Adenosylhomocysteinase-like 1 (AHCYL1)

Adenosylhomocysteinase-like 1 (AHCYL1), also known as IRBIT, is a multifunctional regulatory protein expressed widely in epithelial and neuronal cell types[1][2]. Although structurally similar to S-adenosylhomocysteine hydrolase, AHCYL1 lacks catalytic activity and instead functions as a modulator of intracellular signaling and epithelial transport[2]. The protein binds the inositol 1,4,5-trisphosphate receptor (ITPR1), regulating calcium signaling by competing with IP₃ and modulating Ca⁺² release from intracellular stores, thus influencing apoptosis and ion/fluid transport in epithelia[1][2]. AHCYL1/IRBIT also interacts with mRNA processing machinery to regulate polyadenylation and mRNA export, and serves as a regulator of cell cycle progression by controlling deoxyribonucleotide synthesis[1][2]. Dysregulation of AHCYL1 is implicated in diseases including certain cancers, notably where it forms an oncogenic fusion with FGFR2 in intrahepatic cholangiocarcinoma, a context in which FGFR inhibitors show therapeutic promise[1].

Other names

IRBITXPVKONADCALPPP1R78PRO0233Inositol 1,4,5-trisphosphate receptor-binding proteinS-adenosylhomocysteine hydrolase-like protein 1DC-expressed AHCY-like moleculeIP(3)Rs binding protein released with IP(3)S-adenosyl-L-homocysteine hydrolase 2Putative adenosylhomocysteinase 2Adenosylhomocysteinase 2AdoHcyase 2Dendritic cell expressed AHCY-like proteinEpididymis secretory sperm binding proteinS-adenosyl homocysteine hydrolase homologProtein phosphatase 1, regulatory subunit 78

FGFR inhibitors block aberrant FGFR2-AHCYL1 fusion protein signaling in intrahepatic cholangiocarcinoma