PMADS

Id:	acc0873
Group:	2sens
Protein:	PTEN
Gene Symbol:	PTEN
Protein Id:	P60484
Protein Name:	PTEN_HUMAN
PTM:	phosphorylation
Site:	Ser380
Site Sequence:	DNEPDHYRYSDTTDSDPENEP
Disease Category:	Cancer
Disease:	Melanoma
Disease Subtype:
Disease Cellline:	A375
Disease Info:
Drug:	chondroitin-4-sulfate(CHSA)
Drug Info:	Chondroitin-4-sulfate (CHSA) is a sulfated glycosaminoglycan commonly used as a dietary supplement to support joint health and alleviate symptoms of osteoarthritis by promoting cartilage integrity and reducing inflammation.
Effect:	modulate
Effect Info:	CHSA treatment increased the phosphorylation levels of AKT and PTEN in A375 and SK-MEL-5 cells and enhanced the cell proliferation rate.
Note:
Score:	4.0
Pubmed(PMID):	29547721
Sentence Index:	29547721_3-4
Sentence:	"Here we report that chondroitin-4-sulfate (CHSA), a natural glycosaminoglycan approved as a dietary supplement used for osteoarthritis, selectively promotes the tumor growth potential of BRAF V600E-expressing human melanoma cells in patient- and cell line-derived xenograft mice and confers resistance to BRAF inhibitors. Mechanistically, chondroitin sulfate glucuronyltransferase (CSGlcA-T) signals through its product CHSA to enhance casein kinase 2 (CK2)-PTEN binding and consequent phosphorylation and inhibition of PTEN, which requires CHSA chains and is essential to sustain AKT activation in BRAF V600E-expressing melanoma cells."

Sequence & Structure:

MTAIIKEIVSRNKRRYQEDGFDLDLTYIYPNIIAMGFPAERLEGVYRNNIDDVVRFLDSKHKNHYKIYNLCAERHYDTAKFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVAAIHCKAGKGRTGVMICAYLLHRGKFLKAQEALDFYGEVRTRDKKGVTIPSQRRYVYYYSYLLKNHLDYRPVALLFHKMMFETIPMFSGGTCNPQFVVCQLKVKIYSSNSGPTRREDKFMYFEFPQPLPVCGDIKVEFFHKQNKMLKKDKMFHFWVNTFFIPGPEETSEKVENGSLCDQEIDSICSIERADNDKEYLVLTLTKNDLDKANKDKANRYFSPNFKVKLYFTKTVEEPSNPEASSSTSVTPDVSDNEPDHYRYSDTTDSDPENEPFDEDQHTQITKV

Select PDB:

Known Drugs:

source: Multi-Sources

(see table)

No data.

Protein Tractability:

source: Open Targets

Small molecule

Antibody

PROTAC

Other modalities

Approved Drug

Advanced Clinical

Phase 1 Clinical

Structure with Ligand

High-Quality Ligand

High-Quality Pocket

Med-Quality Pocket

Druggable Family

Approved Drug

Advanced Clinical

Phase 1 Clinical

UniProt loc high conf

GO CC high conf

UniProt loc med conf

UniProt SigP or TMHMM

GO CC med conf

Human Protein Atlas loc

Approved Drug

Advanced Clinical

Phase 1 Clinical

Literature

UniProt Ubiquitination

Database Ubiquitination

Half-life Data

Small Molecule Binder

Approved Drug

Advanced Clinical

Phase 1 Clinical

PTM Intensity:

source: CPTAC

No intensity data of this site,
show all other sites!

PTEN-Ser294
Cancer	Intensity
BRCA
COAD	-0.741
HGSC
ccRCC	-0.738
GBM
HNSC	1.65
LUAD	-0.543
LUSC	0.557
non_ccRCC	-1.263
PDAC	0.989
UCEC	0.088

PTEN-Ser364
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC
LUAD	0.707
LUSC
non_ccRCC
PDAC
UCEC	-0.707

PTEN-Ser370
Cancer	Intensity
BRCA
COAD	-1.229
HGSC
ccRCC	0.576
GBM
HNSC
LUAD	1.014
LUSC
non_ccRCC
PDAC
UCEC	-0.361

PTEN-Ser467
Cancer	Intensity
BRCA	0.471
COAD
HGSC	-1.149
ccRCC
GBM	0.677
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC

PTEN-Thr363
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC
GBM
HNSC
LUAD	0.707
LUSC
non_ccRCC
PDAC
UCEC	-0.707

PTEN-Thr366
Cancer	Intensity
BRCA
COAD
HGSC
ccRCC	0.707
GBM
HNSC
LUAD
LUSC
non_ccRCC
PDAC
UCEC	-0.707

PTM-Disease Association:

source: PTMD

Residue	Position	State	Disease	Class	PMID
S	380	U	Lymphocytic leukemia	Phosphorylation	20576813
S	380	U	Granulomatosis with polyangiitis	Phosphorylation	37720230
S	380	U	Gastric cancer	Phosphorylation	22521126

State Note: Based on the distinct PTM states in diseases, PTMD classified all disease-associated PTMs into six classes, including whether the up-regulation (U) or down-regulation (D) of PTM levels, the absence (A) or presence (P) of PTMs, and the creation (C) or disruption (N) of PTM sites are associated with diseases.

PTM-Drug Perturbation Response:

source: DecryptM

No data.

Function score:

source: funscoR

No data.

Cross Links:

CTD
DMRdb