E3 ubiquitin-protein ligase NEDD4 - Rattus norvegicus (Rat)

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Q62940 (NEDD4_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 108. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase NEDD4
EC=6.3.2.-

Gene names

Name:	Nedd4
Synonyms:	Nedd4a

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	887 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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. Monoubiquitinates IGF1R at multiple sites, thus leading to receptor internalization and degradation in lysosomes. Ubiquitinates FGFR1, leading to receptor internalization and degradation in lysosomes. Involved in the pathway leading to the degradation of VEGFR-2/KDFR, independently of its ubiquitin-ligase activity. Is involved in ubiquitination of ERBB4 intracellular domain E4ICD. Part of a signaling complex composed of NEDD4, RAP2A and TNIK which regulates neuronal dendrite extension and arborization during development. Ubiquitinates TNK2 and regulates EGF-induced degradation of EGFR and TNF2 By similarity. Ref.2
Enzyme regulation	Activated by NDFIP1- and NDFIP2-binding By similarity.
Pathway	Protein modification; protein ubiquitination.
Subunit structure	Interacts with UBE2D2. Binds, in vitro, through the WW2 and WW3 domains, to neural isoforms of ENAH that contain the PPSY motif. Interacts with BEAN1, LITAF, RNF11, WBP1, WBP2, TMEPAI, NDFIP1, and PRRG2 By similarity. Interacts (via C2 domain) with GRB10 (via SH2 domain) By similarity. Binds SCNN1A, SCNN1B and SCNN1G. Interacts with ERBB4. Interacts with NDFIP1 and NDFIP2; this interaction activates the E3 ubiquitin-protein ligase and may induce its recruitment to exosomes By similarity. Interacts with TNIK; the interaction is direct, allows the TNIK-dependent recruitment of RAP2A and its ubiquitination by NEDD4. Interacts (via WW3 domain) with TNK2; EGF promotes this interaction. Interacts (via WW3 domain) with FGFR1 (via C-terminus). Interacts with OTUD7B By similarity. Ref.1 Ref.2 Ref.3
Subcellular location	Cytoplasm. Cell membrane; Peripheral membrane protein By similarity. Note: Recruited to the plasma membrane by GRB10. Once complexed with GRB10 and IGF1R, follows IGF1R internalization, remaining associated with early endosomes. Uncouples from IGF1R-containing endosomes before the sorting of the receptor to the lysosomal compartment By similarity. May be recruited to exosomes by NDFIP1 By similarity. Ref.2
Tissue specificity	Ubiquitously expressed. Expression is highest in lung, kidney and brain. Ref.2
Developmental stage	Down-regulated after synapse formation. Ref.2
Domain	The WW domains mediate interaction with LITAF, RNF11, WBP1, WBP2, TMEPAI, NDFIP1 and PRRG2 By similarity.
Post-translational modification	Auto-ubiquitinated By similarity.
Miscellaneous	A cysteine residue is required for ubiquitin-thioester formation.
Sequence similarities	Contains 1 C2 domain. Contains 1 HECT (E6AP-type E3 ubiquitin-protein ligase) domain. Contains 3 WW domains.

Ontologies

Keywords
Biological process	Neurogenesis Ubl conjugation pathway
Cellular component	Cell membrane Cytoplasm Membrane
Domain	Repeat
Molecular function	Ligase
PTM	Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	immune response Inferred from expression pattern PubMed 11248052. Source: RGD negative regulation of vascular endothelial growth factor receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB protein K63-linked ubiquitination Inferred from direct assay Ref.2. Source: UniProtKB protein ubiquitination involved in ubiquitin-dependent protein catabolic process Inferred from Biological aspect of Ancestor. Source: RefGenome regulation of dendrite morphogenesis Inferred from direct assay Ref.2. Source: UniProtKB
Cellular_component	cytoplasm Inferred from Biological aspect of Ancestor. Source: RefGenome membrane raft Inferred from direct assay PubMed 11248052. Source: RGD microvillus Inferred from direct assay PubMed 9227416. Source: RGD nucleus Inferred from Biological aspect of Ancestor. Source: RefGenome plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	protein C-terminus binding Inferred from direct assay PubMed 9923703. Source: RGD ubiquitin-protein ligase activity Inferred from direct assay Ref.2. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 887

887

E3 ubiquitin-protein ligase NEDD4

PRO_0000120321

Regions

Domain

62 – 163

102

Domain

246 – 279

WW 1

Domain

402 – 435

WW 2

Domain

459 – 492

WW 3

Domain

551 – 887

337

HECT

Region

214 – 548

335

Mediates interaction with TNIK By similarity

Sites

Active site

854

Glycyl thioester intermediate By similarity

Amino acid modifications

Modified residue

284

Phosphothreonine By similarity

Modified residue

306

Phosphoserine By similarity

Modified residue

382

Phosphoserine By similarity

Secondary structure

887

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

Q62940 [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: D74B1097688CD9A1
Show »

FASTA

887

102,395

        10         20         30         40         50         60 
MAADDTEAPV LSEDEVWEFC LDKNEEGGGS PGSDVTDTCE PPCGCWELNP SSLEEEHVLF 

        70         80         90        100        110        120 
TAESIISSFN NDDTRVVRVK VIAGIGLAKK DILGASDPYV RVTLYDPMSG VLTSVQTKTI 

       130        140        150        160        170        180 
KKSLNPKWNE EILFRVLPQQ HRILFEVFDE NRLTRDDFLG QVDVPLYPLP TENPRMERPY 

       190        200        210        220        230        240 
TFKDFVLHPR SHKSRVKGYL RLKMTYLPKN GSDDENADQA EELEPGWVVL DQPDAATHLQ 

       250        260        270        280        290        300 
HPPEPSPLPP GWEERQDVLG RTYYVNHESR TTQWKRPSPE DDLTDDENGD IQLQAHGAFT 

       310        320        330        340        350        360 
TRRQISEDVD GPDNHESPEN WEIVREDENT IYSGQAVQSP PSGHPDVQVR LAEELDTRLT 

       370        380        390        400        410        420 
MYGNPATSQP VTSSNHSSRG GSSQTCIFEE QPTLPVLLPT SSGLPPGWEE KQDDRGRSYY 

       430        440        450        460        470        480 
VDHNSKTTTW SKPTMQDDPR SKIPAHLRGK TPVDSNDLGP LPPGWEERTH TDGRVFFINH 

       490        500        510        520        530        540 
NIKKTQWEDP RMQNVAITGP AEPYSRDYKR KYEFFRRKLK KQTDIPNKFE MKLRRANILE 

       550        560        570        580        590        600 
DSYRRIMGVK RADFLKARLW IEFDGEKGLD YGGVAREWFF LISKEMFNPY YGLFEYSATE 

       610        620        630        640        650        660 
DNYTLQINPN SGLCNEDHLS YFKFIGRVAG MAVYHGKLLD GFFIRPFYKM MLQKLITLHD 

       670        680        690        700        710        720 
MESVDSEYYS SLRWILENDP TELDLRFIID EELFGQTHQH ELKTGGSEVV VTNKNKKEYI 

       730        740        750        760        770        780 
YLVIQWRFVN RIQKQMAAFK EGFFELIPQD LIKIFDENEL ELLMCGLGDV DVNDWREHTK 

       790        800        810        820        830        840 
YKNGYSLNHQ VIHWFWKAVL MMDSEKRIRL LQFVTGTSRV PMNGFAELYG SNGPQSFTVE 

       850        860        870        880 
QWGTPDKLPR AHTCFNRLDL PPYESFDELW DKLQMAIENT QGFDGVD

« Hide

References

[1]	"WW domains of Nedd4 bind to the proline-rich PY motifs in the epithelial Na+ channel deleted in Liddle's syndrome." Staub O., Dho S., Henry P., Correa J., Ishikawa T., McGlade J., Rotin D. EMBO J. 15:2371-2380(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH SCNN1A; SCNN1B AND SCNN1G. Tissue: Lung.
[2]	"Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development." Kawabe H., Neeb A., Dimova K., Young S.M. Jr., Takeda M., Katsurabayashi S., Mitkovski M., Malakhova O.A., Zhang D.E., Umikawa M., Kariya K., Goebbels S., Nave K.A., Rosenmund C., Jahn O., Rhee J., Brose N. Neuron 65:358-372(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH RAP2A AND TNIK, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY.
[3]	"Solution structure of a Nedd4 WW domain-ENaC peptide complex." Kanelis V., Rotin D., Forman-Kay J.D. Nat. Struct. Biol. 8:407-412(2001) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 452-499 IN COMPLEX WITH SCNN1B, INTERACTION WITH SCNN1A; SCNN1B AND SCNN1G.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U50842 mRNA. Translation: AAB48949.1.

IPI

IPI00876592.

PIR

S70642.

RefSeq

NP_037118.1. NM_012986.1.

UniGene

Rn.99540.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1I5H	NMR	-	W	452-499	[»]

ProteinModelPortal

Q62940.

SMR

Q62940. Positions 70-208, 247-278, 401-435, 451-499, 505-878.

ModBase

Search...

Protein-protein interaction databases

STRING

10116.ENSRNOP00000009747.

PTM databases

PhosphoSite

Q62940.

Proteomic databases

PaxDb

Q62940.

PRIDE

Q62940.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

25489.

KEGG

rno:25489.

UCSC

RGD:3157. rat.

Organism-specific databases

CTD

4734.

RGD

3157. Nedd4.

Phylogenomic databases

eggNOG

COG5021.

HOGENOM

HOG000208451.

HOVERGEN

HBG004134.

InParanoid

Q62940.

K10591.

Enzyme and pathway databases

UniPathway

UPA00143.

Gene expression databases

ArrayExpress

Q62940.

Genevestigator

Q62940.

Family and domain databases

InterPro

IPR000008. C2_Ca-dep.
IPR008973. C2_Ca/lipid-bd_dom_CaLB.
IPR018029. C2_membr_targeting.
IPR024928. E3_ub_ligase_SMURF1.
IPR000569. HECT.
IPR001202. WW_dom.
[Graphical view]

Pfam

PF00168. C2. 1 hit.
PF00632. HECT. 1 hit.
PF00397. WW. 3 hits.
[Graphical view]

PIRSF

PIRSF001569. E3_ub_ligase_SMURF1. 1 hit.

SMART

SM00239. C2. 1 hit.
SM00119. HECTc. 1 hit.
SM00456. WW. 3 hits.
[Graphical view]

SUPFAM

SSF49562. C2_CaLB. 1 hit.
SSF56204. HECT. 1 hit.
SSF51045. WW_Rsp5_WWP. 3 hits.

PROSITE

PS50004. C2. 1 hit.
PS50237. HECT. 1 hit.
PS01159. WW_DOMAIN_1. 3 hits.
PS50020. WW_DOMAIN_2. 3 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q62940.

NextBio

606851.

Entry information

Entry name

NEDD4_RAT

Accession

Primary (citable) accession number: Q62940

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 3, 2003
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 108 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

PATHWAY comments

Index of metabolic and biosynthesis pathways

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents