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P40145 (ADCY8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 132. 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·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:ADCY8
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1251 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Catalytic activity

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

Cofactor

Binds 2 magnesium ions per subunit By similarity.

Enzyme regulation

Activated by calcium/calmodulin.

Subcellular location

Membrane; Multi-pass membrane protein.

Sequence similarities

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

Contains 2 guanylate cyclase domains.

Ontologies

Keywords
   Biological processcAMP biosynthesis
   Cellular componentMembrane
   Coding sequence diversityPolymorphism
   DomainRepeat
Transmembrane
Transmembrane helix
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionLyase
   PTMGlycoprotein
   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

cellular response to glucagon stimulus

Traceable author statement. Source: Reactome

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

learning or memory

Traceable author statement Ref.1. Source: ProtInc

long-term memory

Inferred from electronic annotation. Source: Ensembl

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_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Traceable author statement PubMed 8163524. Source: ProtInc

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

adenylate cyclase activity

Traceable author statement Ref.1. Source: ProtInc

calcium- and calmodulin-responsive adenylate cyclase activity

Traceable author statement PubMed 8163524. Source: ProtInc

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12511251Adenylate cyclase type 8
PRO_0000195705

Regions

Topological domain1 – 182182Cytoplasmic Potential
Transmembrane183 – 20321Helical; Potential
Transmembrane212 – 23221Helical; Potential
Transmembrane247 – 26721Helical; Potential
Transmembrane274 – 29421Helical; Potential
Transmembrane296 – 31621Helical; Potential
Transmembrane321 – 34121Helical; Potential
Topological domain342 – 715374Cytoplasmic Potential
Transmembrane716 – 73621Helical; Potential
Transmembrane738 – 75821Helical; Potential
Transmembrane787 – 80721Helical; Potential
Transmembrane831 – 85121Helical; Potential
Transmembrane861 – 88121Helical; Potential
Transmembrane894 – 91421Helical; Potential
Topological domain915 – 1251337Cytoplasmic Potential

Sites

Metal binding4191Magnesium 1 By similarity
Metal binding4191Magnesium 2 By similarity
Metal binding4201Magnesium 2; via carbonyl oxygen By similarity
Metal binding4631Magnesium 1 By similarity
Metal binding4631Magnesium 2 By similarity

Amino acid modifications

Glycosylation8171N-linked (GlcNAc...) Potential
Glycosylation8211N-linked (GlcNAc...) Potential
Glycosylation8881N-linked (GlcNAc...) Potential

Natural variations

Natural variant801A → T.
Corresponds to variant rs2228949 [ dbSNP | Ensembl ].
VAR_029188
Natural variant8811F → L in a colorectal cancer sample; somatic mutation. Ref.4
VAR_036328

Sequences

Sequence LengthMass (Da)Tools
P40145 [UniParc].

Last modified February 1, 1995. Version 1.
Checksum: ABF25C40493E07C3

FASTA1,251140,122
        10         20         30         40         50         60 
MELSDVRCLT GSEELYTIHP TPPAGDGRSA SRPQRLLWQT AVRHITEQRF IHGHRGGSGS 

        70         80         90        100        110        120 
GSGGSGKASD PAGGGPNHHA PQLSGDSALP LYSLGPGERA HSTCGTKVFP ERSGSGSASG 

       130        140        150        160        170        180 
SGGGGDLGFL HLDCAPSNSD FFLNGGYSYR GVIFPTLRNS FKSRDLERLY QRYFLGQRRK 

       190        200        210        220        230        240 
SEVVMNVLDV LTKLTLLVLH LSLASAPMDP LKGILLGFFT GIEVVICALV VVRKDTTSHT 

       250        260        270        280        290        300 
YLQYSGVVTW VAMTTQILAA GLGYGLLGDG IGYVLFTLFA TYSMLPLPLT WAILAGLGTS 

       310        320        330        340        350        360 
LLQVILQVVI PRLAVISINQ VVAQAVLFMC MNTAGIFISY LSDRAQRQAF LETRRCVEAR 

       370        380        390        400        410        420 
LRLETENQRQ ERLVLSVLPR FVVLEMINDM TNVEDEHLQH QFHRIYIHRY ENVSILFADV 

       430        440        450        460        470        480 
KGFTNLSTTL SAQELVRMLN ELFARFDRLA HEHHCLRIKI LGDCYYCVSG LPEPRQDHAH 

       490        500        510        520        530        540 
CCVEMGLSMI KTIRYVRSRT KHDVDMRIGI HSGSVLCGVL GLRKWQFDVW SWDVDIANKL 

       550        560        570        580        590        600 
ESGGIPGRIH ISKATLDCLN GDYNVEEGHG KERNEFLRKH NIETYLIKQP EDSLLSLPED 

       610        620        630        640        650        660 
IVKESVSSSD RRNSGATFTE GSWSPELPFD NIVGKQNTLA ALTRNSINLL PNHLAQALHV 

       670        680        690        700        710        720 
QSGPEEINKR IEHTIDLRSG DKLRREHIKP FSLMFKDSSL EHKYSQMRDE VFKSNLVCAF 

       730        740        750        760        770        780 
IVLLFITAIQ SLLPSSRVMP MTIQFSILIM LHSALVLITT AEDYKCLPLI LRKTCCWINE 

       790        800        810        820        830        840 
TYLARNVIIF ASILINFLGA ILNILWCDFD KSIPLKNLTF NSSAVFTDIC SYPEYFVFTG 

       850        860        870        880        890        900 
VLAMVTCAVF LRLNSVLKLA VLLIMIAIYA LLTETVYAGL FLRYDNLNHS GEDFLGTKEV 

       910        920        930        940        950        960 
SLLLMAMFLL AVFYHGQQLE YTARLDFLWR VQAKEEINEM KELREHNENM LRNILPSHVA 

       970        980        990       1000       1010       1020 
RHFLEKDRDN EELYSQSYDA VGVMFASIPG FADFYSQTEM NNQGVECLRL LNEIIADFDE 

      1030       1040       1050       1060       1070       1080 
LLGEDRFQDI EKIKTIGSTY MAVSGLSPEK QQCEDKWGHL CALADFSLAL TESIQEINKH 

      1090       1100       1110       1120       1130       1140 
SFNNFELRIG ISHGSVVAGV IGAKKPQYDI WGKTVNLASR MDSTGVSGRI QVPEETYLIL 

      1150       1160       1170       1180       1190       1200 
KDQGFAFDYR GEIYVKGISE QEGKIKTYFL LGRVQPNPFI LPPRRLPGQY SLAAVVLGLV 

      1210       1220       1230       1240       1250 
QSLNRQRQKQ LLNENNNTGI IKGHYNRRTL LSPSGTEPGA QAEGTDKSDL P 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of the human type VIII adenylyl cyclase."
Defer N., Marinx O., Stengel D., Danisova A., Iourgenko V., Matsuoka I., Caput D., Hanoune J.
FEBS Lett. 351:109-113(1994) [PubMed] [Europe PMC] [Abstract]
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]"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.
[4]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-881.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z35309 mRNA. Translation: CAA84552.1.
M83533 mRNA. Translation: AAA35523.2.
CCDSCCDS6363.1.
PIRPQ0227.
S48687.
RefSeqNP_001106.1. NM_001115.2.
UniGeneHs.591859.

3D structure databases

ProteinModelPortalP40145.
SMRP40145. Positions 402-587, 971-1145.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106627. 2 interactions.
IntActP40145. 1 interaction.
STRING9606.ENSP00000286355.

Chemistry

BindingDBP40145.
ChEMBLCHEMBL2097167.

PTM databases

PhosphoSiteP40145.

Polymorphism databases

DMDM729242.

Proteomic databases

PaxDbP40145.
PRIDEP40145.

Protocols and materials databases

DNASU114.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000286355; ENSP00000286355; ENSG00000155897.
GeneID114.
KEGGhsa:114.
UCSCuc003ytd.4. human.

Organism-specific databases

CTD114.
GeneCardsGC08M131861.
HGNCHGNC:239. ADCY8.
HPACAB018652.
HPA024291.
MIM103070. gene.
neXtProtNX_P40145.
PharmGKBPA29.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2114.
HOGENOMHOG000006941.
HOVERGENHBG050458.
InParanoidP40145.
KOK08048.
OMADVRCLSG.
OrthoDBEOG7B8S30.
PhylomeDBP40145.
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

ArrayExpressP40145.
BgeeP40145.
CleanExHS_ADCY8.
GenevestigatorP40145.

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

ChiTaRSADCY8. human.
GeneWikiADCY8.
GenomeRNAi114.
NextBio441.
PROP40145.
SOURCESearch...

Entry information

Entry nameADCY8_HUMAN
AccessionPrimary (citable) accession number: P40145
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: July 9, 2014
This is version 132 of the entry and version 1 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 8

Human chromosome 8: entries, gene names and cross-references to MIM