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O43306

- ADCY6_HUMAN

UniProt

O43306 - ADCY6_HUMAN

Protein

Adenylate cyclase type 6

Gene

ADCY6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 145 (01 Oct 2014)
      Sequence version 2 (11 Jan 2001)
      Previous versions | rss
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    Functioni

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

    Catalytic activityi

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

    Cofactori

    Binds 2 magnesium ions per subunit.By similarity

    Enzyme regulationi

    Inhibition by calcium in the submicromolar concentration range By similarity. Phosphorylation by RAF1 results in its activation.By similarity1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi384 – 3841Magnesium 1PROSITE-ProRule annotation
    Metal bindingi384 – 3841Magnesium 2PROSITE-ProRule annotation
    Metal bindingi385 – 3851Magnesium 2; via carbonyl oxygenPROSITE-ProRule annotation
    Metal bindingi428 – 4281Magnesium 1PROSITE-ProRule annotation
    Metal bindingi428 – 4281Magnesium 2PROSITE-ProRule annotation

    GO - Molecular functioni

    1. adenylate cyclase activity Source: BHF-UCL
    2. ATP binding Source: UniProtKB-KW
    3. metal ion binding Source: UniProtKB-KW
    4. protein binding Source: UniProtKB
    5. protein kinase binding Source: BHF-UCL

    GO - Biological processi

    1. activation of phospholipase C activity Source: Reactome
    2. activation of protein kinase A activity Source: Reactome
    3. adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: Reactome
    4. adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway Source: Reactome
    5. cAMP biosynthetic process Source: BHF-UCL
    6. cellular response to catecholamine stimulus Source: BHF-UCL
    7. cellular response to glucagon stimulus Source: Reactome
    8. cellular response to prostaglandin E stimulus Source: BHF-UCL
    9. dopamine receptor signaling pathway Source: BHF-UCL
    10. energy reserve metabolic process Source: Reactome
    11. epidermal growth factor receptor signaling pathway Source: Reactome
    12. fibroblast growth factor receptor signaling pathway Source: Reactome
    13. innate immune response Source: Reactome
    14. intracellular signal transduction Source: InterPro
    15. negative regulation of neuron projection development Source: ParkinsonsUK-UCL
    16. neurotrophin TRK receptor signaling pathway Source: Reactome
    17. signal transduction Source: Reactome
    18. small molecule metabolic process Source: Reactome
    19. synaptic transmission Source: Reactome
    20. transmembrane transport Source: Reactome
    21. water transport Source: Reactome

    Keywords - Molecular functioni

    Lyase

    Keywords - Biological processi

    cAMP biosynthesis

    Keywords - Ligandi

    ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi4.6.1.1. 2681.
    ReactomeiREACT_15312. Adenylate cyclase activating pathway.
    REACT_15333. Adenylate cyclase inhibitory pathway.
    REACT_15530. PKA activation.
    REACT_1665. Glucagon signaling in metabolic regulation.
    REACT_18274. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
    REACT_18339. Adrenaline,noradrenaline inhibits insulin secretion.
    REACT_19231. G alpha (i) signalling events.
    REACT_19327. G alpha (s) signalling events.
    REACT_19333. G alpha (z) signalling events.
    REACT_1946. PKA activation in glucagon signalling.
    REACT_24023. Regulation of water balance by renal Aquaporins.

    Names & Taxonomyi

    Protein namesi
    Recommended 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 namesi
    Name:ADCY6
    Synonyms:KIAA0422
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:237. ADCY6.

    Subcellular locationi

    GO - Cellular componenti

    1. cilium Source: UniProtKB-SubCell
    2. integral component of membrane Source: UniProtKB-KW
    3. membrane Source: BHF-UCL
    4. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Cell projection, Cilium, Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA27.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 11681168Adenylate cyclase type 6PRO_0000195699Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei556 – 5561PhosphoserineBy similarity
    Modified residuei576 – 5761Phosphoserine2 Publications
    Modified residuei662 – 6621PhosphoserineBy similarity
    Glycosylationi793 – 7931N-linked (GlcNAc...)Sequence Analysis
    Modified residuei919 – 9191PhosphothreonineBy similarity

    Post-translational modificationi

    Phosphorylated by RAF1.2 Publications

    Keywords - PTMi

    Glycoprotein, Phosphoprotein

    Proteomic databases

    MaxQBiO43306.
    PaxDbiO43306.
    PRIDEiO43306.

    PTM databases

    PhosphoSiteiO43306.

    Expressioni

    Gene expression databases

    ArrayExpressiO43306.
    BgeeiO43306.
    CleanExiHS_ADCY6.
    GenevestigatoriO43306.

    Organism-specific databases

    HPAiCAB018365.

    Interactioni

    Subunit structurei

    Part of a complex containing AKAP5, ADCY5, PDE4C and PKD2 By similarity. Interacts with RAF1.By similarity1 Publication

    Protein-protein interaction databases

    BioGridi106625. 5 interactions.
    IntActiO43306. 1 interaction.
    MINTiMINT-2856766.
    STRINGi9606.ENSP00000311405.

    Structurei

    3D structure databases

    ProteinModelPortaliO43306.
    SMRiO43306. Positions 364-553, 970-1145.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 151151CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini306 – 673368CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini760 – 81960ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini914 – 1168255CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei152 – 16817HelicalSequence AnalysisAdd
    BLAST
    Transmembranei181 – 19717HelicalSequence AnalysisAdd
    BLAST
    Transmembranei214 – 23017HelicalSequence AnalysisAdd
    BLAST
    Transmembranei239 – 25517HelicalSequence AnalysisAdd
    BLAST
    Transmembranei259 – 27517HelicalSequence AnalysisAdd
    BLAST
    Transmembranei289 – 30517HelicalSequence AnalysisAdd
    BLAST
    Transmembranei674 – 69118HelicalSequence AnalysisAdd
    BLAST
    Transmembranei702 – 71817HelicalSequence AnalysisAdd
    BLAST
    Transmembranei743 – 75917HelicalSequence AnalysisAdd
    BLAST
    Transmembranei820 – 83617HelicalSequence AnalysisAdd
    BLAST
    Transmembranei839 – 85517HelicalSequence AnalysisAdd
    BLAST
    Transmembranei897 – 91317HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.PROSITE-ProRule annotation
    Contains 2 guanylate cyclase domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG2114.
    HOGENOMiHOG000006941.
    HOVERGENiHBG050458.
    InParanoidiO43306.
    KOiK08046.
    OMAiRSCWRRL.
    OrthoDBiEOG7B8S30.
    PhylomeDBiO43306.
    TreeFamiTF313845.

    Family and domain databases

    Gene3Di3.30.70.1230. 2 hits.
    InterProiIPR001054. A/G_cyclase.
    IPR018297. A/G_cyclase_CS.
    IPR009398. Adenylate_cyclase-like.
    [Graphical view]
    PfamiPF06327. DUF1053. 1 hit.
    PF00211. Guanylate_cyc. 2 hits.
    [Graphical view]
    SMARTiSM00044. CYCc. 2 hits.
    [Graphical view]
    SUPFAMiSSF55073. SSF55073. 2 hits.
    PROSITEiPS00452. GUANYLATE_CYCLASE_1. 2 hits.
    PS50125. GUANYLATE_CYCLASE_2. 2 hits.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

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

    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.

    « Hide

    MSWFSGLLVP KVDERKTAWG ERNGQKRSRR RGTRAGGFCT PRYMSCLRDA     50
    EPPSPTPAGP PRCPWQDDAF IRRGGPGKGK ELGLRAVALG FEDTEVTTTA 100
    GGTAEVAPDA VPRSGRSCWR RLVQVFQSKQ FRSAKLERLY QRYFFQMNQS 150
    SLTLLMAVLV LLTAVLLAFH AAPARPQPAY VALLACAAAL FVGLMVVCNR 200
    HSFRQDSMWV VSYVVLGILA AVQVGGALAA DPRSPSAGLW CPVFFVYIAY 250
    TLLPIRMRAA VLSGLGLSTL HLILAWQLNR GDAFLWKQLG ANVLLFLCTN 300
    VIGICTHYPA EVSQRQAFQE TRGYIQARLH LQHENRQQER LLLSVLPQHV 350
    AMEMKEDINT KKEDMMFHKI YIQKHDNVSI LFADIEGFTS LASQCTAQEL 400
    VMTLNELFAR FDKLAAENHC LRIKILGDCY YCVSGLPEAR ADHAHCCVEM 450
    GVDMIEAISL VREVTGVNVN MRVGIHSGRV HCGVLGLRKW QFDVWSNDVT 500
    LANHMEAGGR AGRIHITRAT LQYLNGDYEV EPGRGGERNA YLKEQHIETF 550
    LILGASQKRK EEKAMLAKLQ RTRANSMEGL MPRWVPDRAF SRTKDSKAFR 600
    QMGIDDSSKD NRGTQDALNP EDEVDEFLSR AIDARSIDQL RKDHVRRFLL 650
    TFQREDLEKK YSRKVDPRFG AYVACALLVF CFICFIQLLI FPHSTLMLGI 700
    YASIFLLLLI TVLICAVYSC GSLFPKALQR LSRSIVRSRA HSTAVGIFSV 750
    LLVFTSAIAN MFTCNHTPIR SCAARMLNLT PADITACHLQ QLNYSLGLDA 800
    PLCEGTMPTC SFPEYFIGNM LLSLLASSVF LHISSIGKLA MIFVLGLIYL 850
    VLLLLGPPAT IFDNYDLLLG VHGLASSNET FDGLDCPAAG RVALKYMTPV 900
    ILLVFALALY LHAQQVESTA RLDFLWKLQA TGEKEEMEEL QAYNRRLLHN 950
    ILPKDVAAHF LARERRNDEL YYQSCECVAV MFASIANFSE FYVELEANNE 1000
    GVECLRLLNE IIADFDEIIS EERFRQLEKI KTIGSTYMAA SGLNASTYDQ 1050
    VGRSHITALA DYAMRLMEQM KHINEHSFNN FQMKIGLNMG PVVAGVIGAR 1100
    KPQYDIWGNT VNVSSRMDST GVPDRIQVTT DLYQVLAAKG YQLECRGVVK 1150
    VKGKGEMTTY FLNGGPSS 1168
    Length:1,168
    Mass (Da):130,615
    Last modified:January 11, 2001 - v2
    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

    Sequence cautioni

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

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti674 – 6741A → S.
    Corresponds to variant rs3730071 [ dbSNP | Ensembl ].
    VAR_048249

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei762 – 81453Missing in isoform 2. 1 PublicationVSP_000244Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF250226 mRNA. Translation: AAF82478.1.
    AB007882 mRNA. Translation: BAA24852.2. Different initiation.
    BC064923 mRNA. No translation available.
    CCDSiCCDS8767.1. [O43306-1]
    CCDS8768.1. [O43306-2]
    RefSeqiNP_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]
    UniGeneiHs.525401.
    Hs.694408.

    Genome annotation databases

    EnsembliENST00000307885; ENSP00000311405; ENSG00000174233. [O43306-1]
    ENST00000357869; ENSP00000350536; ENSG00000174233. [O43306-2]
    ENST00000550422; ENSP00000446730; ENSG00000174233. [O43306-2]
    GeneIDi112.
    KEGGihsa:112.
    UCSCiuc001rsh.4. human. [O43306-1]
    uc001rsi.4. human. [O43306-2]

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF250226 mRNA. Translation: AAF82478.1 .
    AB007882 mRNA. Translation: BAA24852.2 . Different initiation.
    BC064923 mRNA. No translation available.
    CCDSi CCDS8767.1. [O43306-1 ]
    CCDS8768.1. [O43306-2 ]
    RefSeqi NP_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 ]
    UniGenei Hs.525401.
    Hs.694408.

    3D structure databases

    ProteinModelPortali O43306.
    SMRi O43306. Positions 364-553, 970-1145.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 106625. 5 interactions.
    IntActi O43306. 1 interaction.
    MINTi MINT-2856766.
    STRINGi 9606.ENSP00000311405.

    Chemistry

    BindingDBi O43306.
    ChEMBLi CHEMBL2097167.

    PTM databases

    PhosphoSitei O43306.

    Proteomic databases

    MaxQBi O43306.
    PaxDbi O43306.
    PRIDEi O43306.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000307885 ; ENSP00000311405 ; ENSG00000174233 . [O43306-1 ]
    ENST00000357869 ; ENSP00000350536 ; ENSG00000174233 . [O43306-2 ]
    ENST00000550422 ; ENSP00000446730 ; ENSG00000174233 . [O43306-2 ]
    GeneIDi 112.
    KEGGi hsa:112.
    UCSCi uc001rsh.4. human. [O43306-1 ]
    uc001rsi.4. human. [O43306-2 ]

    Organism-specific databases

    CTDi 112.
    GeneCardsi GC12M049159.
    HGNCi HGNC:237. ADCY6.
    HPAi CAB018365.
    MIMi 600294. gene.
    neXtProti NX_O43306.
    PharmGKBi PA27.
    HUGEi Search...
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG2114.
    HOGENOMi HOG000006941.
    HOVERGENi HBG050458.
    InParanoidi O43306.
    KOi K08046.
    OMAi RSCWRRL.
    OrthoDBi EOG7B8S30.
    PhylomeDBi O43306.
    TreeFami TF313845.

    Enzyme and pathway databases

    BRENDAi 4.6.1.1. 2681.
    Reactomei REACT_15312. Adenylate cyclase activating pathway.
    REACT_15333. Adenylate cyclase inhibitory pathway.
    REACT_15530. PKA activation.
    REACT_1665. Glucagon signaling in metabolic regulation.
    REACT_18274. Glucagon-like Peptide-1 (GLP1) regulates insulin secretion.
    REACT_18339. Adrenaline,noradrenaline inhibits insulin secretion.
    REACT_19231. G alpha (i) signalling events.
    REACT_19327. G alpha (s) signalling events.
    REACT_19333. G alpha (z) signalling events.
    REACT_1946. PKA activation in glucagon signalling.
    REACT_24023. Regulation of water balance by renal Aquaporins.

    Miscellaneous databases

    GeneWikii ADCY6.
    GenomeRNAii 112.
    NextBioi 431.
    PROi O43306.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O43306.
    Bgeei O43306.
    CleanExi HS_ADCY6.
    Genevestigatori O43306.

    Family and domain databases

    Gene3Di 3.30.70.1230. 2 hits.
    InterProi IPR001054. A/G_cyclase.
    IPR018297. A/G_cyclase_CS.
    IPR009398. Adenylate_cyclase-like.
    [Graphical view ]
    Pfami PF06327. DUF1053. 1 hit.
    PF00211. Guanylate_cyc. 2 hits.
    [Graphical view ]
    SMARTi SM00044. CYCc. 2 hits.
    [Graphical view ]
    SUPFAMi SSF55073. SSF55073. 2 hits.
    PROSITEi PS00452. GUANYLATE_CYCLASE_1. 2 hits.
    PS50125. GUANYLATE_CYCLASE_2. 2 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-576, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Platelet.
    8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.

    Entry informationi

    Entry nameiADCY6_HUMAN
    AccessioniPrimary (citable) accession number: O43306
    Secondary accession number(s): Q9NR75, Q9UDB0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1999
    Last sequence update: January 11, 2001
    Last modified: October 1, 2014
    This is version 145 of the entry and version 2 of the sequence. [Complete history]
    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.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: entries, gene names and cross-references to MIM
    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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3