Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Entry version 179 (22 Apr 2020)
Sequence version 1 (01 Feb 1995)
Previous versions | rss
Help videoAdd a publicationFeedback
Protein

Adenylate cyclase type 8

Gene

ADCY8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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. 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. 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. 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

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the 'Function' section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Mg2+By similarity, Mn2+By similarityNote: Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).By similarity

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

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. 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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the 'Description' field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi419Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi419Magnesium 2; catalyticPROSITE-ProRule annotation1
Metal bindingi420Magnesium 2; via carbonyl oxygen; catalyticPROSITE-ProRule annotation1
Metal bindingi463Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi463Magnesium 2; catalyticPROSITE-ProRule annotation1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei507ATPBy similarity1
Binding sitei1034ATPBy similarity1
Binding sitei1156ATPBy similarity1
<p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei1199Essential for autoinhibition maintenance by promoting interaction of the N and C terminiBy similarity1
Sitei1200Essential for autoinhibition maintenanceBy similarity1
Sitei1203Essential for autoinhibition maintenance by promoting interaction of the N and C terminiBy similarity1
Sitei1205Essential for CALM1 interactionBy similarity1
Sitei1207Essential for CALM1 interactionBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi419 – 424ATPBy similarity6
Nucleotide bindingi461 – 463ATPBy similarity3
Nucleotide bindingi1109 – 1111ATPBy similarity3
Nucleotide bindingi1116 – 1120ATPBy similarity5

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionLyase
Biological processcAMP biosynthesis
LigandATP-binding, Magnesium, Manganese, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-HSA-163359 Glucagon signaling in metabolic regulation
R-HSA-163615 PKA activation
R-HSA-164378 PKA activation in glucagon signalling
R-HSA-170660 Adenylate cyclase activating pathway
R-HSA-170670 Adenylate cyclase inhibitory pathway
R-HSA-381676 Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
R-HSA-418555 G alpha (s) signalling events
R-HSA-418594 G alpha (i) signalling events
R-HSA-418597 G alpha (z) signalling events
R-HSA-432040 Vasopressin regulates renal water homeostasis via Aquaporins
R-HSA-442720 CREB1 phosphorylation through the activation of Adenylate Cyclase
R-HSA-5610787 Hedgehog 'off' state

SIGNOR Signaling Network Open Resource

More...
SIGNORi
P40145

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Adenylate cyclase type 8Curated (EC:4.6.1.1By similarity)
Alternative name(s):
ATP pyrophosphate-lyase 8
Adenylate cyclase type VIII1 Publication
Adenylyl cyclase 81 Publication
Short name:
AC8
Ca(2+)/calmodulin-activated adenylyl cyclase
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:ADCY8
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 8

Organism-specific databases

Human Gene Nomenclature Database

More...
HGNCi
HGNC:239 ADCY8

Online Mendelian Inheritance in Man (OMIM)

More...
MIMi
103070 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_P40145

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini1 – 182CytoplasmicSequence analysisAdd BLAST182
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei183 – 203HelicalSequence analysisAdd BLAST21
Transmembranei212 – 232HelicalSequence analysisAdd BLAST21
Transmembranei247 – 267HelicalSequence analysisAdd BLAST21
Transmembranei274 – 294HelicalSequence analysisAdd BLAST21
Transmembranei296 – 316HelicalSequence analysisAdd BLAST21
Transmembranei321 – 341HelicalSequence analysisAdd BLAST21
Topological domaini342 – 715CytoplasmicSequence analysisAdd BLAST374
Transmembranei716 – 736HelicalSequence analysisAdd BLAST21
Transmembranei738 – 758HelicalSequence analysisAdd BLAST21
Transmembranei787 – 807HelicalSequence analysisAdd BLAST21
Transmembranei831 – 851HelicalSequence analysisAdd BLAST21
Transmembranei861 – 881HelicalSequence analysisAdd BLAST21
Transmembranei894 – 914HelicalSequence analysisAdd BLAST21
Topological domaini915 – 1251CytoplasmicSequence analysisAdd BLAST337

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Coated pit, Cytoplasmic vesicle, Membrane, Synapse

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Organism-specific databases

DisGeNET

More...
DisGeNETi
114

Open Targets

More...
OpenTargetsi
ENSG00000155897

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...
PharmGKBi
PA29

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...
Pharosi
P40145 Tbio

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...
ChEMBLi
CHEMBL2097167

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...
BioMutai
ADCY8

Domain mapping of disease mutations (DMDM)

More...
DMDMi
729242

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001957051 – 1251Adenylate cyclase type 8Add BLAST1251

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei55Omega-N-methylarginineBy similarity1
Modified residuei614PhosphoserineBy similarity1
Modified residuei624PhosphoserineBy similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi817N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi821N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi888N-linked (GlcNAc...) asparagineSequence analysis1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Phosphorylated by PKA; mediates inhibition of adenylate cyclase activity at membrane raft; does not influence either CALM1 or PPP2CA interaction with ADCY8.By similarity
N-glycosylated; N-glycosylation is responsible for raft-targeting; is not necessary for CCE-stimulated adenylate cyclase activity.By similarity

Keywords - PTMi

Glycoprotein, Methylation, Phosphoprotein

Proteomic databases

jPOST - Japan Proteome Standard Repository/Database

More...
jPOSTi
P40145

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...
MassIVEi
P40145

PaxDb, a database of protein abundance averages across all three domains of life

More...
PaxDbi
P40145

PeptideAtlas

More...
PeptideAtlasi
P40145

PRoteomics IDEntifications database

More...
PRIDEi
P40145

ProteomicsDB: a multi-organism proteome resource

More...
ProteomicsDBi
55337

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...
iPTMneti
P40145

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...
PhosphoSitePlusi
P40145

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Detected in brain cortex (PubMed:1715695). Expressed in islet (PubMed:25403481).2 Publications

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSG00000155897 Expressed in spinal cord and 86 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...
ExpressionAtlasi
P40145 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...
Genevisiblei
P40145 HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
ENSG00000155897 Tissue enhanced (brain, epididymis)

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer; via transmembrane domain. Monomer. Heterodimer. Oligemer; via transmembrane domain.

Interacts with PRKAR2A and AKAP5; inhibits adenylate cyclase activity through PKA phosphorylation.

Interacts with PPP2CA and PPP2R1A; does not mediate the inhibitory effects of PKA on adenylate cyclase activity; interaction is dependent of catalytically active PPP2CA; antagonizes interaction with calmodulin.

Interacts with AKAP5 (palmitoylated form); promotes the phosphorylation of ADCY8 after store-operated calcium entry (SOCE) stimulation at membrane raft.

Interacts with ORAI1; interaction is calcium store depletion independent; interaction occurs in membrane raft; interaction increases markedly after store depletion; positively regulates SOCE-induced adenylate cyclase activity; contributes to the targeting of ADCY8 to discrete regions of the plasma membrane that are shielded from other calcium events.

Interacts with STIM1.

Interacts with actin; interaction is calcium independent; interaction is affected by calcium-calmodulin; interaction controls the distribution and regulation of ADCY8.

Interacts with calmodulin; at rest, interacts via N-terminal domain; upon a calcium rise, calmodulin becomes calcium-saturated and subsequently binds to the C-terminal domain forming an autoinhibitory complex; fully calcium-saturated calmodulin leaves the N-terminal domain, binding solely to the C-terminal domain leading to dissociation of autoinhibitory complex and resulting in activation of adenylate cyclase; antagonizes interaction with PPP2CA; interaction is calcium dependent.

Interacts with PPP2R5D.

By similarity

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

More...
BioGridi
106627, 3 interactors

Protein interaction database and analysis system

More...
IntActi
P40145, 1 interactor

STRING: functional protein association networks

More...
STRINGi
9606.ENSP00000286355

Chemistry databases

BindingDB database of measured binding affinities

More...
BindingDBi
P40145

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...
RNActi
P40145 protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...
SMRi
P40145

Database of comparative protein structure models

More...
ModBasei
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni1 – 182Involved in ORAI1, STIM1, PPP2CA and PPP2R1A interactionBy similarityAdd BLAST182
Regioni1 – 109Involved in AKAP5 and PRKAR2A interactionBy similarityAdd BLAST109
Regioni1109 – 1251Involved in CALM1 interactionBy similarityAdd BLAST143
Regioni1200 – 1215Required for both calcium stimulation and maintenance of autoinhibitionBy similarityAdd BLAST16

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi38 – 40Essential for CALM1 interactionBy similarity3
Motifi49 – 51Essential for CALM1 interactionBy similarity3

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The protein contains two modules with six transmembrane helices each; both are required for catalytic activity. Isolated N-terminal or C-terminal guanylate cyclase domains have no catalytic activity, but when they are brought together, enzyme activity is restored. The active site is at the interface of the two domains. Both contribute substrate-binding residues, but the catalytic metal ions are bound exclusively via the N-terminal guanylate cyclase domain. The two transmembrane clusters are necessary and suficient for the plasma membrane targeting and oligomers assembly. The N-terminal and C-terminal domains interact at rest as part of a larger autoinhibitory complex, with calmodulin pre-associated at the N-terminal domain; the binding is specifically inhibited by fully calcium-saturated calmodulin, resulting in activation of AC8.By similarity

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...
eggNOGi
KOG3619 Eukaryota
COG2114 LUCA

Ensembl GeneTree

More...
GeneTreei
ENSGT00940000158742

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...
HOGENOMi
CLU_001072_3_0_1

InParanoid: Eukaryotic Ortholog Groups

More...
InParanoidi
P40145

KEGG Orthology (KO)

More...
KOi
K08048

Identification of Orthologs from Complete Genome Data

More...
OMAi
YKCLPLM

Database of Orthologous Groups

More...
OrthoDBi
107368at2759

Database for complete collections of gene phylogenies

More...
PhylomeDBi
P40145

TreeFam database of animal gene trees

More...
TreeFami
TF313845

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

More...
Gene3Di
3.30.70.1230, 2 hits

Integrated resource of protein families, domains and functional sites

More...
InterProi
View protein in InterPro
IPR001054 A/G_cyclase
IPR018297 A/G_cyclase_CS
IPR032628 AC_N
IPR030672 Adcy
IPR009398 Adcy_conserved_dom
IPR029787 Nucleotide_cyclase

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF16214 AC_N, 1 hit
PF06327 DUF1053, 1 hit
PF00211 Guanylate_cyc, 2 hits

PIRSF; a whole-protein classification database

More...
PIRSFi
PIRSF039050 Ade_cyc, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

More...
SMARTi
View protein in SMART
SM00044 CYCc, 2 hits

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF55073 SSF55073, 2 hits

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS00452 GUANYLATE_CYCLASE_1, 2 hits
PS50125 GUANYLATE_CYCLASE_2, 2 hits

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All

P40145-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MELSDVRCLT GSEELYTIHP TPPAGDGRSA SRPQRLLWQT AVRHITEQRF
60 70 80 90 100
IHGHRGGSGS GSGGSGKASD PAGGGPNHHA PQLSGDSALP LYSLGPGERA
110 120 130 140 150
HSTCGTKVFP ERSGSGSASG SGGGGDLGFL HLDCAPSNSD FFLNGGYSYR
160 170 180 190 200
GVIFPTLRNS FKSRDLERLY QRYFLGQRRK SEVVMNVLDV LTKLTLLVLH
210 220 230 240 250
LSLASAPMDP LKGILLGFFT GIEVVICALV VVRKDTTSHT YLQYSGVVTW
260 270 280 290 300
VAMTTQILAA GLGYGLLGDG IGYVLFTLFA TYSMLPLPLT WAILAGLGTS
310 320 330 340 350
LLQVILQVVI PRLAVISINQ VVAQAVLFMC MNTAGIFISY LSDRAQRQAF
360 370 380 390 400
LETRRCVEAR LRLETENQRQ ERLVLSVLPR FVVLEMINDM TNVEDEHLQH
410 420 430 440 450
QFHRIYIHRY ENVSILFADV KGFTNLSTTL SAQELVRMLN ELFARFDRLA
460 470 480 490 500
HEHHCLRIKI LGDCYYCVSG LPEPRQDHAH CCVEMGLSMI KTIRYVRSRT
510 520 530 540 550
KHDVDMRIGI HSGSVLCGVL GLRKWQFDVW SWDVDIANKL ESGGIPGRIH
560 570 580 590 600
ISKATLDCLN GDYNVEEGHG KERNEFLRKH NIETYLIKQP EDSLLSLPED
610 620 630 640 650
IVKESVSSSD RRNSGATFTE GSWSPELPFD NIVGKQNTLA ALTRNSINLL
660 670 680 690 700
PNHLAQALHV QSGPEEINKR IEHTIDLRSG DKLRREHIKP FSLMFKDSSL
710 720 730 740 750
EHKYSQMRDE VFKSNLVCAF IVLLFITAIQ SLLPSSRVMP MTIQFSILIM
760 770 780 790 800
LHSALVLITT AEDYKCLPLI LRKTCCWINE TYLARNVIIF ASILINFLGA
810 820 830 840 850
ILNILWCDFD KSIPLKNLTF NSSAVFTDIC SYPEYFVFTG VLAMVTCAVF
860 870 880 890 900
LRLNSVLKLA VLLIMIAIYA LLTETVYAGL FLRYDNLNHS GEDFLGTKEV
910 920 930 940 950
SLLLMAMFLL AVFYHGQQLE YTARLDFLWR VQAKEEINEM KELREHNENM
960 970 980 990 1000
LRNILPSHVA RHFLEKDRDN EELYSQSYDA VGVMFASIPG FADFYSQTEM
1010 1020 1030 1040 1050
NNQGVECLRL LNEIIADFDE LLGEDRFQDI EKIKTIGSTY MAVSGLSPEK
1060 1070 1080 1090 1100
QQCEDKWGHL CALADFSLAL TESIQEINKH SFNNFELRIG ISHGSVVAGV
1110 1120 1130 1140 1150
IGAKKPQYDI WGKTVNLASR MDSTGVSGRI QVPEETYLIL KDQGFAFDYR
1160 1170 1180 1190 1200
GEIYVKGISE QEGKIKTYFL LGRVQPNPFI LPPRRLPGQY SLAAVVLGLV
1210 1220 1230 1240 1250
QSLNRQRQKQ LLNENNNTGI IKGHYNRRTL LSPSGTEPGA QAEGTDKSDL

P
Length:1,251
Mass (Da):140,122
Last modified:February 1, 1995 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iABF25C40493E07C3
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E7EVL1E7EVL1_HUMAN
Adenylate cyclase type 8
ADCY8
1,120Annotation score:

Annotation score:3 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
E5RFR2E5RFR2_HUMAN
Adenylate cyclase type 8
ADCY8
252Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_02918880A → T. Corresponds to variant dbSNP:rs2228949Ensembl.1
Natural variantiVAR_036328881F → L in a colorectal cancer sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

More...
GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
Z35309 mRNA Translation: CAA84552.1
M83533 mRNA Translation: AAA35523.2

The Consensus CDS (CCDS) project

More...
CCDSi
CCDS6363.1

Protein sequence database of the Protein Information Resource

More...
PIRi
PQ0227
S48687

NCBI Reference Sequences

More...
RefSeqi
NP_001106.1, NM_001115.2

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000286355; ENSP00000286355; ENSG00000155897

Database of genes from NCBI RefSeq genomes

More...
GeneIDi
114

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...
KEGGi
hsa:114

UCSC genome browser

More...
UCSCi
uc003ytd.5 human

Keywords - Coding sequence diversityi

Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z35309 mRNA Translation: CAA84552.1
M83533 mRNA Translation: AAA35523.2
CCDSiCCDS6363.1
PIRiPQ0227
S48687
RefSeqiNP_001106.1, NM_001115.2

3D structure databases

SMRiP40145
ModBaseiSearch...

Protein-protein interaction databases

BioGridi106627, 3 interactors
IntActiP40145, 1 interactor
STRINGi9606.ENSP00000286355

Chemistry databases

BindingDBiP40145
ChEMBLiCHEMBL2097167

PTM databases

iPTMnetiP40145
PhosphoSitePlusiP40145

Polymorphism and mutation databases

BioMutaiADCY8
DMDMi729242

Proteomic databases

jPOSTiP40145
MassIVEiP40145
PaxDbiP40145
PeptideAtlasiP40145
PRIDEiP40145
ProteomicsDBi55337

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...
Antibodypediai
4355 214 antibodies

The DNASU plasmid repository

More...
DNASUi
114

Genome annotation databases

EnsembliENST00000286355; ENSP00000286355; ENSG00000155897
GeneIDi114
KEGGihsa:114
UCSCiuc003ytd.5 human

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
114
DisGeNETi114

GeneCards: human genes, protein and diseases

More...
GeneCardsi
ADCY8
HGNCiHGNC:239 ADCY8
HPAiENSG00000155897 Tissue enhanced (brain, epididymis)
MIMi103070 gene
neXtProtiNX_P40145
OpenTargetsiENSG00000155897
PharmGKBiPA29

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG3619 Eukaryota
COG2114 LUCA
GeneTreeiENSGT00940000158742
HOGENOMiCLU_001072_3_0_1
InParanoidiP40145
KOiK08048
OMAiYKCLPLM
OrthoDBi107368at2759
PhylomeDBiP40145
TreeFamiTF313845

Enzyme and pathway databases

ReactomeiR-HSA-163359 Glucagon signaling in metabolic regulation
R-HSA-163615 PKA activation
R-HSA-164378 PKA activation in glucagon signalling
R-HSA-170660 Adenylate cyclase activating pathway
R-HSA-170670 Adenylate cyclase inhibitory pathway
R-HSA-381676 Glucagon-like Peptide-1 (GLP1) regulates insulin secretion
R-HSA-418555 G alpha (s) signalling events
R-HSA-418594 G alpha (i) signalling events
R-HSA-418597 G alpha (z) signalling events
R-HSA-432040 Vasopressin regulates renal water homeostasis via Aquaporins
R-HSA-442720 CREB1 phosphorylation through the activation of Adenylate Cyclase
R-HSA-5610787 Hedgehog 'off' state
SIGNORiP40145

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
ADCY8 human

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
ADCY8

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
114
PharosiP40145 Tbio

Protein Ontology

More...
PROi
PR:P40145
RNActiP40145 protein

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000155897 Expressed in spinal cord and 86 other tissues
ExpressionAtlasiP40145 baseline and differential
GenevisibleiP40145 HS

Family and domain databases

Gene3Di3.30.70.1230, 2 hits
InterProiView protein in InterPro
IPR001054 A/G_cyclase
IPR018297 A/G_cyclase_CS
IPR032628 AC_N
IPR030672 Adcy
IPR009398 Adcy_conserved_dom
IPR029787 Nucleotide_cyclase
PfamiView protein in Pfam
PF16214 AC_N, 1 hit
PF06327 DUF1053, 1 hit
PF00211 Guanylate_cyc, 2 hits
PIRSFiPIRSF039050 Ade_cyc, 1 hit
SMARTiView protein in SMART
SM00044 CYCc, 2 hits
SUPFAMiSSF55073 SSF55073, 2 hits
PROSITEiView protein in PROSITE
PS00452 GUANYLATE_CYCLASE_1, 2 hits
PS50125 GUANYLATE_CYCLASE_2, 2 hits

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiADCY8_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P40145
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: April 22, 2020
This is version 179 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again