DegronMD - Q9BT67(NDFIP1)

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 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). {ECO:0000250|UniProtKB:Q8R0W6, ECO:0000269|PubMed:19343052, ECO:0000269|PubMed:19706893, ECO:0000269|PubMed:20534535, ECO:0000269|PubMed:23087404, ECO:0000269|PubMed:25631046, ECO:0000269|PubMed:25801959, ECO:0000269|PubMed:26319551, ECO:0000269|PubMed:26363003}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.D37G	TCGA-76-6283	GBM	TCGA	PPPY	ITCH	39:42	Mutation rewiring degron network	0.2778
p.D37G	DO223727	GBM	ICGC	PPPY	ITCH	39:42	Mutation rewiring degron network	0.2778
p.Y55C	TCGA-AX-A060	UCEC	TCGA	PPSY	ITCH	64:67	Mutation blocking phosphorylation signal	0.5278
p.Y55C	DO42576	UCEC	ICGC	PPSY	ITCH	64:67	Mutation blocking phosphorylation signal	0.5278
p.T72A	TCGA-B5-A1MR	UCEC	TCGA	PPSY	ITCH	64:67	Mutation rewiring degron network	0.1944
p.T72A	DO41758	UCEC	ICGC	PPSY	ITCH	64:67	Mutation rewiring degron network	0.1944
p.A50T	TCGA-B5-A3FA	UCEC	TCGA	PPPY	ITCH	39:42	Mutation rewiring degron network	0.1111
p.A50T	DO52402	UCEC	ICGC	PPPY	ITCH	39:42	Mutation rewiring degron network	0.1111
p.D54V	TCGA-E2-A108	BRCA	TCGA	PPSY	ITCH	64:67	Mutation rewiring degron network	0.0556
p.D54V	DO5731	BRCA	ICGC	PPSY	ITCH	64:67	Mutation rewiring degron network	0.0556
p.I45N	TCGA-EB-A430	SKCM	TCGA	PPPY	ITCH	39:42	Mutation rewiring degron network	0.25
p.I45N	DO37906	SKCM	ICGC	PPPY	ITCH	39:42	Mutation rewiring degron network	0.25
p.G60W	TCGA-ER-A2NH	SKCM	TCGA	PPSY	ITCH	64:67	Mutation rewiring degron network	0.2222
p.G60W	DO47683	SKCM	ICGC	PPSY	ITCH	64:67	Mutation rewiring degron network	0.2222
p.A38S	TCGA-VQ-A94T	STAD	TCGA	PPPY	ITCH	39:42	Mutation rewiring degron network	0.3056
p.A38S	DO222375	STAD	ICGC	PPPY	ITCH	39:42	Mutation rewiring degron network	0.3056
p.E48D	DO228976	LICA	ICGC	PPPY	ITCH	39:42	Mutation rewiring degron network	0.1667
p.A35T	SIDM01045	Endometrial Carcinoma	GDSC	PPPY	ITCH	39:42	Mutation rewiring degron network	0.2222
p.A35T	ACH-000978	Endometrial/Uterine Cancer	CCLE	PPPY	ITCH	39:42	Mutation rewiring degron network	0.2222
p.A35T	EN	endometrium	COSMIC	PPPY	ITCH	39:42	Mutation rewiring degron network	0.2222
p.N68S	SIDM01083	Oral Cavity Carcinoma	GDSC	PPSY	ITCH	64:67	Mutation rewiring degron network	0.3056
p.N68S	ACH-000254	Head and Neck Cancer	CCLE	PPSY	ITCH	64:67	Mutation rewiring degron network	0.3056
p.N68S	SCC-15	upper aerodigestive tract	COSMIC	PPSY	ITCH	64:67	Mutation rewiring degron network	0.3056

Kaplan plot for NDFIP1 in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

NDFIP1

UniProt ID: Q9BT67

Entrez ID: 80762

Protein name: NEDD4 family-interacting protein 1 (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)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for NDFIP1 in