NFIP2_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: NFIP2_HUMAN
• UniProt AC: Q9NV92
• Protein Name: NEDD4 family-interacting protein 2
• Gene Name: NDFIP2
• Organism: Homo sapiens (Human).
• Sequence Length: 336
• Subcellular Localization: Endosome membrane ; Multi-pass membrane protein . Golgi apparatus membrane . Endosome, multivesicular body membrane .
• Protein Description: 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]
• Protein Sequence: MARRRSQRVCASGPSMLNSARGAPELLRGTATNAEVSAAAAGATGSEELPPGDRGCRNGGGRGPAATTSSTGVAVGAEHGEDSLSRKPDPEPGRMDHHQPGTGRYQVLLNEEDNSESSAIEQPPTSNPAPQIVQAASSAPALETDSSPPPYSSITVEVPTTSDTEVYGEFYPVPPPYSVATSLPTYDEAEKAKAAAMAAAAAETSQRIQEEECPPRDDFSDADQLRVGNDGIFMLAFFMAFIFNWLGFCLSFCITNTIAGRYGAICGFGLSLIKWILIVRFSDYFTGYFNGQYWLWWIFLVLGLLLFFRGFVNYLKVRNMSESMAAAHRTRYFFLL

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
12	Phosphorylation	RSQRVCASGPSMLNS CCCCCCCCCHHHHHH	46.22	-
83	Phosphorylation	GAEHGEDSLSRKPDP CCCCCCCHHCCCCCC	24.76	28555341
85	Phosphorylation	EHGEDSLSRKPDPEP CCCCCHHCCCCCCCC	42.06	24260401
87	Ubiquitination	GEDSLSRKPDPEPGR CCCHHCCCCCCCCCC	50.85	-
151	Phosphorylation	TDSSPPPYSSITVEV CCCCCCCCCEEEEEE	22.33	20534535
167	Phosphorylation	TTSDTEVYGEFYPVP CCCCCEEEEEEECCC	12.52	20534535
171	Phosphorylation	TEVYGEFYPVPPPYS CEEEEEEECCCCCCC	10.06	20534535
177	Phosphorylation	FYPVPPPYSVATSLP EECCCCCCCCCCCCC	22.88	25884760
186	Phosphorylation	VATSLPTYDEAEKAK CCCCCCCCCHHHHHH	15.17	25884760
191	Ubiquitination	PTYDEAEKAKAAAMA CCCCHHHHHHHHHHH	63.33	-
193	Ubiquitination	YDEAEKAKAAAMAAA CCHHHHHHHHHHHHH	50.02	21890473
204	Phosphorylation	MAAAAAETSQRIQEE HHHHHHHHHHHHHHH	25.98	29255136
205	Phosphorylation	AAAAAETSQRIQEEE HHHHHHHHHHHHHHH	14.68	29255136
220	Phosphorylation	CPPRDDFSDADQLRV CCCCCCCCCHHHHCC	38.59	23312004
262	Phosphorylation	TNTIAGRYGAICGFG HHHHHHCHHHHHHHH	15.25	-
271	Phosphorylation	AICGFGLSLIKWILI HHHHHHHHHHHHHHH	28.55	24719451
321	Phosphorylation	YLKVRNMSESMAAAH HHHHCCCCHHHHHHH	30.03	19845377
330	Phosphorylation	SMAAAHRTRYFFLL- HHHHHHHHHEEEEC-	21.61	19845377

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
151	Y	Phosphorylation	Kinase	SRC	P12931	Uniprot
167	Y	Phosphorylation	Kinase	SRC	P12931	Uniprot
171	Y	Phosphorylation	Kinase	SRC	P12931	Uniprot
177	Y	Phosphorylation	Kinase	SRC	P12931	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	NEDD4	P46934	PMID:15252135
-	K	Ubiquitination	E3 ubiquitin ligase	NEDD4L	Q96PU5	PMID:15252135

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of NFIP2_HUMAN !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of NFIP2_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
NEDD4_HUMAN	NEDD4	physical	12796489
NEDD4_HUMAN	NEDD4	physical	15252135
PTEN_HUMAN	PTEN	physical	20534535
EGFR_HUMAN	EGFR	physical	20534535
LYN_HUMAN	LYN	physical	20534535
FYN_HUMAN	FYN	physical	20534535
SRC_HUMAN	SRC	physical	20534535
NEDD4_HUMAN	NEDD4	physical	20522958
ITCH_HUMAN	ITCH	physical	20522958
WWP2_HUMAN	WWP2	physical	20522958
NEDD4_HUMAN	NEDD4	physical	12050153
NED4L_HUMAN	NEDD4L	physical	12050153

Drug and Disease Associations

• Kegg Disease
• OMIM Disease
• There are no disease associations of PTM sites.
• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Phosphorylation

"Regulation of PTEN/Akt and MAP kinase signaling pathways by theubiquitin ligase activators Ndfip1 and Ndfip2.";
Mund T., Pelham H.R.;
Proc. Natl. Acad. Sci. U.S.A. 107:11429-11434(2010).
Cited for: FUNCTION, INTERACTION WITH LYN; NDFIP1; NEDD4; PTEN AND SRC,SUBCELLULAR LOCATION, TOPOLOGY, PHOSPHORYLATION AT TYR-151; TYR-167;TYR-171 AND TYR-177, AND MUTAGENESIS OF 149-PRO--TYR-151; TYR-167;175-PRO--TYR-177 AND 184-PRO--TYR-186.
PubMed: 20534535