HERC5 (HECT and RLD domain containing E3 ubiquitin protein ligase 5)

Gene

• Entrez ID: 51191
• Gene name: HECT and RLD domain containing E3 ubiquitin protein ligase 5
• Gene symbol: HERC5
• Synonyms (NCBI Gene): CEB1, CEBP1
• Chromosome: 4
• Chromosome location: 4q22.1
• Summary: This gene is a member of the HERC family of ubiquitin ligases and encodes a protein with a HECT domain and five RCC1 repeats. Pro-inflammatory cytokines upregulate expression of this gene in endothelial cells. The protein localizes to the cytoplasm and pe

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT023970	hsa-miR-1-3p	Microarray	18668037
MIRT616823	hsa-miR-3529-3p	HITS-CLIP	23824327
MIRT616823	hsa-miR-3529-3p	HITS-CLIP	23824327
MIRT1044403	hsa-miR-3065-5p	CLIP-seq
MIRT1044404	hsa-miR-3123	CLIP-seq
MIRT1044405	hsa-miR-3925-5p	CLIP-seq
MIRT1044406	hsa-miR-4520a-3p	CLIP-seq
MIRT1044407	hsa-miR-4520b-3p	CLIP-seq
MIRT1044408	hsa-miR-4687-3p	CLIP-seq
MIRT1044404	hsa-miR-3123	CLIP-seq
MIRT2545656	hsa-miR-135a	CLIP-seq
MIRT2545657	hsa-miR-135b	CLIP-seq
MIRT2545658	hsa-miR-3074-5p	CLIP-seq
MIRT2545659	hsa-miR-3124-3p	CLIP-seq
MIRT2545660	hsa-miR-3155	CLIP-seq
MIRT2545661	hsa-miR-3155b	CLIP-seq
MIRT2545662	hsa-miR-34c-3p	CLIP-seq
MIRT2545663	hsa-miR-3646	CLIP-seq
MIRT2545664	hsa-miR-370	CLIP-seq
MIRT2545665	hsa-miR-4778-3p	CLIP-seq
MIRT2545666	hsa-miR-484	CLIP-seq
MIRT2545667	hsa-miR-548aa	CLIP-seq
MIRT2545668	hsa-miR-548ac	CLIP-seq
MIRT2545669	hsa-miR-548d-3p	CLIP-seq
MIRT2545670	hsa-miR-548z	CLIP-seq
MIRT2545671	hsa-miR-642a	CLIP-seq
MIRT2545658	hsa-miR-3074-5p	CLIP-seq
MIRT2545659	hsa-miR-3124-3p	CLIP-seq
MIRT2545664	hsa-miR-370	CLIP-seq
MIRT2545665	hsa-miR-4778-3p	CLIP-seq
MIRT2545671	hsa-miR-642a	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000079	Process	Regulation of cyclin-dependent protein serine/threonine kinase activity	TAS	10581175
GO:0002376	Process	Immune system process	IEA
GO:0003723	Function	RNA binding	HDA	22658674
GO:0004842	Function	Ubiquitin-protein transferase activity	IEA
GO:0004842	Function	Ubiquitin-protein transferase activity	TAS
GO:0005515	Function	Protein binding	IPI	20133869, 20308324
GO:0005737	Component	Cytoplasm	IBA
GO:0005737	Component	Cytoplasm	IDA	16407192
GO:0005737	Component	Cytoplasm	IDA	10581175
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	TAS
GO:0006511	Process	Ubiquitin-dependent protein catabolic process	IBA
GO:0016567	Process	Protein ubiquitination	IBA
GO:0016567	Process	Protein ubiquitination	IDA	15331633
GO:0016740	Function	Transferase activity	IEA
GO:0032020	Process	ISG15-protein conjugation	IBA
GO:0032020	Process	ISG15-protein conjugation	IDA	16407192
GO:0032020	Process	ISG15-protein conjugation	IDA	16407192, 20308324
GO:0039585	Process	PKR/eIFalpha signaling	TAS
GO:0042296	Function	ISG15 transferase activity	IBA
GO:0042296	Function	ISG15 transferase activity	IDA	16407192, 20308324
GO:0045087	Process	Innate immune response	IDA	28724761
GO:0045087	Process	Innate immune response	IDA	28724761
GO:0045087	Process	Innate immune response	IEA
GO:0048471	Component	Perinuclear region of cytoplasm	IEA
GO:0050688	Process	Regulation of defense response to virus	IDA	20308324
GO:0051607	Process	Defense response to virus	IEA
GO:0061630	Function	Ubiquitin protein ligase activity	IBA
GO:0061630	Function	Ubiquitin protein ligase activity	IDA	15331633

Other IDs

• MIM: 608242
• HGNC: 24368
• e!Ensembl: ENSG00000138646

Protein

• UniProt ID: Q9UII4
• Protein name: E3 ISG15--protein ligase HERC5 (EC 2.3.2.-) (Cyclin-E-binding protein 1) (HECT domain and RCC1-like domain-containing protein 5)
• Protein 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 ISGyl
• PDB: 8Y4Z
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00415	RCC1	156 → 206	Regulator of chromosome condensation (RCC1) repeat	Repeat
  PF00415	RCC1	209 → 258	Regulator of chromosome condensation (RCC1) repeat	Repeat
  PF00415	RCC1	261 → 310	Regulator of chromosome condensation (RCC1) repeat	Repeat
  PF00415	RCC1	315 → 373	Regulator of chromosome condensation (RCC1) repeat	Repeat
  PF00632	HECT	731 → 1024	HECT-domain (ubiquitin-transferase)	Domain

• Tissue specificity: TISSUE SPECIFICITY: Expressed in testis and to a lesser degree in brain, ovary and placenta. Found in most tissues at low levels. {ECO:0000269|PubMed:10581175, ECO:0000269|PubMed:15331633}.
• Sequence:

  MERRSRRKSRRNGRSTAGKAAATQPAKSPGAQLWLFPSAAGLHRALLRRVEVTRQLCCSP
  GRLAVLERGGAGVQVHQLLAGSGGARTPKCIKLGKNMKIHSVDQGAEHMLILSSDGKPFE
  YDNYSMKHLRFESILQEKKIIQITCGDYHSLALSKGGELFAWGQNLHGQLGVGRKFPSTT
  TPQIVEHLAGVPLAQISAGEAHSMALSMSGNIYSWGKNECGQLGLGHTESKDDPSLIEGL
  DNQKVEFVACGGSHSALLTQDGLLFTFGAGKHGQLGHNSTQNELRPCLVAELVGYRVTQI
  ACGRWHTLAYVSDLGKVFSFGSGKDGQLGNGGTRDQLMPLPVKVSSSEELKLESHTSEKE
  LIMIAGGNQSILLWIKKENSYVNLKRTIPTLNEGTVKRWIADVETKRWQSTKREIQEIFS
  SPACLTGSFLRKRRTTEMMPVYLDLNKARNIFKELTQKDWITNMITTCLKDNLLKRLPFH
  SPPQEALEIFFLLPECPMMHISNNWESLVVPFAKVVCKMSDQSSLVLEEYWATLQESTFS
  KLVQMFKTAVICQLDYWDESAEENGNVQALLEMLKKLHRVNQVKCQLPESIFQVDELLHR
  LNFFVEVCRRYLWKMTVDASENVQCCVIFSHFPFIFNNLSKIKLLHTDTLLKIESKKHKA
  YLRSAAIEEERESEFALRPTFDLTVRRNHLIEDVLNQLSQFENEDLRKELWVSFSGEIGY
  DLGGVKKEFFYCLFAEMIQPEYGMFMYPEGASCMWFPVKPKFEKKRYFFFGVLCGLSLFN
  CNVANLPFPLALFKKLLDQMPSLEDLKELSPDLGKNLQTLLDDEGDNFEEVFYIHFNVHW
  DRNDTNLIPNGSSITVNQTNKRDYVSKYINYIFNDSVKAVYEEFRRGFYKMCDEDIIKLF
  HPEELKDVIVGNTDYDWKTFEKNARYEPGYNSSHPTIVMFWKAFHKLTLEEKKKFLVFLT
  GTDRLQMKDLNNMKITFCCPESWNERDPIRALTCFSVLFLPKYSTMETVEEALQEAINNN
  RGFG

• Sequence length: 1024

Pathways

Reactome:

ISG15 antiviral mechanism
DDX58/IFIH1-mediated induction of interferon-alpha/beta
Negative regulators of DDX58/IFIH1 signaling
Antigen processing: Ubiquitination & Proteasome degradation