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Protein

Adenylate cyclase type 8

Gene

ADCY8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

Mg2+By similarity, Mn2+By similarityNote: Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).By similarity

Enzyme regulationi

Activated by calcium/calmodulin.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi419Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi419Magnesium 2; catalyticPROSITE-ProRule annotation1
Metal bindingi420Magnesium 2; via carbonyl oxygen; catalyticPROSITE-ProRule annotation1
Metal bindingi463Magnesium 1; catalyticPROSITE-ProRule annotation1
Metal bindingi463Magnesium 2; catalyticPROSITE-ProRule annotation1
Binding sitei507ATPBy similarity1
Binding sitei1034ATPBy similarity1
Binding sitei1156ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi419 – 424ATPBy similarity6
Nucleotide bindingi461 – 463ATPBy similarity3
Nucleotide bindingi1109 – 1111ATPBy similarity3
Nucleotide bindingi1116 – 1120ATPBy similarity5

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

cAMP biosynthesis

Keywords - Ligandi

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

Enzyme and pathway databases

BioCyciZFISH:HS08079-MONOMER.
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-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-442720. CREB phosphorylation through the activation of Adenylate Cyclase.
R-HSA-5610787. Hedgehog 'off' state.
SIGNORiP40145.

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 VIII1 Publication
Adenylyl cyclase 8
Short name:
AC8
Ca(2+)/calmodulin-activated adenylyl cyclase
Gene namesi
Name:ADCY8
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:239. ADCY8.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 182CytoplasmicSequence analysisAdd BLAST182
Transmembranei183 – 203HelicalSequence analysisAdd BLAST21
Transmembranei212 – 232HelicalSequence analysisAdd BLAST21
Transmembranei247 – 267HelicalSequence analysisAdd BLAST21
Transmembranei274 – 294HelicalSequence analysisAdd BLAST21
Transmembranei296 – 316HelicalSequence analysisAdd BLAST21
Transmembranei321 – 341HelicalSequence analysisAdd BLAST21
Topological domaini342 – 715CytoplasmicSequence analysisAdd BLAST374
Transmembranei716 – 736HelicalSequence analysisAdd BLAST21
Transmembranei738 – 758HelicalSequence analysisAdd BLAST21
Transmembranei787 – 807HelicalSequence analysisAdd BLAST21
Transmembranei831 – 851HelicalSequence analysisAdd BLAST21
Transmembranei861 – 881HelicalSequence analysisAdd BLAST21
Transmembranei894 – 914HelicalSequence analysisAdd BLAST21
Topological domaini915 – 1251CytoplasmicSequence analysisAdd BLAST337

GO - Cellular componenti

  • integral component of membrane Source: UniProtKB-KW
  • intracellular Source: GOC
  • membrane Source: ProtInc
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi114.
OpenTargetsiENSG00000155897.
PharmGKBiPA29.

Chemistry databases

ChEMBLiCHEMBL2097167.

Polymorphism and mutation databases

BioMutaiADCY8.
DMDMi729242.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001957051 – 1251Adenylate cyclase type 8Add BLAST1251

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei55Omega-N-methylarginineBy similarity1
Modified residuei614PhosphoserineBy similarity1
Modified residuei624PhosphoserineBy similarity1
Glycosylationi817N-linked (GlcNAc...)Sequence analysis1
Glycosylationi821N-linked (GlcNAc...)Sequence analysis1
Glycosylationi888N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Glycoprotein, Methylation, Phosphoprotein

Proteomic databases

EPDiP40145.
PaxDbiP40145.
PeptideAtlasiP40145.
PRIDEiP40145.

PTM databases

iPTMnetiP40145.
PhosphoSitePlusiP40145.

Expressioni

Tissue specificityi

Detected in brain cortex.1 Publication

Gene expression databases

BgeeiENSG00000155897.
CleanExiHS_ADCY8.
ExpressionAtlasiP40145. baseline and differential.
GenevisibleiP40145. HS.

Organism-specific databases

HPAiCAB018652.
HPA024291.

Interactioni

Protein-protein interaction databases

BioGridi106627. 3 interactors.
IntActiP40145. 1 interactor.
STRINGi9606.ENSP00000286355.

Structurei

3D structure databases

ProteinModelPortaliP40145.
SMRiP40145.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

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

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

eggNOGiKOG3619. Eukaryota.
COG2114. LUCA.
GeneTreeiENSGT00760000119042.
HOGENOMiHOG000006941.
HOVERGENiHBG050458.
InParanoidiP40145.
KOiK08048.
OMAiVVLFMCM.
OrthoDBiEOG091G05JR.
PhylomeDBiP40145.
TreeFamiTF313845.

Family and domain databases

Gene3Di3.30.70.1230. 2 hits.
InterProiIPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
IPR032628. AC_N.
IPR030672. Adcy.
IPR009398. Adcy_conserved_dom.
IPR029787. Nucleotide_cyclase.
[Graphical view]
PfamiPF16214. AC_N. 1 hit.
PF06327. DUF1053. 1 hit.
PF00211. Guanylate_cyc. 2 hits.
[Graphical view]
PIRSFiPIRSF039050. Ade_cyc. 1 hit.
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

        10         20         30         40         50
MELSDVRCLT GSEELYTIHP TPPAGDGRSA SRPQRLLWQT AVRHITEQRF
60 70 80 90 100
IHGHRGGSGS GSGGSGKASD PAGGGPNHHA PQLSGDSALP LYSLGPGERA
110 120 130 140 150
HSTCGTKVFP ERSGSGSASG SGGGGDLGFL HLDCAPSNSD FFLNGGYSYR
160 170 180 190 200
GVIFPTLRNS FKSRDLERLY QRYFLGQRRK SEVVMNVLDV LTKLTLLVLH
210 220 230 240 250
LSLASAPMDP LKGILLGFFT GIEVVICALV VVRKDTTSHT YLQYSGVVTW
260 270 280 290 300
VAMTTQILAA GLGYGLLGDG IGYVLFTLFA TYSMLPLPLT WAILAGLGTS
310 320 330 340 350
LLQVILQVVI PRLAVISINQ VVAQAVLFMC MNTAGIFISY LSDRAQRQAF
360 370 380 390 400
LETRRCVEAR LRLETENQRQ ERLVLSVLPR FVVLEMINDM TNVEDEHLQH
410 420 430 440 450
QFHRIYIHRY ENVSILFADV KGFTNLSTTL SAQELVRMLN ELFARFDRLA
460 470 480 490 500
HEHHCLRIKI LGDCYYCVSG LPEPRQDHAH CCVEMGLSMI KTIRYVRSRT
510 520 530 540 550
KHDVDMRIGI HSGSVLCGVL GLRKWQFDVW SWDVDIANKL ESGGIPGRIH
560 570 580 590 600
ISKATLDCLN GDYNVEEGHG KERNEFLRKH NIETYLIKQP EDSLLSLPED
610 620 630 640 650
IVKESVSSSD RRNSGATFTE GSWSPELPFD NIVGKQNTLA ALTRNSINLL
660 670 680 690 700
PNHLAQALHV QSGPEEINKR IEHTIDLRSG DKLRREHIKP FSLMFKDSSL
710 720 730 740 750
EHKYSQMRDE VFKSNLVCAF IVLLFITAIQ SLLPSSRVMP MTIQFSILIM
760 770 780 790 800
LHSALVLITT AEDYKCLPLI LRKTCCWINE TYLARNVIIF ASILINFLGA
810 820 830 840 850
ILNILWCDFD KSIPLKNLTF NSSAVFTDIC SYPEYFVFTG VLAMVTCAVF
860 870 880 890 900
LRLNSVLKLA VLLIMIAIYA LLTETVYAGL FLRYDNLNHS GEDFLGTKEV
910 920 930 940 950
SLLLMAMFLL AVFYHGQQLE YTARLDFLWR VQAKEEINEM KELREHNENM
960 970 980 990 1000
LRNILPSHVA RHFLEKDRDN EELYSQSYDA VGVMFASIPG FADFYSQTEM
1010 1020 1030 1040 1050
NNQGVECLRL LNEIIADFDE LLGEDRFQDI EKIKTIGSTY MAVSGLSPEK
1060 1070 1080 1090 1100
QQCEDKWGHL CALADFSLAL TESIQEINKH SFNNFELRIG ISHGSVVAGV
1110 1120 1130 1140 1150
IGAKKPQYDI WGKTVNLASR MDSTGVSGRI QVPEETYLIL KDQGFAFDYR
1160 1170 1180 1190 1200
GEIYVKGISE QEGKIKTYFL LGRVQPNPFI LPPRRLPGQY SLAAVVLGLV
1210 1220 1230 1240 1250
QSLNRQRQKQ LLNENNNTGI IKGHYNRRTL LSPSGTEPGA QAEGTDKSDL

P
Length:1,251
Mass (Da):140,122
Last modified:February 1, 1995 - v1
Checksum:iABF25C40493E07C3
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02918880A → T.Corresponds to variant rs2228949dbSNPEnsembl.1
Natural variantiVAR_036328881F → L in a colorectal cancer sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z35309 mRNA. Translation: CAA84552.1.
M83533 mRNA. Translation: AAA35523.2.
CCDSiCCDS6363.1.
PIRiPQ0227.
S48687.
RefSeqiNP_001106.1. NM_001115.2.
UniGeneiHs.591859.

3D structure databases

ProteinModelPortaliP40145.
SMRiP40145.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106627. 3 interactors.
IntActiP40145. 1 interactor.
STRINGi9606.ENSP00000286355.

Chemistry databases

ChEMBLiCHEMBL2097167.

PTM databases

iPTMnetiP40145.
PhosphoSitePlusiP40145.

Polymorphism and mutation databases

BioMutaiADCY8.
DMDMi729242.

Proteomic databases

EPDiP40145.
PaxDbiP40145.
PeptideAtlasiP40145.
PRIDEiP40145.

Protocols and materials databases

DNASUi114.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000286355; ENSP00000286355; ENSG00000155897.
GeneIDi114.
KEGGihsa:114.
UCSCiuc003ytd.5. human.

Organism-specific databases

CTDi114.
DisGeNETi114.
GeneCardsiADCY8.
HGNCiHGNC:239. ADCY8.
HPAiCAB018652.
HPA024291.
MIMi103070. gene.
neXtProtiNX_P40145.
OpenTargetsiENSG00000155897.
PharmGKBiPA29.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3619. Eukaryota.
COG2114. LUCA.
GeneTreeiENSGT00760000119042.
HOGENOMiHOG000006941.
HOVERGENiHBG050458.
InParanoidiP40145.
KOiK08048.
OMAiVVLFMCM.
OrthoDBiEOG091G05JR.
PhylomeDBiP40145.
TreeFamiTF313845.

Enzyme and pathway databases

BioCyciZFISH:HS08079-MONOMER.
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-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-442720. CREB phosphorylation through the activation of Adenylate Cyclase.
R-HSA-5610787. Hedgehog 'off' state.
SIGNORiP40145.

Miscellaneous databases

ChiTaRSiADCY8. human.
GeneWikiiADCY8.
GenomeRNAii114.
PROiP40145.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000155897.
CleanExiHS_ADCY8.
ExpressionAtlasiP40145. baseline and differential.
GenevisibleiP40145. HS.

Family and domain databases

Gene3Di3.30.70.1230. 2 hits.
InterProiIPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
IPR032628. AC_N.
IPR030672. Adcy.
IPR009398. Adcy_conserved_dom.
IPR029787. Nucleotide_cyclase.
[Graphical view]
PfamiPF16214. AC_N. 1 hit.
PF06327. DUF1053. 1 hit.
PF00211. Guanylate_cyc. 2 hits.
[Graphical view]
PIRSFiPIRSF039050. Ade_cyc. 1 hit.
SMARTiSM00044. CYCc. 2 hits.
[Graphical view]
SUPFAMiSSF55073. SSF55073. 2 hits.
PROSITEiPS00452. GUANYLATE_CYCLASE_1. 2 hits.
PS50125. GUANYLATE_CYCLASE_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

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: November 2, 2016
This is version 154 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.