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Protein

Adenylate cyclase type 1

Gene

ADCY1

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the formation of the signaling molecule cAMP in response to G-protein signaling (PubMed:2472670, PubMed:2022671. PubMed:19029295). Mediates responses to increased cellular Ca2+/calmodulin levels (PubMed:2022671, PubMed:19029295). May be involved in regulatory processes in the central nervous system. May play a role in memory and learning. Plays a role in the regulation of the circadian rhythm of daytime contrast sensitivity probably by modulating the rhythmic synthesis of cyclic AMP in the retina (By similarity).By similarity3 Publications

Catalytic activityi

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

Cofactori

Mg2+1 Publication, Mn2+1 PublicationNote: Binds 2 magnesium ions per subunit. Is also active with manganese (in vitro).By similarity

Enzyme regulationi

Activated by calcium/calmodulin (PubMed:2022671, PubMed:19029295). Activated by forskolin (PubMed:2472670). Activated by the G protein alpha subunit GNAS (PubMed:2022671). Inhibited by the G protein beta and gamma subunit complex (PubMed:2022671). Inhibited by the ATP analogs adenosine, 2'-deoxyadenosine and 2'-deoxy-3'-AMP (PubMed:2022671).3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi310 – 3101Magnesium 1; catalyticPROSITE-ProRule annotation
Metal bindingi310 – 3101Magnesium 2; catalyticPROSITE-ProRule annotation
Metal bindingi311 – 3111Magnesium 2; via carbonyl oxygen; catalyticPROSITE-ProRule annotation
Metal bindingi354 – 3541Magnesium 1; catalyticPROSITE-ProRule annotation
Metal bindingi354 – 3541Magnesium 2; catalyticPROSITE-ProRule annotation
Binding sitei398 – 3981ATPBy similarity
Binding sitei923 – 9231ATPBy similarity
Binding sitei1047 – 10471ATPBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi310 – 3156ATPBy similarity
Nucleotide bindingi352 – 3543ATPBy similarity
Nucleotide bindingi1000 – 10023ATPBy similarity
Nucleotide bindingi1007 – 10115ATPBy similarity

GO - Molecular functioni

GO - Biological processi

  • adenylate cyclase-activating G-protein coupled receptor signaling pathway Source: UniProtKB
  • adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway Source: GO_Central
  • cAMP biosynthetic process Source: UniProtKB
  • cAMP-mediated signaling Source: UniProtKB
  • cellular response to calcium ion Source: UniProtKB
  • cellular response to forskolin Source: UniProtKB
  • regulation of circadian rhythm Source: UniProtKB
  • rhythmic process Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Lyase

Keywords - Biological processi

Biological rhythms, cAMP biosynthesis

Keywords - Ligandi

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

Enzyme and pathway databases

BRENDAi4.6.1.1. 908.

Names & Taxonomyi

Protein namesi
Recommended name:
Adenylate cyclase type 1 (EC:4.6.1.13 Publications)
Alternative name(s):
ATP pyrophosphate-lyase 1
Adenylate cyclase type I
Adenylyl cyclase 1Curated
Short name:
AC11 Publication
Ca(2+)/calmodulin-activated adenylyl cyclaseCurated
Gene namesi
Name:ADCY1
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Unplaced

Subcellular locationi

  • Membrane 2 Publications; Multi-pass membrane protein 2 Publications
  • Cell membrane 2 Publications; Multi-pass membrane protein 1 Publication
  • Cytoplasm By similarity
  • Membrane raft 1 Publication

  • Note: Expressed in the cytoplasm of supporting cells and hair cells of the cochlea vestibule, as well as to the cochlear hair cell nuclei and stereocilia.By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 6565CytoplasmicSequence analysisAdd
BLAST
Transmembranei66 – 8621HelicalSequence analysisAdd
BLAST
Transmembranei90 – 11021HelicalSequence analysisAdd
BLAST
Transmembranei127 – 14721HelicalSequence analysisAdd
BLAST
Transmembranei154 – 17421HelicalSequence analysisAdd
BLAST
Transmembranei184 – 20421HelicalSequence analysisAdd
BLAST
Transmembranei216 – 23621HelicalSequence analysisAdd
BLAST
Topological domaini237 – 612376CytoplasmicSequence analysisAdd
BLAST
Transmembranei613 – 63321HelicalSequence analysisAdd
BLAST
Transmembranei637 – 65721HelicalSequence analysisAdd
BLAST
Transmembranei676 – 69621HelicalSequence analysisAdd
BLAST
Topological domaini697 – 72630ExtracellularSequence analysisAdd
BLAST
Transmembranei727 – 74721HelicalSequence analysisAdd
BLAST
Transmembranei755 – 77521HelicalSequence analysisAdd
BLAST
Transmembranei777 – 79721HelicalSequence analysisAdd
BLAST
Topological domaini798 – 1134337CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • membrane raft Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi503 – 5031F → A: Impairs interaction with CALM and responses to Ca(2+)/calmodulin. 1 Publication

Chemistry

ChEMBLiCHEMBL3549.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11341134Adenylate cyclase type 1PRO_0000195681Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei553 – 5531PhosphoserineBy similarity
Glycosylationi706 – 7061N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PaxDbiP19754.
PRIDEiP19754.

PTM databases

iPTMnetiP19754.

Expressioni

Tissue specificityi

Detected in brain cortex (at protein level). Detected in brain.1 Publication

Interactioni

Subunit structurei

Interacts with CALM.1 Publication

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000012528.

Chemistry

BindingDBiP19754.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1AWKmodel-A295-1058[»]
ProteinModelPortaliP19754.
SMRiP19754. Positions 290-479, 862-1057.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini305 – 432128Guanylate cyclase 1PROSITE-ProRule annotationAdd
BLAST
Domaini871 – 1013143Guanylate cyclase 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni495 – 52228Interaction with calmodulinCuratedAdd
BLAST
Regioni1027 – 105024Interaction with calmodulinBy similarityAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi3 – 3432Gly-richAdd
BLAST

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.
HOGENOMiHOG000006941.
HOVERGENiHBG050458.
InParanoidiP19754.
KOiK08041.

Family and domain databases

Gene3Di3.30.70.1230. 2 hits.
InterProiIPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
IPR032628. AC_N.
IPR030672. Adcy.
IPR029787. Nucleotide_cyclase.
[Graphical view]
PfamiPF16214. AC_N. 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.

P19754-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAGAPRGRGG GGGGGGAGES GGAERAAGPG GRRGLRACDE EFACPELEAL
60 70 80 90 100
FRGYTLRLEQ AATLKALAVL SLLAGALALA ELLGAPGPAP GLAKGSHPVH
110 120 130 140 150
CVLFLALLVV TNVRSLQVPQ LQQVGQLALL FSLTFALLCC PFALGGPAGA
160 170 180 190 200
HAGAAAVPAT ADQGVWQLLL VTFVSYALLP VRSLLAIGFG LVVAASHLLV
210 220 230 240 250
TATLVPAKRP RLWRTLGANA LLFLGVNVYG IFVRILAERA QRKAFLQARN
260 270 280 290 300
CIEDRLRLED ENEKQERLLM SLLPRNVAME MKEDFLKPPE RIFHKIYIQR
310 320 330 340 350
HDNVSILFAD IVGFTGLASQ CTAQELVKLL NELFGKFDEL ATENHCRRIK
360 370 380 390 400
ILGDCYYCVS GLTQPKTDHA HCCVEMGLDM IDTITSVAEA TEVDLNMRVG
410 420 430 440 450
LHTGRVLCGV LGLRKWQYDV WSNDVTLANV MEAAGLPGKV HITKTTLACL
460 470 480 490 500
NGDYEVEPGH GHERNSFLKT HNIETFFIVP SHRRKIFPGL ILSDIKPAKR
510 520 530 540 550
MKFKTVCYLL VQLMHCRKMF KAEIPFSNVM TCEDDDKRRA LRTASEKLRN
560 570 580 590 600
RSSFSTNVVQ TTPGTRVNRY IGRLLEARQM ELEMADLNFF TLKYKQAERE
610 620 630 640 650
RKYHQLQDEY FTSAVVLALI LAALFGLVYL LIIPQSVAVL LLLVFCICFL
660 670 680 690 700
VACVLYLHIT RVQCFPGCLT IQIRTVLCIF IVVLIYSVAQ GCVVGCLPWS
710 720 730 740 750
WSSSPNGSLV VLSSGGRDPV LPVPPCESAP HALLCGLVGT LPLAIFLRVS
760 770 780 790 800
SLPKMILLAV LTTSYILVLE LSGYTKAMGA GAISGRSFEP IMAILLFSCT
810 820 830 840 850
LALHARQVDV KLRLDYLWAA QAEEERDDME KVKLDNKRIL FNLLPAHVAQ
860 870 880 890 900
HFLMSNPRNM DLYYQSYSQV GVMFASIPNF NDFYIELDGN NMGVECLRLL
910 920 930 940 950
NEIIADFDEL MDKDFYKDLE KIKTIGSTYM AAVGLAPTAG TKAKKCISSH
960 970 980 990 1000
LSTLADFAIE MFDVLDEINY QSYNDFVLRV GINVGPVVAG VIGARRPQYD
1010 1020 1030 1040 1050
IWGNTVNVAS RMDSTGVQGR IQVTEEVHRL LRRGSYRFVC RGKVSVKGKG
1060 1070 1080 1090 1100
EMLTYFLEGR TDGNGSQTRS LNSERKMYPF GRAGLQTRLA AGHPPVPPAA
1110 1120 1130
GLPVGAGPGA LQGSGLAPGP PGQHLPPGAS GKEA
Length:1,134
Mass (Da):123,979
Last modified:February 1, 1991 - v1
Checksum:iCC4A10BCE224DFF3
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M25579 mRNA. Translation: AAA79957.1.
PIRiA41350.
RefSeqiNP_776654.1. NM_174229.2.
UniGeneiBt.517.

Genome annotation databases

GeneIDi281601.
KEGGibta:281601.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M25579 mRNA. Translation: AAA79957.1.
PIRiA41350.
RefSeqiNP_776654.1. NM_174229.2.
UniGeneiBt.517.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1AWKmodel-A295-1058[»]
ProteinModelPortaliP19754.
SMRiP19754. Positions 290-479, 862-1057.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9913.ENSBTAP00000012528.

Chemistry

BindingDBiP19754.
ChEMBLiCHEMBL3549.

PTM databases

iPTMnetiP19754.

Proteomic databases

PaxDbiP19754.
PRIDEiP19754.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi281601.
KEGGibta:281601.

Organism-specific databases

CTDi107.

Phylogenomic databases

eggNOGiKOG3619. Eukaryota.
COG2114. LUCA.
HOGENOMiHOG000006941.
HOVERGENiHBG050458.
InParanoidiP19754.
KOiK08041.

Enzyme and pathway databases

BRENDAi4.6.1.1. 908.

Miscellaneous databases

PROiP19754.

Family and domain databases

Gene3Di3.30.70.1230. 2 hits.
InterProiIPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
IPR032628. AC_N.
IPR030672. Adcy.
IPR029787. Nucleotide_cyclase.
[Graphical view]
PfamiPF16214. AC_N. 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...

Publicationsi

  1. "Adenylyl cyclase amino acid sequence: possible channel- or transporter-like structure."
    Krupinski J., Coussen F., Bakalyar H.A., Tang W.-J., Feinstein P.G., Orth K., Slaughter C., Reed R.R., Gilman A.G.
    Science 244:1558-1564(1989) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, CATALYTIC ACTIVITY, ENZYME REGULATION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
    Tissue: Brain.
  2. "Expression and characterization of calmodulin-activated (type I) adenylylcyclase."
    Tang W.J., Krupinski J., Gilman A.G.
    J. Biol. Chem. 266:8595-8603(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, ENZYME REGULATION, GLYCOSYLATION.
  3. "Distinct mechanisms of regulation by Ca2+/calmodulin of type 1 and 8 adenylyl cyclases support their different physiological roles."
    Masada N., Ciruela A., Macdougall D.A., Cooper D.M.
    J. Biol. Chem. 284:4451-4463(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, ENZYME REGULATION, MUTAGENESIS OF PHE-503, INTERACTION WITH CALM.
  4. "Catalytic mechanism of the adenylyl and guanylyl cyclases: modeling and mutational analysis."
    Liu Y., Ruoho A.E., Rao V.D., Hurley J.H.
    Proc. Natl. Acad. Sci. U.S.A. 94:13414-13419(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: 3D-STRUCTURE MODELING OF 295-450; 861-936 AND 950-1045.

Entry informationi

Entry nameiADCY1_BOVIN
AccessioniPrimary (citable) accession number: P19754
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 1, 1991
Last modified: June 8, 2016
This is version 131 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. 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.