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Entry version 190 (16 Oct 2019)
Sequence version 2 (11 Jan 2001)
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Protein

Adenylate cyclase type 6

Gene

ADCY6

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 the signaling molecule cAMP downstream of G protein-coupled receptors (PubMed:17916776, PubMed:17110384). Functions in signaling cascades downstream of beta-adrenergic receptors in the heart and in vascular smooth muscle cells (PubMed:17916776). Functions in signaling cascades downstream of the vasopressin receptor in the kidney and has a role in renal water reabsorption. Functions in signaling cascades downstream of PTH1R and plays a role in regulating renal phosphate excretion. Functions in signaling cascades downstream of the VIP and SCT receptors in pancreas and contributes to the regulation of pancreatic amylase and fluid secretion (By similarity). Signaling mediates cAMP-dependent activation of protein kinase PKA. This promotes increased phosphorylation of various proteins, including AKT. Plays a role in regulating cardiac sarcoplasmic reticulum Ca2+ uptake and storage, and is required for normal heart ventricular contractibility. May contribute to normal heart function (By similarity). Mediates vasodilatation after activation of beta-adrenergic receptors by isoproterenol (PubMed:17916776). Contributes to bone cell responses to mechanical stimuli (By similarity).By similarity2 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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+1 Publication, Mn2+1 PublicationNote: 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_section">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

Activated by forskolin (PubMed:17916776, PubMed:17110384). Inhibited by calcium ions, already at micromolar concentrations (By similarity). Inhibited by adenosine, AMP and their analogs (By similarity). Activated by GNAS (PubMed:17110384). Is further activated by the complex formed by GNB1 and GNG2 (PubMed:17110384). Phosphorylation by RAF1 results in its activation (By similarity).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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 bindingi384Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi384Magnesium 2; catalyticPROSITE-ProRule annotation1
Metal bindingi385Magnesium 2; via carbonyl oxygen; catalyticPROSITE-ProRule annotation1
Metal bindingi428Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi428Magnesium 2; catalyticPROSITE-ProRule annotation1
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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 sitei472ATPBy similarity1
Binding sitei1031ATPBy similarity1
Binding sitei1152ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function_section">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 bindingi384 – 389ATPBy similarity6
Nucleotide bindingi426 – 428ATPBy similarity3
Nucleotide bindingi1105 – 1107ATPBy similarity3
Nucleotide bindingi1112 – 1116ATPBy 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-400042 Adrenaline,noradrenaline inhibits 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-5610787 Hedgehog 'off' state

SIGNOR Signaling Network Open Resource

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SIGNORi
O43306

<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_and_taxonomy_section">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 6 (EC:4.6.1.12 Publications)
Alternative name(s):
ATP pyrophosphate-lyase 6
Adenylate cyclase type VI
Adenylyl cyclase 61 Publication
Ca(2+)-inhibitable adenylyl cyclase
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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:ADCY6
Synonyms:KIAA0422
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">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_and_taxonomy_section">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_and_taxonomy_section">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_and_taxonomy_section">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_manual">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 12

Organism-specific databases

Human Gene Nomenclature Database

More...
HGNCi
HGNC:237 ADCY6

Online Mendelian Inheritance in Man (OMIM)

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MIMi
600294 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_O43306

<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_location_section">'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 – 151CytoplasmicSequence analysisAdd BLAST151
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'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>Transmembranei152 – 168HelicalSequence analysisAdd BLAST17
Transmembranei181 – 197HelicalSequence analysisAdd BLAST17
Transmembranei214 – 230HelicalSequence analysisAdd BLAST17
Transmembranei239 – 255HelicalSequence analysisAdd BLAST17
Transmembranei259 – 275HelicalSequence analysisAdd BLAST17
Transmembranei289 – 305HelicalSequence analysisAdd BLAST17
Topological domaini306 – 673CytoplasmicSequence analysisAdd BLAST368
Transmembranei674 – 691HelicalSequence analysisAdd BLAST18
Transmembranei702 – 718HelicalSequence analysisAdd BLAST17
Transmembranei743 – 759HelicalSequence analysisAdd BLAST17
Topological domaini760 – 819ExtracellularSequence analysisAdd BLAST60
Transmembranei820 – 836HelicalSequence analysisAdd BLAST17
Transmembranei839 – 855HelicalSequence analysisAdd BLAST17
Transmembranei897 – 913HelicalSequence analysisAdd BLAST17
Topological domaini914 – 1168CytoplasmicSequence analysisAdd BLAST255

Keywords - Cellular componenti

Cell membrane, Cell projection, Cilium, Membrane

<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

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Lethal congenital contracture syndrome 8 (LCCS8)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy and congenital non-progressive joint contractures. The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. LCCS8 is an axoglial form of arthrogryposis multiplex congenita, characterized by congenital distal joint contractures, reduced fetal movements, and severe motor paralysis leading to death early in the neonatal period.
Related information in OMIM
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_0734341116R → C in LCCS8. 1 PublicationCorresponds to variant dbSNP:rs786204798EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNET

More...
DisGeNETi
112

MalaCards human disease database

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MalaCardsi
ADCY6
MIMi616287 phenotype

Open Targets

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OpenTargetsi
ENSG00000174233

Orphanet; a database dedicated to information on rare diseases and orphan drugs

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Orphaneti
2680 Hypomyelination neuropathy-arthrogryposis syndrome

The Pharmacogenetics and Pharmacogenomics Knowledge Base

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PharmGKBi
PA27

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

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Pharosi
O43306

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL2097167

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
1283

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

More...
BioMutai
ADCY6

<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.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00001956991 – 1168Adenylate cyclase type 6Add BLAST1168

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 residuei54PhosphoserineCombined sources1
Modified residuei556PhosphoserineBy similarity1
Modified residuei576PhosphoserineCombined sources1
Modified residuei662PhosphoserineBy similarity1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">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>Glycosylationi793N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei919PhosphothreonineBy similarity1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">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

Phosphorylation by RAF1 increases enzyme activity. Phosphorylation by PKA at Ser-662 inhibits the GNAS-mediated increase in catalytic activity. Phosphorylation by PKC at Ser-556, Ser-662 and Thr-919 inhibits catalytic activity.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
O43306

MassIVE - Mass Spectrometry Interactive Virtual Environment

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MassIVEi
O43306

MaxQB - The MaxQuant DataBase

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MaxQBi
O43306

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

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PaxDbi
O43306

PeptideAtlas

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PeptideAtlasi
O43306

PRoteomics IDEntifications database

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PRIDEi
O43306

ProteomicsDB: a multi-organism proteome resource

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ProteomicsDBi
48880 [O43306-1]
48881 [O43306-2]

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
O43306

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

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PhosphoSitePlusi
O43306

SwissPalm database of S-palmitoylation events

More...
SwissPalmi
O43306

<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 peripheral blood mononuclear leukocytes (at protein level) (PubMed:17916776). Detected in thyroid (PubMed:10978539).1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSG00000174233 Expressed in 170 organ(s), highest expression level in heart left ventricle

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
O43306 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
O43306 HS

Organism-specific databases

Human Protein Atlas

More...
HPAi
CAB018365

<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_section">'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_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Part of a complex containing AKAP5, ADCY5, PDE4C and PKD2 (By similarity).

Interacts with RAF1 (PubMed:15385642).

Interacts (via cytoplasmic N-terminus) with GNAS, GNB1 and GNG2 (PubMed:17110384).

By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
106625, 26 interactors

Protein interaction database and analysis system

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IntActi
O43306, 22 interactors

Molecular INTeraction database

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MINTi
O43306

STRING: functional protein association networks

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STRINGi
9606.ENSP00000311405

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
O43306

<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

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SMRi
O43306

Database of comparative protein structure models

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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

<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.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

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eggNOGi
KOG3619 Eukaryota
COG2114 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000155687

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000006941

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
O43306

KEGG Orthology (KO)

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KOi
K08046

Identification of Orthologs from Complete Genome Data

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OMAi
PLCEGTM

Database of Orthologous Groups

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OrthoDBi
215180at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
O43306

TreeFam database of animal gene trees

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TreeFami
TF313845

Family and domain databases

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
3.30.70.1230, 2 hits

Integrated resource of protein families, domains and functional sites

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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

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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

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PIRSFi
PIRSF039050 Ade_cyc, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00044 CYCc, 2 hits

Superfamily database of structural and functional annotation

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SUPFAMi
SSF55073 SSF55073, 2 hits

PROSITE; a protein domain and family database

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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_length">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>Sequences (2+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">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 describes 2 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

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

Isoform 1 (identifier: O43306-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MSWFSGLLVP KVDERKTAWG ERNGQKRSRR RGTRAGGFCT PRYMSCLRDA
60 70 80 90 100
EPPSPTPAGP PRCPWQDDAF IRRGGPGKGK ELGLRAVALG FEDTEVTTTA
110 120 130 140 150
GGTAEVAPDA VPRSGRSCWR RLVQVFQSKQ FRSAKLERLY QRYFFQMNQS
160 170 180 190 200
SLTLLMAVLV LLTAVLLAFH AAPARPQPAY VALLACAAAL FVGLMVVCNR
210 220 230 240 250
HSFRQDSMWV VSYVVLGILA AVQVGGALAA DPRSPSAGLW CPVFFVYIAY
260 270 280 290 300
TLLPIRMRAA VLSGLGLSTL HLILAWQLNR GDAFLWKQLG ANVLLFLCTN
310 320 330 340 350
VIGICTHYPA EVSQRQAFQE TRGYIQARLH LQHENRQQER LLLSVLPQHV
360 370 380 390 400
AMEMKEDINT KKEDMMFHKI YIQKHDNVSI LFADIEGFTS LASQCTAQEL
410 420 430 440 450
VMTLNELFAR FDKLAAENHC LRIKILGDCY YCVSGLPEAR ADHAHCCVEM
460 470 480 490 500
GVDMIEAISL VREVTGVNVN MRVGIHSGRV HCGVLGLRKW QFDVWSNDVT
510 520 530 540 550
LANHMEAGGR AGRIHITRAT LQYLNGDYEV EPGRGGERNA YLKEQHIETF
560 570 580 590 600
LILGASQKRK EEKAMLAKLQ RTRANSMEGL MPRWVPDRAF SRTKDSKAFR
610 620 630 640 650
QMGIDDSSKD NRGTQDALNP EDEVDEFLSR AIDARSIDQL RKDHVRRFLL
660 670 680 690 700
TFQREDLEKK YSRKVDPRFG AYVACALLVF CFICFIQLLI FPHSTLMLGI
710 720 730 740 750
YASIFLLLLI TVLICAVYSC GSLFPKALQR LSRSIVRSRA HSTAVGIFSV
760 770 780 790 800
LLVFTSAIAN MFTCNHTPIR SCAARMLNLT PADITACHLQ QLNYSLGLDA
810 820 830 840 850
PLCEGTMPTC SFPEYFIGNM LLSLLASSVF LHISSIGKLA MIFVLGLIYL
860 870 880 890 900
VLLLLGPPAT IFDNYDLLLG VHGLASSNET FDGLDCPAAG RVALKYMTPV
910 920 930 940 950
ILLVFALALY LHAQQVESTA RLDFLWKLQA TGEKEEMEEL QAYNRRLLHN
960 970 980 990 1000
ILPKDVAAHF LARERRNDEL YYQSCECVAV MFASIANFSE FYVELEANNE
1010 1020 1030 1040 1050
GVECLRLLNE IIADFDEIIS EERFRQLEKI KTIGSTYMAA SGLNASTYDQ
1060 1070 1080 1090 1100
VGRSHITALA DYAMRLMEQM KHINEHSFNN FQMKIGLNMG PVVAGVIGAR
1110 1120 1130 1140 1150
KPQYDIWGNT VNVSSRMDST GVPDRIQVTT DLYQVLAAKG YQLECRGVVK
1160
VKGKGEMTTY FLNGGPSS
Length:1,168
Mass (Da):130,615
Last modified:January 11, 2001 - v2
<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:i127BB6E67F73AA61
GO
Isoform 2 (identifier: O43306-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     762-814: Missing.

Note: No experimental confirmation available.
Show »
Length:1,115
Mass (Da):124,865
Checksum:iD1D26C1E15FAC0B0
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 is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F8VZJ5F8VZJ5_HUMAN
Adenylate cyclase type 6
ADCY6
82Annotation 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>

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence BAA24852 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_048249674A → S No effect on basal enzyme activity, but increased enzyme activity upon activation via G-proteins or forskolin. Corresponds to variant dbSNP:rs3730071Ensembl.1
Natural variantiVAR_0734341116R → C in LCCS8. 1 PublicationCorresponds to variant dbSNP:rs786204798EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_000244762 – 814Missing in isoform 2. 1 PublicationAdd BLAST53

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
AF250226 mRNA Translation: AAF82478.1
AB007882 mRNA Translation: BAA24852.2 Different initiation.
BC064923 mRNA No translation available.

The Consensus CDS (CCDS) project

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CCDSi
CCDS8767.1 [O43306-1]

NCBI Reference Sequences

More...
RefSeqi
NP_056085.1, NM_015270.4 [O43306-1]
XP_006719273.1, XM_006719210.3 [O43306-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000307885; ENSP00000311405; ENSG00000174233 [O43306-1]
ENST00000357869; ENSP00000350536; ENSG00000174233 [O43306-2]
ENST00000550422; ENSP00000446730; ENSG00000174233 [O43306-2]

Database of genes from NCBI RefSeq genomes

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GeneIDi
112

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
hsa:112

UCSC genome browser

More...
UCSCi
uc001rsh.5 human [O43306-1]

Keywords - Coding sequence diversityi

Alternative splicing, 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
AF250226 mRNA Translation: AAF82478.1
AB007882 mRNA Translation: BAA24852.2 Different initiation.
BC064923 mRNA No translation available.
CCDSiCCDS8767.1 [O43306-1]
RefSeqiNP_056085.1, NM_015270.4 [O43306-1]
XP_006719273.1, XM_006719210.3 [O43306-1]

3D structure databases

SMRiO43306
ModBaseiSearch...

Protein-protein interaction databases

BioGridi106625, 26 interactors
IntActiO43306, 22 interactors
MINTiO43306
STRINGi9606.ENSP00000311405

Chemistry databases

BindingDBiO43306
ChEMBLiCHEMBL2097167
GuidetoPHARMACOLOGYi1283

PTM databases

iPTMnetiO43306
PhosphoSitePlusiO43306
SwissPalmiO43306

Polymorphism and mutation databases

BioMutaiADCY6

Proteomic databases

jPOSTiO43306
MassIVEiO43306
MaxQBiO43306
PaxDbiO43306
PeptideAtlasiO43306
PRIDEiO43306
ProteomicsDBi48880 [O43306-1]
48881 [O43306-2]

Genome annotation databases

EnsembliENST00000307885; ENSP00000311405; ENSG00000174233 [O43306-1]
ENST00000357869; ENSP00000350536; ENSG00000174233 [O43306-2]
ENST00000550422; ENSP00000446730; ENSG00000174233 [O43306-2]
GeneIDi112
KEGGihsa:112
UCSCiuc001rsh.5 human [O43306-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
112
DisGeNETi112

GeneCards: human genes, protein and diseases

More...
GeneCardsi
ADCY6
HGNCiHGNC:237 ADCY6
HPAiCAB018365
MalaCardsiADCY6
MIMi600294 gene
616287 phenotype
neXtProtiNX_O43306
OpenTargetsiENSG00000174233
Orphaneti2680 Hypomyelination neuropathy-arthrogryposis syndrome
PharmGKBiPA27

Human Unidentified Gene-Encoded large proteins database

More...
HUGEi
Search...

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiKOG3619 Eukaryota
COG2114 LUCA
GeneTreeiENSGT00940000155687
HOGENOMiHOG000006941
InParanoidiO43306
KOiK08046
OMAiPLCEGTM
OrthoDBi215180at2759
PhylomeDBiO43306
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-400042 Adrenaline,noradrenaline inhibits 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-5610787 Hedgehog 'off' state
SIGNORiO43306

Miscellaneous databases

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

More...
ChiTaRSi
ADCY6 human

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
ADCY6

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

More...
GenomeRNAii
112
PharosiO43306

Protein Ontology

More...
PROi
PR:O43306

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000174233 Expressed in 170 organ(s), highest expression level in heart left ventricle
ExpressionAtlasiO43306 baseline and differential
GenevisibleiO43306 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 nameiADCY6_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: O43306
Secondary accession number(s): Q9NR75, Q9UDB0
<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_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 11, 2001
Last modified: October 16, 2019
This is version 190 of the entry and version 2 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

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  5. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
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