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Protein

E3 ubiquitin-protein ligase HUWE1

Gene

Huwe1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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). Mediates polyubiquitination of PA2G4 (By similarity).By similarity2 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei289 – 2891Glycyl thioester intermediatePROSITE-ProRule annotation

GO - Molecular functioni

  • DNA binding Source: UniProtKB
  • ligase activity Source: UniProtKB-KW
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Differentiation, DNA damage, DNA repair, Ubl conjugation pathway

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase HUWE1 (EC:6.3.2.-)
Alternative name(s):
HECT, UBA and WWE domain-containing protein 1
Upstream regulatory element-binding protein 1
Short name:
URE-B1
Short name:
URE-binding protein 1
Gene namesi
Name:Huwe1
Synonyms:Ureb1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi1561763. Huwe1.

Subcellular locationi

  • Cytoplasm By similarity
  • Nucleus By similarity

  • Note: Mainly expressed in the cytoplasm of most tissues, except in the nucleus of spermatogonia, primary spermatocytes and neuronal cells.By similarity

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi219 – 2191Y → D: Abolishes its ability to inhibit transactivation of TP53. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini‹1 – 322›322E3 ubiquitin-protein ligase HUWE1PRO_0000120342Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei219 – 2191Phosphotyrosine1 Publication

Post-translational modificationi

Phosphorylated on tyrosine, phosphorylation is probably required for its ability to inhibit TP53 transactivation.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP51593.
PRIDEiP51593.

PTM databases

iPTMnetiP51593.

Expressioni

Tissue specificityi

Widely expressed.1 Publication

Developmental stagei

During spermatogenesis highest expression at postnatal day 10 and then gradually decreases to day 40, after which it remains constant at low levels. Protein peaks at postnatal day 20, and then gradually decreases by day 45.1 Publication

Interactioni

Subunit structurei

Interacts with isoform p19ARF of CDKN2A which strongly inhibits HUWE1 ubiquitin ligase activity. Interacts with MYCN, POLB and CDC6. Interacts with PA2G4.By similarity

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000003882.

Structurei

3D structure databases

ProteinModelPortaliP51593.
SMRiP51593. Positions 1-313.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini‹1 – 322›322HECTPROSITE-ProRule annotationAdd
BLAST

Domaini

The HECT domain mediates inhibition of the transcriptional activity of p53.By similarity

Sequence similaritiesi

Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0939. Eukaryota.
COG5021. LUCA.
HOGENOMiHOG000208451.
HOVERGENiHBG004134.
InParanoidiP51593.
PhylomeDBiP51593.

Family and domain databases

InterProiIPR000569. HECT_dom.
[Graphical view]
PfamiPF00632. HECT. 1 hit.
[Graphical view]
SMARTiSM00119. HECTc. 1 hit.
[Graphical view]
SUPFAMiSSF56204. SSF56204. 1 hit.
PROSITEiPS50237. HECT. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Fragment.

P51593-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
EEGQDAGGLL REWYMIISRE MFNPMYALFR TSPGDRVTYT INPSSHCNPN
60 70 80 90 100
HLSYFKFVGR IVAKAVYDNR LLECYFTRSF YKHILGKSVR YTDMESEDYH
110 120 130 140 150
FYQGLVYLLE NDVSTLGYDL TFSTEVQEFG VCEVRDLKPN GANILVTEEN
160 170 180 190 200
KKEYVHLVCQ MRMTGAIRKQ LAAFLEGFYE IIPKRLISIF TEQELELLIS
210 220 230 240 250
GLPTIDIDDL KSNTEYHKYQ SNSIQIQWFW RALRSFDQAD RAKFLQFVTG
260 270 280 290 300
TSKVPLQGFA ALEGMNGIQK FQIHRDDRST DRLPSAHTCF NQLDLPAYES
310 320
FEKLRHMLLL AIQECSEGFG LA
Length:322
Mass (Da):37,361
Last modified:July 19, 2004 - v2
Checksum:iE7794791E7AB3AF3
GO

Sequence cautioni

The sequence AAA81950 differs from that shown. Reason: Frameshift at several positions. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Non-terminal residuei1 – 11

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U08214 mRNA. Translation: AAA81950.1. Frameshift.
UniGeneiRn.12130.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U08214 mRNA. Translation: AAA81950.1. Frameshift.
UniGeneiRn.12130.

3D structure databases

ProteinModelPortaliP51593.
SMRiP51593. Positions 1-313.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000003882.

PTM databases

iPTMnetiP51593.

Proteomic databases

PaxDbiP51593.
PRIDEiP51593.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

RGDi1561763. Huwe1.

Phylogenomic databases

eggNOGiKOG0939. Eukaryota.
COG5021. LUCA.
HOGENOMiHOG000208451.
HOVERGENiHBG004134.
InParanoidiP51593.
PhylomeDBiP51593.

Enzyme and pathway databases

UniPathwayiUPA00143.

Family and domain databases

InterProiIPR000569. HECT_dom.
[Graphical view]
PfamiPF00632. HECT. 1 hit.
[Graphical view]
SMARTiSM00119. HECTc. 1 hit.
[Graphical view]
SUPFAMiSSF56204. SSF56204. 1 hit.
PROSITEiPS50237. HECT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHUWE1_RAT
AccessioniPrimary (citable) accession number: P51593
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 19, 2004
Last modified: July 6, 2016
This is version 105 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.