Ahcyl1
entrez
229709
canonical
uniprot
Q80SW1
canonical
ensembl
ENSMUSG00000027893
resolver
ensp
ENSMUSP00000029490
resolver
enst
ENSMUST00000029490
resolver
genesymbol
Ahcyl1
resolver
genesymbol_syn
Irbit
resolver
uniprot_entry
SAHH2_MOUSE
resolver
amino_acid_sequence
MSMPDAMPLPGVGEELKQAKEIEDAEKYSFMATVTKAPKKQIQFADDMQEFTKFPTKTGRRSLSRSISQSSTDSYSSAASYTDSSDDEVSPREKQQTNSKGSSNFCVKNIKQAEFGRREIEIAEQDMSALISLRKRAQGEKPLAGAKIVGCTHITAQTAVLIETLCALGAQCRWSACNIYSTQNEVAAALAEAGVAVFAWKGESEDDFWWCIDRCVNMDGWQANMILDDGGDLTHWVYKKYPNVFKKIRGIVEESVTGVHRLYQLSKAGKLCVPAMNVNDSVTKQKFDNLYCCRESILDGLKRTTDVMFGGKQVVVCGYGEVGKGCCAALKALGAIVYITEIDPICALQACMDGFRVVKLNEVIRQVDVVITCTGNKNVVTREHLDRMKNSCIVCNMGHSNTEIDVTSLRTPELTWERVRSQVDHVIWPDGKRVVLLAEGRLLNLSCSTVPTFVLSITATTQALALIELYNAPEGRYKQDVYLLPKKMDEYVASLHLPSFDAHLTELTDDQAKYLGLNKNGPFKPNYYRY
uniprot
proteins
function
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 (By similarity). 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 (By similarity). In the pancreatic and salivary ducts, at resting state, attenuates inositol 1,4,5-trisphosphate-induced calcium release by interacting with ITPR1 (By similarity). 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 (PubMed:12525476, PubMed:23542070). Also activates basolateral SLC4A4 isoform 1 to coordinate fluid and HCO3(-) secretion (PubMed:19224921). Inhibits the effect of STK39 on SLC4A4 and CFTR by recruiting PP1 phosphatase which activates SLC4A4, SLC26A6 and CFTR through dephosphorylation (PubMed:19033647, PubMed:21317537). Mediates the induction of SLC9A3 surface expression produced by Angiotensin-2. Depending on the cell type, activates SLC9A3 in response to calcium or reverses SLC9A3R2-dependent calcium inhibition. 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. Acts as a (dATP)-dependent inhibitor of ribonucleotide reductase large subunit RRM1, controlling the endogenous dNTP pool and ensuring normal cell cycle progression (By similarity). In vitro does not exhibit any S-adenosyl-L-homocysteine hydrolase activity (PubMed:12525476). 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 (By similarity). {ECO:0000250|UniProtKB:B5DFN2, ECO:0000250|UniProtKB:O43865, ECO:0000269|PubMed:12525476, ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:19033647, ECO:0000269|PubMed:19224921, ECO:0000269|PubMed:21317537, ECO:0000269|PubMed:23542070}.
uniprot
proteins
mass_dalton
58951
uniprot
proteins
mutagenesis
MUTAGEN 42..44; /note="IQF->AQA: Inhibits SLC4A4 dephosphorylation by PP1 phosphatase and activity."; /evidence="ECO:0000269|PubMed:21317537"; MUTAGEN 70..73; /note="Missing: Inhibits interaction with ITPR1."; /evidence="ECO:0000269|PubMed:16527252"; MUTAGEN 73; /note="D->R: Inhibits interaction with ITPR1."; /evidence="ECO:0000269|PubMed:16527252"; MUTAGEN 82..88; /note="Missing: Inhibits interaction with ITPR1."; /evidence="ECO:0000269|PubMed:16527252"; MUTAGEN 86..88; /note="DDE->KKK: Does not inhibit interaction with ITPR1."; /evidence="ECO:0000269|PubMed:16527252
uniprot
proteins
post_translational_modification
PTM: Phosphorylated at Ser/Thr residues between Ser-68 and Thr-72 in the PEST region: required for interaction with dATP-bound RRM1 and ITPR1. Phosphorylation at Ser-68 by PRKD1 and CAMK4 is required for further phosphorylations by CSNK1A1. Phosphorylation is induced by oxidative stress. Probably phosphorylated by CAMK2A; phosphorylation at Ser-68 may be required for interaction with SLC9A3. Dephosphorylated in response to apoptotic stress conditions which causes translocation of both AHCYL1 and BCL2L10 from mitochondria-associated endoplasmic reticulum membranes and promotes apoptosis. {ECO:0000250|UniProtKB:O43865}.
uniprot
proteins
protein_family
Adenosylhomocysteinase family
uniprot
proteins
pubmed
11904675
uniprot
proteins
pubmed
12525476
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16527252
uniprot
proteins
pubmed
16769890
uniprot
proteins
pubmed
17242355
uniprot
proteins
pubmed
19033647
uniprot
proteins
pubmed
19220705
uniprot
proteins
pubmed
19224921
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
21317537
uniprot
proteins
pubmed
23542070
uniprot
proteins
pubmed
23806337
uniprot
proteins
sequence_length
530
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum {ECO:0000269|PubMed:16527252}. Cytoplasm, cytosol {ECO:0000269|PubMed:19220705}. Apical cell membrane {ECO:0000250|UniProtKB:B5DFN2}; Peripheral membrane protein {ECO:0000305}. Microsome {ECO:0000269|PubMed:19220705}. Note=Associates with membranes when phosphorylated, probably through interaction with ITPR1 (PubMed:19220705). Localizes to mitochondria-associated endoplasmic reticulum membranes (MAMs) (By similarity). Localization to MAMs is greatly reduced under apoptotic stress conditions (By similarity). {ECO:0000250|UniProtKB:O43865, ECO:0000269|PubMed:19220705}.
uniprot
proteins