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Protein

NEDD4 family-interacting protein 2

Gene

NDFIP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. May modulate EGFR signaling.3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei186Not phosphorylated by SRC1

GO - Molecular functioni

  • signal transducer activity Source: UniProtKB
  • WW domain binding Source: BHF-UCL

GO - Biological processi

  • negative regulation of gene expression Source: UniProtKB
  • negative regulation of protein transport Source: UniProtKB
  • negative regulation of transporter activity Source: UniProtKB
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • positive regulation of protein ubiquitination Source: UniProtKB
Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
NEDD4 family-interacting protein 2
Alternative name(s):
NEDD4 WW domain-binding protein 5A
Putative MAPK-activating protein PM04/PM05/PM06/PM07
Putative NF-kappa-B-activating protein 413
Gene namesi
Name:NDFIP2
Synonyms:KIAA1165, N4WBP5A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 13

Organism-specific databases

HGNCiHGNC:18537. NDFIP2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 231CytoplasmicSequence analysisAdd BLAST231
Transmembranei232 – 252HelicalSequence analysisAdd BLAST21
Topological domaini253 – 257ExtracellularSequence analysis5
Transmembranei258 – 278HelicalSequence analysisAdd BLAST21
Topological domaini279 – 287CytoplasmicSequence analysis9
Transmembranei288 – 308HelicalSequence analysisAdd BLAST21
Topological domaini309 – 336ExtracellularSequence analysisAdd BLAST28

GO - Cellular componenti

  • cytoplasm Source: BHF-UCL
  • endoplasmic reticulum Source: BHF-UCL
  • Golgi apparatus Source: BHF-UCL
  • Golgi membrane Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB-KW
  • intracellular membrane-bounded organelle Source: HPA
  • mitochondrion Source: BHF-UCL
  • multivesicular body membrane Source: UniProtKB-SubCell
  • perinuclear region of cytoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endosome, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi150 – 151PY → AG: Loss of E3 ubiquitin-protein ligase activation; when associated with 175-P--G-177 AND 184-P--G-186. Greatly decreases NEDD4-binding; when associated with 175-P--G-177 and 184-P--G-186. No effect on PTEN-binding; when associated with 175-P--G-177 AND 184-P--G-186. 2
Mutagenesisi167Y → F: Loss of NDFIP2 phosphorylation by SRC. 1 Publication1
Mutagenesisi176 – 177PY → AG: Loss of E3 ubiquitin-protein ligase activation; when associated with 149-P--G-151 AND 184-P--G-186. Greatly decreases NEDD4-binding; when associated with 149-P-G-151 AND 184-P--G-186. No effect on PTEN-binding; when associated with 149-P--G-151 AND 184-P--G-186. 2
Mutagenesisi185 – 186TY → AG: Loss of E3 ubiquitin-protein ligase activation; when associated with 149-P--G-151 AND 175-P--G-177. Greatly decreases NEDD4-binding; when associated with 149-P--G-151 AND 175-P--G-177. No effect on PTEN-binding; when associated with 149-P--G-151 AND 175-P--G-177. 2

Organism-specific databases

DisGeNETi54602.
OpenTargetsiENSG00000102471.
PharmGKBiPA134953250.

Polymorphism and mutation databases

BioMutaiNDFIP2.
DMDMi73921209.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000967941 – 336NEDD4 family-interacting protein 2Add BLAST336

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei151Phosphotyrosine; by SRC; dependent on Y-1671 Publication1
Modified residuei167Phosphotyrosine; by SRC1 Publication1
Modified residuei171Phosphotyrosine; by SRC; dependent on Y-1671 Publication1
Modified residuei177Phosphotyrosine; by SRC; dependent on Y-1671 Publication1

Post-translational modificationi

Ubiquitinated by NEDD4 and ITCH. Also ubiquitinated by NEDD4L. Ubiquitination by NEDD4 or NEDD4L does not affect turnover (By similarity).By similarity
Undergoes transient tyrosine-phosphorylation following EGF stimulation, most probably catalyzed by SRC. Also phosphorylated by LYN and FYN.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9NV92.
MaxQBiQ9NV92.
PaxDbiQ9NV92.
PeptideAtlasiQ9NV92.
PRIDEiQ9NV92.

PTM databases

iPTMnetiQ9NV92.
PhosphoSitePlusiQ9NV92.

Expressioni

Tissue specificityi

Expressed in brain, lung, heart, skeletal muscle, kidney, liver and placenta.1 Publication

Inductioni

By T-cell activation.1 Publication

Gene expression databases

BgeeiENSG00000102471.
CleanExiHS_NDFIP2.
ExpressionAtlasiQ9NV92. baseline and differential.
GenevisibleiQ9NV92. HS.

Organism-specific databases

HPAiHPA009160.

Interactioni

Subunit structurei

Forms heterodimers with NDFIP1. Interacts with HECT domain-containing E3 ubiquitin-protein ligases, including NEDD4. Interacts with NEDD4L (By similarity). Interacts with PTEN. When phosphorylated at Tyr-167, interacts with SRC and LYN SH2 domain. May thus act as a scaffold that recruits SRC to NDFIP1, enhancing NDFIP1 phosphorylation. Interacts with SLC11A2/DMT1. May interact with phosphorylated EGFR.By similarity3 Publications

GO - Molecular functioni

  • WW domain binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi120074. 17 interactors.
IntActiQ9NV92. 1 interactor.
STRINGi9606.ENSP00000218652.

Structurei

3D structure databases

ProteinModelPortaliQ9NV92.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni148 – 151Interaction with NEDD4By similarity4

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi149 – 151WW-binding 13
Motifi175 – 177WW-binding 23
Motifi184 – 186WW-binding 33

Domaini

The PY/WW-binding motifs are required for E3 ubiquitin-protein ligase activation and for ubiquitination.

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4812. Eukaryota.
ENOG4111M6U. LUCA.
GeneTreeiENSGT00390000012721.
HOGENOMiHOG000038752.
HOVERGENiHBG057103.
InParanoidiQ9NV92.
OMAiSPPPYCS.
OrthoDBiEOG091G0IMV.
PhylomeDBiQ9NV92.
TreeFamiTF324911.

Sequencei

Sequence statusi: Complete.

Q9NV92-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MARRRSQRVC ASGPSMLNSA RGAPELLRGT ATNAEVSAAA AGATGSEELP
60 70 80 90 100
PGDRGCRNGG GRGPAATTSS TGVAVGAEHG EDSLSRKPDP EPGRMDHHQP
110 120 130 140 150
GTGRYQVLLN EEDNSESSAI EQPPTSNPAP QIVQAASSAP ALETDSSPPP
160 170 180 190 200
YSSITVEVPT TSDTEVYGEF YPVPPPYSVA TSLPTYDEAE KAKAAAMAAA
210 220 230 240 250
AAETSQRIQE EECPPRDDFS DADQLRVGND GIFMLAFFMA FIFNWLGFCL
260 270 280 290 300
SFCITNTIAG RYGAICGFGL SLIKWILIVR FSDYFTGYFN GQYWLWWIFL
310 320 330
VLGLLLFFRG FVNYLKVRNM SESMAAAHRT RYFFLL
Length:336
Mass (Da):36,390
Last modified:August 30, 2005 - v2
Checksum:iA7E386C12886321E
GO

Sequence cautioni

The sequence AAH21988 differs from that shown. Reason: Erroneous initiation.Curated
The sequence AAH26126 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAA91863 differs from that shown. Reason: Erroneous initiation.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_061687124P → S.Corresponds to variant rs55887763dbSNPEnsembl.1
Natural variantiVAR_023414136A → V.3 PublicationsCorresponds to variant rs11549502dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB097019 mRNA. Translation: BAC77372.1.
AB097028 mRNA. Translation: BAC77381.1.
AB097029 mRNA. Translation: BAC77382.1.
AB097030 mRNA. Translation: BAC77383.1.
AB097031 mRNA. Translation: BAC77384.1.
AL136442, AL355603 Genomic DNA. Translation: CAH71782.1.
AL355603, AL136442 Genomic DNA. Translation: CAH73355.1.
AK001723 mRNA. Translation: BAA91863.1. Different initiation.
AB032991 mRNA. Translation: BAA86479.1.
BC021988 mRNA. Translation: AAH21988.1. Different initiation.
BC026126 mRNA. Translation: AAH26126.1. Different initiation.
CCDSiCCDS31998.1.
RefSeqiNP_061953.2. NM_019080.2.
UniGeneiHs.525093.

Genome annotation databases

EnsembliENST00000218652; ENSP00000218652; ENSG00000102471.
ENST00000612570; ENSP00000480798; ENSG00000102471.
GeneIDi54602.
KEGGihsa:54602.
UCSCiuc001vlf.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB097019 mRNA. Translation: BAC77372.1.
AB097028 mRNA. Translation: BAC77381.1.
AB097029 mRNA. Translation: BAC77382.1.
AB097030 mRNA. Translation: BAC77383.1.
AB097031 mRNA. Translation: BAC77384.1.
AL136442, AL355603 Genomic DNA. Translation: CAH71782.1.
AL355603, AL136442 Genomic DNA. Translation: CAH73355.1.
AK001723 mRNA. Translation: BAA91863.1. Different initiation.
AB032991 mRNA. Translation: BAA86479.1.
BC021988 mRNA. Translation: AAH21988.1. Different initiation.
BC026126 mRNA. Translation: AAH26126.1. Different initiation.
CCDSiCCDS31998.1.
RefSeqiNP_061953.2. NM_019080.2.
UniGeneiHs.525093.

3D structure databases

ProteinModelPortaliQ9NV92.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120074. 17 interactors.
IntActiQ9NV92. 1 interactor.
STRINGi9606.ENSP00000218652.

PTM databases

iPTMnetiQ9NV92.
PhosphoSitePlusiQ9NV92.

Polymorphism and mutation databases

BioMutaiNDFIP2.
DMDMi73921209.

Proteomic databases

EPDiQ9NV92.
MaxQBiQ9NV92.
PaxDbiQ9NV92.
PeptideAtlasiQ9NV92.
PRIDEiQ9NV92.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000218652; ENSP00000218652; ENSG00000102471.
ENST00000612570; ENSP00000480798; ENSG00000102471.
GeneIDi54602.
KEGGihsa:54602.
UCSCiuc001vlf.4. human.

Organism-specific databases

CTDi54602.
DisGeNETi54602.
GeneCardsiNDFIP2.
HGNCiHGNC:18537. NDFIP2.
HPAiHPA009160.
MIMi610041. gene.
neXtProtiNX_Q9NV92.
OpenTargetsiENSG00000102471.
PharmGKBiPA134953250.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4812. Eukaryota.
ENOG4111M6U. LUCA.
GeneTreeiENSGT00390000012721.
HOGENOMiHOG000038752.
HOVERGENiHBG057103.
InParanoidiQ9NV92.
OMAiSPPPYCS.
OrthoDBiEOG091G0IMV.
PhylomeDBiQ9NV92.
TreeFamiTF324911.

Miscellaneous databases

ChiTaRSiNDFIP2. human.
GeneWikiiNDFIP2.
GenomeRNAii54602.
PROiQ9NV92.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000102471.
CleanExiHS_NDFIP2.
ExpressionAtlasiQ9NV92. baseline and differential.
GenevisibleiQ9NV92. HS.

Family and domain databases

ProtoNetiSearch...

Entry informationi

Entry nameiNFIP2_HUMAN
AccessioniPrimary (citable) accession number: Q9NV92
Secondary accession number(s): Q7Z2H3
, Q7Z428, Q8TAR3, Q9ULQ5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: August 30, 2005
Last modified: November 2, 2016
This is version 124 of the entry and version 2 of the sequence. [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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 13
    Human chromosome 13: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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.