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Gene Review

AHCYL1  -  adenosylhomocysteinase-like 1

Homo sapiens

Synonyms: AdoHcyase 2, DC-expressed AHCY-like molecule, DCAL, IP(3)Rs binding protein released with IP(3), IRBIT, ...
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High impact information on AHCYL1


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


  1. IRBIT suppresses IP3 receptor activity by competing with IP3 for the common binding site on the IP3 receptor. Ando, H., Mizutani, A., Kiefer, H., Tsuzurugi, D., Michikawa, T., Mikoshiba, K. Mol. Cell (2006) [Pubmed]
  2. Suppression and overexpression of adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) influences zebrafish embryo development: a possible role for AHCYL1 in inositol phospholipid signaling. Cooper, B.J., Key, B., Carter, A., Angel, N.Z., Hart, D.N., Kato, M. J. Biol. Chem. (2006) [Pubmed]
  3. IRBIT, a novel inositol 1,4,5-trisphosphate (IP3) receptor-binding protein, is released from the IP3 receptor upon IP3 binding to the receptor. Ando, H., Mizutani, A., Matsu-ura, T., Mikoshiba, K. J. Biol. Chem. (2003) [Pubmed]
  4. Validation of a [13C]bicarbonate tracer technique to measure neonatal energy expenditure. Shew, S.B., Beckett, P.R., Keshen, T.H., Jahoor, F., Jaksic, T. Pediatr. Res. (2000) [Pubmed]
  5. Identification of an S-adenosylhomocysteine hydrolase-like transcript induced during dendritic cell differentiation. Dekker, J.W., Budhia, S., Angel, N.Z., Cooper, B.J., Clark, G.J., Hart, D.N., Kato, M. Immunogenetics (2002) [Pubmed]
  6. Inositol 1,4,5-trisphosphate IP(3) receptors and their role in neuronal cell function. Mikoshiba, K. J. Neurochem. (2006) [Pubmed]
  7. X-ray crystallographic characterization of two polymorphs of 8-(2-methoxycarbonylamino-6-methylbenzyloxy)-2-methyl-3-(2- propynyl)-imidazo [1,2-a]pyridine. Miyamae, A., Koda, S., Kitamura, S., Okamoto, Y., Morimoto, Y. Journal of pharmaceutical sciences. (1990) [Pubmed]
  8. Solid-state characterization of chlordiazepoxide polymorphs. Singh, D., Marshall, P.V., Shields, L., York, P. Journal of pharmaceutical sciences. (1998) [Pubmed]
  9. Binding of IRBIT to the IP3 receptor: determinants and functional effects. Devogelaere, B., Nadif Kasri, N., Derua, R., Waelkens, E., Callewaert, G., Missiaen, L., Parys, J.B., De Smedt, H. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
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