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Protein

NEDD4-like E3 ubiquitin-protein ligase WWP1

Gene

Wwp1

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. Ubiquitinates and promotes degradation of SMAD2 in response to TGF-beta signaling, which requires interaction with TGIF (By similarity). Ubiquitinates ERBB4 isoforms JM-A CYT-1 and JM-B CYT-1, KLF2, KLF5 and TP63 and promotes their proteasomal degradation. Ubiquitinates RNF11 without targeting it for degradation. Ubiquitinates and promotes degradation of TGFBR1; the ubiquitination is enhanced by SMAD7. Ubiquitinates SMAD6 and SMAD7.By similarity5 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.

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 sitei886Glycyl thioester intermediatePROSITE-ProRule annotation1
Sitei886Required for ubiquitin-thioester formation1

GO - Molecular functioni

  • ubiquitin protein ligase activity Source: MGI
  • ubiquitin-protein transferase activity Source: UniProtKB

GO - Biological processi

  • lung development Source: UniProtKB
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • protein ubiquitination Source: UniProtKB
  • T cell differentiation Source: UniProtKB

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway

Enzyme and pathway databases

ReactomeiR-MMU-1253288 Downregulation of ERBB4 signaling
R-MMU-2672351 Stimuli-sensing channels
R-MMU-983168 Antigen processing: Ubiquitination & Proteasome degradation
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
NEDD4-like E3 ubiquitin-protein ligase WWP1 (EC:2.3.2.26)
Alternative name(s):
HECT-type E3 ubiquitin transferase WWP1
WW domain-containing protein 1
Gene namesi
Name:Wwp1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:1861728 Wwp1

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

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi886C → S: Loss of catalytic activity. No effect on RNF11-binding. No effect on KLF2 ubiquitination. Abolishes ubiquitination of KLF5. 3 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001203371 – 918NEDD4-like E3 ubiquitin-protein ligase WWP1Add BLAST918

Post-translational modificationi

Auto-ubiquitinated and ubiquitinated by RNF11.By similarity

Keywords - PTMi

Ubl conjugation

Proteomic databases

EPDiQ8BZZ3
MaxQBiQ8BZZ3
PaxDbiQ8BZZ3
PRIDEiQ8BZZ3

PTM databases

iPTMnetiQ8BZZ3
PhosphoSitePlusiQ8BZZ3
SwissPalmiQ8BZZ3

Expressioni

Gene expression databases

BgeeiENSMUSG00000041058
GenevisibleiQ8BZZ3 MM

Interactioni

Subunit structurei

Binds SCNN1A, SCNN1B, SCNN1G, WBP1, WBP2, DRPLA and adenovirus type 2 PIII. Interacts with TGIF (By similarity). Binds KLF2 AND HIVEP3. Interacts with RNF11. Interacts with SPART. Interacts with NDFIP1 and NDFIP2; this interaction activates the E3 ubiquitin-protein ligase (By similarity). Interacts with ERBB4 isoforms JM-B CYT-1 and JM-A CYT-1. Does not interact with ERB4 isoform JMA-A CYT-2. Interacts with SMAD1, SMAD2, SMAD3, SMAD5, SMAD6, SMAD7, TGFBR1 AND TGFBR2. Associates with the TGFBR1:TGFBR2 receptor complex in presence of SMAD7. Interacts with SKIL isoform 1. Interacts with TP63 isoform 1 and isoform 2. Interacts (via WW domains) with ARRDC1, ARRDC2 and ARRDC3 (By similarity).By similarity6 Publications

Protein-protein interaction databases

BioGridi223399, 2 interactors
IntActiQ8BZZ3, 1 interactor
STRINGi10090.ENSMUSP00000041627

Structurei

3D structure databases

ProteinModelPortaliQ8BZZ3
SMRiQ8BZZ3
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini5 – 98C2PROSITE-ProRule annotationAdd BLAST94
Domaini345 – 378WW 1PROSITE-ProRule annotationAdd BLAST34
Domaini377 – 410WW 2PROSITE-ProRule annotationAdd BLAST34
Domaini452 – 485WW 3PROSITE-ProRule annotationAdd BLAST34
Domaini492 – 525WW 4PROSITE-ProRule annotationAdd BLAST34
Domaini584 – 918HECTPROSITE-ProRule annotationAdd BLAST335

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni345 – 525Interaction with ERBB41 PublicationAdd BLAST181

Domaini

The WW domains mediate interaction with PPxY motif-containing proteins.By similarity

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0940 Eukaryota
COG5021 LUCA
GeneTreeiENSGT00760000118966
HOGENOMiHOG000208453
HOVERGENiHBG004134
InParanoidiQ8BZZ3
KOiK05633
OMAiRVDSNDR
OrthoDBiEOG091G0SS8
PhylomeDBiQ8BZZ3
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
PF00168 C2, 1 hit
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
PS50004 C2, 1 hit
PS50237 HECT, 1 hit
PS01159 WW_DOMAIN_1, 4 hits
PS50020 WW_DOMAIN_2, 4 hits

Sequencei

Sequence statusi: Complete.

Q8BZZ3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MATASPRSDT SDIHSGRLQL KVTVSSAKLK RKKNWFGTAI YTEVIVDGEV
60 70 80 90 100
KKTAKSSSSS NPKWDEQLIV NVTPQTTLEF RVWSHHTLKA DALLGKATVD
110 120 130 140 150
LKQVLLTHNR KLEKVKEQLK LSLENKNGIV QTGELTVVLD GLVIEQEPVT
160 170 180 190 200
NRSSSPPIEI QQNGDALHEN GDPATRTTPR LPVEGTIGID NHVSTNTVVP
210 220 230 240 250
NSCCSHVVNG ENTPSSPSQV AARPKNAPAP KPVTSAPTSD TVNGESSSVL
260 270 280 290 300
ADNTSTMGTL LPSEDTTSTS NCTSTTTQEP PVQEPPASSE HSECIPSASA
310 320 330 340 350
EVGPEARSLI DPDSDSRNNS VFDKVRQPEG CVEPLRPQSG NTNTEALPSG
360 370 380 390 400
WEQRKDPHGR TYYVDHNTRT TTWERPQPLP PGWERRVDDR GRVYYVDHNT
410 420 430 440 450
RTTTWQRPTM ESVRNFEQWQ SQRNQLQGAM QQFNQRYLYS ASMLAAENDP
460 470 480 490 500
YGPLPPGWEK RVDSTDRVYF VNHNTKTTQW EDPRTQGLPN EEPLPEGWEI
510 520 530 540 550
RYTREGVRYF VDHNTRTTTF KDPRNGKSSV TKGGPQIAYE RSFRWKLAHF
560 570 580 590 600
RYLCQSNALP SHVKINVSRQ TLFEDSFQQI MALKPYDLRR RLYVIFRGEE
610 620 630 640 650
GLDYGGLARE WFFLLSHEVL NPMYCLFEYA GKNNYCLQIN PASTINPDHL
660 670 680 690 700
SYFCFIGRFI AMALFHGKFI DTGFSLPFYK RMLSKKLTIK DLESIDTEFY
710 720 730 740 750
NSLIWIRDNN IEECGLEMYF SVDMEILGKV TSHDLKLGGS NILVTEENKD
760 770 780 790 800
EYIGLMTEWR FSRGVQEQTK AFLDGFNEVV PLQWLQYFDE KELEVMLCGM
810 820 830 840 850
QEVDLADWQR NTVYRHYTRN SKQIIWFWQF VKETDNEVRM RLLQFVTGTC
860 870 880 890 900
RLPLGGFAEL MGSNGPQKFC IEKVGKDTWL PRSHTCFNRL DLPPYKSYEQ
910
LKEKLLFAIE ETEGFGQE
Length:918
Mass (Da):104,694
Last modified:June 20, 2003 - v2
Checksum:i01478A3C1CFFDAA9
GO

Sequence cautioni

The sequence AAH21470 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAC38473 differs from that shown. Chimera. The second part of the clone maps to another chromosome.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti302V → L in BAC28168 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK033138 mRNA Translation: BAC28168.1
AK082346 mRNA Translation: BAC38473.1 Sequence problems.
BC021470 mRNA Translation: AAH21470.1 Different initiation.
BC051405 mRNA Translation: AAH51405.1
CCDSiCCDS38697.1
RefSeqiNP_001263221.1, NM_001276292.1
NP_796301.2, NM_177327.5
UniGeneiMm.474845
Mm.78312

Genome annotation databases

EnsembliENSMUST00000035982; ENSMUSP00000041627; ENSMUSG00000041058
ENSMUST00000108246; ENSMUSP00000103881; ENSMUSG00000041058
GeneIDi107568
KEGGimmu:107568
UCSCiuc008scc.2 mouse

Similar proteinsi

Entry informationi

Entry nameiWWP1_MOUSE
AccessioniPrimary (citable) accession number: Q8BZZ3
Secondary accession number(s): Q8BIV9, Q8VDP8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 20, 2003
Last sequence update: June 20, 2003
Last modified: May 23, 2018
This is version 147 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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