Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0038187 (
starvation
)
24,951
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The intracellular targeting determinants of oxysterol binding protein (OSBP)-related protein 3 (
ORP3
) were studied using a series of truncated and point mutated constructs. The pleckstrin homology (PH) domain of
ORP3
binds the phosphoinositide-3-kinase (PI3K) products, PI(3,4)P2 and PI(3,4,5)P3. A functional PH domain and flanking sequences are crucial for the plasma membrane (PM) targeting of
ORP3
. The endoplasmic reticulum (ER) targeting of
ORP3
is regulated the by a FFAT motif (EFFDAxE), which mediates interaction with VAMP-associated protein (VAP)-A. The targeting function of the FFAT motif dominates over that of the PH domain. In addition, the exon 10/11 region modulates interaction of
ORP3
with the ER and the nuclear membrane. Analysis of a chimeric
ORP3
:OSBP protein suggests that ligand binding by the C-terminal domain of OSBP induces allosteric changes that activate the N-terminal targeting modules of
ORP3
. Notably, over-expression of
ORP3
together with VAP-A induces stacked ER membrane structures also known as organized smooth ER (OSER). Moreover, lipid
starvation
promotes formation of dilated peripheral ER (DPER) structures dependent on the
ORP3
protein. Based on the present data, we introduce a model for the inter-relationships of the functional domains of
ORP3
in the membrane targeting of the protein.
...
PMID:Targeting of OSBP-related protein 3 (ORP3) to endoplasmic reticulum and plasma membrane is controlled by multiple determinants. 1614 24
