UniProt:Q9UII4 HERC5

chain
  • chain:1-1024
checksum 1449C51A58269A6C
comment
  • FUNCTION Major E3 ligase for ISG15 conjugation (PubMed:26355087, PubMed:27534820, PubMed:27564865, PubMed:34572049, PubMed:37279284). Acts as a positive regulator of innate antiviral response in cells induced by interferon. Functions as part of the ISGylation machinery that recognizes target proteins in a broad and relatively non-specific manner. Catalyzes ISGylation of IRF3 which results in sustained activation, it attenuates IRF3-PIN1 interaction, which antagonizes IRF3 ubiquitination and degradation, and boosts the antiviral response. Mediates ISGylation of the phosphatase PTEN leading to its degradation, thus alleviating its suppression of the PI3K-AKT signaling pathway and promoting the production of cytokines that facilitate bacterial clearance (PubMed:37279284). Interferes with the function of key viral structural proteins such as ebolavirus structural protein VP40 or HIV-1 protein GAG (PubMed:22093708, PubMed:34572049). Catalyzes ISGylation of influenza A viral NS1 which attenuates virulence; ISGylated NS1 fails to form homodimers and thus to interact with its RNA targets. Catalyzes ISGylation of papillomavirus type 16 L1 protein which results in dominant-negative effect on virus infectivity. Physically associated with polyribosomes, broadly modifies newly synthesized proteins in a cotranslational manner. In an interferon-stimulated cell, newly translated viral proteins are primary targets of ISG15. Promotes parkin/PRKN ubiquitin E3 ligase activity by suppressing the intramolecular interaction that maintains its autoinhibited conformation (PubMed:27534820).FUNCTION (Microbial infection) Functions as an E3 ligase for ISGylation of hepatitis B virus protein X leading to enhanced viral replication due to increased interferon resistance.SUBUNIT (Microbial infection) Interacts with human cytomegalovirus protein UL26; this interaction inhibits global protein ISGylation.SUBUNIT (Microbial infection) Interacts with Kaposi's sarcoma-associated herpesvirus protein v-IRF1; this interaction inhibits global protein ISGylation.SUBUNIT Binds to CCNA1, CCNB1, CCND1 and CCNE1. Interacts with UBE2L6. Interacts with IRF3, this interaction is marginal in resting cells but enhanced upon viral infection. Interacts with influenza A virus NS1.INTERACTION Associated with the polyribosomes, probably via the 60S subunit.TISSUE SPECIFICITY Expressed in testis and to a lesser degree in brain, ovary and placenta. Found in most tissues at low levels.INDUCTION By IFNB1/IFN-beta. In endothelial cells, by TNF, IL1B/interleukin-1B and by bacterial lipopolysaccharides (LPS), hardly induced in other cells of the vascular wall such as primary smooth muscle cells and fibroblasts. By viral infection.PTM ISGylated.CAUTION Was thought to be a ubiquitin ligase ubiquitinated by UBE2D1, but was confirmed by numerous studies that its main function is as E3 ISG15 ligase.
created [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10
crossReference
databaseName UniProt
dbId 145290
description
  • recommendedName: E3 ISG15--protein ligase HERC5 ecNumber evidence="14"2.3.2.- alternativeName: Cyclin-E-binding protein 1 alternativeName: HECT domain and RCC1-like domain-containing protein 5
displayName UniProt:Q9UII4 HERC5
geneName
  • HERC5
  • CEB1
  • CEBP1
identifier Q9UII4
isSequenceChanged false
keyword
  • 3D-structure
  • Antiviral defense
  • Cytoplasm
  • Host-virus interaction
  • Immunity
  • Innate immunity
  • Proteomics identification
  • Reference proteome
  • Repeat
  • Transferase
  • Ubl conjugation
  • Ubl conjugation pathway
modified [InstanceEdit:9983091] Weiser, Joel, 2026-02-20
moleculeType Protein
name
  • HERC5
otherIdentifier
  • 11755374_a_at
  • 16968765
  • 219863_PM_at
  • 219863_at
  • 2735410
  • 2735411
  • 2735412
  • 2735413
  • 2735414
  • 2735415
  • 2735416
  • 2735417
  • 2735419
  • 2735420
  • 2735421
  • 2735422
  • 2735423
  • 2735424
  • 2735425
  • 2735426
  • 2735427
  • 2735428
  • 2735429
  • 2735430
  • 2735431
  • 2735432
  • 2735433
  • 2735434
  • 2735435
  • 2735436
  • 2735437
  • 2735438
  • 2735439
  • 2735440
  • 2735441
  • 2735442
  • 2735443
  • 2735444
  • 51191
  • 61371_at
  • 8096361
  • A_23_P110196
  • GE53687
  • GO:0000079
  • GO:0000209
  • GO:0002376
  • GO:0003723
  • GO:0003824
  • GO:0004842
  • GO:0005515
  • GO:0005737
  • GO:0005829
  • GO:0006511
  • GO:0016567
  • GO:0016740
  • GO:0032020
  • GO:0039585
  • GO:0042296
  • GO:0045087
  • GO:0048471
  • GO:0050688
  • GO:0051607
  • GO:0061630
  • GO:0098542
  • GO:0140096
  • HMNXSV003027708
  • ILMN_1729749
  • PH_hs_0002353
  • TC04000485.hg
  • g7705930_3p_at
physicalEntity
referenceDatabase [ReferenceDatabase:2] UniProt
referenceGene
referenceTranscript
schemaClass ReferenceGeneProduct
secondaryIdentifier
  • HERC5_HUMAN
  • B2RTQ1
  • Q69G20
sequenceLength 1024
species [Species:48887] Homo sapiens
stId uniprot:Q9UII4
url http://purl.uniprot.org/uniprot/Q9UII4
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