SG ID

SG00001781 

UniProt Accession

HUWE1_RAT;P51593;  

Theoretical PI

FRAGMENT  

Molecular Weight

37361 Da  

Genbank Nucleotide ID

U08214;  

Genbank Protein ID

AAA81950.1; 

Gene Name

Huwe1 

Gene Synonyms/Alias

Ureb1 

Protein Name

E3 ubiquitin-protein ligase HUWE1 

Protein Synonyms/Alias

EC=6.3.2.- HECT, UBA and WWE domain-containing protein 1; Upstream regulatory element-binding protein 1;URE-B1URE-binding protein 1Flags: Fragment 

Rattus norvegicus (Rat) 

10116 

Temporarily unavailable 

The information of related literatures

1. Z. Liu, D. Miao, Q. Xia, L. Hermo and S. S. Wing (2007) Regulated expression of the ubiquitin protein ligase, E3(Histone)/LASU1/Mule/ARF-BP1/HUWE1, during spermatogenesis. Dev Dyn 236(10): 2889-98. 

Abstract
A ubiquitin protein ligase (E3), E3(Histone)/LASU1 (Mule/ARF-BP1/HUWE1), was recently identified that mediates ubiquitination of core histones, the Mcl-1 anti-apoptotic protein, and the p53 tumor suppressor protein. However, the expression of E3(Histone)/LASU1 remains poorly studied. Because we identified E3(Histone)/LASU1 from the testis, we explored its regulation during spermatogenesis. In the first wave of rat spermatogenesis, E3(Histone)/LASU1 mRNA and protein had peak expression at days 10 and 20, respectively, and decreased with age. Consistent with these findings, immunohistochemistry revealed that E3(Histone)/LASU1 was highly expressed in nuclei from spermatogonia to mid-pachytene spermatocytes. There was no obvious staining in spermatids, when histones are ubiquitinated and degraded. E3(Histone)/LASU1 was also expressed in other tissues. However, except in neuronal cells of the brain, expression was cytoplasmic. Thus, E3(Histone)/LASU1 may play a role in chromatin modification in early germ cells of the testis, but also has functions in other tissues. PMID: [17823942] 

2. Z. Liu, R. Oughtred and S. S. Wing (2005) Characterization of E3Histone, a novel testis ubiquitin protein ligase which ubiquitinates histones. Mol Cell Biol 25(7): 2819-31. 

Abstract
During spermatogenesis, a large fraction of cellular proteins is degraded as the spermatids evolve to their elongated mature forms. In particular, histones must be degraded in early elongating spermatids to permit chromatin condensation. Our laboratory previously demonstrated the activation of ubiquitin conjugation during spermatogenesis. This activation is dependent on the ubiquitin-conjugating enzyme (E2) UBC4, and a testis-particular isoform, UBC4-testis, is induced when histones are degraded. Therefore, we tested whether there are UBC4-dependent ubiquitin protein ligases (E3s) that can ubiquitinate histones. Indeed, a novel enzyme, E3Histone, which could conjugate ubiquitin to histones H1, H2A, H2B, H3, and H4 in vitro, was found. Only the UBC4/UBC5 family of E2s supported E3Histone-dependent ubiquitination of histone H2A, and of this family, UBC4-1 and UBC4-testis are the preferred E2s. We purified this ligase activity 3,600-fold to near homogeneity. Mass spectrometry of the final material revealed the presence of a 482-kDa HECT domain-containing protein, which was previously named LASU1. Anti-LASU1 antibodies immunodepleted E3Histone activity. Mass spectrometry and size analysis by gel filtration and glycerol gradient centrifugation suggested that E3Histone is a monomer of LASU1. Our assays also show that this enzyme is the major UBC4-1-dependent histone-ubiquitinating E3. E3Histone is therefore a HECT domain E3 that likely plays an important role in the chromatin condensation that occurs during spermatid maturation. PMID: [15767685] 

Figures for illustrating the function of this protein/gene

Function

E3 ubiquitin-protein ligase which mediatesubiquitination and subsequent proteasomal degradation of targetproteins. Regulates apoptosis by catalyzing the polyubiquitinationand degradation of MCL1. Mediates monoubiquitination of DNApolymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', therebyplaying a role in base-excision repair. Also ubiquitinates thep53/TP53 tumor suppressor and core histones including H1, H2A,H2B, H3 and H4 (By similarity). Binds to an upstream initiator-like sequence in the preprodynorphin gene. Regulates neuraldifferentiation and proliferation by catalyzing thepolyubiquitination and degradation of MYCN. May regulate abundanceof CDC6 after DNA damage by polyubiquitinating and targeting CDC6to degradation (By similarity). 

Subcellular Location

Cytoplasm. Nucleus. Note=Mainly expressed inthe cytoplasm of most tissues, except in the nucleus ofspermatogonia, primary spermatocytes and neuronal cells (Bysimilarity). 

Tissue Specificity

Widely expressed. 

Gene Ontology

GO ID	GO term	Evidence
GO:0005737	C:cytoplasm	ISS:UniProtKB.
GO:0005634	C:nucleus	IDA:UniProtKB.
GO:0003677	F:DNA binding	IDA:UniProtKB.
GO:0004842	F:ubiquitin-protein ligase activity	ISS:UniProtKB.
GO:0006284	P:base-excision repair	ISS:UniProtKB.
GO:0030154	P:cell differentiation	IEA:UniProtKB-KW.
GO:0016574	P:histone ubiquitination	ISS:UniProtKB.
GO:0006513	P:protein monoubiquitination	ISS:UniProtKB.
GO:0000209	P:protein polyubiquitination	ISS:UniProtKB.
GO:0042787	P:protein ubiquitination involved in ubiquitin-dependent protein catabolic process	IBA:RefGenome.

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Interpro

IPR000569;    HECT.
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Pfam

PF00632;    HECT;    1.
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SMART

SM00119;    HECTc;    1.
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PROSITE

PS50237;    HECT;    1.
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PRINTS

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Created Date

18-Oct-2012 

Record Type

Experiment identified 

Protein sequence Annotation

Nucleotide Sequence

Length: 2370 bp   Go to nucleotide: FASTA

Protein Sequence

Length: 322 bp   Go to amino acid: FASTA

The verified Protein-Protein interaction information

UniProt

Gene Symbol

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Other Protein-Protein interaction resources

String database  

UniProt

Gene Symbol

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