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Protein

NEDD4-like E3 ubiquitin-protein ligase WWP2

Gene

Wwp2

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. 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

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 sitei838 – 8381Glycyl thioester intermediatePROSITE-ProRule annotation

GO - Molecular functioni

  • ligase activity Source: UniProtKB-KW
  • 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

Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
NEDD4-like E3 ubiquitin-protein ligase WWP2 (EC:6.3.2.-)
Alternative name(s):
WW domain-containing protein 2
Gene namesi
Name:Wwp2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:1914144. Wwp2.

Subcellular locationi

  • Nucleus By similarity

GO - Cellular componenti

  • cytoplasm Source: BHF-UCL
  • extracellular exosome Source: MGI
  • membrane Source: MGI
  • nucleus Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 870870NEDD4-like E3 ubiquitin-protein ligase WWP2PRO_0000120339Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei211 – 2111PhosphoserineBy similarity

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.
PhosphoSiteiQ9DBH0.

Expressioni

Gene expression databases

BgeeiQ9DBH0.
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.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 interactions.
IntActiQ9DBH0. 1 interaction.
STRINGi10090.ENSMUSP00000132224.

Structurei

3D structure databases

ProteinModelPortaliQ9DBH0.
SMRiQ9DBH0. Positions 17-143, 302-867.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini20 – 10081C2Add
BLAST
Domaini300 – 33334WW 1PROSITE-ProRule annotationAdd
BLAST
Domaini330 – 36334WW 2PROSITE-ProRule annotationAdd
BLAST
Domaini405 – 43733WW 3PROSITE-ProRule annotationAdd
BLAST
Domaini444 – 47734WW 4PROSITE-ProRule annotationAdd
BLAST
Domaini536 – 870335HECTPROSITE-ProRule annotationAdd
BLAST

Domaini

The C2 domain is involved in autoinhibition of the catalytic activity by interacting with the HECT domain.By similarity

Sequence similaritiesi

Contains 1 C2 domain.Curated
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.
InParanoidiQ9DBH0.
KOiK05630.
OMAiPENRHQP.
OrthoDBiEOG7RFTGT.
PhylomeDBiQ9DBH0.
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]
PfamiPF00632. 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.
PROSITEiPS50237. HECT. 1 hit.
PS01159. WW_DOMAIN_1. 4 hits.
PS50020. WW_DOMAIN_2. 4 hits.
[Graphical view]

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_006531299.2.
UniGeneiMm.390058.

Genome annotation databases

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

Cross-referencesi

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_006531299.2.
UniGeneiMm.390058.

3D structure databases

ProteinModelPortaliQ9DBH0.
SMRiQ9DBH0. Positions 17-143, 302-867.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi211793. 12 interactions.
IntActiQ9DBH0. 1 interaction.
STRINGi10090.ENSMUSP00000132224.

PTM databases

iPTMnetiQ9DBH0.
PhosphoSiteiQ9DBH0.

Proteomic databases

EPDiQ9DBH0.
MaxQBiQ9DBH0.
PaxDbiQ9DBH0.
PRIDEiQ9DBH0.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi11060.
MGIiMGI:1914144. Wwp2.

Phylogenomic databases

eggNOGiKOG0940. Eukaryota.
COG5021. LUCA.
GeneTreeiENSGT00760000118966.
HOGENOMiHOG000208453.
HOVERGENiHBG004134.
InParanoidiQ9DBH0.
KOiK05630.
OMAiPENRHQP.
OrthoDBiEOG7RFTGT.
PhylomeDBiQ9DBH0.
TreeFamiTF323658.

Enzyme and pathway databases

UniPathwayiUPA00143.

Miscellaneous databases

ChiTaRSiWwp2. mouse.
PROiQ9DBH0.
SOURCEiSearch...

Gene expression databases

BgeeiQ9DBH0.
ExpressionAtlasiQ9DBH0. baseline and differential.
GenevisibleiQ9DBH0. 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]
PfamiPF00632. 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.
PROSITEiPS50237. HECT. 1 hit.
PS01159. WW_DOMAIN_1. 4 hits.
PS50020. WW_DOMAIN_2. 4 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J and NOD.
    Tissue: Brain, Liver and Thymus.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J and FVB/N.
    Tissue: Brain and Mammary tumor.
  3. "Wwp2-mediated ubiquitination of the RNA polymerase II large subunit in mouse embryonic pluripotent stem cells."
    Li H., Zhang Z., Wang B., Zhang J., Zhao Y., Jin Y.
    Mol. Cell. Biol. 27:5296-5305(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN UBIQUITINATION OF RPB1, INTERACTION WITH RBP1.
  4. "Regulation of the divalent metal ion transporter DMT1 and iron homeostasis by a ubiquitin-dependent mechanism involving Ndfips and WWP2."
    Foot N.J., Dalton H.E., Shearwin-Whyatt L.M., Dorstyn L., Tan S.S., Yang B., Kumar S.
    Blood 112:4268-4275(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN UBIQUITINATION OF SLC11A2, INTERACTION WITH SLC11A2.
  5. "The HECT-type E3 ubiquitin ligase AIP2 inhibits activation-induced T-cell death by catalyzing EGR2 ubiquitination."
    Chen A., Gao B., Zhang J., McEwen T., Ye S.Q., Zhang D., Fang D.
    Mol. Cell. Biol. 29:5348-5356(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN UBIQUITINATION OF EGR2, INTERACTION WITH EGR2.
  6. "Wwp2 mediates Oct4 ubiquitination and its own auto-ubiquitination in a dosage-dependent manner."
    Liao B., Jin Y.
    Cell Res. 20:332-344(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN UBIQUITINATION OF POU5F1, AUTOUBIQUITINATION.

Entry informationi

Entry nameiWWP2_MOUSE
AccessioniPrimary (citable) accession number: Q9DBH0
Secondary accession number(s): Q8BTG4, Q923F6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2003
Last sequence update: June 1, 2001
Last modified: July 6, 2016
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

A cysteine residue is required for ubiquitin-thioester formation.

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.