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Protein

NEDD4 family-interacting protein 2

Gene

NDFIP2

Organism
Homo sapiens (Human)
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 (PubMed:26363003). May modulate EGFR signaling. 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 (By similarity).By similarity4 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei186Not phosphorylated by SRC1

GO - Molecular functioni

  • WW domain binding Source: BHF-UCL

GO - Biological processi

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

EuPathDBiHostDB:ENSG00000102471.13
HGNCiHGNC:18537 NDFIP2
MIMi610041 gene
neXtProtiNX_Q9NV92

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 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

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 SRC1 Publication1
Modified residuei167Phosphotyrosine; by SRC1 Publication1
Modified residuei171Phosphotyrosine; by SRC1 Publication1
Modified residuei177Phosphotyrosine; by SRC1 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. Phosphorylation on Tyr-151, Tyr-171 and Tyr-177 are dependent on the phosphorylation on Tyr-167. Also phosphorylated by LYN and FYN.1 Publication

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9NV92
MaxQBiQ9NV92
PaxDbiQ9NV92
PeptideAtlasiQ9NV92
PRIDEiQ9NV92
ProteomicsDBi82762

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 Expressed in 204 organ(s), highest expression level in parietal lobe
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 (PubMed:12796489). Interacts with NEDD4L (PubMed:26363003). 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 (PubMed:18776082). May interact with phosphorylated EGFR. Interacts with KCNH2 (PubMed:26363003).By similarity4 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi120074, 32 interactors
IntActiQ9NV92, 4 interactors
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
Motifi148 – 151PPxY motif 14
Motifi174 – 177PPxY motif 24
Motifi184 – 186PPxY motif 33

Domaini

The PPxY 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
OMAiGEFYPVP
OrthoDBiEOG091G0IMV
PhylomeDBiQ9NV92
TreeFamiTF324911

Family and domain databases

InterProiView protein in InterPro
IPR019325 NEDD4/Bsd2
PANTHERiPTHR13396 PTHR13396, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B4DGY6B4DGY6_HUMAN
cDNA FLJ53039, highly similar to NE...
NDFIP2
222Annotation score:
A0A0C4DGW0A0A0C4DGW0_HUMAN
NEDD4 family-interacting protein 2
NDFIP2
242Annotation score:
H7C5F7H7C5F7_HUMAN
NEDD4 family-interacting protein 2
NDFIP2
146Annotation score:

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 dbSNP:rs55887763Ensembl.1
Natural variantiVAR_023414136A → V3 PublicationsCorresponds to variant dbSNP:rs11549502Ensembl.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 Genomic DNA No translation available.
AL355603 Genomic DNA No translation available.
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

Similar proteinsi

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 Genomic DNA No translation available.
AL355603 Genomic DNA No translation available.
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, 32 interactors
IntActiQ9NV92, 4 interactors
STRINGi9606.ENSP00000218652

PTM databases

iPTMnetiQ9NV92
PhosphoSitePlusiQ9NV92

Polymorphism and mutation databases

BioMutaiNDFIP2
DMDMi73921209

Proteomic databases

EPDiQ9NV92
MaxQBiQ9NV92
PaxDbiQ9NV92
PeptideAtlasiQ9NV92
PRIDEiQ9NV92
ProteomicsDBi82762

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
EuPathDBiHostDB:ENSG00000102471.13
GeneCardsiNDFIP2
HGNCiHGNC:18537 NDFIP2
HPAiHPA009160
MIMi610041 gene
neXtProtiNX_Q9NV92
OpenTargetsiENSG00000102471
PharmGKBiPA134953250
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4812 Eukaryota
ENOG4111M6U LUCA
GeneTreeiENSGT00390000012721
HOGENOMiHOG000038752
HOVERGENiHBG057103
InParanoidiQ9NV92
OMAiGEFYPVP
OrthoDBiEOG091G0IMV
PhylomeDBiQ9NV92
TreeFamiTF324911

Miscellaneous databases

ChiTaRSiNDFIP2 human
GeneWikiiNDFIP2
GenomeRNAii54602
PROiPR:Q9NV92
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000102471 Expressed in 204 organ(s), highest expression level in parietal lobe
CleanExiHS_NDFIP2
ExpressionAtlasiQ9NV92 baseline and differential
GenevisibleiQ9NV92 HS

Family and domain databases

InterProiView protein in InterPro
IPR019325 NEDD4/Bsd2
PANTHERiPTHR13396 PTHR13396, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiNFIP2_HUMAN
AccessioniPrimary (citable) accession number: Q9NV92
Secondary accession number(s): Q7Z2H3
, Q7Z428, Q8TAR3, Q9ULQ5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 30, 2005
Last sequence update: August 30, 2005
Last modified: November 7, 2018
This is version 138 of the entry and version 2 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

Complete proteome, Reference proteome

Documents

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

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