UniProtKB - Q9BT67 (NFIP1_HUMAN)
NEDD4 family-interacting protein 1
NDFIP1
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 cell-mediated inflammation by activating ITCH and thus controlling JUNB degradation (By similarity).
Promotes pancreatic beta cell death through degradation of JUNB and inhibition of the unfolded protein response, leading to reduction of insulin secretion (PubMed:26319551).
Restricts the production of pro-inflammatory cytokines in effector Th17 T-cells by promoting ITCH-mediated ubiquitination and degradation of RORC (By similarity).
Together with NDFIP2, 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).
Regulates peripheral T-cell tolerance to self and foreign antigens, forcing the exit of naive CD4+ T-cells from the cell cycle before they become effector T-cells (By similarity).
Negatively regulates RLR-mediated antiviral response by promoting SMURF1-mediated ubiquitination and subsequent degradation of MAVS (PubMed:23087404).
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 where it mediates KCNH2 degradation (PubMed:26363003).
In cortical neurons, mediates the ubiquitination of the divalent metal transporter SLC11A2/DMT1 by NEDD4L, leading to its down-regulation and protection of the cells from cobalt and iron toxicity (PubMed:19706893).
Important for normal development of dendrites and dendritic spines in cortex (By similarity).
Enhances the ubiquitination of BRAT1 mediated by: NEDD4, NEDD4L and ITCH and is required for the nuclear localization of ubiquitinated BRAT1 (PubMed:25631046).
Enhances the ITCH-mediated ubiquitination of MAP3K7 by recruiting E2 ubiquitin-conjugating enzyme UBE2L3 to ITCH (By similarity).
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).
Inhibits cell proliferation by promoting PTEN nuclear localization and changing its signaling specificity (PubMed:25801959).
By similarity8 PublicationsGO - Molecular functioni
- WW domain binding Source: GO_Central
GO - Biological processi
- cellular iron ion homeostasis Source: UniProtKB
- metal ion transport Source: GO_Central
- negative regulation of gene expression Source: UniProtKB
- negative regulation of inflammatory response Source: Ensembl
- negative regulation of interleukin-4 production Source: Ensembl
- negative regulation of isotype switching to IgE isotypes Source: Ensembl
- negative regulation of protein transport Source: UniProtKB
- negative regulation of T cell proliferation Source: Ensembl
- negative regulation of transporter activity Source: UniProtKB
- negative regulation of type 2 immune response Source: Ensembl
- positive regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
- positive regulation of protein catabolic process Source: Ensembl
- positive regulation of protein ubiquitination Source: UniProtKB
- regulation of isotype switching to IgG isotypes Source: Ensembl
- regulation of lymphocyte differentiation Source: Ensembl
- regulation of myeloid leukocyte differentiation Source: Ensembl
- ubiquitin-dependent protein catabolic process Source: GO_Central
- vacuolar transport Source: InterPro
Enzyme and pathway databases
PathwayCommonsi | Q9BT67 |
SignaLinki | Q9BT67 |
SIGNORi | Q9BT67 |
Names & Taxonomyi
Protein namesi | Recommended name: NEDD4 family-interacting protein 1Alternative 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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:17592, NDFIP1 |
MIMi | 612050, gene |
neXtProti | NX_Q9BT67 |
VEuPathDBi | HostDB:ENSG00000131507 |
Subcellular locationi
Extracellular region or secreted
- Secreted 1 Publication
Endosome
- Endosome membrane 1 Publication; Multi-pass membrane protein 1 Publication
Golgi apparatus
- Golgi apparatus membrane 1 Publication
Other locations
- synaptosome By similarity
- dendrite By similarity
Note: Detected in exosomes and secreted via the exosomal pathway (PubMed:18819914).
Endoplasmic reticulum
- endoplasmic reticulum Source: GO_Central
Endosome
- endosome membrane Source: UniProtKB-SubCell
Extracellular region or secreted
- extracellular region Source: UniProtKB-SubCell
Golgi apparatus
- Golgi apparatus Source: GO_Central
- Golgi membrane Source: UniProtKB-SubCell
Other locations
- cell cortex Source: Ensembl
- dendrite Source: UniProtKB-SubCell
- integral component of membrane Source: UniProtKB-KW
- perinuclear region of cytoplasm Source: UniProtKB
- synapse Source: UniProtKB-SubCell
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 2 – 116 | CytoplasmicSequence analysisAdd BLAST | 115 | |
Transmembranei | 117 – 137 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 138 – 143 | ExtracellularSequence analysis | 6 | |
Transmembranei | 144 – 164 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 165 – 172 | CytoplasmicSequence analysis | 8 | |
Transmembranei | 173 – 193 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 194 – 221 | ExtracellularSequence analysisAdd BLAST | 28 |
Keywords - Cellular componenti
Cell junction, Cell projection, Endosome, Golgi apparatus, Membrane, Secreted, Synapse, SynaptosomePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 41 – 42 | PY → 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 | 2 | |
Mutagenesisi | 66 – 67 | SY → 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 | 2 | |
Mutagenesisi | 75 – 76 | SY → 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 | 2 |
Organism-specific databases
DisGeNETi | 80762 |
OpenTargetsi | ENSG00000131507 |
PharmGKBi | PA134943402 |
Miscellaneous databases
Pharosi | Q9BT67, Tbio |
Genetic variation databases
BioMutai | NDFIP1 |
DMDMi | 74733098 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000076269 | 2 – 221 | NEDD4 family-interacting protein 1Add BLAST | 220 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Ubl conjugationProteomic databases
EPDi | Q9BT67 |
jPOSTi | Q9BT67 |
MassIVEi | Q9BT67 |
MaxQBi | Q9BT67 |
PaxDbi | Q9BT67 |
PeptideAtlasi | Q9BT67 |
PRIDEi | Q9BT67 |
ProteomicsDBi | 78953 [Q9BT67-1] 78954 [Q9BT67-2] |
PTM databases
iPTMneti | Q9BT67 |
PhosphoSitePlusi | Q9BT67 |
SwissPalmi | Q9BT67 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000131507, Expressed in primary visual cortex and 247 other tissues |
Genevisiblei | Q9BT67, HS |
Organism-specific databases
HPAi | ENSG00000131507, Low tissue specificity |
Interactioni
Subunit structurei
Forms heterodimers with NDFIP2 (PubMed:20534535).
Interacts with several E3 ubiquitin-protein ligases, including ITCH, NEDD4, NEDD4L and WWP2 (PubMed:18776082, PubMed:19706893, PubMed:26363003). The interaction with NEDD4, NEDD4L and ITCH leads to relocalization of these proteins to exosomes and eventually to exosomal secretion (By similarity).
Interacts with U2SURP (By similarity).
Interacts with SLC11A2/DMT1 (PubMed:18776082, PubMed:19706893).
Interacts with PTEN (PubMed:20534535, PubMed:25801959). May interact with phosphorylated EGFR (PubMed:20534535).
Interacts with BRAT1 (PubMed:25631046).
Interacts with KCNH2 (PubMed:26363003).
Interacts with MAVS (PubMed:23087404).
Part of a complex containing ITCH, NDFIP1 and MAP3K7 (By similarity).
Interacts (via N-terminus) with UBE2L3; the interaction mediates recruitment of UBE2L3 to ITCH (PubMed:25632008).
By similarity8 PublicationsBinary interactionsi
Q9BT67
With | #Exp. | IntAct |
---|---|---|
SLC11A2 [P49281] | 2 | EBI-11732799,EBI-4319335 |
UQCRH [P07919] | 3 | EBI-11732799,EBI-1224427 |
GO - Molecular functioni
- WW domain binding Source: GO_Central
Protein-protein interaction databases
BioGRIDi | 123296, 98 interactors |
CORUMi | Q9BT67 |
DIPi | DIP-48958N |
IntActi | Q9BT67, 36 interactors |
MINTi | Q9BT67 |
STRINGi | 9606.ENSP00000253814 |
Miscellaneous databases
RNActi | Q9BT67, protein |
Structurei
3D structure databases
AlphaFoldDBi | Q9BT67 |
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 2 – 41 | Interaction with UBE2L3By similarityAdd BLAST | 40 | |
Regioni | 18 – 45 | DisorderedSequence analysisAdd BLAST | 28 | |
Regioni | 42 – 76 | Interaction with ITCHBy similarityAdd BLAST | 35 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 39 – 42 | PPxY motif 1 | 4 | |
Motifi | 64 – 67 | PPxY motif 2 | 4 | |
Motifi | 74 – 76 | PPxY motif 3 | 3 |
Domaini
Keywords - Domaini
Repeat, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG4812, Eukaryota |
GeneTreei | ENSGT00390000012721 |
HOGENOMi | CLU_074980_2_0_1 |
InParanoidi | Q9BT67 |
OMAi | TGRQPHH |
OrthoDBi | 1495850at2759 |
PhylomeDBi | Q9BT67 |
TreeFami | TF324911 |
Family and domain databases
InterProi | View protein in InterPro IPR019325, NEDD4/Bsd2 |
PANTHERi | PTHR13396, PTHR13396, 1 hit |
Pfami | View protein in Pfam PF10176, DUF2370, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 20 | Q → W in BAC11670 (PubMed:16303743).Curated | 1 | |
Sequence conflicti | 104 | F → L in BAC11670 (PubMed:16303743).Curated | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_016474 | 76 – 153 | YDEAE…AISGF → CFYDISHLIFFIFYLRNMKK KYTKMVKLLHKSAPAQSDSC KCPFICCVCISRISIGSRSG YQYIMHRSVGCLKAKQEN in isoform 2. 1 PublicationAdd BLAST | 78 | |
Alternative sequenceiVSP_016475 | 154 – 221 | Missing in isoform 2. 1 PublicationAdd BLAST | 68 |
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 |
CCDSi | CCDS4273.1 [Q9BT67-1] |
RefSeqi | NP_085048.1, NM_030571.3 [Q9BT67-1] |
Genome annotation databases
Ensembli | ENST00000253814.6; ENSP00000253814.3; ENSG00000131507.11 |
GeneIDi | 80762 |
KEGGi | hsa:80762 |
MANE-Selecti | ENST00000253814.6; ENSP00000253814.3; NM_030571.4; NP_085048.1 |
UCSCi | uc003lmi.5, human [Q9BT67-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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 |
CCDSi | CCDS4273.1 [Q9BT67-1] |
RefSeqi | NP_085048.1, NM_030571.3 [Q9BT67-1] |
3D structure databases
AlphaFoldDBi | Q9BT67 |
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 123296, 98 interactors |
CORUMi | Q9BT67 |
DIPi | DIP-48958N |
IntActi | Q9BT67, 36 interactors |
MINTi | Q9BT67 |
STRINGi | 9606.ENSP00000253814 |
PTM databases
iPTMneti | Q9BT67 |
PhosphoSitePlusi | Q9BT67 |
SwissPalmi | Q9BT67 |
Genetic variation databases
BioMutai | NDFIP1 |
DMDMi | 74733098 |
Proteomic databases
EPDi | Q9BT67 |
jPOSTi | Q9BT67 |
MassIVEi | Q9BT67 |
MaxQBi | Q9BT67 |
PaxDbi | Q9BT67 |
PeptideAtlasi | Q9BT67 |
PRIDEi | Q9BT67 |
ProteomicsDBi | 78953 [Q9BT67-1] 78954 [Q9BT67-2] |
Protocols and materials databases
Antibodypediai | 2434, 210 antibodies from 32 providers |
DNASUi | 80762 |
Genome annotation databases
Ensembli | ENST00000253814.6; ENSP00000253814.3; ENSG00000131507.11 |
GeneIDi | 80762 |
KEGGi | hsa:80762 |
MANE-Selecti | ENST00000253814.6; ENSP00000253814.3; NM_030571.4; NP_085048.1 |
UCSCi | uc003lmi.5, human [Q9BT67-1] |
Organism-specific databases
CTDi | 80762 |
DisGeNETi | 80762 |
GeneCardsi | NDFIP1 |
HGNCi | HGNC:17592, NDFIP1 |
HPAi | ENSG00000131507, Low tissue specificity |
MIMi | 612050, gene |
neXtProti | NX_Q9BT67 |
OpenTargetsi | ENSG00000131507 |
PharmGKBi | PA134943402 |
VEuPathDBi | HostDB:ENSG00000131507 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4812, Eukaryota |
GeneTreei | ENSGT00390000012721 |
HOGENOMi | CLU_074980_2_0_1 |
InParanoidi | Q9BT67 |
OMAi | TGRQPHH |
OrthoDBi | 1495850at2759 |
PhylomeDBi | Q9BT67 |
TreeFami | TF324911 |
Enzyme and pathway databases
PathwayCommonsi | Q9BT67 |
SignaLinki | Q9BT67 |
SIGNORi | Q9BT67 |
Miscellaneous databases
BioGRID-ORCSi | 80762, 10 hits in 1077 CRISPR screens |
ChiTaRSi | NDFIP1, human |
GenomeRNAii | 80762 |
Pharosi | Q9BT67, Tbio |
PROi | PR:Q9BT67 |
RNActi | Q9BT67, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000131507, Expressed in primary visual cortex and 247 other tissues |
Genevisiblei | Q9BT67, HS |
Family and domain databases
InterProi | View protein in InterPro IPR019325, NEDD4/Bsd2 |
PANTHERi | PTHR13396, PTHR13396, 1 hit |
Pfami | View protein in Pfam PF10176, DUF2370, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | NFIP1_HUMAN | |
Accessioni | Q9BT67Primary (citable) accession number: Q9BT67 Secondary accession number(s): B2RDB8 Q8N2F9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 6, 2005 |
Last sequence update: | June 1, 2001 | |
Last modified: | May 25, 2022 | |
This is version 145 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human chromosome 5
Human chromosome 5: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot