Itpr1 (rat, P29994) - manual literature synthesis

No deep-research provider was run for this gene (no API keys in this environment). This file
summarises the literature read directly from the cached publications in publications/.
Every assertion carries an inline citation with a verbatim quote.

Identity and molecular function

Itpr1 encodes the type 1 inositol 1,4,5-trisphosphate receptor (IP3R1, InsP3R1), a 2,750-residue
multi-pass ER membrane protein that assembles into a tetrameric IP3- and Ca2+-gated Ca2+ release
channel.

• Channel activity of recombinant rat IP3R1 was recorded directly in planar lipid bilayers
  PMID:15533917, with a high-affinity
  ATP modulatory site PMID:15533917.
• On-nucleus patch clamp of rat IP3R1 expressed in IP3R-null DT40 cells showed biphasic Ca2+ and
  ATP regulation PMID:22547632.
• Cryo-EM of nanodisc-reconstituted rat IP3R1 resolved IP3, Ca2+ and ATP sites [PMID:36376291
  "These structures provide unprecedented details governing binding of IP3, Ca2+ and ATP,
  revealing conformational changes that couple ligand-binding to channel opening."; "The CIA-IP3R1
  structure reveals a previously unseen ATP-binding site located at the interface between the ILD
  and LNK domains"].
• Tetrameric assembly; six transmembrane segments define the pore region PMID:10506212;
  proteolytic fragments still assemble into functional tetramers PMID:23479737.
• cAMP directly sensitises all IP3R subtypes, including rat IP3R1 expressed in DT40 cells, to IP3
  independent of PKA PMID:20189985.

Localisation

• ER membrane: rat IP3R1 is co-translationally targeted to the ER by TMD1 PMID:19845505
  and diffuses freely in a continuous ER PMID:21550988.
• Other membranes are reported but secretory-vesicle localisation is contentious PMID:19845505.
• Nuclear envelope / inner nuclear membrane in rat myotubes, where nuclear IP3R1 releases Ca2+
  PMID:16014380.
• Purkinje neuron ER, including smooth ER subcompartments PMID:1311032.
• ER-mitochondria contacts, coupled to VDAC1 through GRP75 PMID:17178908.
• Junctional ER under the plasma membrane in rat chromaffin cells PMID:15911880.
• Perinuclear ER in A7r5 smooth muscle cells PMID:12615969.

Interacting proteins (regulatory)

HAP1A/huntingtin PMID:12873381, 4.1N PMID:12676536, syntaxin 1B PMID:21424589, ANO1
PMID:23982204, polycystin-2 PMID:16223735, ataxin-3 PMID:19036964, calcineurin via Bcl-2
PMID:15212990, AKAP9/PKA PMID:19236309, Herp-mediated degradation PMID:22045699. These are
regulators or scaffolds that tune IP3R1-mediated Ca2+ release; none changes the core activity.

Physiological roles (downstream of Ca2+ release)

Hepatocyte proliferation in early liver regeneration PMID:24814243, neurite outgrowth in PC12
cells PMID:21211516, neuronal death after neonatal anoxia PMID:28072885, preconditioning
neuroprotection PMID:20434434. All are knockdown or pharmacology phenotypes downstream of the Ca2+
signal. Expression is induced by hypoxia PMID:17285299.