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P40145

- ADCY8_HUMAN

UniProt

P40145 - ADCY8_HUMAN

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Protein

Adenylate cyclase type 8

Gene

ADCY8

Organism
Homo sapiens (Human)
Status
Reviewed - 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 similarityNote: 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
Complete GO annotation...

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. Vasopressin regulates renal water homeostasis via Aquaporins.
REACT_267634. Hedgehog 'off' state.

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 182182CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei183 – 20321HelicalSequence AnalysisAdd
BLAST
Transmembranei212 – 23221HelicalSequence AnalysisAdd
BLAST
Transmembranei247 – 26721HelicalSequence AnalysisAdd
BLAST
Transmembranei274 – 29421HelicalSequence AnalysisAdd
BLAST
Transmembranei296 – 31621HelicalSequence AnalysisAdd
BLAST
Transmembranei321 – 34121HelicalSequence AnalysisAdd
BLAST
Topological domaini342 – 715374CytoplasmicSequence 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
Topological domaini915 – 1251337CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

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

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

BgeeiP40145.
CleanExiHS_ADCY8.
ExpressionAtlasiP40145. baseline and differential.
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...

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.
GeneTreeiENSGT00760000119042.
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.
IPR029787. Nucleotide_cyclase.
[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

        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)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:
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.4. human.

Polymorphism databases

DMDMi729242.

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 .
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

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.
GeneTreei ENSGT00760000119042.
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. Vasopressin regulates renal water homeostasis via Aquaporins.
REACT_267634. Hedgehog 'off' state.

Miscellaneous databases

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

Gene expression databases

Bgeei P40145.
CleanExi HS_ADCY8.
ExpressionAtlasi P40145. baseline and differential.
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.
IPR029787. Nucleotide_cyclase.
[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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 136 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