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P40145

- ADCY8_HUMAN

UniProt

P40145 - ADCY8_HUMAN

Protein

Adenylate cyclase type 8

Gene

ADCY8

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 134 (01 Oct 2014)
      Sequence version 1 (01 Feb 1995)
      Previous versions | rss
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    Functioni

    This is a membrane-bound, calcium-stimulable adenylyl cyclase. May be involved in learning, in memory and in drug dependence By similarity.By similarity

    Catalytic activityi

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

    Cofactori

    Binds 2 magnesium ions per subunit.By similarity

    Enzyme regulationi

    Activated by calcium/calmodulin.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi419 – 4191Magnesium 1PROSITE-ProRule annotation
    Metal bindingi419 – 4191Magnesium 2PROSITE-ProRule annotation
    Metal bindingi420 – 4201Magnesium 2; via carbonyl oxygenPROSITE-ProRule annotation
    Metal bindingi463 – 4631Magnesium 1PROSITE-ProRule annotation
    Metal bindingi463 – 4631Magnesium 2PROSITE-ProRule annotation

    GO - Molecular functioni

    1. adenylate cyclase activity Source: ProtInc
    2. ATP binding Source: UniProtKB-KW
    3. calcium- and calmodulin-responsive adenylate cyclase activity Source: ProtInc
    4. metal ion binding Source: UniProtKB-KW

    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. cellular response to glucagon stimulus Source: Reactome
    6. energy reserve metabolic process Source: Reactome
    7. epidermal growth factor receptor signaling pathway Source: Reactome
    8. fibroblast growth factor receptor signaling pathway Source: Reactome
    9. innate immune response Source: Reactome
    10. intracellular signal transduction Source: InterPro
    11. learning or memory Source: ProtInc
    12. long-term memory Source: Ensembl
    13. neurotrophin TRK receptor signaling pathway Source: Reactome
    14. signal transduction Source: Reactome
    15. small molecule metabolic process Source: Reactome
    16. synaptic transmission Source: Reactome
    17. transmembrane transport Source: Reactome
    18. 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_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_20625. CREB phosphorylation through the activation of Adenylate Cyclase.
    REACT_24023. Regulation of water balance by renal Aquaporins.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Adenylate cyclase type 8 (EC:4.6.1.1)
    Alternative name(s):
    ATP pyrophosphate-lyase 8
    Adenylate cyclase type VIII
    Adenylyl cyclase 8
    Short name:
    AC8
    Ca(2+)/calmodulin-activated adenylyl cyclase
    Gene namesi
    Name:ADCY8
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 8

    Organism-specific databases

    HGNCiHGNC:239. ADCY8.

    Subcellular locationi

    GO - Cellular componenti

    1. integral component of membrane Source: UniProtKB-KW
    2. membrane Source: ProtInc
    3. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Membrane

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA29.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 12511251Adenylate cyclase type 8PRO_0000195705Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi817 – 8171N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi821 – 8211N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi888 – 8881N-linked (GlcNAc...)Sequence Analysis

    Keywords - PTMi

    Glycoprotein

    Proteomic databases

    PaxDbiP40145.
    PRIDEiP40145.

    PTM databases

    PhosphoSiteiP40145.

    Expressioni

    Gene expression databases

    ArrayExpressiP40145.
    BgeeiP40145.
    CleanExiHS_ADCY8.
    GenevestigatoriP40145.

    Organism-specific databases

    HPAiCAB018652.
    HPA024291.

    Interactioni

    Protein-protein interaction databases

    BioGridi106627. 2 interactions.
    IntActiP40145. 1 interaction.
    STRINGi9606.ENSP00000286355.

    Structurei

    3D structure databases

    ProteinModelPortaliP40145.
    SMRiP40145. Positions 402-587, 971-1145.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 182182CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini342 – 715374CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini915 – 1251337CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei183 – 20321HelicalSequence AnalysisAdd
    BLAST
    Transmembranei212 – 23221HelicalSequence AnalysisAdd
    BLAST
    Transmembranei247 – 26721HelicalSequence AnalysisAdd
    BLAST
    Transmembranei274 – 29421HelicalSequence AnalysisAdd
    BLAST
    Transmembranei296 – 31621HelicalSequence AnalysisAdd
    BLAST
    Transmembranei321 – 34121HelicalSequence AnalysisAdd
    BLAST
    Transmembranei716 – 73621HelicalSequence AnalysisAdd
    BLAST
    Transmembranei738 – 75821HelicalSequence AnalysisAdd
    BLAST
    Transmembranei787 – 80721HelicalSequence AnalysisAdd
    BLAST
    Transmembranei831 – 85121HelicalSequence AnalysisAdd
    BLAST
    Transmembranei861 – 88121HelicalSequence AnalysisAdd
    BLAST
    Transmembranei894 – 91421HelicalSequence 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.
    InParanoidiP40145.
    KOiK08048.
    OMAiDVRCLSG.
    OrthoDBiEOG7B8S30.
    PhylomeDBiP40145.
    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]

    Sequencei

    Sequence statusi: Complete.

    P40145-1 [UniParc]FASTAAdd to Basket

    « Hide

    MELSDVRCLT GSEELYTIHP TPPAGDGRSA SRPQRLLWQT AVRHITEQRF     50
    IHGHRGGSGS GSGGSGKASD PAGGGPNHHA PQLSGDSALP LYSLGPGERA 100
    HSTCGTKVFP ERSGSGSASG SGGGGDLGFL HLDCAPSNSD FFLNGGYSYR 150
    GVIFPTLRNS FKSRDLERLY QRYFLGQRRK SEVVMNVLDV LTKLTLLVLH 200
    LSLASAPMDP LKGILLGFFT GIEVVICALV VVRKDTTSHT YLQYSGVVTW 250
    VAMTTQILAA GLGYGLLGDG IGYVLFTLFA TYSMLPLPLT WAILAGLGTS 300
    LLQVILQVVI PRLAVISINQ VVAQAVLFMC MNTAGIFISY LSDRAQRQAF 350
    LETRRCVEAR LRLETENQRQ ERLVLSVLPR FVVLEMINDM TNVEDEHLQH 400
    QFHRIYIHRY ENVSILFADV KGFTNLSTTL SAQELVRMLN ELFARFDRLA 450
    HEHHCLRIKI LGDCYYCVSG LPEPRQDHAH CCVEMGLSMI KTIRYVRSRT 500
    KHDVDMRIGI HSGSVLCGVL GLRKWQFDVW SWDVDIANKL ESGGIPGRIH 550
    ISKATLDCLN GDYNVEEGHG KERNEFLRKH NIETYLIKQP EDSLLSLPED 600
    IVKESVSSSD RRNSGATFTE GSWSPELPFD NIVGKQNTLA ALTRNSINLL 650
    PNHLAQALHV QSGPEEINKR IEHTIDLRSG DKLRREHIKP FSLMFKDSSL 700
    EHKYSQMRDE VFKSNLVCAF IVLLFITAIQ SLLPSSRVMP MTIQFSILIM 750
    LHSALVLITT AEDYKCLPLI LRKTCCWINE TYLARNVIIF ASILINFLGA 800
    ILNILWCDFD KSIPLKNLTF NSSAVFTDIC SYPEYFVFTG VLAMVTCAVF 850
    LRLNSVLKLA VLLIMIAIYA LLTETVYAGL FLRYDNLNHS GEDFLGTKEV 900
    SLLLMAMFLL AVFYHGQQLE YTARLDFLWR VQAKEEINEM KELREHNENM 950
    LRNILPSHVA RHFLEKDRDN EELYSQSYDA VGVMFASIPG FADFYSQTEM 1000
    NNQGVECLRL LNEIIADFDE LLGEDRFQDI EKIKTIGSTY MAVSGLSPEK 1050
    QQCEDKWGHL CALADFSLAL TESIQEINKH SFNNFELRIG ISHGSVVAGV 1100
    IGAKKPQYDI WGKTVNLASR MDSTGVSGRI QVPEETYLIL KDQGFAFDYR 1150
    GEIYVKGISE QEGKIKTYFL LGRVQPNPFI LPPRRLPGQY SLAAVVLGLV 1200
    QSLNRQRQKQ LLNENNNTGI IKGHYNRRTL LSPSGTEPGA QAEGTDKSDL 1250
    P 1251
    Length:1,251
    Mass (Da):140,122
    Last modified:February 1, 1995 - v1
    Checksum:iABF25C40493E07C3
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti80 – 801A → T.
    Corresponds to variant rs2228949 [ dbSNP | Ensembl ].
    VAR_029188
    Natural varianti881 – 8811F → L in a colorectal cancer sample; somatic mutation. 1 Publication
    VAR_036328

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z35309 mRNA. Translation: CAA84552.1.
    M83533 mRNA. Translation: AAA35523.2.
    CCDSiCCDS6363.1.
    PIRiPQ0227.
    S48687.
    RefSeqiNP_001106.1. NM_001115.2.
    UniGeneiHs.591859.

    Genome annotation databases

    EnsembliENST00000286355; ENSP00000286355; ENSG00000155897.
    GeneIDi114.
    KEGGihsa:114.
    UCSCiuc003ytd.4. human.

    Polymorphism databases

    DMDMi729242.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    Z35309 mRNA. Translation: CAA84552.1 .
    M83533 mRNA. Translation: AAA35523.2 .
    CCDSi CCDS6363.1.
    PIRi PQ0227.
    S48687.
    RefSeqi NP_001106.1. NM_001115.2.
    UniGenei Hs.591859.

    3D structure databases

    ProteinModelPortali P40145.
    SMRi P40145. Positions 402-587, 971-1145.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 106627. 2 interactions.
    IntActi P40145. 1 interaction.
    STRINGi 9606.ENSP00000286355.

    Chemistry

    BindingDBi P40145.
    ChEMBLi CHEMBL2097167.

    PTM databases

    PhosphoSitei P40145.

    Polymorphism databases

    DMDMi 729242.

    Proteomic databases

    PaxDbi P40145.
    PRIDEi P40145.

    Protocols and materials databases

    DNASUi 114.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000286355 ; ENSP00000286355 ; ENSG00000155897 .
    GeneIDi 114.
    KEGGi hsa:114.
    UCSCi uc003ytd.4. human.

    Organism-specific databases

    CTDi 114.
    GeneCardsi GC08M131861.
    HGNCi HGNC:239. ADCY8.
    HPAi CAB018652.
    HPA024291.
    MIMi 103070. gene.
    neXtProti NX_P40145.
    PharmGKBi PA29.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG2114.
    HOGENOMi HOG000006941.
    HOVERGENi HBG050458.
    InParanoidi P40145.
    KOi K08048.
    OMAi DVRCLSG.
    OrthoDBi EOG7B8S30.
    PhylomeDBi P40145.
    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_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_20625. CREB phosphorylation through the activation of Adenylate Cyclase.
    REACT_24023. Regulation of water balance by renal Aquaporins.

    Miscellaneous databases

    ChiTaRSi ADCY8. human.
    GeneWikii ADCY8.
    GenomeRNAii 114.
    NextBioi 441.
    PROi P40145.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P40145.
    Bgeei P40145.
    CleanExi HS_ADCY8.
    Genevestigatori P40145.

    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. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Brain stem.
    2. "Sequence of a human brain adenylyl cyclase partial cDNA: evidence for a consensus cyclase specific domain."
      Parma J., Stengel D., Gannage M.H., Poyard M., Barouki R., Hanoune J.
      Biochem. Biophys. Res. Commun. 179:455-462(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 577-1251.
      Tissue: Brain.
    3. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    4. Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-881.

    Entry informationi

    Entry nameiADCY8_HUMAN
    AccessioniPrimary (citable) accession number: P40145
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1995
    Last sequence update: February 1, 1995
    Last modified: October 1, 2014
    This is version 134 of the entry and version 1 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 8
      Human chromosome 8: 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