Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

NEDD4 family-interacting protein 1

Gene

NDFIP1

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 NEDD4 and ITCH, and consequently modulates the stability of their targets. As a result, controls many cellular processes. Prevents chronic T-helper cells-mediated inflammation by activating ITCH and thus controlling JUNB degradation (By similarity). In cortical neurons, mediates the ubiquitination of SLC11A2/DMT1 by NEDD4L, leading to down-regulation of the divalent metal transporter and protection of the cells from cobalt and iron toxicity (PubMed:19706893). Modulates EGFR signaling through multiple pathways. In particular, may regulate the ratio of AKT1-to-MAPK8 signaling in response to EGF, acting on AKT1 probably through PTEN destabilization and on MAPK8 through ITCH-dependent MAP2K4 inactivation. As a result, may control cell growth rate (PubMed:20534535). Enhances the ubiquitination of BRAT1 mediated by E3 ubiquitin-protein ligases: NEDD4, NEDD4L and ITCH, and is required for the nuclear localization of ubiquitinated BRAT1 (PubMed:25631046).By similarity4 Publications

GO - Molecular functioni

  • signal transducer activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
NEDD4 family-interacting protein 1
Alternative name(s):
Breast cancer-associated protein SGA-1M
NEDD4 WW domain-binding protein 5
Putative MAPK-activating protein PM13
Putative NF-kappa-B-activating protein 164
Putative NFKB and MAPK-activating protein
Gene namesi
Name:NDFIP1
Synonyms:N4WBP5
ORF Names:PSEC0192, PSEC0223
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:17592. NDFIP1.

Subcellular locationi

  • Endosome membrane 1 Publication; Multi-pass membrane protein 1 Publication
  • Golgi apparatus membrane By similarity
  • Secreted 1 Publication

  • Note: Detected in exosomes and secreted via the exosomal pathway (PubMed:18819914).

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini2 – 116115CytoplasmicSequence analysisAdd
BLAST
Transmembranei117 – 13721HelicalSequence analysisAdd
BLAST
Topological domaini138 – 1436ExtracellularSequence analysis
Transmembranei144 – 16421HelicalSequence analysisAdd
BLAST
Topological domaini165 – 1728CytoplasmicSequence analysis
Transmembranei173 – 19321HelicalSequence analysisAdd
BLAST
Topological domaini194 – 22128ExtracellularSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endosome, Golgi apparatus, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi41 – 422PY → AG: Loss of phosphorylation; when associated with 66-S-Y-67 and 75-S-Y-76. Greatly decreases NEDD4-binding; when associated with 66-S-Y-67 and 75-S-Y-76. No effect on PTEN-binding; when associated with 66-S-Y-67 and 75-S-Y-76. 1 Publication
Mutagenesisi66 – 672SY → AG: Loss of phosphorylation; when associated with 41-P-Y-42 and 75-S-Y-76. Greatly decreases NEDD4-binding; when associated with 41-P-Y-42 and 75-S-Y-76. No effect on PTEN-binding; when associated with 41-P-Y-42 and 75-S-Y-76. 1 Publication
Mutagenesisi75 – 762SY → AG: Loss of phosphorylation; when associated with 41-P-Y-42 and 66-S-Y-67. Greatly decreases NEDD4-binding; when associated with 41-P-Y-42 and 66-S-Y-67. No effect on PTEN-binding; when associated with 41-P-Y-42 and 66-S-Y-67. 1 Publication

Organism-specific databases

PharmGKBiPA134943402.

Polymorphism and mutation databases

BioMutaiNDFIP1.
DMDMi74733098.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources
Chaini2 – 221220NEDD4 family-interacting protein 1PRO_0000076269Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineCombined sources

Post-translational modificationi

Ubiquitinated by NEDD4 and ITCH; mono-, di- and polyubiquitinated forms are detected. Ubiquitination regulates its degradation.1 Publication
Undergoes transient tyrosine phosphorylation following EGF stimulation, most probably by catalyzed by SRC. Phosphorylation SRC is enhanced in the presence of NDFIP2 which may act as a scaffold to recruit SRC to NDFIP1.1 Publication

Keywords - PTMi

Acetylation, Ubl conjugation

Proteomic databases

EPDiQ9BT67.
MaxQBiQ9BT67.
PaxDbiQ9BT67.
PeptideAtlasiQ9BT67.
PRIDEiQ9BT67.

PTM databases

iPTMnetiQ9BT67.
PhosphoSiteiQ9BT67.
SwissPalmiQ9BT67.

Expressioni

Tissue specificityi

Widely expressed. Higher levels are detected in cerebellum, pituitary, thalamus, kidney, liver, testis, salivary glands and placenta. Also expressed in fetal brain, kidney and lung.1 Publication

Inductioni

Increased protein expression in neuronal cells in response to Co2+ or Fe2+ ions.1 Publication

Gene expression databases

BgeeiENSG00000131507.
CleanExiHS_NDFIP1.
GenevisibleiQ9BT67. HS.

Organism-specific databases

HPAiHPA009682.

Interactioni

Subunit structurei

Forms heterodimers with NDFIP2. Interacts with several E3 ubiquitin-protein ligases, including NEDD4, NEDD4L and WWP2. Interacts with ITCH, U2SURP and WWP2 (By similarity). The interaction with NEDD4, NEDD4L and ITCH leads to relocalization of these proteins to exosomes and eventually to exosomal secretion. Interacts with SLC11A2/DMT1. Interacts with PTEN. May interact with phosphorylated EGFR. Interacts with BRAT1.By similarity4 Publications

Protein-protein interaction databases

BioGridi123296. 38 interactions.
DIPiDIP-48958N.
IntActiQ9BT67. 1 interaction.
STRINGi9606.ENSP00000253814.

Structurei

3D structure databases

ProteinModelPortaliQ9BT67.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi40 – 423WW-binding 1
Motifi65 – 673WW-binding 2
Motifi74 – 763WW-binding 3

Domaini

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

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4812. Eukaryota.
ENOG4111M6U. LUCA.
GeneTreeiENSGT00390000012721.
HOGENOMiHOG000038752.
HOVERGENiHBG057103.
InParanoidiQ9BT67.
OMAiPDQMRIG.
OrthoDBiEOG091G0IMV.
PhylomeDBiQ9BT67.
TreeFamiTF324911.

Family and domain databases

InterProiIPR019325. NEDD4/Bsd2.
[Graphical view]
PfamiPF10176. DUF2370. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform 1 (identifier: Q9BT67-1) [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
MALALAALAA VEPACGSRYQ QLQNEEESGE PEQAAGDAPP PYSSISAESA
60 70 80 90 100
AYFDYKDESG FPKPPSYNVA TTLPSYDEAE RTKAEATIPL VPGRDEDFVG
110 120 130 140 150
RDDFDDADQL RIGNDGIFML TFFMAFLFNW IGFFLSFCLT TSAAGRYGAI
160 170 180 190 200
SGFGLSLIKW ILIVRFSTYF PGYFDGQYWL WWVFLVLGFL LFLRGFINYA
210 220
KVRKMPETFS NLPRTRVLFI Y
Length:221
Mass (Da):24,899
Last modified:June 1, 2001 - v1
Checksum:i526A579D7B32FCA4
GO
Isoform 2 (identifier: Q9BT67-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     76-153: YDEAERTKAE...AGRYGAISGF → CFYDISHLIF...VGCLKAKQEN
     154-221: Missing.

Note: No experimental confirmation available.
Show »
Length:153
Mass (Da):16,915
Checksum:iD8A2706965DD8A23
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti20 – 201Q → W in BAC11670 (PubMed:16303743).Curated
Sequence conflicti104 – 1041F → L in BAC11670 (PubMed:16303743).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei76 – 15378YDEAE…AISGF → CFYDISHLIFFIFYLRNMKK KYTKMVKLLHKSAPAQSDSC KCPFICCVCISRISIGSRSG YQYIMHRSVGCLKAKQEN in isoform 2. 1 PublicationVSP_016474Add
BLAST
Alternative sequencei154 – 22168Missing in isoform 2. 1 PublicationVSP_016475Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY192728 mRNA. Translation: AAP13460.1.
AB097010 mRNA. Translation: BAC77363.1.
AB097037 mRNA. Translation: BAC77390.1.
AK075495 mRNA. Translation: BAC11652.1.
AK075524 mRNA. Translation: BAC11670.1.
AK315481 mRNA. Translation: BAG37865.1.
CH471062 Genomic DNA. Translation: EAW61888.1.
CH471062 Genomic DNA. Translation: EAW61889.1.
BC004317 mRNA. Translation: AAH04317.1.
AL832993 mRNA. Translation: CAH56294.1.
CCDSiCCDS4273.1. [Q9BT67-1]
RefSeqiNP_085048.1. NM_030571.3. [Q9BT67-1]
UniGeneiHs.653510.
Hs.9788.

Genome annotation databases

EnsembliENST00000253814; ENSP00000253814; ENSG00000131507. [Q9BT67-1]
GeneIDi80762.
KEGGihsa:80762.
UCSCiuc003lmi.5. human. [Q9BT67-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY192728 mRNA. Translation: AAP13460.1.
AB097010 mRNA. Translation: BAC77363.1.
AB097037 mRNA. Translation: BAC77390.1.
AK075495 mRNA. Translation: BAC11652.1.
AK075524 mRNA. Translation: BAC11670.1.
AK315481 mRNA. Translation: BAG37865.1.
CH471062 Genomic DNA. Translation: EAW61888.1.
CH471062 Genomic DNA. Translation: EAW61889.1.
BC004317 mRNA. Translation: AAH04317.1.
AL832993 mRNA. Translation: CAH56294.1.
CCDSiCCDS4273.1. [Q9BT67-1]
RefSeqiNP_085048.1. NM_030571.3. [Q9BT67-1]
UniGeneiHs.653510.
Hs.9788.

3D structure databases

ProteinModelPortaliQ9BT67.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123296. 38 interactions.
DIPiDIP-48958N.
IntActiQ9BT67. 1 interaction.
STRINGi9606.ENSP00000253814.

PTM databases

iPTMnetiQ9BT67.
PhosphoSiteiQ9BT67.
SwissPalmiQ9BT67.

Polymorphism and mutation databases

BioMutaiNDFIP1.
DMDMi74733098.

Proteomic databases

EPDiQ9BT67.
MaxQBiQ9BT67.
PaxDbiQ9BT67.
PeptideAtlasiQ9BT67.
PRIDEiQ9BT67.

Protocols and materials databases

DNASUi80762.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000253814; ENSP00000253814; ENSG00000131507. [Q9BT67-1]
GeneIDi80762.
KEGGihsa:80762.
UCSCiuc003lmi.5. human. [Q9BT67-1]

Organism-specific databases

CTDi80762.
GeneCardsiNDFIP1.
HGNCiHGNC:17592. NDFIP1.
HPAiHPA009682.
MIMi612050. gene.
neXtProtiNX_Q9BT67.
PharmGKBiPA134943402.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4812. Eukaryota.
ENOG4111M6U. LUCA.
GeneTreeiENSGT00390000012721.
HOGENOMiHOG000038752.
HOVERGENiHBG057103.
InParanoidiQ9BT67.
OMAiPDQMRIG.
OrthoDBiEOG091G0IMV.
PhylomeDBiQ9BT67.
TreeFamiTF324911.

Miscellaneous databases

ChiTaRSiNDFIP1. human.
GenomeRNAii80762.
PROiQ9BT67.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000131507.
CleanExiHS_NDFIP1.
GenevisibleiQ9BT67. HS.

Family and domain databases

InterProiIPR019325. NEDD4/Bsd2.
[Graphical view]
PfamiPF10176. DUF2370. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNFIP1_HUMAN
AccessioniPrimary (citable) accession number: Q9BT67
Secondary accession number(s): B2RDB8
, D3DQF0, Q658T8, Q8N2E3, Q8N2F9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: June 1, 2001
Last modified: September 7, 2016
This is version 106 of the entry and version 1 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 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. 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.