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Q08462 (ADCY2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 138. 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 2

EC=4.6.1.1
Alternative name(s):
ATP pyrophosphate-lyase 2
Adenylate cyclase type II
Adenylyl cyclase 2
Gene names
Name:ADCY2
Synonyms:KIAA1060
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1091 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

This is a membrane-bound, calmodulin-insensitive adenylyl cyclase.

Catalytic activity

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

Cofactor

Binds 2 magnesium ions per subunit By similarity.

Enzyme regulation

Insensitive to calcium/calmodulin. Stimulated by the G protein beta and gamma subunit complex By similarity. Phosphorylation by RAF1 results in its activation. Ref.6

Subunit structure

Interacts with RAF1. Ref.6

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Expressed in brain.

Post-translational modification

Phosphorylated by RAF1. Ref.6

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
Phosphoprotein
   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

adenylate cyclase-modulating G-protein coupled receptor signaling pathway

Inferred from sequence or structural similarity. Source: BHF-UCL

cAMP biosynthetic process

Inferred from sequence or structural similarity. Source: BHF-UCL

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

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_componentcytoplasm

Inferred from direct assay PubMed 11549699. Source: UniProtKB

dendrite

Inferred from sequence or structural similarity. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

intracellular

Inferred from sequence or structural similarity. Source: BHF-UCL

membrane

Inferred from sequence or structural similarity. Source: UniProtKB

membrane raft

Inferred from sequence or structural similarity. Source: BHF-UCL

plasma membrane

Inferred from direct assay PubMed 11549699. Source: UniProtKB

protein complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

adenylate cyclase activity

Non-traceable author statement Ref.4. Source: UniProtKB

adenylate cyclase binding

Inferred from sequence or structural similarity. Source: BHF-UCL

calcium- and calmodulin-responsive adenylate cyclase activity

Inferred from electronic annotation. Source: Ensembl

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein heterodimerization activity

Inferred from sequence or structural similarity. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 10911091Adenylate cyclase type 2
PRO_0000195684

Regions

Topological domain1 – 4545Cytoplasmic Potential
Transmembrane46 – 6621Helical; Potential
Transmembrane76 – 9621Helical; Potential
Transmembrane108 – 12821Helical; Potential
Transmembrane133 – 15321Helical; Potential
Transmembrane159 – 17921Helical; Potential
Transmembrane187 – 20721Helical; Potential
Topological domain208 – 601394Cytoplasmic Potential
Transmembrane602 – 62221Helical; Potential
Transmembrane628 – 65225Helical; Potential
Transmembrane680 – 70122Helical; Potential
Transmembrane734 – 75522Helical; Potential
Transmembrane763 – 78018Helical; Potential
Transmembrane801 – 82121Helical; Potential
Topological domain822 – 1091270Cytoplasmic Potential

Sites

Metal binding2951Magnesium 1 By similarity
Metal binding2951Magnesium 2 By similarity
Metal binding2961Magnesium 2; via carbonyl oxygen By similarity
Metal binding3391Magnesium 1 By similarity
Metal binding3391Magnesium 2 By similarity

Amino acid modifications

Glycosylation7131N-linked (GlcNAc...) Potential
Glycosylation7161N-linked (GlcNAc...) Potential

Natural variations

Natural variant1471V → L. Ref.2
Corresponds to variant rs13166360 [ dbSNP | Ensembl ].
VAR_029012
Natural variant1631V → I.
Corresponds to variant rs34043481 [ dbSNP | Ensembl ].
VAR_048247

Experimental info

Sequence conflict188 – 20720VWQIL…LAGAY → GLADPGQCDHFHLWEPGXTN in AAP97285. Ref.1
Sequence conflict6751R → Q in CAA52282. Ref.4
Sequence conflict6751R → Q in AAA64923. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Q08462 [UniParc].

Last modified November 28, 2006. Version 5.
Checksum: 41FD8BC607C075D1

FASTA1,091123,603
        10         20         30         40         50         60 
MWQEAMRRRR YLRDRSEEAA GGGDGLPRSR DWLYESYYCM SQQHPLIVFL LLIVMGSCLA 

        70         80         90        100        110        120 
LLAVFFALGL EVEDHVAFLI TVPTALAIFF AIFILVCIES VFKKLLRLFS LVIWICLVAM 

       130        140        150        160        170        180 
GYLFMCFGGT VSPWDQVSFF LFIIFVVYTM LPFNMRDAII ASVLTSSSHT IVLSVCLSAT 

       190        200        210        220        230        240 
PGGKEHLVWQ ILANVIIFIC GNLAGAYHKH LMELALQQTY QDTCNCIKSR IKLEFEKRQQ 

       250        260        270        280        290        300 
ERLLLSLLPA HIAMEMKAEI IQRLQGPKAG QMENTNNFHN LYVKRHTNVS ILYADIVGFT 

       310        320        330        340        350        360 
RLASDCSPGE LVHMLNELFG KFDQIAKENE CMRIKILGDC YYCVSGLPIS LPNHAKNCVK 

       370        380        390        400        410        420 
MGLDMCEAIK KVRDATGVDI NMRVGVHSGN VLCGVIGLQK WQYDVWSHDV TLANHMEAGG 

       430        440        450        460        470        480 
VPGRVHISSV TLEHLNGAYK VEEGDGDIRD PYLKQHLVKT YFVINPKGER RSPQHLFRPR 

       490        500        510        520        530        540 
HTLDGAKMRA SVRMTRYLES WGAAKPFAHL HHRDSMTTEN GKISTTDVPM GQHNFQNRTL 

       550        560        570        580        590        600 
RTKSQKKRFE EELNERMIQA IDGINAQKQW LKSEDIQRIS LLFYNKVLEK EYRATALPAF 

       610        620        630        640        650        660 
KYYVTCACLI FFCIFIVQIL VLPKTSVLGI SFGAAFLLLA FILFVCFAGQ LLQCSKKASP 

       670        680        690        700        710        720 
LLMWLLKSSG IIANRPWPRI SLTIITTAII LMMAVFNMFF LSDSEETIPP TANTTNTSFS 

       730        740        750        760        770        780 
ASNNQVAILR AQNLFFLPYF IYSCILGLIS CSVFLRVNYE LKMLIMMVAL VGYNTILLHT 

       790        800        810        820        830        840 
HAHVLGDYSQ VLFERPGIWK DLKTMGSVSL SIFFITLLVL GRQNEYYCRL DFLWKNKFKK 

       850        860        870        880        890        900 
EREEIETMEN LNRVLLENVL PAHVAEHFLA RSLKNEELYH QSYDCVCVMF ASIPDFKEFY 

       910        920        930        940        950        960 
TESDVNKEGL ECLRLLNEII ADFDDLLSKP KFSGVEKIKT IGSTYMAATG LSAVPSQEHS 

       970        980        990       1000       1010       1020 
QEPERQYMHI GTMVEFAFAL VGKLDAINKH SFNDFKLRVG INHGPVIAGV IGAQKPQYDI 

      1030       1040       1050       1060       1070       1080 
WGNTVNVASR MDSTGVLDKI QVTEETSLVL QTLGYTCTCR GIINVKGKGD LKTYFVNTEM 

      1090 
SRSLSQSNVA S 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning of human adenylyl cyclase gene."
Guo J.H., Yu L.
Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LEU-147.
[3]"Prediction of the coding sequences of unidentified human genes. XIV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 6:197-205(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 205-1091.
Tissue: Brain.
[4]"Different chromosomal localization of two adenylyl cyclase genes expressed in human brain."
Stengel D., Parma J., Gannage M.-H., Roeckel N., Mattei M.-G., Barouki R., Hanoune J.
Hum. Genet. 90:126-130(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 616-1091.
Tissue: Brain.
[5]"A novel adenylyl cyclase sequence cloned from the human erythroleukemia cell line."
Hellevuo K., Yoshimura M., Kao M., Hoffman P.L., Cooper D.M.F., Tabakoff B.
Biochem. Biophys. Res. Commun. 192:311-318(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 948-1017.
[6]"Raf kinase activation of adenylyl cyclases: isoform-selective regulation."
Ding Q., Gros R., Gray I.D., Taussig R., Ferguson S.S., Feldman R.D.
Mol. Pharmacol. 66:921-928(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY RAF1, INTERACTION WITH RAF1, ENZYME REGULATION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF410885 mRNA. Translation: AAP97285.1.
BC111743 mRNA. Translation: AAI11744.1.
AB028983 mRNA. Translation: BAA83012.1.
X74210 mRNA. Translation: CAA52282.1.
L21993 mRNA. Translation: AAA64923.1.
PIRI37136.
RefSeqNP_065433.2. NM_020546.2.
UniGeneHs.481545.

3D structure databases

ProteinModelPortalQ08462.
SMRQ08462. Positions 278-464, 879-1078.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106622. 2 interactions.
DIPDIP-422N.
STRING9606.ENSP00000342952.

Chemistry

BindingDBQ08462.
ChEMBLCHEMBL2097167.

PTM databases

PhosphoSiteQ08462.

Polymorphism databases

DMDM118572617.

Proteomic databases

PaxDbQ08462.
PRIDEQ08462.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000338316; ENSP00000342952; ENSG00000078295.
GeneID108.
KEGGhsa:108.
UCSCuc003jdz.1. human.

Organism-specific databases

CTD108.
GeneCardsGC05P007449.
HGNCHGNC:233. ADCY2.
HPACAB031482.
HPA038015.
HPA038483.
MIM103071. gene.
neXtProtNX_Q08462.
PharmGKBPA24561.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2114.
HOGENOMHOG000006941.
HOVERGENHBG050458.
InParanoidQ08462.
KOK08042.
OMAFLPYFIY.
OrthoDBEOG76X5ZC.
PhylomeDBQ08462.
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

ArrayExpressQ08462.
BgeeQ08462.
CleanExHS_ADCY2.
GenevestigatorQ08462.

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

ChiTaRSADCY2. human.
GeneWikiADCY2.
GenomeRNAi108.
NextBio419.
PROQ08462.
SOURCESearch...

Entry information

Entry nameADCY2_HUMAN
AccessionPrimary (citable) accession number: Q08462
Secondary accession number(s): Q2NKL8, Q9UDB2, Q9UPU2
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: November 28, 2006
Last modified: April 16, 2014
This is version 138 of the entry and version 5 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 5

Human chromosome 5: entries, gene names and cross-references to MIM