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FLASH GENE

Symbol

NDFIP1

contributors: mct/ - updated : 21-09-2018

HGNC name	Nedd4 family interacting protein 1
HGNC id	17592

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_030571 8 - 3599 NP_085048 24.7 221 - 2015 26363003

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive liver         Endocrine parathyroid       predominantly Nervous brain hindbrain cerebellum   highly   brain diencephalon thalamus   highly   brain forebrain cerebral cortex     Homo sapiens Reproductive male system testis       Respiratory lung         Urinary kidney

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron Homo sapiens

cell lineage
cell lines	embryonic kidney cell line HEK 293T
fluid/secretion

at STAGE

physiological period

fetal

Text	brain, kidney, lung

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	three transmembrane domains
	two PPXY motifs
	PY motifs by which they bind NEDD4 family members and bring them close to target proteins

HOMOLOGY

interspecies

homolog to murine Ndfip1

Homologene

FAMILY

CATEGORY

adaptor , transport carrier

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,organelle,endosome
	intracellular,nuclear envelope
text	golgi-associated protein
	is primarily localized in the Golgi apparatus where it recruits NEDD4L to mediate the degradation of mature KCNH2 during channel trafficking to the plasma membrane

basic FUNCTION	may act as an adaptor for NEDD4-like proteins and their putative targets to control ubiquitin-dependent protein sorting and trafficking
	a role in positive regulation of I-kappa B kinase/NF-kappa B cascade
	may be involved in the structural maintenance of the Golgi complex
	expression of NDFIP1 results in recruitment of NEDD4, NEDD4L, ITCH proteins into exosomes (important role for protein trafficking via exosomes)
	may play a major role in mediating exosomal transfer of other ubiquitinated proteins
	exosomal transport of NDFIP1 and its associated cargo proteins would provide an additional and rapid route for removal of unwanted proteins to enhance neuronal survival
	regulating SLC11A2, and playing a critical role for in regulating metal transport in neurons
	promote ubiquitination both of Jun proteins, which have a PY motif, and of endophilin, which does not
	related endosomal membrane proteins that bind to and activate members of the NEDD4 family of E3 ubiquitin ligases
	appears to be a key regulator of the Nedd4-like Itch protein in T cells, acting to dampen signaling from the T-cell receptor
	is an adaptor and activator for NEDD4-family ubiquitin ligases for increasing substrate specificity
	promotes death of pancreatic beta cells
	NDFIP1/NDFIP2 regulate the cross talk between the T-cell receptor and cytokine signalling pathways to limit inappropriate T-cell responses
	NDFIP1 restricts production of the proinflammatory cytokines in Th17 cells

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

signal transduction

a component

important component of the signaling machinery, with the ability to modulate the relative activities of different pathways emanating from a single growth factor

INTERACTION

DNA

RNA

small molecule

protein	binds NEDD4 WW domains (positive roles of NDFIP1/NEDD4 in improving neuronal survival during brain injury)
	can interact with WW domains of a number of NEDD4 family members
	activate the catalytic activity of ITCH and of several other HECT ligases by binding to them
	interacting with SLC11A2 (interacts with 2 WW domain-interacting proteins, NDFIP1 and NDFIP2)
	physically and functionally associated with multiple components of the EGF signaling cascade, and their levels modulate the relative output of different signaling pathways
	NDFIP1 is a critical mediator of SLC11A2 regulation particularly under iron restricted conditions
	is an adaptor for the E3 ubiquitin ligase ITCH
	PTEN secretion in exosomes required NDFIP1, an adaptor protein for members of the NEDD4 family of E3 ubiquitin ligases
	enforces a requirement for CD28 costimulation by limiting IL2 production
	nuclear trafficking of PTEN required both RAB5A as well as the E3 ligase adaptor protein NDFIP1
	NDFIP1 acts as an adaptor for UBE2L3 and ITCH
	NDFIP1 is primarily localized in the Golgi apparatus where it recruits NEDD4L to mediate the degradation of mature KCNH2 proteins during channel trafficking to the plasma membrane
	important negative regulatory function for NEDD4L and NDFIP1 in IgE-dependent mast cell activity
	NDFIP1 mediates the ubiquitination of NTRK2, resulting in receptor trafficking predominantly on RAB7A containing late endosomes, highlighting a pathway for NTRK2 degradation at the lysosome

cell & other

REGULATION

Other

a potential target for ubiquitination by the Nedd4 family of proteins

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   with NEDD4 proteins are up-regulated in stressed neurons during brain injury constitutional     --over   in cortical neurons following traumatic brain injury, and this over-expression is protective against neuronal apoptosis constitutional     --over   in the substantia nigra of Parkinsonian brains is associated with elevated iron levels

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	mice lacking Ndfip1 have increased numbers of Th17 cells, and this increase is cell intrinsic
	Th2 inflammation, such as that observed in Ndfip1(-/-) mice, can increase Th17 differentiation by recruiting Il6-producing eosinophils into secondary lymphoid organs and tissues