Q9NV92 · NFIP2_HUMAN
- ProteinNEDD4 family-interacting protein 2
- GeneNDFIP2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids336 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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).
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).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 186 | Not phosphorylated by SRC | ||||
Sequence: Y |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | endoplasmic reticulum | |
Cellular Component | Golgi apparatus | |
Cellular Component | Golgi membrane | |
Cellular Component | intracellular membrane-bounded organelle | |
Cellular Component | mitochondrion | |
Cellular Component | multivesicular body membrane | |
Cellular Component | perinuclear region of cytoplasm | |
Molecular Function | WW domain binding | |
Biological Process | metal ion transport | |
Biological Process | negative regulation of gene expression | |
Biological Process | negative regulation of protein transport | |
Biological Process | negative regulation of transporter activity | |
Biological Process | positive regulation of canonical NF-kappaB signal transduction | |
Biological Process | positive regulation of protein ubiquitination | |
Biological Process | ubiquitin-dependent protein catabolic process | |
Biological Process | vacuolar transport |
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameNEDD4 family-interacting protein 2
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9NV92
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Endosome membrane ; Multi-pass membrane protein
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-231 | Cytoplasmic | ||||
Sequence: MARRRSQRVCASGPSMLNSARGAPELLRGTATNAEVSAAAAGATGSEELPPGDRGCRNGGGRGPAATTSSTGVAVGAEHGEDSLSRKPDPEPGRMDHHQPGTGRYQVLLNEEDNSESSAIEQPPTSNPAPQIVQAASSAPALETDSSPPPYSSITVEVPTTSDTEVYGEFYPVPPPYSVATSLPTYDEAEKAKAAAMAAAAAETSQRIQEEECPPRDDFSDADQLRVGNDG | ||||||
Transmembrane | 232-252 | Helical | ||||
Sequence: IFMLAFFMAFIFNWLGFCLSF | ||||||
Topological domain | 253-257 | Extracellular | ||||
Sequence: CITNT | ||||||
Transmembrane | 258-278 | Helical | ||||
Sequence: IAGRYGAICGFGLSLIKWILI | ||||||
Topological domain | 279-287 | Cytoplasmic | ||||
Sequence: VRFSDYFTG | ||||||
Transmembrane | 288-308 | Helical | ||||
Sequence: YFNGQYWLWWIFLVLGLLLFF | ||||||
Topological domain | 309-336 | Extracellular | ||||
Sequence: RGFVNYLKVRNMSESMAAAHRTRYFFLL |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_061687 | 124 | in dbSNP:rs55887763 | |||
Sequence: P → S | ||||||
Natural variant | VAR_023414 | 136 | in dbSNP:rs11549502 | |||
Sequence: A → V | ||||||
Mutagenesis | 150-151 | 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. | ||||
Sequence: PY → AG | ||||||
Mutagenesis | 167 | Loss of NDFIP2 phosphorylation by SRC. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 176-177 | 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. | ||||
Sequence: PY → AG | ||||||
Mutagenesis | 185-186 | 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. | ||||
Sequence: TY → AG |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 428 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000096794 | 1-336 | UniProt | NEDD4 family-interacting protein 2 | |||
Sequence: MARRRSQRVCASGPSMLNSARGAPELLRGTATNAEVSAAAAGATGSEELPPGDRGCRNGGGRGPAATTSSTGVAVGAEHGEDSLSRKPDPEPGRMDHHQPGTGRYQVLLNEEDNSESSAIEQPPTSNPAPQIVQAASSAPALETDSSPPPYSSITVEVPTTSDTEVYGEFYPVPPPYSVATSLPTYDEAEKAKAAAMAAAAAETSQRIQEEECPPRDDFSDADQLRVGNDGIFMLAFFMAFIFNWLGFCLSFCITNTIAGRYGAICGFGLSLIKWILIVRFSDYFTGYFNGQYWLWWIFLVLGLLLFFRGFVNYLKVRNMSESMAAAHRTRYFFLL | |||||||
Modified residue | 151 | UniProt | Phosphotyrosine; by SRC | ||||
Sequence: Y | |||||||
Modified residue | 167 | UniProt | Phosphotyrosine; by SRC | ||||
Sequence: Y | |||||||
Modified residue | 171 | UniProt | Phosphotyrosine; by SRC | ||||
Sequence: Y | |||||||
Modified residue | 177 | UniProt | Phosphotyrosine; by SRC | ||||
Sequence: Y | |||||||
Modified residue (large scale data) | 204 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 205 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 220 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Ubiquitinated by NEDD4 and ITCH. Also ubiquitinated by NEDD4L. Ubiquitination by NEDD4 or NEDD4L does not affect turnover (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.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in brain, lung, heart, skeletal muscle, kidney, liver and placenta.
Induction
By T-cell activation.
Gene expression databases
Organism-specific databases
Interaction
Subunit
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).
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).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9NV92 | SMN2 Q16637 | 3 | EBI-2933200, EBI-395421 | |
BINARY | Q9NV92 | UQCRH P07919 | 3 | EBI-2933200, EBI-1224427 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-24 | Disordered | ||||
Sequence: MARRRSQRVCASGPSMLNSARGAP | ||||||
Region | 37-156 | Disordered | ||||
Sequence: SAAAAGATGSEELPPGDRGCRNGGGRGPAATTSSTGVAVGAEHGEDSLSRKPDPEPGRMDHHQPGTGRYQVLLNEEDNSESSAIEQPPTSNPAPQIVQAASSAPALETDSSPPPYSSITV | ||||||
Compositional bias | 80-98 | Basic and acidic residues | ||||
Sequence: GEDSLSRKPDPEPGRMDHH | ||||||
Compositional bias | 108-156 | Polar residues | ||||
Sequence: LLNEEDNSESSAIEQPPTSNPAPQIVQAASSAPALETDSSPPPYSSITV | ||||||
Region | 148-151 | Interaction with NEDD4 | ||||
Sequence: PPPY | ||||||
Motif | 148-151 | PPxY motif 1 | ||||
Sequence: PPPY | ||||||
Motif | 174-177 | PPxY motif 2 | ||||
Sequence: PPPY | ||||||
Motif | 184-186 | PPxY motif 3 | ||||
Sequence: PTY |
Domain
The PPxY motifs are required for E3 ubiquitin-protein ligase activation and for ubiquitination.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length336
- Mass (Da)36,390
- Last updated2005-08-30 v2
- ChecksumA7E386C12886321E
Computationally mapped potential isoform sequences
There are 16 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
B4DGY6 | B4DGY6_HUMAN | NDFIP2 | 222 | ||
A0A0C4DGW0 | A0A0C4DGW0_HUMAN | NDFIP2 | 242 | ||
H7C5F7 | H7C5F7_HUMAN | NDFIP2 | 146 | ||
A0A8V8TRG3 | A0A8V8TRG3_HUMAN | NDFIP2 | 178 | ||
A0A8V8TRH3 | A0A8V8TRH3_HUMAN | NDFIP2 | 241 | ||
A0A8V8TRH4 | A0A8V8TRH4_HUMAN | NDFIP2 | 49 | ||
A0A8V8TQM3 | A0A8V8TQM3_HUMAN | NDFIP2 | 260 | ||
A0A8V8TQN2 | A0A8V8TQN2_HUMAN | NDFIP2 | 249 | ||
A0A8V8TQN7 | A0A8V8TQN7_HUMAN | NDFIP2 | 240 | ||
A0A8V8TQP7 | A0A8V8TQP7_HUMAN | NDFIP2 | 145 | ||
A0A8V8TQQ2 | A0A8V8TQQ2_HUMAN | NDFIP2 | 144 | ||
A0A8V8TR80 | A0A8V8TR80_HUMAN | NDFIP2 | 36 | ||
A0A8V8TQ43 | A0A8V8TQ43_HUMAN | NDFIP2 | 149 | ||
A0A8V8TQ57 | A0A8V8TQ57_HUMAN | NDFIP2 | 142 | ||
A0A8V8TQ62 | A0A8V8TQ62_HUMAN | NDFIP2 | 78 | ||
A0A3B3IRK3 | A0A3B3IRK3_HUMAN | NDFIP2 | 129 |
Sequence caution
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 80-98 | Basic and acidic residues | ||||
Sequence: GEDSLSRKPDPEPGRMDHH | ||||||
Compositional bias | 108-156 | Polar residues | ||||
Sequence: LLNEEDNSESSAIEQPPTSNPAPQIVQAASSAPALETDSSPPPYSSITV |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB097019 EMBL· GenBank· DDBJ | BAC77372.1 EMBL· GenBank· DDBJ | mRNA | ||
AB097028 EMBL· GenBank· DDBJ | BAC77381.1 EMBL· GenBank· DDBJ | mRNA | ||
AB097029 EMBL· GenBank· DDBJ | BAC77382.1 EMBL· GenBank· DDBJ | mRNA | ||
AB097030 EMBL· GenBank· DDBJ | BAC77383.1 EMBL· GenBank· DDBJ | mRNA | ||
AB097031 EMBL· GenBank· DDBJ | BAC77384.1 EMBL· GenBank· DDBJ | mRNA | ||
AL136442 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL355603 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AK001723 EMBL· GenBank· DDBJ | BAA91863.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AB032991 EMBL· GenBank· DDBJ | BAA86479.1 EMBL· GenBank· DDBJ | mRNA | ||
BC021988 EMBL· GenBank· DDBJ | AAH21988.1 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BC026126 EMBL· GenBank· DDBJ | AAH26126.1 EMBL· GenBank· DDBJ | mRNA | Different initiation |