AHCYL1
entrez
10768
canonical
uniprot
O43865
canonical
ensembl
ENSG00000168710
resolver
ensp
ENSP00000352092
resolver
ensp
ENSP00000358814
resolver
ensp
ENSP00000377238
resolver
ensp
ENSP00000665091
resolver
ensp
ENSP00000790570
resolver
genesymbol
AHCYL1
resolver
genesymbol_syn
DCAL
resolver
genesymbol_syn
IRBIT
resolver
genesymbol_syn
XPVKONA
resolver
hgnc
HGNC:344
resolver
uniprot
A0A024R0A8
resolver
uniprot
A0A384N6B4
resolver
uniprot
B4E168
resolver
uniprot
Q2TAJ6
resolver
uniprot
Q502W8
resolver
uniprot
Q5VSM0
resolver
uniprot
Q6P171
resolver
uniprot
Q96PK4
resolver
uniprot
Q9UG84
resolver
uniprot_entry
A0A024R0A8_HUMAN
resolver
uniprot_entry
SAHH2_HUMAN
resolver
uniprot_sec
A0A384N6B4
resolver
uniprot_sec
B4E168
resolver
uniprot_sec
Q2TAJ6
resolver
uniprot_sec
Q502W8
resolver
uniprot_sec
Q5VSM0
resolver
uniprot_sec
Q6P171
resolver
uniprot_sec
Q96PK4
resolver
uniprot_sec
Q9UG84
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 (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). {ECO:0000250|UniProtKB:B5DFN2, ECO:0000250|UniProtKB:Q80SW1, ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:18829453, ECO:0000269|PubMed:19224921, ECO:0000269|PubMed:20584908, ECO:0000269|PubMed:25237103, ECO:0000269|PubMed:27995898, ECO:0000269|PubMed:33993848}.
uniprot
proteins
mass_dalton
58951
uniprot
proteins
mutagenesis
MUTAGEN 52; /note="T->A: No effect on interaction with SLC4A4."; /evidence="ECO:0000269|PubMed:16769890"; MUTAGEN 58; /note="T->A: No effect on interaction with SLC4A4."; /evidence="ECO:0000269|PubMed:16769890"; MUTAGEN 62; /note="S->A: No effect on interaction with SLC4A4. No effect on interaction with FIP1L1."; /evidence="ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:19224921"; MUTAGEN 64; /note="S->A: No effect on interaction with ITPR1. No effect on phosphorylation. No effect on interaction with SLC4A4. No effect on interaction with FIP1L1."; /evidence="ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"; MUTAGEN 66; /note="S->A: Slightly decreases interaction with ITPR1. Slightly decreases phosphorylation. No effect on interaction with SLC4A4. Abolishes interaction with FIP1L1."; /evidence="ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"; MUTAGEN 68; /note="S->A: Highly decreases phosphorylation. Abolishes interaction with ITPR1. No effect on interaction with BCL2L10. Marked decrease in interaction of BCL2L10 with ITPR1. Decreased ability of BCL2L10 to reduce ITPR1-mediated calcium release and to prevent apoptosis. No effect on formation of multimers. Abolishes interaction with SLC4A4. Abolishes interaction with FIP1L1. Highly decreases interaction with SLC9A3. Highly decreases interaction with SLC9A3; when associated with A-71 and A-74."; /evidence="ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921, ECO:0000269|PubMed:20584908, ECO:0000269|PubMed:27995898"; MUTAGEN 70; /note="S->A: Highly decreases interaction with ITPR1. No effect on phosphorylation. No effect on interaction with SLC4A4. Abolishes interaction with FIP1L1."; /evidence="ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"; MUTAGEN 71; /note="S->A: Abolishes interaction with ITPR1. Highly decreases phosphorylation. Abolishes interaction with SLC4A4. Abolishes interaction with FIP1L1. Highly decreases interaction with SLC9A3; when associated with A-68 and A-74."; /evidence="ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921, ECO:0000269|PubMed:20584908"; MUTAGEN 72; /note="T->A: Highly decreases interaction with ITPR1. Slightly increases phosphorylation. No effect on interaction with SLC4A4. Highly decreases interaction with FIP1L1."; /evidence="ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"; MUTAGEN 74; /note="S->G: Abolishes interaction with ITPR1. Slightly decreases phosphorylation. Strongly decreases interaction with SLC4A4. Abolishes interaction with FIP1L1. Highly decreases interaction with SLC9A3; when associated with A-68 and A-71."; /evidence="ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921, ECO:0000269|PubMed:20584908"; MUTAGEN 76; /note="S->G: No effect on interaction with ITPR1. No effect on phosphorylation. No effect on interaction with SLC4A4. No effect on interaction with FIP1L1."; /evidence="ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"; MUTAGEN 77; /note="S->A: Highly decreases interaction with ITPR1. Slightly decreases phosphorylation. Strongly decreases interaction with SLC4A4. Abolishes interaction with FIP1L1."; /evidence="ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"; MUTAGEN 80; /note="S->A: No effect on interaction with SLC4A4. Highly decreases interaction with FIP1L1."; /evidence="ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"; MUTAGEN 82; /note="T->A: No effect on interaction with ITPR1. No effect on phosphorylation. No effect on interaction with SLC4A4. Decreases interaction with FIP1L1."; /evidence="ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"; MUTAGEN 84; /note="S->A: Slightly decreases interaction with ITPR1. No effect on phosphorylation. No effect on interaction with SLC4A4. Decreases interaction with FIP1L1."; /evidence="ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"; MUTAGEN 85; /note="S->A: Slightly decreases interaction with ITPR1. No effect on phosphorylation. No effect on interaction with SLC4A4. Decreases interaction with FIP1L1."; /evidence="ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"; MUTAGEN 90; /note="S->A: No effect on interaction with ITPR1. No effect on phosphorylation. No effect on interaction with SLC4A4. No effect on interaction with FIP1L1."; /evidence="ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"; MUTAGEN 97; /note="T->A: No effect on interaction with ITPR1. No effect on interaction with SLC4A4. No effect on interaction with FIP1L1."; /evidence="ECO:0000269|PubMed:16769890, ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921"; MUTAGEN 155; /note="T->A: Complete loss of SAH-enhanced interaction with PIK3C3; when associated with A-157."; /evidence="ECO:0000269|PubMed:33993848"; MUTAGEN 157; /note="Q->A: Complete loss of SAH-enhanced interaction with PIK3C3; when associated with A-155."; /evidence="ECO:0000269|PubMed:33993848
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 (PubMed:16793548). Phosphorylation is induced by oxidative stress (PubMed:19224921). Probably phosphorylated by CAMK2A; phosphorylation at Ser-68 may be required for interaction with SLC9A3 (PubMed:20584908). Dephosphorylated in response to apoptotic stress conditions which causes translocation of both AHCYL1 and BCL2L10 from mitochondria-associated endoplasmic reticulum membranes and promotes apoptosis (PubMed:27995898). {ECO:0000269|PubMed:16793548, ECO:0000269|PubMed:19224921, ECO:0000269|PubMed:25237103, ECO:0000269|PubMed:27995898, ECO:0000305|PubMed:20584908}.
uniprot
proteins
protein_family
Adenosylhomocysteinase family
uniprot
proteins
pubmed
11904675
uniprot
proteins
pubmed
12878157
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
16754674
uniprot
proteins
pubmed
16769890
uniprot
proteins
pubmed
16793548
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18829453
uniprot
proteins
pubmed
19220705
uniprot
proteins
pubmed
19224921
uniprot
proteins
pubmed
20584908
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
25237103
uniprot
proteins
pubmed
27995898
uniprot
proteins
pubmed
28647132
uniprot
proteins
pubmed
31799605
uniprot
proteins
pubmed
33993848
uniprot
proteins
pubmed
7782076
uniprot
proteins
sequence_length
530
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum {ECO:0000269|PubMed:27995898, ECO:0000269|PubMed:28647132}. Cytoplasm, cytosol {ECO:0000269|PubMed:27995898}. Apical cell membrane {ECO:0000250|UniProtKB:B5DFN2}; Peripheral membrane protein {ECO:0000305}. Microsome {ECO:0000250|UniProtKB:Q80SW1}. Note=Associates with membranes when phosphorylated, probably through interaction with ITPR1 (By similarity). Localizes to mitochondria-associated endoplasmic reticulum membranes (MAMs) (PubMed:27995898). Localization to MAMs is greatly reduced under apoptotic stress conditions (PubMed:27995898). {ECO:0000250|UniProtKB:Q80SW1, ECO:0000269|PubMed:27995898}.
uniprot
proteins