Seroatlas · Human Serome Atlas

ISG15

Ubiquitin-like protein ISG15

Also known as: G1P2, IFI15, ISG15_HUMAN, UCRP

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession
P05161
Gene
ISG15
Ensembl
ENSG00000187608
Chromosome
1
Canonical length
165 aa
Protein class
Disease related genes, Human disease related genes, Predicted intracellular proteins, Predicted secreted proteins
Secretome location
Secreted to blood
Quaternary structure
Homodimer

OverviewNCBI Gene

The protein encoded by this gene is a ubiquitin-like protein that is conjugated to intracellular target proteins upon activation by interferon-alpha and interferon-beta. Several functions have been ascribed to the encoded protein, including chemotactic activity towards neutrophils, direction of ligated target proteins to intermediate filaments, cell-to-cell signaling, and antiviral activity during viral infections. While conjugates of this protein have been found to be noncovalently attached to intermediate filaments, this protein is sometimes secreted. [provided by RefSeq, Dec 2012]

Canonical amino-acid sequenceUniProt

165 residues, UniProt reviewed canonical sequence.

>P05161|ISG15
     1  MGWDLTVKML AGNEFQVSLS SSMSVSELKA QITQKIGVHA FQQRLAVHPS GVALQDRVPL
    61  ASQGLGPGST VLLVVDKCDE PLSILVRNNK GRSSTYEVRL TQTVAHLKQQ VSGLEGVQDD
   121  LFWLTFEGKP LEDQLPLGEY GLKPLSTVFM NLRLRGGGTE PGGRS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ISG15 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability
Secreted
Secreted
Yes
Transmembrane segments
0
Mean surface accessibility (rSASA)
0.35
Highest tissue expression
301 nTPM

Expression across tissuesHPA

Tissue

  • salivary gland: 301 nTPM
  • bone marrow: 129 nTPM
  • choroid plexus: 122 nTPM
  • liver: 120 nTPM
  • amygdala: 111 nTPM
  • midbrain: 109 nTPM

Single-cell type

  • extravillous trophoblasts: 788 nCPM
  • enterocytes: 459 nCPM
  • gastric progenitor cells: 374 nCPM
  • hofbauer cells: 358 nCPM
  • epididymal efferent duct ciliated cells: 236 nCPM
  • decidual stromal cells: 231 nCPM

Immune cell

  • eosinophil: 874 nTPM
  • neutrophil: 668 nTPM
  • T-reg: 511 nTPM
  • basophil: 511 nTPM
  • intermediate monocyte: 426 nTPM
  • non-classical monocyte: 383 nTPM

Brain region

  • spinal cord: 243 nTPM
  • medulla oblongata: 92 nTPM
  • pons: 90 nTPM
  • thalamus: 58 nTPM
  • cerebral cortex: 49 nTPM
  • amygdala: 45 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ISG15.

Disease | AllUniProt

Conditions ISG15 is implicated in, by any mechanism.

  • Immunodeficiency 38, with basal ganglia calcification (IMD38) MIM:616126

Disease | GeneticClinVar

4 pathogenic / likely-pathogenic of 157 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

  • Mendelian susceptibility to mycobacterial diseases due to complete ISG15 deficiency

Disease | ImmuneIEDB

Conditions an epitope on ISG15 was assayed in.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)
1.69
gnomAD pLI
0.41
gnomAD missense Z
-0.04
DepMap mean gene effect
-0.08
DepMap dependency class
selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of ISG15 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads ISG15 as an antibody target. Whether an autoantibody or antibody against ISG15 could matter depends on whether native ISG15 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

ISG15 is annotated as secreted, so native ISG15 circulates and is directly accessible to antibodies. Secreted and cell-surface proteins are the autoantibody targets most likely to act like drugs, blocking or depleting the native protein.

Annotation status

The present source text does not explicitly label ISG15 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

Canonical record: https://seroatlas.com/gene/ISG15. Study-independent annotations aggregated from UniProt, Human Protein Atlas, PubMed, IEDB, Pfam, InterPro, Gene Ontology, AlphaFold, gnomAD, DepMap, ClinVar, TCGA. Catalog release seroatlas-reviewed-human-uniprot-20260313.

Seroatlas is the reference for exploring autoantibody and antibody serology at the human-protein level: the autoreactome and human serome, multiplex serology (HuProt, HuScan, VirScan, PhIP-Seq).

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