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Protein

NEDD4-like E3 ubiquitin-protein ligase WWP1

Gene

WWP1

Organism
Homo sapiens (Human)
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 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. Ubiquitinates and promotes degradation of SMAD2 in response to TGF-beta signaling, which requires interaction with TGIF.3 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.

Activity regulationi

Activated by NDFIP1- and NDFIP2-binding.

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 sitei890Glycyl thioester intermediatePROSITE-ProRule annotation1
Sitei890Required for ubiquitin-thioester formationBy similarity1

GO - Molecular functioni

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

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processHost-virus interaction, Ubl conjugation pathway

Enzyme and pathway databases

BRENDAi6.3.2.19 2681
ReactomeiR-HSA-1253288 Downregulation of ERBB4 signaling
R-HSA-2672351 Stimuli-sensing channels
R-HSA-8939902 Regulation of RUNX2 expression and activity
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiQ9H0M0
SIGNORiQ9H0M0
UniPathwayi
UPA00143

Protein family/group databases

MoonDBiQ9H0M0 Predicted

Names & Taxonomyi

Protein namesi
Recommended name:
NEDD4-like E3 ubiquitin-protein ligase WWP1 (EC:2.3.2.26)
Alternative name(s):
Atrophin-1-interacting protein 5
Short name:
AIP5
HECT-type E3 ubiquitin transferase WWP1
TGIF-interacting ubiquitin ligase 1
Short name:
Tiul1
WW domain-containing protein 1
Gene namesi
Name:WWP1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000123124.13
HGNCiHGNC:17004 WWP1
MIMi602307 gene
neXtProtiNX_Q9H0M0

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
Mutagenesisi614E → A: Reduces ubiquitin transfer. 1 Publication1
Mutagenesisi621H → A: Strongly reduces ubiquitin transfer. 1 Publication1
Mutagenesisi675D → A: Reduces ubiquitin transfer. 1 Publication1
Mutagenesisi798E → A: Reduces ubiquitin transfer. Strongly reduces ubiquitin transfer; when associated with A-845. 1 Publication1
Mutagenesisi804M → P: Strongly reduces ubiquitin transfer; when associated with P-806. 1 Publication1
Mutagenesisi806E → P: Strongly reduces ubiquitin transfer; when associated with P-804. 1 Publication1
Mutagenesisi845R → A: No effect. 1 Publication1
Mutagenesisi848Q → A: Abolishes ubiquitin transfer; when associated with A-855. 1 Publication1
Mutagenesisi855R → A: Abolishes ubiquitin transfer; when associated with A-848. 1 Publication1

Organism-specific databases

DisGeNETi11059
OpenTargetsiENSG00000123124
PharmGKBiPA134960138

Polymorphism and mutation databases

BioMutaiWWP1
DMDMi32171908

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001203361 – 922NEDD4-like E3 ubiquitin-protein ligase WWP1Add BLAST922

Post-translational modificationi

Auto-ubiquitinated and ubiquitinated by RNF11.3 Publications

Keywords - PTMi

Ubl conjugation

Proteomic databases

EPDiQ9H0M0
PaxDbiQ9H0M0
PeptideAtlasiQ9H0M0
PRIDEiQ9H0M0
ProteomicsDBi80294
80295 [Q9H0M0-2]
80296 [Q9H0M0-3]
80297 [Q9H0M0-6]

PTM databases

iPTMnetiQ9H0M0
PhosphoSitePlusiQ9H0M0

Expressioni

Tissue specificityi

Detected in heart, placenta, pancreas, kidney, liver, skeletal muscle, bone marrow, fetal brain, and at much lower levels in adult brain and lung. Isoform 1 and isoform 5 predominate in all tissues tested, except in testis and bone marrow, where isoform 5 is expressed at much higher levels than isoform 1.2 Publications

Gene expression databases

BgeeiENSG00000123124 Expressed in 247 organ(s), highest expression level in skeletal muscle tissue of rectus abdominis
CleanExiHS_WWP1
ExpressionAtlasiQ9H0M0 baseline and differential
GenevisibleiQ9H0M0 HS

Organism-specific databases

HPAiHPA023180

Interactioni

Subunit structurei

Binds KLF2 AND HIVEP3 (By similarity). Binds SCNN1A, SCNN1B, SCNN1G, WBP1, WBP2, DRPLA and adenovirus type 2 PIII. Interacts with RNF11 (By similarity). Interacts with SPART. Interacts with ERBB4 isoforms JM-B CYT-1 and JM-A CYT-1. 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 with STAMBP and RNF11. Interacts with NDFIP1 and NDFIP2 (Probable); this interaction activates the E3 ubiquitin-protein ligase. Interacts with TGIF. Interacts (via WW domains) with ARRDC1, ARRDC2 and ARRDC3 (PubMed:21191027).By similarity8 Publications
(Microbial infection) Interacts with HTLV-1 protein Gag.1 Publication
(Microbial infection) Interacts with ebola virus protein VP40.1 Publication

Binary interactionsi

Protein-protein interaction databases

BioGridi116243, 120 interactors
IntActiQ9H0M0, 37 interactors
MINTiQ9H0M0
STRINGi9606.ENSP00000265428

Structurei

Secondary structure

1922
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9H0M0
SMRiQ9H0M0
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9H0M0

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini5 – 98C2PROSITE-ProRule annotationAdd BLAST94
Domaini349 – 382WW 1PROSITE-ProRule annotationAdd BLAST34
Domaini381 – 414WW 2PROSITE-ProRule annotationAdd BLAST34
Domaini456 – 489WW 3PROSITE-ProRule annotationAdd BLAST34
Domaini496 – 529WW 4PROSITE-ProRule annotationAdd BLAST34
Domaini588 – 922HECTPROSITE-ProRule annotationAdd BLAST335

Domaini

The WW domains mediate interaction with PPxY motif-containing proteins.1 Publication

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0940 Eukaryota
COG5021 LUCA
GeneTreeiENSGT00760000118966
HOGENOMiHOG000208453
HOVERGENiHBG004134
InParanoidiQ9H0M0
KOiK05633
OMAiFKVWSHH
OrthoDBiEOG091G0SS8
PhylomeDBiQ9H0M0
TreeFamiTF323658

Family and domain databases

CDDicd00078 HECTc, 1 hit
cd00201 WW, 3 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

Sequences (6+)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket
Note: Additional isoforms seem to exist.

This entry has 6 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9H0M0-1) [UniParc]FASTAAdd to basket
Also known as: A

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MATASPRSDT SNNHSGRLQL QVTVSSAKLK RKKNWFGTAI YTEVVVDGEI
60 70 80 90 100
TKTAKSSSSS NPKWDEQLTV NVTPQTTLEF QVWSHRTLKA DALLGKATID
110 120 130 140 150
LKQALLIHNR KLERVKEQLK LSLENKNGIA QTGELTVVLD GLVIEQENIT
160 170 180 190 200
NCSSSPTIEI QENGDALHEN GEPSARTTAR LAVEGTNGID NHVPTSTLVQ
210 220 230 240 250
NSCCSYVVNG DNTPSSPSQV AARPKNTPAP KPLASEPADD TVNGESSSFA
260 270 280 290 300
PTDNASVTGT PVVSEENALS PNCTSTTVED PPVQEILTSS ENNECIPSTS
310 320 330 340 350
AELESEARSI LEPDTSNSRS SSAFEAAKSR QPDGCMDPVR QQSGNANTET
360 370 380 390 400
LPSGWEQRKD PHGRTYYVDH NTRTTTWERP QPLPPGWERR VDDRRRVYYV
410 420 430 440 450
DHNTRTTTWQ RPTMESVRNF EQWQSQRNQL QGAMQQFNQR YLYSASMLAA
460 470 480 490 500
ENDPYGPLPP GWEKRVDSTD RVYFVNHNTK TTQWEDPRTQ GLQNEEPLPE
510 520 530 540 550
GWEIRYTREG VRYFVDHNTR TTTFKDPRNG KSSVTKGGPQ IAYERGFRWK
560 570 580 590 600
LAHFRYLCQS NALPSHVKIN VSRQTLFEDS FQQIMALKPY DLRRRLYVIF
610 620 630 640 650
RGEEGLDYGG LAREWFFLLS HEVLNPMYCL FEYAGKNNYC LQINPASTIN
660 670 680 690 700
PDHLSYFCFI GRFIAMALFH GKFIDTGFSL PFYKRMLSKK LTIKDLESID
710 720 730 740 750
TEFYNSLIWI RDNNIEECGL EMYFSVDMEI LGKVTSHDLK LGGSNILVTE
760 770 780 790 800
ENKDEYIGLM TEWRFSRGVQ EQTKAFLDGF NEVVPLQWLQ YFDEKELEVM
810 820 830 840 850
LCGMQEVDLA DWQRNTVYRH YTRNSKQIIW FWQFVKETDN EVRMRLLQFV
860 870 880 890 900
TGTCRLPLGG FAELMGSNGP QKFCIEKVGK DTWLPRSHTC FNRLDLPPYK
910 920
SYEQLKEKLL FAIEETEGFG QE
Length:922
Mass (Da):105,202
Last modified:March 1, 2001 - v1
Checksum:i35B6E1C03A3147DA
GO
Isoform 2 (identifier: Q9H0M0-2) [UniParc]FASTAAdd to basket
Also known as: B

The sequence of this isoform differs from the canonical sequence as follows:
     112-120: LERVKEQLK → CWLLKARME
     121-922: Missing.

Show »
Length:120
Mass (Da):13,453
Checksum:i952B6A78C5D4B93D
GO
Isoform 3 (identifier: Q9H0M0-3) [UniParc]FASTAAdd to basket
Also known as: C

The sequence of this isoform differs from the canonical sequence as follows:
     112-242: LERVKEQLKL...LASEPADDTV → F

Show »
Length:792
Mass (Da):91,548
Checksum:i833D351CC08D9998
GO
Isoform 4 (identifier: Q9H0M0-4)
Also known as: D
Sequence is not available
Length:
Mass (Da):
Isoform 5 (identifier: Q9H0M0-5)
Also known as: E
Sequence is not available
Length:
Mass (Da):
Isoform 6 (identifier: Q9H0M0-6) [UniParc]FASTAAdd to basket
Also known as: F

The sequence of this isoform differs from the canonical sequence as follows:
     23-240: Missing.

Show »
Length:704
Mass (Da):81,649
Checksum:iB39DCB6841290CF0
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YBS9H0YBS9_HUMAN
NEDD4-like E3 ubiquitin-protein lig...
WWP1
55Annotation score:
H0YBA4H0YBA4_HUMAN
NEDD4-like E3 ubiquitin-protein lig...
WWP1
232Annotation score:

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_00760023 – 240Missing in isoform 6. 1 PublicationAdd BLAST218
Alternative sequenceiVSP_007602112 – 242LERVK…ADDTV → F in isoform 3. 1 PublicationAdd BLAST131
Alternative sequenceiVSP_007601112 – 120LERVKEQLK → CWLLKARME in isoform 2. 1 Publication9
Alternative sequenceiVSP_007603121 – 922Missing in isoform 2. 1 PublicationAdd BLAST802

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL136739 mRNA Translation: CAB66673.1
AY043361 mRNA Translation: AAK94668.1
AY345857 mRNA Translation: AAQ22764.1
AC083845 Genomic DNA No translation available.
AC103817 Genomic DNA No translation available.
BC015380 mRNA Translation: AAH15380.2
BC036065 mRNA Translation: AAH36065.1
U96113 mRNA Translation: AAC51324.1
CCDSiCCDS6242.1 [Q9H0M0-1]
RefSeqiNP_008944.1, NM_007013.3 [Q9H0M0-1]
XP_005250817.1, XM_005250760.3 [Q9H0M0-1]
UniGeneiHs.655189

Genome annotation databases

EnsembliENST00000265428; ENSP00000265428; ENSG00000123124 [Q9H0M0-1]
ENST00000517970; ENSP00000427793; ENSG00000123124 [Q9H0M0-1]
GeneIDi11059
KEGGihsa:11059
UCSCiuc003ydt.4 human [Q9H0M0-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AL136739 mRNA Translation: CAB66673.1
AY043361 mRNA Translation: AAK94668.1
AY345857 mRNA Translation: AAQ22764.1
AC083845 Genomic DNA No translation available.
AC103817 Genomic DNA No translation available.
BC015380 mRNA Translation: AAH15380.2
BC036065 mRNA Translation: AAH36065.1
U96113 mRNA Translation: AAC51324.1
CCDSiCCDS6242.1 [Q9H0M0-1]
RefSeqiNP_008944.1, NM_007013.3 [Q9H0M0-1]
XP_005250817.1, XM_005250760.3 [Q9H0M0-1]
UniGeneiHs.655189

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ND7X-ray2.10A546-917[»]
2OP7NMR-A494-532[»]
5HPSX-ray2.05A537-917[»]
5HPTX-ray2.84A/D/G537-917[»]
ProteinModelPortaliQ9H0M0
SMRiQ9H0M0
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116243, 120 interactors
IntActiQ9H0M0, 37 interactors
MINTiQ9H0M0
STRINGi9606.ENSP00000265428

Protein family/group databases

MoonDBiQ9H0M0 Predicted

PTM databases

iPTMnetiQ9H0M0
PhosphoSitePlusiQ9H0M0

Polymorphism and mutation databases

BioMutaiWWP1
DMDMi32171908

Proteomic databases

EPDiQ9H0M0
PaxDbiQ9H0M0
PeptideAtlasiQ9H0M0
PRIDEiQ9H0M0
ProteomicsDBi80294
80295 [Q9H0M0-2]
80296 [Q9H0M0-3]
80297 [Q9H0M0-6]

Protocols and materials databases

DNASUi11059
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265428; ENSP00000265428; ENSG00000123124 [Q9H0M0-1]
ENST00000517970; ENSP00000427793; ENSG00000123124 [Q9H0M0-1]
GeneIDi11059
KEGGihsa:11059
UCSCiuc003ydt.4 human [Q9H0M0-1]

Organism-specific databases

CTDi11059
DisGeNETi11059
EuPathDBiHostDB:ENSG00000123124.13
GeneCardsiWWP1
HGNCiHGNC:17004 WWP1
HPAiHPA023180
MIMi602307 gene
neXtProtiNX_Q9H0M0
OpenTargetsiENSG00000123124
PharmGKBiPA134960138
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0940 Eukaryota
COG5021 LUCA
GeneTreeiENSGT00760000118966
HOGENOMiHOG000208453
HOVERGENiHBG004134
InParanoidiQ9H0M0
KOiK05633
OMAiFKVWSHH
OrthoDBiEOG091G0SS8
PhylomeDBiQ9H0M0
TreeFamiTF323658

Enzyme and pathway databases

UniPathwayi
UPA00143

BRENDAi6.3.2.19 2681
ReactomeiR-HSA-1253288 Downregulation of ERBB4 signaling
R-HSA-2672351 Stimuli-sensing channels
R-HSA-8939902 Regulation of RUNX2 expression and activity
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiQ9H0M0
SIGNORiQ9H0M0

Miscellaneous databases

ChiTaRSiWWP1 human
EvolutionaryTraceiQ9H0M0
GeneWikiiWWP1
GenomeRNAii11059
PROiPR:Q9H0M0
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000123124 Expressed in 247 organ(s), highest expression level in skeletal muscle tissue of rectus abdominis
CleanExiHS_WWP1
ExpressionAtlasiQ9H0M0 baseline and differential
GenevisibleiQ9H0M0 HS

Family and domain databases

CDDicd00078 HECTc, 1 hit
cd00201 WW, 3 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
ProtoNetiSearch...

Entry informationi

Entry nameiWWP1_HUMAN
AccessioniPrimary (citable) accession number: Q9H0M0
Secondary accession number(s): O00307, Q5YLC1, Q96BP4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 20, 2003
Last sequence update: March 1, 2001
Last modified: November 7, 2018
This is version 175 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  2. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
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