Human Metabolome Database: Showing Protein Adenylate cyclase type 8 (HMDBP14646)

Identification Biological properties Gene properties Protein properties External links References XML Show 0 metabolites

Identification

HMDB Protein ID

HMDBP14646

Secondary Accession Numbers

None

Name

Adenylate cyclase type 8

Synonyms

ATP pyrophosphate-lyase 8
Adenylate cyclase type VIII
Adenylyl cyclase 8
Ca(2+)/calmodulin-activated adenylyl cyclase

Gene Name

ADCY8

Protein Type

Unknown

Biological Properties

General Function

Not Available

Specific 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:8163524, PubMed:24086669, PubMed:22494970, PubMed:21046358, PubMed:13680124, PubMed:25381556). 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:8163524). 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:21046358, PubMed:13680124, PubMed:25381556). 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 (PubMed:16741924).

Pathways

Adrenergic signaling in cardiomyocytes
Aldosterone synthesis and secretion
Apelin signaling pathway
Bile secretion
Calcium signaling pathway
cAMP signaling pathway
cGMP-PKG signaling pathway
Chemical carcinogenesis - receptor activation
Chemokine signaling pathway
Cholinergic synapse
Circadian entrainment
Cortisol synthesis and secretion
Cushing syndrome
Dilated cardiomyopathy
Endocrine resistance
Estrogen signaling pathway
GABAergic synapse
Gap junction
Gastric acid secretion
Glutamatergic synapse
GnRH signaling pathway
Growth hormone synthesis, secretion and action
Human cytomegalovirus infection
Human T-cell leukemia virus 1 infection
Inflammatory mediator regulation of TRP channels
Insulin secretion
Long-term potentiation
Longevity regulating pathway
Longevity regulating pathway - multiple species
Melanogenesis
Morphine addiction
Oocyte meiosis
Ovarian steroidogenesis
Oxytocin signaling pathway
Pancreatic secretion
Parathyroid hormone synthesis, secretion and action
Phospholipase D signaling pathway
Platelet activation
Progesterone-mediated oocyte maturation
Purine metabolism
Rap1 signaling pathway
Regulation of lipolysis in adipocytes
Relaxin signaling pathway
Retrograde endocannabinoid signaling
Salivary secretion
Taste transduction
Thermogenesis
Thyroid hormone synthesis
Vascular smooth muscle contraction

Reactions

Not Available

GO Classification

Biological Process
locomotory behavior
cAMP-mediated signaling
positive regulation of synaptic plasticity
elevation of cytosolic calcium ion concentration
cellular response to calcium ion
positive regulation of insulin secretion involved in cellular response to glucose stimulus
opioid receptor signaling pathway
cellular response to glucose stimulus
memory
protein oligomerization
neuroinflammatory response
glucose homeostasis
protein homooligomerization
positive regulation of long-term synaptic depression
cytosolic calcium ion homeostasis
positive regulation of long-term synaptic potentiation
response to organic cyclic compound
cAMP biosynthetic process
cellular response to forskolin
cellular response to morphine
regulation of synaptic transmission
glucose mediated signaling pathway
positive regulation of CREB transcription factor activity
regulation of cellular response to stress
activation of protein kinase A activity
adenylate cyclase-activating G-protein coupled receptor signaling pathway
cellular response to glucagon stimulus
long-term memory
Cellular Component
membrane raft
plasma membrane
dendrite
plasma membrane raft
coated pit
basolateral plasma membrane
caveola
hippocampal mossy fiber to CA3 synapse
integral component of presynaptic membrane
excitatory synapse
glutamatergic synapse
neuronal cell body membrane
presynaptic active zone
apical plasma membrane
membrane
Schaffer collateral - CA1 synapse
clathrin-coated vesicle membrane
axon
postsynaptic density
integral to plasma membrane
Molecular Function
protein N-terminus binding
actin binding
protein C-terminus binding
metal ion binding
phosphatase binding
ATP binding
protein homodimerization activity
calcium- and calmodulin-responsive adenylate cyclase activity
calmodulin binding
adenylate cyclase activity
protein heterodimerization activity
protein dimerization activity
protein phosphatase 2A binding

Cellular Location

Not Available

Gene Properties

Chromosome Location

Not Available

Locus

Not Available

SNPs

Not Available

Gene Sequence

Not Available

Protein Properties

Number of Residues

1248

Molecular Weight

139821.455

Theoretical pI

6.953

Pfam Domain Function

DUF1053 (PF06327 )
Guanylate_cyc (PF00211 )
AC_N (PF16214 )

Signals

Not Available

Transmembrane Regions

180-200;209-229;244-264;271-291;293-313;318-338;713-733;735-755;784-804;828-848;858-878;891-911;

Protein Sequence

Not Available

External Links

GenBank ID Protein

Not Available

UniProtKB/Swiss-Prot ID

P40146

UniProtKB/Swiss-Prot Entry Name

ADCY8_RAT

PDB IDs

Not Available

GenBank Gene ID

Not Available

GeneCard ID

Not Available

GenAtlas ID

Not Available

HGNC ID

Not Available

References

General References

Lundby A, Secher A, Lage K, Nordsborg NB, Dmytriyev A, Lundby C, Olsen JV: Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues. Nat Commun. 2012 Jun 6;3:876. doi: 10.1038/ncomms1871. [PubMed:22673903 ]
Cali JJ, Zwaagstra JC, Mons N, Cooper DM, Krupinski J: Type VIII adenylyl cyclase. A Ca2+/calmodulin-stimulated enzyme expressed in discrete regions of rat brain. J Biol Chem. 1994 Apr 22;269(16):12190-5. [PubMed:8163524 ]
Cali JJ, Parekh RS, Krupinski J: Splice variants of type VIII adenylyl cyclase. Differences in glycosylation and regulation by Ca2+/calmodulin. J Biol Chem. 1996 Jan 12;271(2):1089-95. doi: 10.1074/jbc.271.2.1089. [PubMed:8557635 ]
Gu C, Cali JJ, Cooper DM: Dimerization of mammalian adenylate cyclases. Eur J Biochem. 2002 Jan;269(2):413-21. doi: 10.1046/j.0014-2956.2001.02708.x. [PubMed:11856299 ]
Delmeire D, Flamez D, Hinke SA, Cali JJ, Pipeleers D, Schuit F: Type VIII adenylyl cyclase in rat beta cells: coincidence signal detector/generator for glucose and GLP-1. Diabetologia. 2003 Oct;46(10):1383-93. doi: 10.1007/s00125-003-1203-8. Epub 2003 Sep 17. [PubMed:13680124 ]
Steiner D, Avidor-Reiss T, Schallmach E, Saya D, Vogel Z: Inhibition and superactivation of the calcium-stimulated isoforms of adenylyl cyclase: role of Gbetagamma dimers. J Mol Neurosci. 2005;27(2):195-203. doi: 10.1385/jmn:27:2:195. [PubMed:16186630 ]
Clement N, Glorian M, Raymondjean M, Andreani M, Limon I: PGE2 amplifies the effects of IL-1beta on vascular smooth muscle cell de-differentiation: a consequence of the versatility of PGE2 receptors 3 due to the emerging expression of adenylyl cyclase 8. J Cell Physiol. 2006 Sep;208(3):495-505. doi: 10.1002/jcp.20673. [PubMed:16741924 ]
Crossthwaite AJ, Ciruela A, Rayner TF, Cooper DM: A direct interaction between the N terminus of adenylyl cyclase AC8 and the catalytic subunit of protein phosphatase 2A. Mol Pharmacol. 2006 Feb;69(2):608-17. doi: 10.1124/mol.105.018275. Epub 2005 Oct 28. [PubMed:16258073 ]
Pagano M, Clynes MA, Masada N, Ciruela A, Ayling LJ, Wachten S, Cooper DM: Insights into the residence in lipid rafts of adenylyl cyclase AC8 and its regulation by capacitative calcium entry. Am J Physiol Cell Physiol. 2009 Mar;296(3):C607-19. doi: 10.1152/ajpcell.00488.2008. Epub 2009 Jan 21. [PubMed:19158400 ]
Macdougall DA, Wachten S, Ciruela A, Sinz A, Cooper DM: Separate elements within a single IQ-like motif in adenylyl cyclase type 8 impart ca2+/calmodulin binding and autoinhibition. J Biol Chem. 2009 Jun 5;284(23):15573-88. doi: 10.1074/jbc.M809585200. Epub 2009 Mar 21. [PubMed:19305019 ]
Martin AC, Willoughby D, Ciruela A, Ayling LJ, Pagano M, Wachten S, Tengholm A, Cooper DM: Capacitative Ca2+ entry via Orai1 and stromal interacting molecule 1 (STIM1) regulates adenylyl cyclase type 8. Mol Pharmacol. 2009 Apr;75(4):830-42. doi: 10.1124/mol.108.051748. Epub 2009 Jan 26. [PubMed:19171672 ]
Willoughby D, Masada N, Wachten S, Pagano M, Halls ML, Everett KL, Ciruela A, Cooper DM: AKAP79/150 interacts with AC8 and regulates Ca2+-dependent cAMP synthesis in pancreatic and neuronal systems. J Biol Chem. 2010 Jun 25;285(26):20328-42. doi: 10.1074/jbc.M110.120725. Epub 2010 Apr 21. [PubMed:20410303 ]
Delint-Ramirez I, Willoughby D, Hammond GR, Ayling LJ, Cooper DM: Palmitoylation targets AKAP79 protein to lipid rafts and promotes its regulation of calcium-sensitive adenylyl cyclase type 8. J Biol Chem. 2011 Sep 23;286(38):32962-75. doi: 10.1074/jbc.M111.243899. Epub 2011 Jul 19. [PubMed:21771783 ]
Ayling LJ, Briddon SJ, Halls ML, Hammond GR, Vaca L, Pacheco J, Hill SJ, Cooper DM: Adenylyl cyclase AC8 directly controls its micro-environment by recruiting the actin cytoskeleton in a cholesterol-rich milieu. J Cell Sci. 2012 Feb 15;125(Pt 4):869-86. doi: 10.1242/jcs.091090. Epub 2012 Mar 7. [PubMed:22399809 ]
Willoughby D, Halls ML, Everett KL, Ciruela A, Skroblin P, Klussmann E, Cooper DM: A key phosphorylation site in AC8 mediates regulation of Ca(2+)-dependent cAMP dynamics by an AC8-AKAP79-PKA signalling complex. J Cell Sci. 2012 Dec 1;125(Pt 23):5850-9. doi: 10.1242/jcs.111427. Epub 2012 Sep 12. [PubMed:22976297 ]
Willoughby D, Everett KL, Halls ML, Pacheco J, Skroblin P, Vaca L, Klussmann E, Cooper DM: Direct binding between Orai1 and AC8 mediates dynamic interplay between Ca2+ and cAMP signaling. Sci Signal. 2012 Apr 10;5(219):ra29. doi: 10.1126/scisignal.2002299. [PubMed:22494970 ]
Everett KL, Cooper DM: An improved targeted cAMP sensor to study the regulation of adenylyl cyclase 8 by Ca2+ entry through voltage-gated channels. PLoS One. 2013 Sep 23;8(9):e75942. doi: 10.1371/journal.pone.0075942. eCollection 2013. [PubMed:24086669 ]
Dou H, Wang C, Wu X, Yao L, Zhang X, Teng S, Xu H, Liu B, Wu Q, Zhang Q, Hu M, Wang Y, Wang L, Wu Y, Shang S, Kang X, Zheng L, Zhang J, Raoux M, Lang J, Li Q, Su J, Yu X, Chen L, Zhou Z: Calcium influx activates adenylyl cyclase 8 for sustained insulin secretion in rat pancreatic beta cells. Diabetologia. 2015 Feb;58(2):324-33. doi: 10.1007/s00125-014-3437-z. Epub 2014 Nov 9. [PubMed:25381556 ]