Search Results
Overview
| Uniprot ID | O43865 |
|---|---|
| Protein Name | S-adenosylhomocysteine hydrolase-like protein 1 |
| Gene Name | AHCYL1 |
| Organism | Homo sapiens |
Kla Sites from experimental identification
| Position | Flanking peptide |
|---|---|
| 111 | NFCVKNIKQAEFGRR |
| 36 | SFMATVTKAPKKQIQ |
| 39 | ATVTKAPKKQIQFAD |
| 40 | TVTKAPKKQIQFADD |
| 478 | NAPEGRYKQDVYLLP |
| 57 | EFTKFPTKTGRRSLS |
Function
Multifaceted cellular regulator which coordinates several essential cellular functions including regulation of epithelial HCO3(-) and fluid secretion, mRNA processing and DNA replication. Regulates ITPR1 sensitivity to inositol 1,4,5-trisphosphate, competing for the common binding site and acting as endogenous 'pseudoligand' whose inhibitory activity can be modulated by its phosphorylation status. Promotes the formation of contact points between the endoplasmic reticulum (ER) and mitochondria, facilitating transfer of Ca(2+) from the ER to mitochondria (PubMed:27995898). Under normal cellular conditions, functions cooperatively with BCL2L10 to limit ITPR1-mediated Ca(2+) release but, under apoptotic stress conditions, dephosphorylated which promotes dissociation of both AHCYL1 and BCL2L10 from mitochondria-associated endoplasmic reticulum membranes, inhibits BCL2L10 interaction with ITPR1 and leads to increased Ca(2+) transfer to mitochondria which promotes apoptosis (PubMed:27995898). In the pancreatic and salivary ducts, at resting state, attenuates inositol 1,4,5-trisphosphate-induced calcium release by interacting with ITPR1 (PubMed:16793548). When extracellular stimuli induce ITPR1 phosphorylation or inositol 1,4,5-trisphosphate production, dissociates from ITPR1 to interact with CFTR and SLC26A6, mediating their synergistic activation by calcium and cAMP that stimulates the epithelial secretion of electrolytes and fluid (By similarity). Also activates basolateral SLC4A4 isoform 1 to coordinate fluid and HCO3(-) secretion (PubMed:16769890). Inhibits the effect of STK39 on SLC4A4 and CFTR by recruiting PP1 phosphatase which activates SLC4A4, SLC26A6 and CFTR through dephosphorylation (By similarity). Mediates the induction of SLC9A3 surface expression produced by Angiotensin-2 (PubMed:20584908). Depending on the cell type, activates SLC9A3 in response to calcium or reverses SLC9A3R2-dependent calcium inhibition (PubMed:18829453). May modulate the polyadenylation state of specific mRNAs, both by controlling the subcellular location of FIP1L1 and by inhibiting PAPOLA activity, in response to a stimulus that alters its phosphorylation state (PubMed:19224921). Acts as a (dATP)-dependent inhibitor of ribonucleotide reductase large subunit RRM1, controlling the endogenous dNTP pool and ensuring normal cell cycle progression (PubMed:25237103). In vitro does not exhibit any S-adenosyl-L-homocysteine hydrolase activity (By similarity). Functions as a SAH (S-adenosyl-L-homocysteine) sensor that inhibits autophagy through an MTORC1-independent mechanism. Upon SAH binding, interacts with the catalytic domain of PIK3C3, inhibiting its lipid kinase activity and reducing production of phosphatidylinositol-3-phosphate (PtdIns3P), thereby blocking autophagosome formation (PubMed:33993848)
Protein Sequence
Gene Ontology
| Classification | GO ID | Description |
|---|---|---|
| Cellular Component | GO:0016324 | apical plasma membrane |
| Cellular Component | GO:0005737 | cytoplasm |
| Cellular Component | GO:0005829 | cytosol |
| Cellular Component | GO:0005789 | endoplasmic reticulum membrane |
| Cellular Component | GO:0070062 | extracellular exosome |
| Cellular Component | GO:0044233 | mitochondria-associated endoplasmic reticulum membrane contact site |
| Molecular Function | GO:0030234 | enzyme regulator activity |
| Molecular Function | GO:0042802 | identical protein binding |
| Molecular Function | GO:0003723 | RNA binding |
| Biological Process | GO:0038166 | angiotensin-activated signaling pathway |
| Biological Process | GO:0006915 | apoptotic process |
| Biological Process | GO:0042045 | epithelial fluid transport |
| Biological Process | GO:1990456 | mitochondrion-endoplasmic reticulum membrane tethering |
| Biological Process | GO:0006730 | one-carbon metabolic process |
| Biological Process | GO:0010765 | positive regulation of sodium ion transport |
| Biological Process | GO:0031440 | regulation of mRNA 3'-end processing |
| Biological Process | GO:0051592 | response to calcium ion |
| Biological Process | GO:0033353 | S-adenosylmethionine cycle |
Reference
[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.
[2] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.
[3] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.
[4] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.
[5] Shi CM, Wang QC, Li XL, Yang YH, Tang XY et al.. Global Profiling of Protein Lactylation in Human Hippocampi.. Proteomics Clin Appl 19(2):e202400061. 2025 Mar. PMID: 39610256.
[6] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.