Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O43306 (ADCY6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Adenylate cyclase type 6

EC=4.6.1.1
Alternative name(s):
ATP pyrophosphate-lyase 6
Adenylate cyclase type VI
Adenylyl cyclase 6
Ca(2+)-inhibitable adenylyl cyclase
Gene names
Name:ADCY6
Synonyms:KIAA0422
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1168 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Membrane-bound, calcium-inhibitable adenylyl cyclase By similarity.

Catalytic activity

ATP = 3',5'-cyclic AMP + diphosphate.

Cofactor

Binds 2 magnesium ions per subunit By similarity.

Enzyme regulation

Inhibition by calcium in the submicromolar concentration range By similarity. Phosphorylation by RAF1 results in its activation. Ref.6

Subunit structure

Part of a complex containing AKAP5, ADCY5, PDE4C and PKD2 By similarity. Interacts with RAF1. Ref.6

Subcellular location

Membrane; Multi-pass membrane protein. Cell projectioncilium By similarity.

Post-translational modification

Phosphorylated by RAF1. Ref.6

Sequence similarities

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

Contains 2 guanylate cyclase domains.

Sequence caution

The sequence BAA24852.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processcAMP biosynthesis
   Cellular componentCell projection
Cilium
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainRepeat
Transmembrane
Transmembrane helix
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionLyase
   PTMGlycoprotein
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of phospholipase C activity

Traceable author statement. Source: Reactome

activation of protein kinase A activity

Traceable author statement. Source: Reactome

adenylate cyclase-activating G-protein coupled receptor signaling pathway

Traceable author statement. Source: Reactome

adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

Traceable author statement. Source: Reactome

cAMP biosynthetic process

Inferred from direct assay PubMed 18403039. Source: BHF-UCL

cellular response to catecholamine stimulus

Inferred from direct assay PubMed 18403039. Source: BHF-UCL

cellular response to glucagon stimulus

Traceable author statement. Source: Reactome

cellular response to prostaglandin E stimulus

Inferred from direct assay PubMed 18403039. Source: BHF-UCL

dopamine receptor signaling pathway

Inferred from direct assay PubMed 18403039. Source: BHF-UCL

energy reserve metabolic process

Traceable author statement. Source: Reactome

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

innate immune response

Traceable author statement. Source: Reactome

intracellular signal transduction

Inferred from electronic annotation. Source: InterPro

negative regulation of neuron projection development

Inferred from sequence or structural similarity. Source: ParkinsonsUK-UCL

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

signal transduction

Traceable author statement. Source: Reactome

small molecule metabolic process

Traceable author statement. Source: Reactome

synaptic transmission

Traceable author statement. Source: Reactome

transmembrane transport

Traceable author statement. Source: Reactome

water transport

Traceable author statement. Source: Reactome

   Cellular_componentcilium

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Inferred from sequence or structural similarity. Source: BHF-UCL

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

adenylate cyclase activity

Inferred from direct assay PubMed 18403039. Source: BHF-UCL

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 17081159. Source: UniProtKB

protein kinase binding

Inferred from sequence or structural similarity. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O43306-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O43306-2)

The sequence of this isoform differs from the canonical sequence as follows:
     762-814: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 11681168Adenylate cyclase type 6
PRO_0000195699

Regions

Topological domain1 – 151151Cytoplasmic Potential
Transmembrane152 – 16817Helical; Potential
Transmembrane181 – 19717Helical; Potential
Transmembrane214 – 23017Helical; Potential
Transmembrane239 – 25517Helical; Potential
Transmembrane259 – 27517Helical; Potential
Transmembrane289 – 30517Helical; Potential
Topological domain306 – 673368Cytoplasmic Potential
Transmembrane674 – 69118Helical; Potential
Transmembrane702 – 71817Helical; Potential
Transmembrane743 – 75917Helical; Potential
Topological domain760 – 81960Extracellular Potential
Transmembrane820 – 83617Helical; Potential
Transmembrane839 – 85517Helical; Potential
Transmembrane897 – 91317Helical; Potential
Topological domain914 – 1168255Cytoplasmic Potential

Sites

Metal binding3841Magnesium 1 By similarity
Metal binding3841Magnesium 2 By similarity
Metal binding3851Magnesium 2; via carbonyl oxygen By similarity
Metal binding4281Magnesium 1 By similarity
Metal binding4281Magnesium 2 By similarity

Amino acid modifications

Modified residue5561Phosphoserine By similarity
Modified residue5761Phosphoserine Ref.7
Modified residue6621Phosphoserine By similarity
Modified residue9191Phosphothreonine By similarity
Glycosylation7931N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence762 – 81453Missing in isoform 2.
VSP_000244
Natural variant6741A → S.
Corresponds to variant rs3730071 [ dbSNP | Ensembl ].
VAR_048249

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 11, 2001. Version 2.
Checksum: 127BB6E67F73AA61

FASTA1,168130,615
        10         20         30         40         50         60 
MSWFSGLLVP KVDERKTAWG ERNGQKRSRR RGTRAGGFCT PRYMSCLRDA EPPSPTPAGP 

        70         80         90        100        110        120 
PRCPWQDDAF IRRGGPGKGK ELGLRAVALG FEDTEVTTTA GGTAEVAPDA VPRSGRSCWR 

       130        140        150        160        170        180 
RLVQVFQSKQ FRSAKLERLY QRYFFQMNQS SLTLLMAVLV LLTAVLLAFH AAPARPQPAY 

       190        200        210        220        230        240 
VALLACAAAL FVGLMVVCNR HSFRQDSMWV VSYVVLGILA AVQVGGALAA DPRSPSAGLW 

       250        260        270        280        290        300 
CPVFFVYIAY TLLPIRMRAA VLSGLGLSTL HLILAWQLNR GDAFLWKQLG ANVLLFLCTN 

       310        320        330        340        350        360 
VIGICTHYPA EVSQRQAFQE TRGYIQARLH LQHENRQQER LLLSVLPQHV AMEMKEDINT 

       370        380        390        400        410        420 
KKEDMMFHKI YIQKHDNVSI LFADIEGFTS LASQCTAQEL VMTLNELFAR FDKLAAENHC 

       430        440        450        460        470        480 
LRIKILGDCY YCVSGLPEAR ADHAHCCVEM GVDMIEAISL VREVTGVNVN MRVGIHSGRV 

       490        500        510        520        530        540 
HCGVLGLRKW QFDVWSNDVT LANHMEAGGR AGRIHITRAT LQYLNGDYEV EPGRGGERNA 

       550        560        570        580        590        600 
YLKEQHIETF LILGASQKRK EEKAMLAKLQ RTRANSMEGL MPRWVPDRAF SRTKDSKAFR 

       610        620        630        640        650        660 
QMGIDDSSKD NRGTQDALNP EDEVDEFLSR AIDARSIDQL RKDHVRRFLL TFQREDLEKK 

       670        680        690        700        710        720 
YSRKVDPRFG AYVACALLVF CFICFIQLLI FPHSTLMLGI YASIFLLLLI TVLICAVYSC 

       730        740        750        760        770        780 
GSLFPKALQR LSRSIVRSRA HSTAVGIFSV LLVFTSAIAN MFTCNHTPIR SCAARMLNLT 

       790        800        810        820        830        840 
PADITACHLQ QLNYSLGLDA PLCEGTMPTC SFPEYFIGNM LLSLLASSVF LHISSIGKLA 

       850        860        870        880        890        900 
MIFVLGLIYL VLLLLGPPAT IFDNYDLLLG VHGLASSNET FDGLDCPAAG RVALKYMTPV 

       910        920        930        940        950        960 
ILLVFALALY LHAQQVESTA RLDFLWKLQA TGEKEEMEEL QAYNRRLLHN ILPKDVAAHF 

       970        980        990       1000       1010       1020 
LARERRNDEL YYQSCECVAV MFASIANFSE FYVELEANNE GVECLRLLNE IIADFDEIIS 

      1030       1040       1050       1060       1070       1080 
EERFRQLEKI KTIGSTYMAA SGLNASTYDQ VGRSHITALA DYAMRLMEQM KHINEHSFNN 

      1090       1100       1110       1120       1130       1140 
FQMKIGLNMG PVVAGVIGAR KPQYDIWGNT VNVSSRMDST GVPDRIQVTT DLYQVLAAKG 

      1150       1160 
YQLECRGVVK VKGKGEMTTY FLNGGPSS 

« Hide

Isoform 2 [UniParc].

Checksum: D1D26C1E15FAC0B0
Show »

FASTA1,115124,865

References

« Hide 'large scale' references
[1]"Cloning and expression of human adenylyl cyclase type VI in normal thyroid tissues."
Wicker R., Catalan A.G., Cailleux A.-F., Starenki D., Stengel D., Sarasin A., Suarez H.G.
Biochim. Biophys. Acta 1493:279-283(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Thyroid.
[2]"Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro."
Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 4:307-313(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Brain.
[3]"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Retina.
[5]"A novel adenylyl cyclase sequence cloned from the human erythroleukemia cell line."
Hellevuo K., Yoshimura M., Kao M., Hoffman P.L., Cooper D.M.F., Tabakoff B.
Biochem. Biophys. Res. Commun. 192:311-318(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1040-1103.
[6]"Raf kinase activation of adenylyl cyclases: isoform-selective regulation."
Ding Q., Gros R., Gray I.D., Taussig R., Ferguson S.S., Feldman R.D.
Mol. Pharmacol. 66:921-928(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY RAF1, INTERACTION WITH RAF1, ENZYME REGULATION.
[7]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-576, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[8]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF250226 mRNA. Translation: AAF82478.1.
AB007882 mRNA. Translation: BAA24852.2. Different initiation.
BC064923 mRNA. No translation available.
CCDSCCDS8767.1. [O43306-1]
CCDS8768.1. [O43306-2]
RefSeqNP_056085.1. NM_015270.3. [O43306-1]
NP_066193.1. NM_020983.2. [O43306-2]
XP_005268662.1. XM_005268605.1. [O43306-1]
XP_006719273.1. XM_006719210.1. [O43306-1]
UniGeneHs.525401.
Hs.694408.

3D structure databases

ProteinModelPortalO43306.
SMRO43306. Positions 364-553, 970-1145.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106625. 5 interactions.
IntActO43306. 1 interaction.
MINTMINT-2856766.
STRING9606.ENSP00000311405.

Chemistry

BindingDBO43306.
ChEMBLCHEMBL2097167.

PTM databases

PhosphoSiteO43306.

Proteomic databases

MaxQBO43306.
PaxDbO43306.
PRIDEO43306.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000307885; ENSP00000311405; ENSG00000174233. [O43306-1]
ENST00000357869; ENSP00000350536; ENSG00000174233. [O43306-2]
ENST00000550422; ENSP00000446730; ENSG00000174233. [O43306-2]
GeneID112.
KEGGhsa:112.
UCSCuc001rsh.4. human. [O43306-1]
uc001rsi.4. human. [O43306-2]

Organism-specific databases

CTD112.
GeneCardsGC12M049159.
HGNCHGNC:237. ADCY6.
HPACAB018365.
MIM600294. gene.
neXtProtNX_O43306.
PharmGKBPA27.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2114.
HOGENOMHOG000006941.
HOVERGENHBG050458.
InParanoidO43306.
KOK08046.
OMARSCWRRL.
OrthoDBEOG7B8S30.
PhylomeDBO43306.
TreeFamTF313845.

Enzyme and pathway databases

BRENDA4.6.1.1. 2681.
ReactomeREACT_111102. Signal Transduction.
REACT_111217. Metabolism.
REACT_116125. Disease.
REACT_13685. Neuronal System.
REACT_15518. Transmembrane transport of small molecules.
REACT_6900. Immune System.

Gene expression databases

ArrayExpressO43306.
BgeeO43306.
CleanExHS_ADCY6.
GenevestigatorO43306.

Family and domain databases

Gene3D3.30.70.1230. 2 hits.
InterProIPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
IPR009398. Adenylate_cyclase-like.
[Graphical view]
PfamPF06327. DUF1053. 1 hit.
PF00211. Guanylate_cyc. 2 hits.
[Graphical view]
SMARTSM00044. CYCc. 2 hits.
[Graphical view]
SUPFAMSSF55073. SSF55073. 2 hits.
PROSITEPS00452. GUANYLATE_CYCLASE_1. 2 hits.
PS50125. GUANYLATE_CYCLASE_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiADCY6.
GenomeRNAi112.
NextBio431.
PROO43306.
SOURCESearch...

Entry information

Entry nameADCY6_HUMAN
AccessionPrimary (citable) accession number: O43306
Secondary accession number(s): Q9NR75, Q9UDB0
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 11, 2001
Last modified: July 9, 2014
This is version 143 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM