Gene Symbol: AHCYL1
Description: adenosylhomocysteinase like 1
Alias: DCAL, IRBIT, PPP1R78, PRO0233, XPVKONA, S-adenosylhomocysteine hydrolase-like protein 1, DC-expressed AHCY-like molecule, IP(3)Rs binding protein released with IP(3), S-adenosyl homocysteine hydrolase homolog, S-adenosyl-L-homocysteine hydrolase 2, adenosylhomocysteinase 2, adoHcyase 2, dendritic cell expressed AHCY-like protein, inositol 1,4,5-trisphosphate receptor-binding protein, protein phosphatase 1, regulatory subunit 78
Species: human
Products:     AHCYL1

Top Publications

  1. Khamaysi A, Anbtawee Jomaa S, Fremder M, Eini Rider H, Shimshilashvili L, Aharon S, et al. Systemic Succinate Homeostasis and Local Succinate Signaling Affect Blood Pressure and Modify Risks for Calcium Oxalate Lithogenesis. J Am Soc Nephrol. 2019;: pubmed publisher
    ..This interaction is regulated by the scaffolding protein IRBIT, which is released by stimulation of the succinate receptor SUCNR1 and interacts with the NaDC-1/slc26a6 complex ..
  2. Alexander C, Hammer J. An Improved Method for Differentiating Mouse Embryonic Stem Cells into Cerebellar Purkinje Neurons. Cerebellum. 2019;: pubmed publisher
    ..Furthermore, mESC-derived PNs express Calbindin D28K, IP3R1, IRBIT, PLCβ4, PSD93, and myosin IIB-B2, all of which are either PN-specific or highly expressed in PNs...
  3. Vachel L, Shcheynikov N, Yamazaki O, Fremder M, Ohana E, Son A, et al. Modulation of Cl- signaling and ion transport by recruitment of kinases and phosphatases mediated by the regulatory protein IRBIT. Sci Signal. 2018;11: pubmed publisher
    b>IRBIT is a multifunctional protein that controls the activity of various epithelial ion transporters including NBCe1-B...
  4. Han E, Ha W, Jin Y, Bolch W, Lee C. Effective dose conversion coefficients for health care provider exposed to pediatric and adult victims in radiological dispersal device incident. J Radiol Prot. 2015;35:37-45 pubmed publisher
    ..age-specific organ burdens after the inhalation of those radionuclides from the Dose and Risk Calculation Software (DCAL) program...
  5. Ahuja M, Jha A, Maléth J, Park S, Muallem S. cAMP and Ca²⁺ signaling in secretory epithelia: crosstalk and synergism. Cell Calcium. 2014;55:385-93 pubmed publisher
    ..In this review, we discuss crosstalk between the Ca(2+) and cAMP signaling and the function of IRBIT (IP3 receptors binding protein release with IP3) as a third messenger that mediates the synergistic action of the ..
  6. Burmeister T, Meyer C, Gröger D, Hofmann J, Marschalek R. Evidence-based RT-PCR methods for the detection of the 8 most common MLL aberrations in acute leukemias. Leuk Res. 2015;39:242-7 pubmed publisher
    ..600 cases at the Diagnostic Center for Acute Leukemias (DCAL) in Frankfurt, Germany that provide an overview over the experimentally observed fusion transcript variants, we ..
  7. Mikoshiba K. Role of IP3 receptor signaling in cell functions and diseases. Adv Biol Regul. 2015;57:217-27 pubmed publisher
    ..Moreover, IP3 was found not only to release Ca(2+), but also to release IRBIT (IP3receptor binding protein released with inositol trisphosphate) essential for the regulation of acid-base ..
  8. Shcheynikov N, Son A, Hong J, Yamazaki O, Ohana E, Kurtz I, et al. Intracellular Cl- as a signaling ion that potently regulates Na+/HCO3- transporters. Proc Natl Acad Sci U S A. 2015;112:E329-37 pubmed publisher
    ..IP3 receptor binding protein released with IP3 (IRBIT) activation of NBCe1-B unmasks a second high affinity Cl(-) in interacting GXXXP-dependent site...
  9. Kawaai K, Mizutani A, Shoji H, Ogawa N, Ebisui E, Kuroda Y, et al. IRBIT regulates CaMKIIα activity and contributes to catecholamine homeostasis through tyrosine hydroxylase phosphorylation. Proc Natl Acad Sci U S A. 2015;112:5515-20 pubmed publisher
    Inositol 1,4,5-trisphosphate receptor (IP3R) binding protein released with IP3 (IRBIT) contributes to various physiological events (electrolyte transport and fluid secretion, mRNA polyadenylation, and the maintenance of genomic integrity)..

More Information


  1. Jeong W, Kim J, Ahn S, Lee S, Bazer F, Han J, et al. AHCYL1 is mediated by estrogen-induced ERK1/2 MAPK cell signaling and microRNA regulation to effect functional aspects of the avian oviduct. PLoS ONE. 2012;7:e49204 pubmed publisher
    S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1), also known as IP(3) receptor-binding protein released with IP(3) (IRBIT), regulates IP(3)-induced Ca(2+) release into the cytoplasm of cells...
  2. He P, Zhao L, Zhu L, Weinman E, De Giorgio R, Koval M, et al. Restoration of Na+/H+ exchanger NHE3-containing macrocomplexes ameliorates diabetes-associated fluid loss. J Clin Invest. 2015;125:3519-31 pubmed publisher
    ..regulatory factors (NHERFs), inositol trisphosphate (IP₃) receptor-binding protein released with IP₃ (IRBIT), and ezrin, was decreased in the intestinal brush border membrane (BBM) of mice with streptozotocin-induced ..
  3. He P, Zhao L, No Y, Karvar S, Yun C. The NHERF1 PDZ1 domain and IRBIT interact and mediate the activation of Na+/H+ exchanger 3 by ANG II. Am J Physiol Renal Physiol. 2016;311:F343-51 pubmed publisher
    ..shown that inositol 1,4,5-trisphosphate receptor-binding protein released with inositol 1,4,5-trisphosphate (IRBIT) mediates ANG II-induced exocytosis of NHE3 in cultured proximal tubule epithelial cells...
  4. Grbesa I, Kalo A, Beluzić R, Kovacevic L, Lepur A, Rokić F, et al. Mutations in S-adenosylhomocysteine hydrolase (AHCY) affect its nucleocytoplasmic distribution and capability to interact with S-adenosylhomocysteine hydrolase-like 1 protein. Eur J Cell Biol. 2017;96:579-590 pubmed publisher
    ..We investigated previously assumed interaction with AHCY-like-1 protein (AHCYL1), a paralog of AHCY. Indeed, significant interaction between both proteins exists...
  5. Barresi S, Niceta M, Alfieri P, Brankovic V, Piccini G, Bruselles A, et al. Mutations in the IRBIT domain of ITPR1 are a frequent cause of autosomal dominant nonprogressive congenital ataxia. Clin Genet. 2017;91:86-91 pubmed publisher
    ..8%) all localized in the IRBIT (inositol triphosphate receptor binding protein) domain which plays an essential role in the regulation of ..
  6. Borth H, Weber N, Meyer D, Wartenberg A, Arlt E, Zierler S, et al. The IP3 R Binding Protein Released With Inositol 1,4,5-Trisphosphate Is Expressed in Rodent Reproductive Tissue and Spermatozoa. J Cell Physiol. 2016;231:1114-29 pubmed publisher
    Besides its capacity to inhibit the 1,4,5-trisphosphate (IP3) receptor, the regulatory protein IRBIT (IP3 receptor binding protein released with IP3) is also able to control the activity of numerous ion channels and electrolyte ..
  7. Park S, Shcheynikov N, Hong J, Zheng C, Suh S, Kawaai K, et al. Irbit mediates synergy between ca(2+) and cAMP signaling pathways during epithelial transport in mice. Gastroenterology. 2013;145:232-241 pubmed publisher
    ..member 6 (Slc26a6(-/-) mice) and inositol 1,4,5-triphosphate (InsP3) receptor-binding protein released with InsP3 (Irbit(-/-)) mice...
  8. Kawaai K, Ando H, Satoh N, Yamada H, Ogawa N, Hirose M, et al. Splicing variation of Long-IRBIT determines the target selectivity of IRBIT family proteins. Proc Natl Acad Sci U S A. 2017;114:3921-3926 pubmed publisher
    b>IRBIT [inositol 1,4,5-trisphosphate receptor (IP3R) binding protein released with inositol 1,4,5-trisphosphate (IP3)] is a multifunctional protein that regulates several target molecules such as ion channels, ..
  9. Ando H, Kawaai K, Bonneau B, Mikoshiba K. Remodeling of Ca2+ signaling in cancer: Regulation of inositol 1,4,5-trisphosphate receptors through oncogenes and tumor suppressors. Adv Biol Regul. 2018;68:64-76 pubmed publisher
    ..Another regulatory protein of IP3R, IP3R-binding protein released with IP3 (IRBIT), cooperates with or counteracts the Bcl-2 family member depending on cellular states...
  10. Jeong Y, Hong J. Governing effect of regulatory proteins for Cl(-)/HCO3(-) exchanger 2 activity. Channels (Austin). 2016;10:214-24 pubmed publisher
    ..such as spinophilin (SPL), inositol-1,4,5-trisphosphate [IP3] receptors binding protein released with IP3 (IRBIT), STE20/SPS1-related proline/alanine-rich kinase (SPAK) kinase, and carbonic anhydrase XII (CA XII)...
  11. Hong J, Yang D, Shcheynikov N, Ohana E, Shin D, Muallem S. Convergence of IRBIT, phosphatidylinositol (4,5) bisphosphate, and WNK/SPAK kinases in regulation of the Na+-HCO3- cotransporters family. Proc Natl Acad Sci U S A. 2013;110:4105-10 pubmed publisher
    ..HCO3(-) secretion is highly regulated, with the WNK/SPAK kinase pathway setting the resting state and the IRBIT/PP1 pathway setting the stimulated state...
  12. Ando H, Kawaai K, Mikoshiba K. IRBIT: a regulator of ion channels and ion transporters. Biochim Biophys Acta. 2014;1843:2195-204 pubmed publisher
    IRBIT (also called AHCYL1) was originally identified as a binding protein of the intracellular Ca(2+) channel inositol 1,4,5-trisphosphate (IP3) receptor and functions as an inhibitory regulator of this receptor...
  13. Ando H, Hirose M, Gainche L, Kawaai K, Bonneau B, Ijuin T, et al. IRBIT Interacts with the Catalytic Core of Phosphatidylinositol Phosphate Kinase Type Iα and IIα through Conserved Catalytic Aspartate Residues. PLoS ONE. 2015;10:e0141569 pubmed publisher
    ..b>IRBIT (IP3R-binding protein released with inositol 1,4,5-trisphosphate) is a multifunctional protein that regulates ..
  14. Cooper B, Key B, Carter A, Angel N, Hart D, Kato M. Suppression and overexpression of adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) influences zebrafish embryo development: a possible role for AHCYL1 in inositol phospholipid signaling. J Biol Chem. 2006;281:22471-84 pubmed publisher
    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 ..
  15. Dentici M, Barresi S, Nardella M, Bellacchio E, Alfieri P, Bruselles A, et al. Identification of novel and hotspot mutations in the channel domain of ITPR1 in two patients with Gillespie syndrome. Gene. 2017;628:141-145 pubmed publisher
    ..Missense mutations in the InsP3-binding domain (IRBIT) of ITPR1 are frequently associated with early onset cerebellar atrophy...
  16. Ando H, Mizutani A, Matsu ura T, Mikoshiba K. IRBIT, a novel inositol 1,4,5-trisphosphate (IP3) receptor-binding protein, is released from the IP3 receptor upon IP3 binding to the receptor. J Biol Chem. 2003;278:10602-12 pubmed
    ..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) ..
  17. Dekker J, Budhia S, Angel N, Cooper B, Clark G, Hart D, et al. Identification of an S-adenosylhomocysteine hydrolase-like transcript induced during dendritic cell differentiation. Immunogenetics. 2002;53:993-1001 pubmed
    ..Therefore, this molecule was termed DC-expressed AHCY-like molecule (DCAL)...
  18. He P, Klein J, Yun C. Activation of Na+/H+ exchanger NHE3 by angiotensin II is mediated by inositol 1,4,5-triphosphate (IP3) receptor-binding protein released with IP3 (IRBIT) and Ca2+/calmodulin-dependent protein kinase II. J Biol Chem. 2010;285:27869-78 pubmed publisher
    ..previously that inositol 1,4,5-triphosphate receptor-binding protein released with inositol 1,4,5-triphosphate (IRBIT) plays a critical role in stimulation of NHE3 in response to elevated intracellular Ca(2+) concentration ([Ca(2+)](..
  19. Ando H, Mizutani A, Mikoshiba K. An IRBIT homologue lacks binding activity to inositol 1,4,5-trisphosphate receptor due to the unique N-terminal appendage. J Neurochem. 2009;109:539-50 pubmed publisher
    b>IRBIT is an inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R)-binding protein that inhibits the activation of IP(3)R by competing with IP(3) for the common binding site on IP(3)R...
  20. Ando H, Mizutani A, Kiefer H, Tsuzurugi D, Michikawa T, Mikoshiba K. IRBIT suppresses IP3 receptor activity by competing with IP3 for the common binding site on the IP3 receptor. Mol Cell. 2006;22:795-806 pubmed
    ..We previously identified an IP3R binding protein, IRBIT, which binds to the IP3 binding domain of IP3R and is dissociated from IP3R in the presence of IP3...
  21. Tran T, Park M, Lee J, Bae J, Hwang S, Choi S, et al. IRBIT plays an important role in NHE3-mediated pHi regulation in HSG cells. Biochem Biophys Res Commun. 2013;437:18-22 pubmed publisher
    Expression of inositol-1,4,5-trisphosphate (IP3) receptor-binding protein (IRBIT) has been reported in epithelial cells. However, its role in pHi regulation is not well understood...
  22. Sinđić A, Sussman C, Romero M. Primers on molecular pathways: bicarbonate transport by the pancreas. Pancreatology. 2010;10:660-3 pubmed publisher
    ..Most recently, both IRBIT (inositol 1,4,5-trisphosphate receptor-binding protein) and WNK [with no lysine (K)] kinase have been implicated ..
  23. He P, Zhang H, Yun C. IRBIT, inositol 1,4,5-triphosphate (IP3) receptor-binding protein released with IP3, binds Na+/H+ exchanger NHE3 and activates NHE3 activity in response to calcium. J Biol Chem. 2008;283:33544-53 pubmed publisher
    ..In this study, we report the identification of IP3 receptor-binding protein released with IP3 (IRBIT) as a NHE3 interacting protein and its role in regulation of NHE3 activity...
  24. Chang J, Mukerjee R, Bagashev A, Del Valle L, Chabrashvili T, Hawkins B, et al. HIV-1 Tat protein promotes neuronal dysfunction through disruption of microRNAs. J Biol Chem. 2011;286:41125-34 pubmed publisher
    ..Therefore, we conclude that deregulation of neuronal functions by HIV-1 Tat protein is miRNA-dependent...
  25. Yang D, Li Q, So I, Huang C, Ando H, Mizutani A, et al. IRBIT governs epithelial secretion in mice by antagonizing the WNK/SPAK kinase pathway. J Clin Invest. 2011;121:956-65 pubmed publisher
    ..of the NBCe1-B/CFTR activator inositol-1,4,5-trisphosphate (IP(3)) receptor-binding protein released with IP(3) (IRBIT) and by inhibition of protein phosphatase 1 (PP1)...
  26. Bonneau B, Ando H, Kawaai K, Hirose M, Takahashi Iwanaga H, Mikoshiba K. IRBIT controls apoptosis by interacting with the Bcl-2 homolog, Bcl2l10, and by promoting ER-mitochondria contact. elife. 2016;5: pubmed publisher
    b>IRBIT is a molecule that interacts with the inositol 1,4,5-trisphosphate (IP3)-binding pocket of the IP3 receptor (IP3R), whereas the antiapoptotic protein, Bcl2l10, binds to another part of the IP3
  27. Lee S, Boron W, Parker M. Relief of autoinhibition of the electrogenic Na-HCO(3) [corrected] cotransporter NBCe1-B: role of IRBIT vs.amino-terminal truncation. Am J Physiol Cell Physiol. 2012;302:C518-26 pubmed publisher
    ..NBCe1-C of an 87-amino acid sequence that contains an autoinhibitory domain (AID); and 2) binding of the protein IRBIT to elements within the same 87-amino acid module in a different variant, NBCe1-B...
  28. Andersson M, Johansson L, ECKERMAN K, Mattsson S. IDAC-Dose 2.1, an internal dosimetry program for diagnostic nuclear medicine based on the ICRP adult reference voxel phantoms. EJNMMI Res. 2017;7:88 pubmed publisher
    ..The computer program was validated against another ICRP dosimetry program, Dose and Risk Calculation (DCAL), that employs the same computational framework in evaluation of occupational and environmental intakes of ..
  29. Pawlak A, Toussaint C, Levy I, Bulle F, Poyard M, Barouki R, et al. Characterization of a large population of mRNAs from human testis. Genomics. 1995;26:151-8 pubmed
    ..This argues for the value of the combination of random sequencing and analysis of cellular expression for large-scale characterization of gene expression in the testis...
  30. Kiefer H, Mizutani A, Iemura S, Natsume T, Ando H, Kuroda Y, et al. Inositol 1,4,5-triphosphate receptor-binding protein released with inositol 1,4,5-triphosphate (IRBIT) associates with components of the mRNA 3' processing machinery in a phosphorylation-dependent manner and inhibits polyadenylation. J Biol Chem. 2009;284:10694-705 pubmed publisher
    b>IRBIT is a recently identified protein that modulates the activities of both inositol 1,4,5-triphosphate receptor and pancreas-type Na(+)/HCO(3)(-) cotransporter 1, and the multisite phosphorylation of IRBIT is required for achieving ..
  31. Shirakabe K, Priori G, Yamada H, Ando H, Horita S, Fujita T, et al. IRBIT, an inositol 1,4,5-trisphosphate receptor-binding protein, specifically binds to and activates pancreas-type Na+/HCO3- cotransporter 1 (pNBC1). Proc Natl Acad Sci U S A. 2006;103:9542-7 pubmed
    ..We previously identified an IP(3)R binding protein, termed IP(3)R binding protein released with IP(3) (IRBIT)...
  32. Lepur A, Kovacevic L, Beluzić R, Vugrek O. Combining Unique Multiplex Gateway Cloning and Bimolecular Fluorescence Complementation (BiFC) for High-Throughput Screening of Protein-Protein Interactions. J Biomol Screen. 2016;21:1100-1111 pubmed publisher
    ..We have validated the vectors and confirmed self-association of AHCY, AHCYL1, and galectin-3...
  33. Arnaoutov A, Dasso M. Enzyme regulation. IRBIT is a novel regulator of ribonucleotide reductase in higher eukaryotes. Science. 2014;345:1512-5 pubmed publisher
    ..Here, we show that the metazoan protein IRBIT forms a deoxyadenosine triphosphate (dATP)-dependent complex with RNR, which stabilizes dATP in the activity site ..
  34. Jeong W, Kim H, Kim Y, Kim M, Lim W, Kim J, et al. Paradoxical expression of AHCYL1 affecting ovarian carcinogenesis between chickens and women. Exp Biol Med (Maywood). 2012;237:758-67 pubmed publisher
    We investigated S-adenosylhomocysteine hydrolase-like protein 1 (AHCYL1) gene expression in human epithelial ovarian cancer (EOC) using the chicken, which is the most relevant animal model...
  35. Cleaver J, Afzal V, Feeney L, McDowell M, Sadinski W, Volpe J, et al. Increased ultraviolet sensitivity and chromosomal instability related to P53 function in the xeroderma pigmentosum variant. Cancer Res. 1999;59:1102-8 pubmed
    ..The symptoms of elevated solar carcinogenesis in XPV patients may, therefore, be associated with increased genomic instability in cells of the skin in which p53 is inactivated by UV-induced mutations. ..
  36. Witwer K. HIV-1 Tat- and Vpr-responsive microRNAs of neuronal cells. J Biol Chem. 2014;289:3104 pubmed publisher