Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

E3 ISG15--protein ligase HERC5

Gene

HERC5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Major E3 ligase for ISG15 conjugation. 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. 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 ISG15.7 Publications

Caution

Was thought to be a ubiquitin ligase ubiquitinated by UBE2D1, but was confirmed by numerous studies that it's main function is as E3 ISG15 ligase.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei994Glycyl thioester intermediatePROSITE-ProRule annotation1

GO - Molecular functioni

  • ISG15 transferase activity Source: UniProtKB
  • RNA binding Source: UniProtKB
  • ubiquitin-protein transferase activity Source: Reactome

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processAntiviral defense, Immunity, Innate immunity, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-1169408 ISG15 antiviral mechanism
R-HSA-168928 DDX58/IFIH1-mediated induction of interferon-alpha/beta
R-HSA-936440 Negative regulators of DDX58/IFIH1 signaling
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ISG15--protein ligase HERC5 (EC:2.3.2.-)
Alternative name(s):
Cyclin-E-binding protein 1
HECT domain and RCC1-like domain-containing protein 5
Gene namesi
Name:HERC5
Synonyms:CEB1, CEBP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000138646.8
HGNCiHGNC:24368 HERC5
MIMi608242 gene
neXtProtiNX_Q9UII4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi994C → A: Loss of activity; no effect on IRF3 interaction. 6 Publications1

Organism-specific databases

DisGeNETi51191
OpenTargetsiENSG00000138646
PharmGKBiPA134973940

Polymorphism and mutation databases

BioMutaiHERC5
DMDMi296434523

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002066411 – 1024E3 ISG15--protein ligase HERC5Add BLAST1024

Post-translational modificationi

ISGylated.1 Publication

Keywords - PTMi

Ubl conjugation

Proteomic databases

EPDiQ9UII4
MaxQBiQ9UII4
PaxDbiQ9UII4
PeptideAtlasiQ9UII4
PRIDEiQ9UII4
ProteomicsDBi84527

PTM databases

iPTMnetiQ9UII4
PhosphoSitePlusiQ9UII4

Expressioni

Tissue specificityi

Expressed in testis and to a lesser degree in brain, ovary and placenta. Found in most tissues at low levels.2 Publications

Inductioni

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.2 Publications

Gene expression databases

BgeeiENSG00000138646 Expressed in 201 organ(s), highest expression level in female gonad
CleanExiHS_HERC5
ExpressionAtlasiQ9UII4 baseline and differential
GenevisibleiQ9UII4 HS

Organism-specific databases

HPAiHPA043929

Interactioni

Subunit structurei

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 NS1.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
NSP034953EBI-2339540,EBI-2548993From Influenza A virus (strain A/Udorn/307/1972 H3N2).

Protein-protein interaction databases

BioGridi119365, 53 interactors
DIPiDIP-44200N
IntActiQ9UII4, 19 interactors
MINTiQ9UII4
STRINGi9606.ENSP00000264350

Structurei

3D structure databases

ProteinModelPortaliQ9UII4
SMRiQ9UII4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati96 – 155RCC1 1Add BLAST60
Repeati156 – 208RCC1 2Add BLAST53
Repeati209 – 260RCC1 3Add BLAST52
Repeati262 – 312RCC1 4Add BLAST51
Repeati314 – 364RCC1 5Add BLAST51
Domaini702 – 1024HECTPROSITE-ProRule annotationAdd BLAST323

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0941 Eukaryota
COG5021 LUCA
COG5184 LUCA
GeneTreeiENSGT00910000144004
HOGENOMiHOG000208452
HOVERGENiHBG050878
InParanoidiQ9UII4
KOiK22372
OMAiSGNIYSW
OrthoDBiEOG091G028I
PhylomeDBiQ9UII4
TreeFamiTF315189

Family and domain databases

CDDicd00078 HECTc, 1 hit
Gene3Di2.130.10.30, 1 hit
InterProiView protein in InterPro
IPR000569 HECT_dom
IPR035983 Hect_E3_ubiquitin_ligase
IPR009091 RCC1/BLIP-II
IPR000408 Reg_chr_condens
PfamiView protein in Pfam
PF00632 HECT, 1 hit
PF00415 RCC1, 4 hits
PRINTSiPR00633 RCCNDNSATION
SMARTiView protein in SMART
SM00119 HECTc, 1 hit
SUPFAMiSSF50985 SSF50985, 1 hit
SSF56204 SSF56204, 1 hit
PROSITEiView protein in PROSITE
PS50237 HECT, 1 hit
PS00626 RCC1_2, 2 hits
PS50012 RCC1_3, 4 hits

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

Q9UII4-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MERRSRRKSR RNGRSTAGKA AATQPAKSPG AQLWLFPSAA GLHRALLRRV
60 70 80 90 100
EVTRQLCCSP GRLAVLERGG AGVQVHQLLA GSGGARTPKC IKLGKNMKIH
110 120 130 140 150
SVDQGAEHML ILSSDGKPFE YDNYSMKHLR FESILQEKKI IQITCGDYHS
160 170 180 190 200
LALSKGGELF AWGQNLHGQL GVGRKFPSTT TPQIVEHLAG VPLAQISAGE
210 220 230 240 250
AHSMALSMSG NIYSWGKNEC GQLGLGHTES KDDPSLIEGL DNQKVEFVAC
260 270 280 290 300
GGSHSALLTQ DGLLFTFGAG KHGQLGHNST QNELRPCLVA ELVGYRVTQI
310 320 330 340 350
ACGRWHTLAY VSDLGKVFSF GSGKDGQLGN GGTRDQLMPL PVKVSSSEEL
360 370 380 390 400
KLESHTSEKE LIMIAGGNQS ILLWIKKENS YVNLKRTIPT LNEGTVKRWI
410 420 430 440 450
ADVETKRWQS TKREIQEIFS SPACLTGSFL RKRRTTEMMP VYLDLNKARN
460 470 480 490 500
IFKELTQKDW ITNMITTCLK DNLLKRLPFH SPPQEALEIF FLLPECPMMH
510 520 530 540 550
ISNNWESLVV PFAKVVCKMS DQSSLVLEEY WATLQESTFS KLVQMFKTAV
560 570 580 590 600
ICQLDYWDES AEENGNVQAL LEMLKKLHRV NQVKCQLPES IFQVDELLHR
610 620 630 640 650
LNFFVEVCRR YLWKMTVDAS ENVQCCVIFS HFPFIFNNLS KIKLLHTDTL
660 670 680 690 700
LKIESKKHKA YLRSAAIEEE RESEFALRPT FDLTVRRNHL IEDVLNQLSQ
710 720 730 740 750
FENEDLRKEL WVSFSGEIGY DLGGVKKEFF YCLFAEMIQP EYGMFMYPEG
760 770 780 790 800
ASCMWFPVKP KFEKKRYFFF GVLCGLSLFN CNVANLPFPL ALFKKLLDQM
810 820 830 840 850
PSLEDLKELS PDLGKNLQTL LDDEGDNFEE VFYIHFNVHW DRNDTNLIPN
860 870 880 890 900
GSSITVNQTN KRDYVSKYIN YIFNDSVKAV YEEFRRGFYK MCDEDIIKLF
910 920 930 940 950
HPEELKDVIV GNTDYDWKTF EKNARYEPGY NSSHPTIVMF WKAFHKLTLE
960 970 980 990 1000
EKKKFLVFLT GTDRLQMKDL NNMKITFCCP ESWNERDPIR ALTCFSVLFL
1010 1020
PKYSTMETVE EALQEAINNN RGFG
Length:1,024
Mass (Da):116,852
Last modified:May 18, 2010 - v2
Checksum:i1449C51A58269A6C
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PBL0E9PBL0_HUMAN
E3 ISG15--protein ligase HERC5
HERC5
662Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti204M → T in AAR00320 (PubMed:15331633).Curated1
Sequence conflicti419F → S in AAR00320 (PubMed:15331633).Curated1
Sequence conflicti453K → R in BAA88519 (PubMed:10581175).Curated1
Sequence conflicti498M → V in BAA88519 (PubMed:10581175).Curated1
Sequence conflicti498M → V in AAR00320 (PubMed:15331633).Curated1
Sequence conflicti498M → V in AAI40717 (PubMed:15815621).Curated1
Sequence conflicti513A → T in AAR00320 (PubMed:15331633).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_057123301A → T. Corresponds to variant dbSNP:rs17014143Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB027289 mRNA Translation: BAA88519.1
AY337518 mRNA Translation: AAR00320.1
AC083829 Genomic DNA No translation available.
BC140716 mRNA Translation: AAI40717.1
CCDSiCCDS3630.1
RefSeqiNP_057407.2, NM_016323.3
UniGeneiHs.26663

Genome annotation databases

EnsembliENST00000264350; ENSP00000264350; ENSG00000138646
GeneIDi51191
KEGGihsa:51191
UCSCiuc003hrt.5 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB027289 mRNA Translation: BAA88519.1
AY337518 mRNA Translation: AAR00320.1
AC083829 Genomic DNA No translation available.
BC140716 mRNA Translation: AAI40717.1
CCDSiCCDS3630.1
RefSeqiNP_057407.2, NM_016323.3
UniGeneiHs.26663

3D structure databases

ProteinModelPortaliQ9UII4
SMRiQ9UII4
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119365, 53 interactors
DIPiDIP-44200N
IntActiQ9UII4, 19 interactors
MINTiQ9UII4
STRINGi9606.ENSP00000264350

PTM databases

iPTMnetiQ9UII4
PhosphoSitePlusiQ9UII4

Polymorphism and mutation databases

BioMutaiHERC5
DMDMi296434523

Proteomic databases

EPDiQ9UII4
MaxQBiQ9UII4
PaxDbiQ9UII4
PeptideAtlasiQ9UII4
PRIDEiQ9UII4
ProteomicsDBi84527

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000264350; ENSP00000264350; ENSG00000138646
GeneIDi51191
KEGGihsa:51191
UCSCiuc003hrt.5 human

Organism-specific databases

CTDi51191
DisGeNETi51191
EuPathDBiHostDB:ENSG00000138646.8
GeneCardsiHERC5
H-InvDBiHIX0200636
HGNCiHGNC:24368 HERC5
HPAiHPA043929
MIMi608242 gene
neXtProtiNX_Q9UII4
OpenTargetsiENSG00000138646
PharmGKBiPA134973940
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0941 Eukaryota
COG5021 LUCA
COG5184 LUCA
GeneTreeiENSGT00910000144004
HOGENOMiHOG000208452
HOVERGENiHBG050878
InParanoidiQ9UII4
KOiK22372
OMAiSGNIYSW
OrthoDBiEOG091G028I
PhylomeDBiQ9UII4
TreeFamiTF315189

Enzyme and pathway databases

ReactomeiR-HSA-1169408 ISG15 antiviral mechanism
R-HSA-168928 DDX58/IFIH1-mediated induction of interferon-alpha/beta
R-HSA-936440 Negative regulators of DDX58/IFIH1 signaling
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation

Miscellaneous databases

GeneWikiiHERC5
GenomeRNAii51191
PROiPR:Q9UII4
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000138646 Expressed in 201 organ(s), highest expression level in female gonad
CleanExiHS_HERC5
ExpressionAtlasiQ9UII4 baseline and differential
GenevisibleiQ9UII4 HS

Family and domain databases

CDDicd00078 HECTc, 1 hit
Gene3Di2.130.10.30, 1 hit
InterProiView protein in InterPro
IPR000569 HECT_dom
IPR035983 Hect_E3_ubiquitin_ligase
IPR009091 RCC1/BLIP-II
IPR000408 Reg_chr_condens
PfamiView protein in Pfam
PF00632 HECT, 1 hit
PF00415 RCC1, 4 hits
PRINTSiPR00633 RCCNDNSATION
SMARTiView protein in SMART
SM00119 HECTc, 1 hit
SUPFAMiSSF50985 SSF50985, 1 hit
SSF56204 SSF56204, 1 hit
PROSITEiView protein in PROSITE
PS50237 HECT, 1 hit
PS00626 RCC1_2, 2 hits
PS50012 RCC1_3, 4 hits
ProtoNetiSearch...

Entry informationi

Entry nameiHERC5_HUMAN
AccessioniPrimary (citable) accession number: Q9UII4
Secondary accession number(s): B2RTQ1, Q69G20
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: May 18, 2010
Last modified: November 7, 2018
This is version 151 of the entry and version 2 of the sequence. See complete history.
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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again