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Protein

E3 ubiquitin-protein ligase HUWE1

Gene

Huwe1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -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

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.

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)DescriptionActionsGraphical viewLength
Active sitei289Glycyl thioester intermediatePROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDNA-binding, Transferase
Biological processDifferentiation, DNA damage, DNA repair, Ubl conjugation pathway

Enzyme and pathway databases

UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase HUWE1 (EC:2.3.2.26)
Alternative name(s):
HECT, UBA and WWE domain-containing protein 1
HECT-type E3 ubiquitin transferase HUWE1
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi1561763 Huwe1

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, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi219Y → D: Abolishes its ability to inhibit transactivation of TP53. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000120342‹1 – 322E3 ubiquitin-protein ligase HUWE1Add BLAST›322

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei219Phosphotyrosine1 Publication1

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
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini‹1 – 322HECTPROSITE-ProRule annotationAdd BLAST›322

Domaini

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

Phylogenomic databases

eggNOGiKOG0939 Eukaryota
COG5021 LUCA
HOGENOMiHOG000208451
HOVERGENiHBG004134
InParanoidiP51593
PhylomeDBiP51593

Family and domain databases

CDDicd00078 HECTc, 1 hit
InterProiView protein in InterPro
IPR000569 HECT_dom
IPR035983 Hect_E3_ubiquitin_ligase
PfamiView protein in Pfam
PF00632 HECT, 1 hit
SMARTiView protein in SMART
SM00119 HECTc, 1 hit
SUPFAMiSSF56204 SSF56204, 1 hit
PROSITEiView protein in PROSITE
PS50237 HECT, 1 hit

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)DescriptionActionsGraphical viewLength
Non-terminal residuei11

Sequence databases

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

Similar proteinsi

Entry informationi

Entry nameiHUWE1_RAT
AccessioniPrimary (citable) accession number: P51593
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 19, 2004
Last modified: May 23, 2018
This is version 116 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

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