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: EC:3.6.4.4 (
kinesin
)
5,033
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The
IP3R
[IP3 (inositol 1,4,5-trisphosphate) receptor] is responsible for Ca2+ release from the ER (endoplasmic reticulum). We have been working extensively on the P400 protein, which is deficient in Purkinje-neuron-degenerating mutant mice. We have discovered that P400 is an
IP3R
and we have determined the primary sequence. Purified
IP3R
, when incorporated into a lipid bilayer, works as a Ca2+ release channel and overexpression of
IP3R
shows enhanced IP3 binding and channel activity. Addition of an antibody blocks Ca2+ oscillations indicating that IP3R1 works as a Ca2+ oscillator. Studies on the role of
IP3R
during development show that
IP3R
is involved in fertilization and is essential for determination of dorso-ventral axis formation. We found that
IP3R
is involved in neuronal plasticity. A double homozygous mutant of IP3R2 (
IP3R
type 2) and IP3R3 (
IP3R
type 3) shows a deficit of saliva secretion and gastric juice secretion suggesting that IP3Rs are essential for exocrine secretion.
IP3R
has various unique properties: cryo-EM (electron microscopy) studies show that
IP3R
contains multiple cavities;
IP3R
allosterically and dynamically changes its form reversibly (square form-windmill form);
IP3R
is functional even though it is fragmented by proteases into several pieces; the ER forms a meshwork but also forms vesicular ER and moves along microtubules using a
kinesin
motor; X ray analysis of the crystal structure of the IP3 binding core consists of an N-terminal beta-trefoil domain and a C-terminal alpha-helical domain. We have discovered ERp44 as a redox sensor in the ER which binds to the luminal part of IP3R1 and regulates its activity. We have also found the role of IP3 is not only to release Ca2+ but also to release IRBIT which binds to the IP3 binding core of
IP3R
.
...
PMID:The IP3 receptor/Ca2+ channel and its cellular function. 1723 76
