UniProt Accession

 HUWE1_RAT; P51593 

Genbank Protein ID

 U08214 

Genbank Nucleotide ID

 AAA81950.1 

Protein Name

 E3 ubiquitin-protein ligase HUWE1 

Protein Synonyms/Alias

 HECT, UBA and WWE domain-containing protein 1; Upstream regulatory element-binding protein 1; URE-B1; URE-binding protein 1 

Gene Name

 Huwe1 

Gene Synonyms/Alias

 Ureb1 

Created Date

 July 27, 2013 

Organism

 Rattus norvegicus (Rat) 

NCBI Taxa ID

 10116 

Lysine Modification

Position	Peptide	Type	References
64	FVGRIVAKAVYDNRL	ubiquitination	[1]
87	FYKHILGKSVRYTDM	ubiquitination	[2]
138	VCEVRDLKPNGANIL	ubiquitination	[1]
169	RMTGAIRKQLAAFLE	ubiquitination	[1, 2]
243	FDQADRAKFLQFVTG	ubiquitination	[1, 2]
270	EGMNGIQKFQIHRDD	ubiquitination	[1]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965] 

Functional Description

 E3 ubiquitin-protein ligase which mediates ubiquitination and subsequent proteasomal degradation of target proteins. Regulates apoptosis by catalyzing the polyubiquitination and degradation of MCL1. Mediates monoubiquitination of DNA polymerase beta (POLB) at 'Lys-41', 'Lys-61' and 'Lys-81', thereby playing a role in base-excision repair. Also ubiquitinates the p53/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 neural differentiation and proliferation by catalyzing the polyubiquitination and degradation of MYCN. May regulate abundance of CDC6 after DNA damage by polyubiquitinating and targeting CDC6 to degradation (By similarity). 

Sequence Annotation

 DOMAIN <1 322 HECT.
 ACT_SITE 289 289 Glycyl thioester intermediate (By
 MOD_RES 219 219 Phosphotyrosine (Probable).  

Keyword

 Complete proteome; Cytoplasm; Differentiation; DNA damage; DNA repair; DNA-binding; Ligase; Nucleus; Phosphoprotein; Reference proteome; Ubl conjugation pathway. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 322 AA 

Protein Sequence

Gene Ontology

 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. 

Interpro

 IPR000569; HECT. 

Pfam

 PF00632; HECT 

SMART

 SM00119; HECTc 

PROSITE

 PS50237; HECT 

PRINTS