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Protein

NEDD4-like E3 ubiquitin-protein ligase WWP2

Gene

Wwp2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Polyubiquitinates POU5F1 by 'Lys-63'-linked conjugation and promotes it to proteasomal degradation; regulates POU5F1 protein level during differentiation of embryonal carcinoma cells (ECCs) but not in undifferentiated ECCs and embryonic stem cells (ESCs). Ubiquitinates EGR2 and promotes it to proteasomal degradation; in T-cells the ubiquitination inhibits activation-induced cell death. Ubiquitinates SLC11A2; the ubiquitination is enhanced by presence of NDFIP1 and NDFIP2. Ubiquitinates RPB1 and promotes it to proteasomal degradation.4 Publications

Miscellaneous

A cysteine residue is required for ubiquitin-thioester formation.

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.

Enzyme regulationi

Activated by NDFIP1- and NDFIP2-binding.By similarity

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 sitei838Glycyl thioester intermediatePROSITE-ProRule annotation1

GO - Molecular functioni

  • RNA polymerase II transcription factor binding Source: BHF-UCL
  • transcriptional activator activity, RNA polymerase II transcription factor binding Source: MGI
  • transcription factor binding Source: MGI
  • ubiquitin protein ligase activity Source: BHF-UCL
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway

Enzyme and pathway databases

ReactomeiR-MMU-8948751 Regulation of PTEN stability and activity
R-MMU-9013507 NOTCH3 Activation and Transmission of Signal to the Nucleus
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
NEDD4-like E3 ubiquitin-protein ligase WWP2 (EC:2.3.2.26)
Alternative name(s):
HECT-type E3 ubiquitin transferase WWP2
WW domain-containing protein 2
Gene namesi
Name:Wwp2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:1914144 Wwp2

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

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001203391 – 870NEDD4-like E3 ubiquitin-protein ligase WWP2Add BLAST870

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei211PhosphoserineBy similarity1

Post-translational modificationi

Autoubiquitinated. Ubiquitinated by the SCF(FBXL15) complex, leading to its degradation by the proteasome (By similarity).By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9DBH0
MaxQBiQ9DBH0
PaxDbiQ9DBH0
PRIDEiQ9DBH0

PTM databases

iPTMnetiQ9DBH0
PhosphoSitePlusiQ9DBH0

Expressioni

Gene expression databases

BgeeiENSMUSG00000031930
ExpressionAtlasiQ9DBH0 baseline and differential
GenevisibleiQ9DBH0 MM

Interactioni

Subunit structurei

Interacts with SCNN1A, SCNN1B, SCNN1G, WBP1, WBP2 and ATN1. Interacts with ERBB4, NDFIP1 and NDFIP2. Interacts with ARRDC4 (By similarity). Interacts with POU5F1, RBP1, EGR2 and SLC11A2. Interacts (via WW domains) with ARRDC1 (via PPxY motifs); ubiquitinates ARRDC1 (By similarity). Interacts (via WW domains) with ARRDC2 and ARRDC3 (By similarity).By similarity3 Publications

GO - Molecular functioni

  • RNA polymerase II transcription factor binding Source: BHF-UCL
  • transcription factor binding Source: MGI

Protein-protein interaction databases

BioGridi211793, 12 interactors
IntActiQ9DBH0, 1 interactor
STRINGi10090.ENSMUSP00000132224

Structurei

3D structure databases

ProteinModelPortaliQ9DBH0
SMRiQ9DBH0
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini20 – 100C2Add BLAST81
Domaini300 – 333WW 1PROSITE-ProRule annotationAdd BLAST34
Domaini330 – 363WW 2PROSITE-ProRule annotationAdd BLAST34
Domaini405 – 437WW 3PROSITE-ProRule annotationAdd BLAST33
Domaini444 – 477WW 4PROSITE-ProRule annotationAdd BLAST34
Domaini536 – 870HECTPROSITE-ProRule annotationAdd BLAST335

Domaini

The C2 domain is involved in autoinhibition of the catalytic activity by interacting with the HECT domain.By similarity
The WW domains mediate interaction with PPxY motif-containing proteins.By similarity

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0940 Eukaryota
COG5021 LUCA
GeneTreeiENSGT00760000118966
HOGENOMiHOG000208453
HOVERGENiHBG004134
InParanoidiQ9DBH0
KOiK05630
OMAiPGWEIRK
OrthoDBiEOG091G0SS8
PhylomeDBiQ9DBH0
TreeFamiTF323658

Family and domain databases

CDDicd00078 HECTc, 1 hit
cd00201 WW, 4 hits
Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR024928 E3_ub_ligase_SMURF1
IPR000569 HECT_dom
IPR035983 Hect_E3_ubiquitin_ligase
IPR001202 WW_dom
IPR036020 WW_dom_sf
PfamiView protein in Pfam
PF00632 HECT, 1 hit
PF00397 WW, 4 hits
PIRSFiPIRSF001569 E3_ub_ligase_SMURF1, 1 hit
SMARTiView protein in SMART
SM00239 C2, 1 hit
SM00119 HECTc, 1 hit
SM00456 WW, 4 hits
SUPFAMiSSF51045 SSF51045, 4 hits
SSF56204 SSF56204, 1 hit
PROSITEiView protein in PROSITE
PS50237 HECT, 1 hit
PS01159 WW_DOMAIN_1, 4 hits
PS50020 WW_DOMAIN_2, 4 hits

Sequencei

Sequence statusi: Complete.

Q9DBH0-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MASASSSRAG VALPFEKSQL TLKVVSAKPK VHNRQPRINS YVEVAVDGLP
60 70 80 90 100
SETKKTGKRI GSSELLWNEI IVLNVTAQSH LDLKVWSCHT LRNELLGTAS
110 120 130 140 150
VNLSNVLKNN GGKMENTQLT LNLQTENKGS VVSGGELTIF LDGPTVDLGS
160 170 180 190 200
VPNGSAVTDG SQPPSRESSG TAIAPETRHQ PPSTNCFGGR SRTHRHSGGS
210 220 230 240 250
ARTATAASEQ SPGARNRHRQ PVKNSSSSGL ANGTVNEEPT PASEPEESSV
260 270 280 290 300
VGVTSLPAAA LSVSSNPNTT SLPAQSTPAE GEEASTSGTQ QLPAAAQAPD
310 320 330 340 350
ALPAGWEQRE LPNGRVYYVD HNTKTTTWER PLPPGWEKRT DPRGRFYYVD
360 370 380 390 400
HNTRTTTWQR PTAEYVRNYE QWQSQRNQLQ GAMQHFSQRF LYQSSSASTD
410 420 430 440 450
HDPLGPLPPG WEKRQDNGRV YYVNHNTRTT QWEDPRTQGM IQEPALPPGW
460 470 480 490 500
EMKYTSEGVR YFVDHNTRTT TFKDPRPGFE SGTKQGSPGA YDRSFRWKYH
510 520 530 540 550
QFRFLCHSNA LPSHVKISVS RQTLFEDSFQ QIMNMKPYDL RRRLYIIMRG
560 570 580 590 600
EEGLDYGGIA REWFFLLSHE VLNPMYCLFE YAGKNNYCLQ INPASSINPD
610 620 630 640 650
HLTYFRFIGR FIAMALYHGK FIDTGFTLPF YKRMLNKRPT LKDLESIDPE
660 670 680 690 700
FYNSIVWIKE NNLEECGLEL FFIQDMEILG KVTTHELKEG GENIRVTEEN
710 720 730 740 750
KEEYIMLLTD WRFTRGVEEQ TKAFLDGFNE VAPLEWLRYF DEKELELMLC
760 770 780 790 800
GMQEIDMSDW QKNAIYRHYT KSSKQIQWFW QVVKEMDNEK RIRLLQFVTG
810 820 830 840 850
TCRLPVGGFA ELIGSNGPQK FCIDRVGKET WLPRSHTCFN RLDLPPYKSY
860 870
EQLKEKLLYA IEETEGFGQE
Length:870
Mass (Da):98,761
Last modified:June 1, 2001 - v1
Checksum:i72B34A1B727A7FB3
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK004962 mRNA Translation: BAB23702.1
AK088936 mRNA Translation: BAC40661.1
AK090392 mRNA Translation: BAC41195.1
BC004712 mRNA Translation: AAH04712.1
BC039921 mRNA Translation: AAH39921.1
BC048184 mRNA Translation: AAH48184.1
CCDSiCCDS40467.1
RefSeqiNP_080106.1, NM_025830.3
XP_006531362.1, XM_006531299.3
UniGeneiMm.390058

Genome annotation databases

EnsembliENSMUST00000166615; ENSMUSP00000132224; ENSMUSG00000031930
GeneIDi66894
KEGGimmu:66894
UCSCiuc009nhv.1 mouse

Similar proteinsi

Entry informationi

Entry nameiWWP2_MOUSE
AccessioniPrimary (citable) accession number: Q9DBH0
Secondary accession number(s): Q8BTG4, Q923F6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 20, 2003
Last sequence update: June 1, 2001
Last modified: April 25, 2018
This is version 143 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways

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