Adcy8
entrez
11514
canonical
uniprot
P97490
canonical
ensembl
ENSMUSG00000022376
resolver
ensp
ENSMUSP00000023007
resolver
ensp
ENSMUSP00000154029
resolver
ensp
ENSMUSP00000269176
resolver
enst
ENSMUST00000023007
resolver
enst
ENSMUST00000228014
resolver
genesymbol
Adcy8
resolver
uniprot
A0A2I3BQ46
resolver
uniprot
G3X8V9
resolver
uniprot
Q3UUN2
resolver
uniprot_entry
A0A2I3BQ46_MOUSE
resolver
uniprot_entry
ADCY8_MOUSE
resolver
uniprot_entry
Q3UUN2_MOUSE
resolver
uniprot_sec
G3X8V9
resolver
activity_regulation
ACTIVITY REGULATION: At rest, the N- and C-terminal domains interact, as part of a larger autoinhibitory complex, with calmodulin pre-associated at the N-terminal domain. Upon a calcium rise, calmodulin becomes calcium-saturated and subsequently binds to the C-terminal domain. Fully calcium-saturated calmodulin then leaves the N-terminal domain, binding solely to the C-terminal domain, and the whole autoinhibitory complex dissociates, resulting in activation of adenylate cyclase. As local calcium concentrations decrease, the calmodulin becomes calcium free and binds once more to the N-terminal domain, whereupon the whole system returns to rest with the re-association of the autoinhibitory complex (PubMed:14585998). In non-excitable cells, activated by capacitative calcium entry (CCE) through store-operated channels, namely through interaction with ORAI1 and STIM1; membrane raft and caveolae localization and membrane integrity are indispensable. CCE-mediated adenylate cyclase activity is decreased by AKAP5 and AKAP7. CCE-mediated adenylate cyclase activity is up-regulated by AKAP9 and the mitochondrially targeted AKAP1. In excitable cells, activated during membrane depolarization through L-type voltage-gated calcium channels (VGCC), leading to calcium entry; the L-type alpha subunit is sufficient. Activated via stimulation of the GLP1R. Synergistically activated by calcium/calmodulin and GNAS. Stimulated by forskolin. Inhibited by PKA directly bound to AKAP5 at membrane raft. Inhibition by acute activation of OPRM1 and activation by chronic activation of OPRM1 is mediated by pertussis toxin-sensitive G(i) and G(o) G alpha proteins and G beta-gamma dimer. Activity is inhibited by G beta-gamma dimer (By similarity). {ECO:0000250|UniProtKB:P40146, ECO:0000269|PubMed:14585998}.
uniprot
proteins
amino_acid_sequence
MELSDVHCLSGSEELYTIQPTPPAGDDGSGSRPQRLLWQTAVRHITEQRFIHGHRGGGGGGVSRKASNPAGSGPNHHAPQLSSDSVLPLYSLGPGERAHNTGGTKVFPERSGSGSASGSGGGGDLGFLHLDCAPSNSDFFLNGGYSYRGVIFPTLRNSFKSRDLERLYQRYFLGQRRKSEVVMNVLDVLTKLTLLVLHLSLASAPMDPLKGILLGFFTGIEVVICALVVVRKDNTSHTYLQYSGVVTWVAMTTQILAAGLGYGLLGDGIGYVLFTLFATYSMLPLPLTWAILAGLGTSLLQVTLQVLIPRLAVFSINQVLAQVVLFMCMNTAGIFISYLSDRAQRQAFLETRRCVEARLRLETENQRQERLVLSVLPRFVVLEMINDMTNVEDEHLQHQFHRIYIHRYENVSILFADVKGFTNLSTTLSAQELVRMLNELFARFDRLAHEHHCLRIKILGDCYYCVSGLPEPRRDHAHCCVEMGLSMIKTIRFVRSRTKHDVDMRIGIHSGSVLCGVLGLRKWQFDVWSWDVDIANKLESGGIPGRIHISKATLDCLNGDYNVEEGHGKERNEFLRKHNIETYLIKQPEESLLCLPEDIVKESVSCSDRRNSGATFTEGSWSPELPFDNIVGKQNTLAALTRNSINLLPNHLAQALHVQSGPEEINKRIEHTIDLRSGDKLRREHIKPFSLMFKDSSLEHKYSQMRDEVFKSNLVCAFIVLLFITAIQSLLPSSRLMPMTIQFSILIMLHSALVLITTAEDYKCLPLILRKTCCWINETYLARNVIIFASILINFLGAVLNILWCDFDKSIPLKNLTFNSSAVFTDICSYPEYFVFTGVLAMVTCAVFLRLNSVLKLAVLLIMIAIYALLTETIYAGLFLSYDNLNHSGEDFLGTKEASLLLMAMFLLAVFYHGQQLEYTARLDFLWRVQAKEEINEMKELREHNENMLRNILPSHVARHFLEKDRDNEELYSQSYDAVGVMFASIPGFADFYSQTEMNNQGVECLRLLNEIIADFDELLGEDRFQDIEKIKTIGSTYMAVSGLSPEKQQCEDKWGHLCALADFSLALTESIQEINKHSFNNFELRIGISHGSVVAGVIGAKKPQYDIWGKTVNLASRMDSTGVSGRIQVPEETYLILKDQGFAFDYRGEIYVKGISEQEGKIKTYFLLGRVQPNPFILPPRRLPGQYSLAAVVLGLVQSLNRQRQKQLLNENSNSGIIKSHYNRRTLLTPSGPEPGAQAEGTDKSDLP
uniprot
proteins
ec_number
4.6.1.1
uniprot
proteins
function
FUNCTION: Catalyzes the formation of cAMP in response to calcium entry leadings to cAMP signaling activation that affect processes suche as synaptic plasticity and insulin secretion (PubMed:10482244, PubMed:10864938, PubMed:14585998, PubMed:18448650, PubMed:25403481). Plays a role in many brain functions, such as learning, memory, drug addiction, and anxiety modulation through regulation of synaptic plasticity by modulating long-term memory and long-term potentiation (LTP) through CREB transcription factor activity modulation (PubMed:10482244, PubMed:10864938, PubMed:12441059, PubMed:14585998, PubMed:18222416, PubMed:18448650, PubMed:20638449, PubMed:27234425). Plays a central role in insulin secretion by controlling glucose homeostasis through glucagon-like peptide 1 and glucose signaling pathway and maintains insulin secretion through calcium-dependent PKA activation leading to vesicle pool replenishment (PubMed:25403481). Also, allows PTGER3 to induce potentiation of PTGER4-mediated PLA2 secretion by switching from a negative to a positive regulation, during the IL1B induced-dedifferentiation of smooth muscle cells (By similarity). {ECO:0000250|UniProtKB:P40146, ECO:0000269|PubMed:10482244, ECO:0000269|PubMed:10864938, ECO:0000269|PubMed:12441059, ECO:0000269|PubMed:14585998, ECO:0000269|PubMed:18222416, ECO:0000269|PubMed:18448650, ECO:0000269|PubMed:20638449, ECO:0000269|PubMed:25403481, ECO:0000269|PubMed:27234425}.
uniprot
proteins
mass_dalton
140095
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by PKA; mediates inhibition of adenylate cyclase activity at membrane raft; does not influence either CALM1 or PPP2CA interaction with ADCY8. {ECO:0000250|UniProtKB:P40146}.; PTM: N-glycosylated; N-glycosylation is responsible for raft-targeting; is not necessary for CCE-stimulated adenylate cyclase activity. {ECO:0000250|UniProtKB:P40146}.
uniprot
proteins
protein_family
Adenylyl cyclase class-4/guanylyl cyclase family
uniprot
proteins
pubmed
10482244
uniprot
proteins
pubmed
10864938
uniprot
proteins
pubmed
12441059
uniprot
proteins
pubmed
14585998
uniprot
proteins
pubmed
17335981
uniprot
proteins
pubmed
18222416
uniprot
proteins
pubmed
18448650
uniprot
proteins
pubmed
19158400
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
20638449
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
25403481
uniprot
proteins
pubmed
27234425
uniprot
proteins
sequence_length
1249
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:14585998}; Multi-pass membrane protein. Basolateral cell membrane {ECO:0000269|PubMed:14585998}. Apical cell membrane {ECO:0000269|PubMed:14585998}. Synapse {ECO:0000269|PubMed:14585998}. Cell projection, dendrite {ECO:0000269|PubMed:14585998, ECO:0000269|PubMed:17335981}. Cell projection, axon {ECO:0000269|PubMed:14585998, ECO:0000269|PubMed:17335981}. Presynaptic cell membrane {ECO:0000269|PubMed:17335981, ECO:0000269|PubMed:18448650}. Postsynaptic density {ECO:0000269|PubMed:17335981}. Membrane raft {ECO:0000250|UniProtKB:P40146}. Membrane, coated pit {ECO:0000250|UniProtKB:P40146}. Cytoplasmic vesicle, clathrin-coated vesicle membrane {ECO:0000250|UniProtKB:P40146}. Membrane, caveola {ECO:0000250|UniProtKB:P40146}. Note=Localized to dendritic arbors (PubMed:17335981). Monomeric N-glycosylated species localizes in membrane raft. In contrast, monomeric unglycosylated forms are enriched in clathrin-coated pits and vesicles. Dimers are also localized outside of membrane rafts. Membrane raft localization and integrity is indispensable for CCE-stimulated adenylate cyclase activity (By similarity). {ECO:0000250|UniProtKB:P40146, ECO:0000269|PubMed:17335981}.
uniprot
proteins
transmembrane_region
TRANSMEM 181..201; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 210..230; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 245..265; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 272..292; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 294..314; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 319..339; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 714..734; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 736..756; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 785..805; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 829..849; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 859..879; /note="Helical"; /evidence="ECO:0000255"; TRANSMEM 892..912; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins