi		9636

MalaCards human disease database

More...MalaCardsi		ISG15
MIMi616126, phenotype

Open Targets

More...OpenTargetsi		ENSG00000187608

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		319563, Mendelian susceptibility to mycobacterial diseases due to complete ISG15 deficiency

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA28465

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		P05161, Tbio

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		ISG15

Domain mapping of disease mutations (DMDM)

More...DMDMi		52001470

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section indicates that the initiator methionine is cleaved from the mature protein.<p><a href='/help/init_met' target='_top'>More...</a></p>Initiator methionineiRemoved1 Publication
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000359862 – 157Ubiquitin-like protein ISG15Add BLAST156
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section describes a propeptide, which is a part of a protein that is cleaved during maturation or activation. Once cleaved, a propeptide generally has no independent biological function.<p><a href='/help/propep' target='_top'>More...</a></p>PropeptideiPRO_0000035987158 – 165Removed in mature form8

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei78S-nitrosocysteine; alternate1 Publication1
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi78Interchain (with C-87 in UBE2N); alternate1 Publication
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki157Glycyl lysine isopeptide (Gly-Lys) (interchain with K-? in acceptor proteins)PROSITE-ProRule annotation

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

S-nitrosylation decreases its dimerization, thereby increasing the availability as well as the solubility of monomeric ISG15 for its conjugation to cellular proteins.1 Publication
Induced as an inactive, precursor protein that is cleaved by specific proteases to expose the C-terminal diglycine (LRLRGG) motif. This motif is essential not only for its conjugation to substrates but also for its recognition by the relevant processing proteases.2 Publications

Keywords - PTMi

Disulfide bond, Isopeptide bond, S-nitrosylation

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		P05161

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		P05161

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		P05161

MaxQB - The MaxQuant DataBase

More...MaxQBi		P05161

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		P05161

PeptideAtlas

More...PeptideAtlasi		P05161

PRoteomics IDEntifications database

More...PRIDEi		P05161

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		51809

Consortium for Top Down Proteomics

More...TopDownProteomicsi		P05161

PTM databases

GlyGen: Computational and Informatics Resources for Glycoscience

More...GlyGeni		P05161, 1 site, 1 O-linked glycan (1 site)

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P05161

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		P05161

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Detected in lymphoid cells, striated and smooth muscle, several epithelia and neurons. Expressed in neutrophils, monocytes and lymphocytes. Enhanced expression seen in pancreatic adenocarcinoma, endometrial cancer, and bladder cancer, as compared to non-cancerous tissue. In bladder cancer, the increase in expression exhibits a striking positive correlation with more advanced stages of the disease.2 Publications

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

Strongly induced upon exposure to type I interferons, viruses, LPS, and other stresses, including certain genotoxic stresses.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000187608, Expressed in epithelium of bronchus and 240 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P05161, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P05161, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000187608, Tissue enhanced (salivary)

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer; disulfide-linked (PubMed:2440890).

Interacts with, and is conjugated to its targets by UBE1L (E1 enzyme) and UBE2E2 (E2 enzyme) (PubMed:11157743, PubMed:15131269).

Interacts with NEDD4 (PubMed:18305167).

4 Publications

(Microbial infection) Interacts with vaccinia virus protein E3.

1 Publication

(Microbial infection) Interaction with influenza B NS1 protein inhibits its conjugation.

1 Publication

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		114995, 397 interactors

Database of interacting proteins

More...DIPi		DIP-29814N

Protein interaction database and analysis system

More...IntActi		P05161, 64 interactors

Molecular INTeraction database

More...MINTi		P05161

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000368699

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		P05161, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1165
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

AlphaFold Protein Structure Database

More...AlphaFoldDBi		P05161

Biological Magnetic Resonance Data Bank

More...BMRBi		P05161

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		P05161

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		P05161

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini2 – 78Ubiquitin-like 1PROSITE-ProRule annotationAdd BLAST77
Domaini79 – 157Ubiquitin-like 2PROSITE-ProRule annotationAdd BLAST79

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni153 – 157Involved in the ligation of specific target proteinsBy similarity5

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi152 – 157LRLRGG6

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

Both the Ubiquitin-like 1 and Ubiquitin-like 2 domains are required for its efficient conjugation to cellular proteins. The two domains play different roles in the ISGylation pathway: Ubiquitin-like 2 domain is necessary for the first two steps allowing the linking of ISG15 to the E1 and E2 enzymes while Ubiquitin-like 1 domain is essential for the final, E3-mediated transfer of ISG15, from the E2 to the Lys of the target protein (PubMed:18356159).1 Publication

Keywords - Domaini

Repeat

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG0001, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00940000162007

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P05161

Identification of Orthologs from Complete Genome Data

More...OMAi		QCTVFMN

Database of Orthologous Groups

More...OrthoDBi		1367357at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		P05161

TreeFam database of animal gene trees

More...TreeFami		TF338379

Family and domain databases

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR000626, Ubiquitin-like_dom
IPR029071, Ubiquitin-like_domsf
IPR019956, Ubiquitin_dom

Pfam protein domain database

More...Pfami		View protein in Pfam
PF00240, ubiquitin, 2 hits

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR00348, UBIQUITIN

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00213, UBQ, 2 hits

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF54236, SSF54236, 2 hits

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS50053, UBIQUITIN_2, 2 hits

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

P05161-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGWDLTVKML AGNEFQVSLS SSMSVSELKA QITQKIGVHA FQQRLAVHPS 
        60         70         80         90        100
GVALQDRVPL ASQGLGPGST VLLVVDKCDE PLSILVRNNK GRSSTYEVRL 
       110        120        130        140        150
TQTVAHLKQQ VSGLEGVQDD LFWLTFEGKP LEDQLPLGEY GLKPLSTVFM 
       160 
NLRLRGGGTE PGGRS
Length:165
Mass (Da):17,888
Last modified:January 23, 2007 - v5
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iB6858A15AB0FFFDE
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A096LPJ4A0A096LPJ4_HUMAN
Ubiquitin-like protein ISG15
ISG15
157Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A096LNZ9A0A096LNZ9_HUMAN
Ubiquitin-like protein ISG15
ISG15
143Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti35K → N in AAA36128 (PubMed:3476954).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_01618183S → N3 PublicationsCorresponds to variant dbSNP:rs1921EnsemblClinVar.1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
M13755 mRNA Translation: AAA36038.1
M21786 Genomic DNA Translation: AAA36128.1
AY168648 mRNA Translation: AAN86983.1
BT007297 mRNA Translation: AAP35961.1
AL645608 Genomic DNA No translation available.
CH471183 Genomic DNA Translation: EAW56295.1
BC009507 mRNA Translation: AAH09507.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS6.1

Protein sequence database of the Protein Information Resource

More...PIRi		A28304, A28138

NCBI Reference Sequences

More...RefSeqi		NP_005092.1, NM_005101.3

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000649529.1; ENSP00000496832.1; ENSG00000187608.10

Database of genes from NCBI RefSeq genomes

More...GeneIDi		9636

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:9636

Matched Annotation from NCBI and EMBL-EBI (MANE) - Phase one

More...MANE-Selecti		ENST00000649529.1; ENSP00000496832.1; NM_005101.4; NP_005092.1

UCSC genome browser

More...UCSCi		uc001acj.5, human

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross%5Freferences%5Fsection">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesi

Protein Spotlight

On guard - Issue 240 of October 2021

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M13755 mRNA Translation: AAA36038.1
M21786 Genomic DNA Translation: AAA36128.1
AY168648 mRNA Translation: AAN86983.1
BT007297 mRNA Translation: AAP35961.1
AL645608 Genomic DNA No translation available.
CH471183 Genomic DNA Translation: EAW56295.1
BC009507 mRNA Translation: AAH09507.1
CCDSiCCDS6.1
PIRiA28304, A28138
RefSeqiNP_005092.1, NM_005101.3

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1Z2MX-ray2.50A1-155[»]
2HJ8NMR-A79-157[»]
3PHXX-ray1.60B79-156[»]
3PSEX-ray2.30B1-156[»]
3R66X-ray2.30C/D1-157[»]
3RT3X-ray2.01B1-158[»]
3SDLX-ray2.29C/D1-157[»]
5TL6X-ray2.62A/C80-157[»]
5W8TX-ray2.76B/D80-156[»]
5W8UX-ray2.41B/D80-156[»]
6BI8X-ray3.00C/D1-156[»]
6FFAX-ray1.50B79-155[»]
6XA9X-ray2.90B/D/F79-157[»]
7RBSX-ray2.98B/D/F/H/J2-157[»]
7S6PX-ray2.15A/B/C/D/E/F2-157[»]
AlphaFoldDBiP05161
BMRBiP05161
SMRiP05161
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi114995, 397 interactors
DIPiDIP-29814N
IntActiP05161, 64 interactors
MINTiP05161
STRINGi9606.ENSP00000368699

PTM databases

GlyGeniP05161, 1 site, 1 O-linked glycan (1 site)
iPTMnetiP05161
PhosphoSitePlusiP05161

Genetic variation databases

BioMutaiISG15
DMDMi52001470

Proteomic databases

EPDiP05161
jPOSTiP05161
MassIVEiP05161
MaxQBiP05161
PaxDbiP05161
PeptideAtlasiP05161
PRIDEiP05161
ProteomicsDBi51809
TopDownProteomicsiP05161

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		809, 572 antibodies from 40 providers

The DNASU plasmid repository

More...DNASUi		9636

Genome annotation databases

EnsembliENST00000649529.1; ENSP00000496832.1; ENSG00000187608.10
GeneIDi9636
KEGGihsa:9636
MANE-SelectiENST00000649529.1; ENSP00000496832.1; NM_005101.4; NP_005092.1
UCSCiuc001acj.5, human

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		9636
DisGeNETi9636

GeneCards: human genes, protein and diseases

More...GeneCardsi		ISG15
HGNCiHGNC:4053, ISG15
HPAiENSG00000187608, Tissue enhanced (salivary)
MalaCardsiISG15
MIMi147571, gene
616126, phenotype
neXtProtiNX_P05161
OpenTargetsiENSG00000187608
Orphaneti319563, Mendelian susceptibility to mycobacterial diseases due to complete ISG15 deficiency
PharmGKBiPA28465
VEuPathDBiHostDB:ENSG00000187608

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG0001, Eukaryota
GeneTreeiENSGT00940000162007
InParanoidiP05161
OMAiQCTVFMN
OrthoDBi1367357at2759
PhylomeDBiP05161
TreeFamiTF338379

Enzyme and pathway databases

PathwayCommonsiP05161
ReactomeiR-HSA-1169408, ISG15 antiviral mechanism
R-HSA-168276, NS1 Mediated Effects on Host Pathways
R-HSA-168928, DDX58/IFIH1-mediated induction of interferon-alpha/beta
R-HSA-5656169, Termination of translesion DNA synthesis
R-HSA-909733, Interferon alpha/beta signaling
R-HSA-936440, Negative regulators of DDX58/IFIH1 signaling
SignaLinkiP05161

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		9636, 25 hits in 1081 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		ISG15, human
EvolutionaryTraceiP05161

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		ISG15

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		9636
PharosiP05161, Tbio

Protein Ontology

More...PROi		PR:P05161
RNActiP05161, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000187608, Expressed in epithelium of bronchus and 240 other tissues
ExpressionAtlasiP05161, baseline and differential
GenevisibleiP05161, HS

Family and domain databases

InterProiView protein in InterPro
IPR000626, Ubiquitin-like_dom
IPR029071, Ubiquitin-like_domsf
IPR019956, Ubiquitin_dom
PfamiView protein in Pfam
PF00240, ubiquitin, 2 hits
PRINTSiPR00348, UBIQUITIN
SMARTiView protein in SMART
SM00213, UBQ, 2 hits
SUPFAMiSSF54236, SSF54236, 2 hits
PROSITEiView protein in PROSITE
PS50053, UBIQUITIN_2, 2 hits

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiISG15_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P05161
Secondary accession number(s): Q5SVA4, Q7Z2G2, Q96GF0
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 13, 1987
Last sequence update: January 23, 2007
Last modified: May 25, 2022
This is version 228 of the entry and version 5 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>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.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Direct protein sequencing, Reference proteome

Documents

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    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Human entries with genetic variants
    List of human entries with genetic variants
  3. Human variants curated from literature reports
    Index of human variants curated from literature reports
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
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