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Protein

NEDD4 family-interacting protein 2

Gene

Ndfip2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Activates HECT domain-containing E3 ubiquitin-protein ligases, including ITCH, NEDD4, NEDD4L, SMURF2, WWP1 and WWP2, and consequently modulates the stability of their targets. As a result, may control many cellular processes. Recruits ITCH, NEDD4 and SMURF2 to endosomal membranes. Negatively regulates KCNH2 potassium channel activity by decreasing its cell-surface expression and interfering with channel maturation through recruitment of NEDD4L to the Golgi apparatus and multivesicular body where it mediates KCNH2 degradation (By similarity). May modulate EGFR signaling (By similarity). Together with NDFIP1, limits the cytokine signaling and expansion of effector Th2 T-cells by promoting degradation of JAK1, probably by ITCH- and NEDD4L-mediated ubiquitination (PubMed:27088444).By similarity3 Publications

GO - Molecular functioni

GO - Biological processi

Protein family/group databases

TCDBi8.A.30.1.1 the nedd4-family interacting protein-2 (nedd4) family

Names & Taxonomyi

Protein namesi
Recommended name:
NEDD4 family-interacting protein 2
Alternative name(s):
NEDD4 WW domain-binding protein 5A
Gene namesi
Name:Ndfip2
Synonyms:Kiaa1165, N4wbp5A
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1923523 Ndfip2

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini‹1 – 206CytoplasmicSequence analysisAdd BLAST›206
Transmembranei207 – 227HelicalSequence analysisAdd BLAST21
Topological domaini228 – 232ExtracellularSequence analysis5
Transmembranei233 – 253HelicalSequence analysisAdd BLAST21
Topological domaini254 – 262CytoplasmicSequence analysis9
Transmembranei263 – 283HelicalSequence analysisAdd BLAST21
Topological domaini284 – 311ExtracellularSequence analysisAdd BLAST28

Keywords - Cellular componenti

Endosome, Golgi apparatus, Membrane

Pathology & Biotechi

Disruption phenotypei

Mutant mice show no signs of inflammation and have normal T-cell populations in thymus, lymph nodes and spleen.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_0000096795‹1 – 311NEDD4 family-interacting protein 2Add BLAST›311

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei126Phosphotyrosine; by SRCBy similarity1
Modified residuei142Phosphotyrosine; by SRCBy similarity1
Modified residuei146Phosphotyrosine; by SRCBy similarity1
Modified residuei152Phosphotyrosine; by SRCBy similarity1

Post-translational modificationi

Ubiquitinated by NEDD4 and NEDD4L; which does not affect turnover (Probable). Also ubiquitinated by ITCH (By similarity).By similarityCurated
Undergoes transient tyrosine-phosphorylation following EGF stimulation, most probably catalyzed by SRC. Phosphorylation on Tyr-126, Tyr-146 and Tyr-152 are dependent on the phosphorylation on Tyr-142. Also phosphorylated by LYN and FYN (By similarity).By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ91ZP6
PRIDEiQ91ZP6

PTM databases

iPTMnetiQ91ZP6
PhosphoSitePlusiQ91ZP6
SwissPalmiQ91ZP6

Expressioni

Tissue specificityi

Ubiquitously expressed, with highest levels in brain, liver, kidney and testis.1 Publication

Gene expression databases

CleanExiMM_NDFIP2

Interactioni

Subunit structurei

Forms heterodimers with NDFIP1 (By similarity). Interacts with HECT domain-containing E3 ubiquitin-protein ligases, including NEDD4 (PubMed:12050153, PubMed:15252135). Interacts with NEDD4L (PubMed:12050153). When phosphorylated at Tyr-142, interacts with SRC and LYN SH2 domain (By similarity). May thus act as a scaffold that recruits SRC to NDFIP1, enhancing NDFIP1 phosphorylation (By similarity). Interacts with SLC11A2/DMT1 (By similarity). May interact with phosphorylated EGFR (By similarity). Interacts with KCNH2 (By similarity).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-58955N
IntActiQ91ZP6, 1 interactor
STRINGi10090.ENSMUSP00000137875

Structurei

3D structure databases

ProteinModelPortaliQ91ZP6
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni123 – 126Interaction with NEDD4Curated4

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi123 – 126PPxY motif 14
Motifi149 – 152PPxY motif 24
Motifi159 – 161PPxY motif 33

Domaini

The PPxY motifs are required for E3 ubiquitin-protein ligase activation and for ubiquitination.By similarity

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4812 Eukaryota
ENOG4111M6U LUCA
HOVERGENiHBG057103
InParanoidiQ91ZP6
OMAiGEFYPVP
PhylomeDBiQ91ZP6

Family and domain databases

InterProiView protein in InterPro
IPR019325 NEDD4/Bsd2
PANTHERiPTHR13396 PTHR13396, 1 hit
PfamiView protein in Pfam
PF10176 DUF2370, 1 hit

Sequences (2+)i

Sequence statusi: Fragment.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

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

Isoform 1 (identifier: Q91ZP6-1) [UniParc]FASTAAdd to basket

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
RRSASDAELS AGAEGATGSE AAPPGDLGGR TRGGGRGSAA AAATTSTREA
60 70 80 90 100
EGAERRGDTP ARKPDPEAGR MDHHQLGTGR YQVLHNEEDN SESSAVEQPS
110 120 130 140 150
TSSLAAPTVE AAASAPALDP DSPPPYSSIT VEAPTTSDTD VYSEFYPVPP
160 170 180 190 200
PYSVATSLPT YDEAEKAKAA ALAAAAADAP QRNQEEDCTP RDDFSDVEQL
210 220 230 240 250
RVGNDGIFML AFFMAFIFNW LGFCLSFCIT NTIAGRYGAI CGFGLSLIKW
260 270 280 290 300
ILIVRFSDYF TGYFNGQYWL WWIFLVLGLL LFFRGFVNYL KVRNMSESMA
310
AAHRTRYFFL L
Length:311
Mass (Da):33,638
Last modified:August 30, 2005 - v2
Checksum:iAC9A445A83F1B789
GO
Isoform 2 (identifier: Q91ZP6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     256-263: FSDYFTGY → VSILIIFM
     264-311: Missing.

Note: No experimental confirmation available.
Show »
Length:263
Mass (Da):27,656
Checksum:i42B2445A43F30827
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
M0QWK1M0QWK1_MOUSE
NEDD4 family-interacting protein 2
Ndfip2
338Annotation score:
F6RT43F6RT43_MOUSE
NEDD4 family-interacting protein 2
Ndfip2
312Annotation score:

Sequence cautioni

The sequence AAH71237 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAC27240 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAC33869 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAC37471 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Non-terminal residuei11
Sequence conflicti38S → T in BAC33869 (PubMed:16141072).Curated1
Sequence conflicti70R → S in BAC27240 (PubMed:16141072).Curated1
Sequence conflicti113A → T in AAH71237 (PubMed:15489334).Curated1
Sequence conflicti298S → G in BAC37471 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_015438256 – 263FSDYFTGY → VSILIIFM in isoform 2. 1 Publication8
Alternative sequenceiVSP_015439264 – 311Missing in isoform 2. 1 PublicationAdd BLAST48

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC071237 mRNA Translation: AAH71237.1 Different initiation.
AK031073 mRNA Translation: BAC27240.1 Different initiation.
AK049678 mRNA Translation: BAC33869.1 Different initiation.
AK078939 mRNA Translation: BAC37471.1 Different initiation.
AF411608 mRNA Translation: AAL05872.1
AK220371 mRNA Translation: BAD90430.1
UniGeneiMm.290669
Mm.387487

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC071237 mRNA Translation: AAH71237.1 Different initiation.
AK031073 mRNA Translation: BAC27240.1 Different initiation.
AK049678 mRNA Translation: BAC33869.1 Different initiation.
AK078939 mRNA Translation: BAC37471.1 Different initiation.
AF411608 mRNA Translation: AAL05872.1
AK220371 mRNA Translation: BAD90430.1
UniGeneiMm.290669
Mm.387487

3D structure databases

ProteinModelPortaliQ91ZP6
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-58955N
IntActiQ91ZP6, 1 interactor
STRINGi10090.ENSMUSP00000137875

Protein family/group databases

TCDBi8.A.30.1.1 the nedd4-family interacting protein-2 (nedd4) family

PTM databases

iPTMnetiQ91ZP6
PhosphoSitePlusiQ91ZP6
SwissPalmiQ91ZP6

Proteomic databases

PaxDbiQ91ZP6
PRIDEiQ91ZP6

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Organism-specific databases

MGIiMGI:1923523 Ndfip2
RougeiSearch...

Phylogenomic databases

eggNOGiKOG4812 Eukaryota
ENOG4111M6U LUCA
HOVERGENiHBG057103
InParanoidiQ91ZP6
OMAiGEFYPVP
PhylomeDBiQ91ZP6

Miscellaneous databases

ChiTaRSiNdfip2 mouse
SOURCEiSearch...

Gene expression databases

CleanExiMM_NDFIP2

Family and domain databases

InterProiView protein in InterPro
IPR019325 NEDD4/Bsd2
PANTHERiPTHR13396 PTHR13396, 1 hit
PfamiView protein in Pfam
PF10176 DUF2370, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNFIP2_MOUSE
AccessioniPrimary (citable) accession number: Q91ZP6
Secondary accession number(s): Q5DTZ9, Q6IR02, Q8BVC5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: August 30, 2005
Last modified: November 7, 2018
This is version 108 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

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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