Overview
| Uniprot ID | Q9UII4 |
|---|
| Protein Name | E3 ISG15--protein ligase HERC5 |
|---|
| Gene Name | HERC5 |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 541 |
LQESTFSKLVQMFKT |
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)
Protein Sequence
10
MERRSRRKSR
20
RNGRSTAGKA
30
AATQPAKSPG
40
AQLWLFPSAA
50
GLHRALLRRV
60
EVTRQLCCSP
70
GRLAVLERGG
80
AGVQVHQLLA
90
GSGGARTPKC
100
IKLGKNMKIH
110
SVDQGAEHML
120
ILSSDGKPFE
130
YDNYSMKHLR
140
FESILQEKKI
150
IQITCGDYHS
160
LALSKGGELF
170
AWGQNLHGQL
180
GVGRKFPSTT
190
TPQIVEHLAG
200
VPLAQISAGE
210
AHSMALSMSG
220
NIYSWGKNEC
230
GQLGLGHTES
240
KDDPSLIEGL
250
DNQKVEFVAC
260
GGSHSALLTQ
270
DGLLFTFGAG
280
KHGQLGHNST
290
QNELRPCLVA
300
ELVGYRVTQI
310
ACGRWHTLAY
320
VSDLGKVFSF
330
GSGKDGQLGN
340
GGTRDQLMPL
350
PVKVSSSEEL
360
KLESHTSEKE
370
LIMIAGGNQS
380
ILLWIKKENS
390
YVNLKRTIPT
400
LNEGTVKRWI
410
ADVETKRWQS
420
TKREIQEIFS
430
SPACLTGSFL
440
RKRRTTEMMP
450
VYLDLNKARN
460
IFKELTQKDW
470
ITNMITTCLK
480
DNLLKRLPFH
490
SPPQEALEIF
500
FLLPECPMMH
510
ISNNWESLVV
520
PFAKVVCKMS
530
DQSSLVLEEY
540
WATLQESTFS
550
KLVQMFKTAV
560
ICQLDYWDES
570
AEENGNVQAL
580
LEMLKKLHRV
590
NQVKCQLPES
600
IFQVDELLHR
610
LNFFVEVCRR
620
YLWKMTVDAS
630
ENVQCCVIFS
640
HFPFIFNNLS
650
KIKLLHTDTL
660
LKIESKKHKA
670
YLRSAAIEEE
680
RESEFALRPT
690
FDLTVRRNHL
700
IEDVLNQLSQ
710
FENEDLRKEL
720
WVSFSGEIGY
730
DLGGVKKEFF
740
YCLFAEMIQP
750
EYGMFMYPEG
760
ASCMWFPVKP
770
KFEKKRYFFF
780
GVLCGLSLFN
790
CNVANLPFPL
800
ALFKKLLDQM
810
PSLEDLKELS
820
PDLGKNLQTL
830
LDDEGDNFEE
840
VFYIHFNVHW
850
DRNDTNLIPN
860
GSSITVNQTN
870
KRDYVSKYIN
880
YIFNDSVKAV
890
YEEFRRGFYK
900
MCDEDIIKLF
910
HPEELKDVIV
920
GNTDYDWKTF
930
EKNARYEPGY
940
NSSHPTIVMF
950
WKAFHKLTLE
960
EKKKFLVFLT
970
GTDRLQMKDL
980
NNMKITFCCP
990
ESWNERDPIR
1000
ALTCFSVLFL
1010
PKYSTMETVE
1020
EALQEAINNN
RGFG
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0005737 |
cytoplasm |
| Cellular Component |
GO:0005829 |
cytosol |
| Cellular Component |
GO:0048471 |
perinuclear region of cytoplasm |
| Molecular Function |
GO:0042296 |
ISG15 transferase activity |
| Molecular Function |
GO:0003723 |
RNA binding |
| Molecular Function |
GO:0061630 |
ubiquitin protein ligase activity |
| Molecular Function |
GO:0004842 |
ubiquitin-protein transferase activity |
| Biological Process |
GO:0051607 |
defense response to virus |
| Biological Process |
GO:0045087 |
innate immune response |
| Biological Process |
GO:0032020 |
ISG15-protein conjugation |
| Biological Process |
GO:0039585 |
PKR/eIFalpha signaling |
| Biological Process |
GO:0016567 |
protein ubiquitination |
| Biological Process |
GO:0000079 |
regulation of cyclin-dependent protein serine/threonine kinase activity |
| Biological Process |
GO:0050688 |
regulation of defense response to virus |
| Biological Process |
GO:0006511 |
ubiquitin-dependent protein catabolic process |
Reference
[1] Yan M, Tu H, Tang S, Gai Z, Shi Q et al.. Lactylated Proteomic Analysis Reveals Functional Implications of Lysine Lactylation In Asthenozoospermia.. Mol Cell Proteomics 24(12):101439. 2025 Dec. PMID: 41192556.