High impact information on AHCYL1

• IRBIT suppresses IP3 receptor activity by competing with IP3 for the common binding site on the IP3 receptor [1].
• These data suggest that AHCYL1 has a different function from AHCY and plays an important role in embryogenesis by modulating inositol 1,4,5-trisphosphate receptor function for the intracellular calcium release [2].
• AHCYL1 binds to the inositol 1,4,5-trisphosphate receptor, suggesting that AHCYL1 is involved in intracellular calcium release [2].
• Suppression and overexpression of adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) influences zebrafish embryo development: a possible role for AHCYL1 in inositol phospholipid signaling [2].
• Adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) is a novel intracellular protein with approximately 50% protein identity to adenosylhomocysteine hydrolase (AHCY), an important enzyme for metabolizing S-adenosyl-l-homocysteine, the by-product of S-adenosyl-l-homomethionine-dependent methylation [2].

Biological context of AHCYL1

• We propose a unique mode of IP3R regulation in which IP3 sensitivity is regulated by IRBIT acting as an endogenous "pseudoligand" whose inhibitory activity can be modulated by its phosphorylation status [1].
• Herein, we report a novel protein, termed IRBIT (IP(3)R binding protein released with inositol 1,4,5-trisphosphate), which interacts with type 1 IP(3)R (IP(3)R1) and was released upon IP(3) binding to IP(3)R1 [3].
• Linear regression analysis revealed a highly statistically significant equation relating the two energy expenditures: Indircal (kcal/d) = -9.341 + [0.705 x Bicarb (dcal/d)]; p < 0.001, r2 = 96.4% [4].

Anatomical context of AHCYL1

• Identification of an S-adenosylhomocysteine hydrolase-like transcript induced during dendritic cell differentiation [5].
• DCAL mRNA increased markedly during activation of blood and skin DC (Langerhans cells), but was diminished in terminally differentiated tonsil DC [5].
• Cultured monocytes expressed little DCAL mRNA, but levels increased markedly when differentiated into DC by cytokines GM-CSF and IL-4 [5].
• IRBIT was purified from a high salt extract of crude rat brain microsomes with IP(3) elution using an affinity column with the huge immobilized N-terminal cytoplasmic region of IP(3)R1 (residues 1-2217) [3].

Associations of AHCYL1 with chemical compounds

• IP(3) dissociated IRBIT from IP(3)R1 with an EC(50) of approximately 0.5 microm, i.e. it was 50 times more potent than other inositol polyphosphates [3].
• IRBIT binds to and activates Na, Bicarbonate cotransporter [6].
• IP(3) works to release IRBIT from the IP(3) binding core in addition to release Ca(2+) [6].
• Form A crystallized in the monoclinic space group C2/c, with a = 42.936 (14), b = 4.356 (1), c = 21.536 (6) A, beta = 109.92 (4) degrees, z = 8, and dcal = 1.275 g/cm3 [7].
• Single-crystal X-ray analysis was performed on form II which was found to crystallize in the triclinic space group P1 with a = 10.736(2) A, b = 16.921(4) A, c = 17.041(4) A, alpha = 100.76(1) degrees, beta = 95.27(1) degrees, gamma = 97.53(1) degrees, Z = 8, and dcal = 1.33 g/cm3 [8].

Physical interactions of AHCYL1

• Multiserine phosphorylation of IRBIT was essential for the binding, and 10 of the 12 key amino acids in IP3R for IP3 recognition participated in binding to IRBIT [1].

Regulatory relationships of AHCYL1

• In the present study, we showed that IRBIT suppresses the activation of IP3R by competing with IP3 by [3H]IP3 binding assays, in vitro Ca2+ release assays, and Ca2+ imaging of intact cells [1].

Other interactions of AHCYL1

• Binding of IRBIT to the IP3 receptor: determinants and functional effects [9].

References