The protein encoded by this gene belongs to a small group of evolutionarily conserved proteins with three transmembrane domains. It is a potential target for ubiquitination by the Nedd4 family of proteins. This protein is thought to be part of a family of integral Golgi membrane proteins. [provided by RefSeq, Jul 2008] See more...

Aliases for NDFIP1 Gene

Aliases for NDFIP1 Gene

  • Nedd4 Family Interacting Protein 1 2 3 5
  • Putative NF-Kappa-B-Activating Protein 164 3 4
  • Putative NFKB And MAPK-Activating Protein 3 4
  • Breast Cancer-Associated Protein SGA-1M 3 4
  • Putative MAPK-Activating Protein PM13 3 4
  • NEDD4 Family-Interacting Protein 1 3 4
  • N4WBP5 3 4
  • Nedd4 WW Domain-Binding Protein 5 3
  • NEDD4 WW Domain-Binding Protein 5 4

External Ids for NDFIP1 Gene

Previous GeneCards Identifiers for NDFIP1 Gene

  • GC05P142071
  • GC05P141471
  • GC05P141516
  • GC05P141468
  • GC05P136635
  • GC05P141489

Summaries for NDFIP1 Gene

Entrez Gene Summary for NDFIP1 Gene

  • The protein encoded by this gene belongs to a small group of evolutionarily conserved proteins with three transmembrane domains. It is a potential target for ubiquitination by the Nedd4 family of proteins. This protein is thought to be part of a family of integral Golgi membrane proteins. [provided by RefSeq, Jul 2008]

GeneCards Summary for NDFIP1 Gene

NDFIP1 (Nedd4 Family Interacting Protein 1) is a Protein Coding gene. Gene Ontology (GO) annotations related to this gene include obsolete signal transducer activity and WW domain binding. An important paralog of this gene is NDFIP2.

UniProtKB/Swiss-Prot Summary for NDFIP1 Gene

  • 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 proinflammatory 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).

Additional gene information for NDFIP1 Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NDFIP1 Gene

Genomics for NDFIP1 Gene

GeneHancer (GH) Regulatory Elements for NDFIP1 Gene

Promoters and enhancers for NDFIP1 Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NDFIP1 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NDFIP1

Top Transcription factor binding sites by QIAGEN in the NDFIP1 gene promoter:
  • deltaCREB
  • E2F
  • E2F-1
  • E2F-2
  • E2F-3a
  • E2F-4
  • E2F-5
  • ISGF-3
  • Pax-5
  • Pbx1a

Genomic Locations for NDFIP1 Gene

Genomic Locations for NDFIP1 Gene
chr5:142,108,759-142,154,443
(GRCh38/hg38)
Size:
45,685 bases
Orientation:
Plus strand
chr5:141,488,070-141,534,008
(GRCh37/hg19)
Size:
45,939 bases
Orientation:
Plus strand

Genomic View for NDFIP1 Gene

Genes around NDFIP1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NDFIP1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NDFIP1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NDFIP1 Gene

Proteins for NDFIP1 Gene

  • Protein details for NDFIP1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9BT67-NFIP1_HUMAN
    Recommended name:
    NEDD4 family-interacting protein 1
    Protein Accession:
    Q9BT67
    Secondary Accessions:
    • B2RDB8
    • D3DQF0
    • Q658T8
    • Q8N2E3
    • Q8N2F9

    Protein attributes for NDFIP1 Gene

    Size:
    221 amino acids
    Molecular mass:
    24899 Da
    Quaternary structure:
    • 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).

    Alternative splice isoforms for NDFIP1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NDFIP1 Gene

Post-translational modifications for NDFIP1 Gene

  • Ubiquitinated by NEDD4 and ITCH; mono-, di- and polyubiquitinated forms are detected. Ubiquitination regulates its degradation.
  • 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.
  • Ubiquitination at Lys63 and Lys83
  • Modification sites at PhosphoSitePlus

Other Protein References for NDFIP1 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for NDFIP1 Gene

Domains & Families for NDFIP1 Gene

Gene Families for NDFIP1 Gene

Human Protein Atlas (HPA):
  • Predicted membrane proteins

Protein Domains for NDFIP1 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for NDFIP1 Gene

GenScript: Design optimal peptide antigens:
  • Putative NFKB and MAPK-activating protein (NFIP1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9BT67

UniProtKB/Swiss-Prot:

NFIP1_HUMAN :
  • The PPxY motifs are required for E3 ubiquitin-protein ligase binding and activation and for ubiquitination.
Domain:
  • The PPxY motifs are required for E3 ubiquitin-protein ligase binding and activation and for ubiquitination.
genes like me logo Genes that share domains with NDFIP1: view

Function for NDFIP1 Gene

Molecular function for NDFIP1 Gene

UniProtKB/Swiss-Prot Function:
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 proinflammatory 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).
UniProtKB/Swiss-Prot Induction:
Increased protein expression in neuronal cells in response to Co(2+) or Fe(2+) ions.

Phenotypes From GWAS Catalog for NDFIP1 Gene

Gene Ontology (GO) - Molecular Function for NDFIP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 18776082
GO:0050699 WW domain binding IBA 21873635
genes like me logo Genes that share ontologies with NDFIP1: view
genes like me logo Genes that share phenotypes with NDFIP1: view

Animal Models for NDFIP1 Gene

MGI Knock Outs for NDFIP1:

Animal Model Products

CRISPR Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for NDFIP1 Gene

Localization for NDFIP1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NDFIP1 Gene

Endosome membrane; Multi-pass membrane protein. Golgi apparatus membrane. Cell junction, synapse, synaptosome. Cell projection, dendrite. Secreted. Note=Detected in exosomes and secreted via the exosomal pathway (PubMed:18819914).

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NDFIP1 gene
Compartment Confidence
extracellular 4
endosome 4
plasma membrane 3
endoplasmic reticulum 3
golgi apparatus 3
lysosome 2
cytoskeleton 1
mitochondrion 1
nucleus 1
cytosol 1

Gene Ontology (GO) - Cellular Components for NDFIP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000139 Golgi membrane IEA --
GO:0005576 extracellular region IEA --
GO:0005623 cell IEA --
GO:0005768 endosome IEA --
GO:0005783 endoplasmic reticulum IBA 21873635
genes like me logo Genes that share ontologies with NDFIP1: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for NDFIP1 Gene

Pathways & Interactions for NDFIP1 Gene

PathCards logo

SuperPathways for NDFIP1 Gene

No Data Available

Gene Ontology (GO) - Biological Process for NDFIP1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002761 regulation of myeloid leukocyte differentiation IEA --
GO:0002829 negative regulation of type 2 immune response IEA --
GO:0006511 ubiquitin-dependent protein catabolic process IBA 21873635
GO:0006879 cellular iron ion homeostasis IMP 18776082
GO:0007034 vacuolar transport IEA --
genes like me logo Genes that share ontologies with NDFIP1: view

No data available for Pathways by source and SIGNOR curated interactions for NDFIP1 Gene

Drugs & Compounds for NDFIP1 Gene

No Compound Related Data Available

Transcripts for NDFIP1 Gene

mRNA/cDNA for NDFIP1 Gene

1 REFSEQ mRNAs :
13 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for NDFIP1 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3a · 3b ^ 4a · 4b ^ 5 ^ 6a · 6b ^ 7a · 7b ^ 8a · 8b
SP1: - -
SP2: - -
SP3: - -
SP4:
SP5:

Relevant External Links for NDFIP1 Gene

GeneLoc Exon Structure for
NDFIP1

Expression for NDFIP1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NDFIP1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for NDFIP1 Gene

This gene is overexpressed in Breast (30.4) and Adrenal (20.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for NDFIP1 Gene



Protein tissue co-expression partners for NDFIP1 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NDFIP1

SOURCE GeneReport for Unigene cluster for NDFIP1 Gene:

Hs.9788

mRNA Expression by UniProt/SwissProt for NDFIP1 Gene:

Q9BT67-NFIP1_HUMAN
Tissue specificity: 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.

Evidence on tissue expression from TISSUES for NDFIP1 Gene

  • Nervous system(5)
  • Lung(4.8)
  • Stomach(4.3)
  • Pancreas(3.1)
  • Kidney(2.7)
  • Eye(2)
genes like me logo Genes that share expression patterns with NDFIP1: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for NDFIP1 Gene

Orthologs for NDFIP1 Gene

This gene was present in the common ancestor of animals.

Orthologs for NDFIP1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NDFIP1 31 30
  • 99.85 (n)
OneToOne
dog
(Canis familiaris)
Mammalia NDFIP1 31 30
  • 95.05 (n)
OneToOne
cow
(Bos Taurus)
Mammalia NDFIP1 31 30
  • 95 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Ndfip1 17 31 30
  • 93.36 (n)
oppossum
(Monodelphis domestica)
Mammalia NDFIP1 31
  • 93 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Ndfip1 30
  • 92.73 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 72 (a)
ManyToMany
chicken
(Gallus gallus)
Aves -- 31
  • 90 (a)
OneToMany
-- 31
  • 89 (a)
OneToMany
lizard
(Anolis carolinensis)
Reptilia -- 31
  • 90 (a)
OneToMany
-- 31
  • 63 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia ndfip1 30
  • 83.09 (n)
Str.1792 30
zebrafish
(Danio rerio)
Actinopterygii ndfip1l 31
  • 77 (a)
OneToMany
ndfip1 31 30
  • 73.33 (n)
OneToMany
wufc17e11 30
fruit fly
(Drosophila melanogaster)
Insecta Ndfip 31 30
  • 48.09 (n)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP005801 30
  • 46.91 (n)
sea squirt
(Ciona savignyi)
Ascidiacea -- 31
  • 32 (a)
OneToMany
Species where no ortholog for NDFIP1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for NDFIP1 Gene

ENSEMBL:
Gene Tree for NDFIP1 (if available)
TreeFam:
Gene Tree for NDFIP1 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NDFIP1: view image

Paralogs for NDFIP1 Gene

Paralogs for NDFIP1 Gene

(1) SIMAP similar genes for NDFIP1 Gene using alignment to 1 proteins:

  • NFIP1_HUMAN

Pseudogenes.org Pseudogenes for NDFIP1 Gene

genes like me logo Genes that share paralogs with NDFIP1: view

Variants for NDFIP1 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NDFIP1 Gene

SNP ID Clinical significance and condition Chr 05 pos Variation AA Info Type
708909 Benign: not provided 142,140,592(+) T/C SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for NDFIP1 Gene

Structural Variations from Database of Genomic Variants (DGV) for NDFIP1 Gene

Variant ID Type Subtype PubMed ID
esv3606993 CNV loss 21293372
nsv1154058 CNV deletion 26484159
nsv509994 OTHER sequence alteration 20534489
nsv830509 CNV gain 17160897

Variation tolerance for NDFIP1 Gene

Residual Variation Intolerance Score: 38.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.79; 33.77% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NDFIP1 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
NDFIP1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NDFIP1 Gene

Disorders for NDFIP1 Gene

Additional Disease Information for NDFIP1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology

No disorders were found for NDFIP1 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for NDFIP1 Gene

Publications for NDFIP1 Gene

  1. Divalent metal transporter 1 (DMT1) regulation by Ndfip1 prevents metal toxicity in human neurons. (PMID: 19706893) Howitt J … Tan SS (Proceedings of the National Academy of Sciences of the United States of America 2009) 3 4 23 54
  2. Control of the activity of WW-HECT domain E3 ubiquitin ligases by NDFIP proteins. (PMID: 19343052) Mund T … Pelham HR (EMBO reports 2009) 3 4 23 54
  3. Nedd4 family-interacting protein 1 (Ndfip1) is required for the exosomal secretion of Nedd4 family proteins. (PMID: 18819914) Putz U … Tan SS (The Journal of biological chemistry 2008) 3 4 23 54
  4. N4WBP5, a potential target for ubiquitination by the Nedd4 family of proteins, is a novel Golgi-associated protein. (PMID: 11748237) Harvey KF … Kumar S (The Journal of biological chemistry 2002) 2 3 4 54
  5. Nedd4 family interacting protein 1 (Ndfip1) is required for ubiquitination and nuclear trafficking of BRCA1-associated ATM activator 1 (BRAT1) during the DNA damage response. (PMID: 25631046) Low LH … Tan SS (The Journal of biological chemistry 2015) 3 4 54

Products for NDFIP1 Gene

Sources for NDFIP1 Gene