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Protein

NEDD4-like E3 ubiquitin-protein ligase WWP1

Gene

Wwp1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

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)LengthDescriptionGraphical viewFeature identifierActions
Active sitei886 – 8861Glycyl thioester intermediatePROSITE-ProRule annotation
Sitei886 – 8861Required for ubiquitin-thioester formation

GO - Molecular functioni

  • ligase activity Source: UniProtKB-KW
  • 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
  • protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: GO_Central
  • T cell differentiation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-MMU-1253288. Downregulation of ERBB4 signaling.
R-MMU-2672351. Stimuli-sensing channels.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
NEDD4-like E3 ubiquitin-protein ligase WWP1 (EC:6.3.2.-)
Alternative name(s):
WW domain-containing protein 1
Gene namesi
Name:Wwp1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:1861728. Wwp1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi886 – 8861C → S: Loss of catalytic activity. No effect on RNF11-binding. No effect on KLF2 ubiquitination. Abolishes ubiquitination of KLF5. 3 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 918918NEDD4-like E3 ubiquitin-protein ligase WWP1PRO_0000120337Add
BLAST

Post-translational modificationi

Auto-ubiquitinated and ubiquitinated by RNF11.By similarity

Keywords - PTMi

Ubl conjugation

Proteomic databases

EPDiQ8BZZ3.
MaxQBiQ8BZZ3.
PaxDbiQ8BZZ3.
PRIDEiQ8BZZ3.

PTM databases

iPTMnetiQ8BZZ3.
PhosphoSiteiQ8BZZ3.

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 SPG20. 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.By similarity6 Publications

Protein-protein interaction databases

BioGridi223399. 2 interactions.
IntActiQ8BZZ3. 1 interaction.
STRINGi10090.ENSMUSP00000041627.

Structurei

3D structure databases

ProteinModelPortaliQ8BZZ3.
SMRiQ8BZZ3. Positions 19-145, 346-915.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini5 – 9894C2PROSITE-ProRule annotationAdd
BLAST
Domaini345 – 37834WW 1PROSITE-ProRule annotationAdd
BLAST
Domaini377 – 41034WW 2PROSITE-ProRule annotationAdd
BLAST
Domaini452 – 48534WW 3PROSITE-ProRule annotationAdd
BLAST
Domaini492 – 52534WW 4PROSITE-ProRule annotationAdd
BLAST
Domaini584 – 918335HECTPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni345 – 525181Interaction with ERBB4Add
BLAST

Sequence similaritiesi

Contains 1 C2 domain.PROSITE-ProRule annotation
Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain.PROSITE-ProRule annotation
Contains 4 WW domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0940. Eukaryota.
COG5021. LUCA.
GeneTreeiENSGT00760000118966.
HOGENOMiHOG000208453.
HOVERGENiHBG004134.
InParanoidiQ8BZZ3.
KOiK05633.
OMAiVYVELVV.
OrthoDBiEOG091G0SS8.
PhylomeDBiQ8BZZ3.
TreeFamiTF323658.

Family and domain databases

Gene3Di2.60.40.150. 1 hit.
InterProiIPR000008. C2_dom.
IPR024928. E3_ub_ligase_SMURF1.
IPR000569. HECT_dom.
IPR001202. WW_dom.
[Graphical view]
PfamiPF00168. C2. 1 hit.
PF00632. HECT. 1 hit.
PF00397. WW. 4 hits.
[Graphical view]
PIRSFiPIRSF001569. E3_ub_ligase_SMURF1. 1 hit.
SMARTiSM00239. C2. 1 hit.
SM00119. HECTc. 1 hit.
SM00456. WW. 4 hits.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
SSF51045. SSF51045. 4 hits.
SSF56204. SSF56204. 1 hit.
PROSITEiPS50004. C2. 1 hit.
PS50237. HECT. 1 hit.
PS01159. WW_DOMAIN_1. 4 hits.
PS50020. WW_DOMAIN_2. 4 hits.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti302 – 3021V → L in BAC28168 (PubMed:16141072).Curated

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.

Cross-referencesi

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.

3D structure databases

ProteinModelPortaliQ8BZZ3.
SMRiQ8BZZ3. Positions 19-145, 346-915.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi223399. 2 interactions.
IntActiQ8BZZ3. 1 interaction.
STRINGi10090.ENSMUSP00000041627.

PTM databases

iPTMnetiQ8BZZ3.
PhosphoSiteiQ8BZZ3.

Proteomic databases

EPDiQ8BZZ3.
MaxQBiQ8BZZ3.
PaxDbiQ8BZZ3.
PRIDEiQ8BZZ3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi11059.
MGIiMGI:1861728. Wwp1.

Phylogenomic databases

eggNOGiKOG0940. Eukaryota.
COG5021. LUCA.
GeneTreeiENSGT00760000118966.
HOGENOMiHOG000208453.
HOVERGENiHBG004134.
InParanoidiQ8BZZ3.
KOiK05633.
OMAiVYVELVV.
OrthoDBiEOG091G0SS8.
PhylomeDBiQ8BZZ3.
TreeFamiTF323658.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-MMU-1253288. Downregulation of ERBB4 signaling.
R-MMU-2672351. Stimuli-sensing channels.

Miscellaneous databases

ChiTaRSiWwp1. mouse.
PROiQ8BZZ3.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000041058.
GenevisibleiQ8BZZ3. MM.

Family and domain databases

Gene3Di2.60.40.150. 1 hit.
InterProiIPR000008. C2_dom.
IPR024928. E3_ub_ligase_SMURF1.
IPR000569. HECT_dom.
IPR001202. WW_dom.
[Graphical view]
PfamiPF00168. C2. 1 hit.
PF00632. HECT. 1 hit.
PF00397. WW. 4 hits.
[Graphical view]
PIRSFiPIRSF001569. E3_ub_ligase_SMURF1. 1 hit.
SMARTiSM00239. C2. 1 hit.
SM00119. HECTc. 1 hit.
SM00456. WW. 4 hits.
[Graphical view]
SUPFAMiSSF49562. SSF49562. 1 hit.
SSF51045. SSF51045. 4 hits.
SSF56204. SSF56204. 1 hit.
PROSITEiPS50004. C2. 1 hit.
PS50237. HECT. 1 hit.
PS01159. WW_DOMAIN_1. 4 hits.
PS50020. WW_DOMAIN_2. 4 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiWWP1_MOUSE
AccessioniPrimary (citable) accession number: Q8BZZ3
Secondary accession number(s): Q8BIV9, Q8VDP8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2003
Last sequence update: June 20, 2003
Last modified: September 7, 2016
This is version 130 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. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. 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.