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O60503 (ADCY9_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 125. 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 9

EC=4.6.1.1
Alternative name(s):
ATP pyrophosphate-lyase 9
Adenylate cyclase type IX
Adenylyl cyclase 9
Gene names
Name:ADCY9
Synonyms:KIAA0520
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1353 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May play a fundamental role in situations where fine interplay between intracellular calcium and cAMP determines the cellular function. May be a physiologically relevant docking site for calcineurin By similarity.

Catalytic activity

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

Cofactor

Binds 2 magnesium ions per subunit.

Enzyme regulation

Insensitive to calcium/calmodulin, forskolin and somatostatin. Stimulated by beta-adrenergic receptor activation.

Subcellular location

Membrane; Multi-pass membrane protein.

Tissue specificity

Expressed in multiple cells of the lung, with expression highest in airway smooth muscle. Ref.2

Sequence similarities

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

Contains 2 guanylate cyclase domains.

Sequence caution

The sequence AAC24201.1 differs from that shown. Reason: Frameshift at position 1252.

The sequence BAA25446.3 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

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

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_componentaxon

Inferred from electronic annotation. Source: Ensembl

dendrite

Inferred from electronic annotation. Source: Ensembl

integral component of plasma membrane

Traceable author statement Ref.1. 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

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 – 13531353Adenylate cyclase type 9
PRO_0000195708

Regions

Topological domain1 – 117117Cytoplasmic Potential
Transmembrane118 – 13821Helical; Potential
Topological domain139 – 1413Extracellular Potential
Transmembrane142 – 16221Helical; Potential
Topological domain163 – 1719Cytoplasmic Potential
Transmembrane172 – 19221Helical; Potential
Topological domain193 – 21523Extracellular Potential
Transmembrane216 – 23520Helical; Potential
Topological domain236 – 2416Cytoplasmic Potential
Transmembrane242 – 25918Helical; Potential
Topological domain260 – 28021Extracellular Potential
Transmembrane281 – 30121Helical; Potential
Topological domain302 – 786485Cytoplasmic Potential
Transmembrane787 – 80721Helical; Potential
Topological domain808 – 81811Extracellular Potential
Transmembrane819 – 83921Helical; Potential
Topological domain840 – 86728Cytoplasmic Potential
Transmembrane868 – 88821Helical; Potential
Topological domain889 – 8913Extracellular Potential
Transmembrane892 – 91221Helical; Potential
Topological domain913 – 9208Cytoplasmic Potential
Transmembrane921 – 94121Helical; Potential
Topological domain942 – 97534Extracellular Potential
Transmembrane976 – 99621Helical; Potential
Topological domain997 – 1353357Cytoplasmic Potential
Domain394 – 521128Guanylate cyclase 1
Domain1058 – 1198141Guanylate cyclase 2

Sites

Metal binding3991Magnesium 1 By similarity
Metal binding3991Magnesium 2 By similarity
Metal binding4001Magnesium 2; via carbonyl oxygen By similarity
Metal binding4431Magnesium 1 By similarity
Metal binding4431Magnesium 2 By similarity

Amino acid modifications

Modified residue12591Phosphoserine Ref.11
Modified residue13071Phosphoserine Ref.12
Glycosylation2061N-linked (GlcNAc...) Potential
Glycosylation9551N-linked (GlcNAc...) Potential
Glycosylation9641N-linked (GlcNAc...) Potential

Natural variations

Natural variant7721I → M in 37.5% of the Asian population, in 30% of the Caucasian population and in 16.3% of the African-American population; reduced adenylyl cyclase activity in response to stimulation of the beta-adregnergic receptor by the agonists Mn(2+), isoproteronol and NaF; increased albuterol-stimulated adenylyl cyclase activity in the presence of corticosteroid. Ref.2 Ref.3
Corresponds to variant rs2230739 [ dbSNP | Ensembl ].
VAR_023750

Experimental info

Sequence conflict4931G → R in CAB65084. Ref.4
Sequence conflict8841V → A in CAB65084. Ref.4
Sequence conflict11541N → S in CAB65084. Ref.4
Sequence conflict11541N → S in BAA25446. Ref.6
Sequence conflict13081P → R in CAB65084. Ref.4

Sequences

Sequence LengthMass (Da)Tools
O60503 [UniParc].

Last modified December 13, 2002. Version 4.
Checksum: 4CBF051EA49B5B7B

FASTA1,353150,701
        10         20         30         40         50         60 
MASPPHQQLL HHHSTEVSCD SSGDSNSVRV KINPKQLSSN SHPKHCKYSI SSSCSSSGDS 

        70         80         90        100        110        120 
GGVPRRVGGG GRLRRQKKLP QLFERASSRW WDPKFDSVNL EEACLERCFP QTQRRFRYAL 

       130        140        150        160        170        180 
FYIGFACLLW SIYFAVHMRS RLIVMVAPAL CFLLVCVGFF LFTFTKLYAR HYAWTSLALT 

       190        200        210        220        230        240 
LLVFALTLAA QFQVLTPVSG RGDSSNLTAT ARPTDTCLSQ VGSFSMCIEV LFLLYTVMHL 

       250        260        270        280        290        300 
PLYLSLCLGV AYSVLFETFG YHFRDEACFP SPGAGALHWE LLSRGLLHGC IHAIGVHLFV 

       310        320        330        340        350        360 
MSQVRSRSTF LKVGQSIMHG KDLEVEKALK ERMIHSVMPR IIADDLMKQG DEESENSVKR 

       370        380        390        400        410        420 
HATSSPKNRK KKSSIQKAPI AFRPFKMQQI EEVSILFADI VGFTKMSANK SAHALVGLLN 

       430        440        450        460        470        480 
DLFGRFDRLC EETKCEKIST LGDCYYCVAG CPEPRADHAY CCIEMGLGMI KAIEQFCQEK 

       490        500        510        520        530        540 
KEMVNMRVGV HTGTVLCGIL GMRRFKFDVW SNDVNLANLM EQLGVAGKVH ISEATAKYLD 

       550        560        570        580        590        600 
DRYEMEDGKV IERLGQSVVA DQLKGLKTYL ISGQRAKESR CSCAEALLSG FEVIDGSQVS 

       610        620        630        640        650        660 
SGPRGQGTAS SGNVSDLAQT VKTFDNLKTC PSCGITFAPK SEAGAEGGAP QNGCQDEHKN 

       670        680        690        700        710        720 
STKASGGPNP KTQNGLLSPP QEEKLTNSQT SLCEILQEKG RWAGVSLDQS ALLPLRFKNI 

       730        740        750        760        770        780 
REKTDAHFVD VIKEDSLMKD YFFKPPINQF SLNFLDQELE RSYRTSYQEE VIKNSPVKTF 

       790        800        810        820        830        840 
ASPTFSSLLD VFLSTTVFLT LSTTCFLKYE AATVPPPPAA LAVFSAALLL EVLSLAVSIR 

       850        860        870        880        890        900 
MVFFLEDVMA CTKRLLEWIA GWLPRHCIGA ILVSLPALAV YSHVTSEYET NIHFPVFTGS 

       910        920        930        940        950        960 
AALIAVVHYC NFCQLSSWMR SSLATVVGAG PLLLLYVSLC PDSSVLTSPL DAVQNFSSER 

       970        980        990       1000       1010       1020 
NPCNSSVPRD LRRPASLIGQ EVVLVFFLLL LLVWFLNREF EVSYRLHYHG DVEADLHRTK 

      1030       1040       1050       1060       1070       1080 
IQSMRDQADW LLRNIIPYHV AEQLKVSQTY SKNHDSGGVI FASIVNFSEF YEENYEGGKE 

      1090       1100       1110       1120       1130       1140 
CYRVLNELIG DFDELLSKPD YSSIEKIKTI GATYMAASGL NTAQAQDGSH PQEHLQILFE 

      1150       1160       1170       1180       1190       1200 
FAKEMMRVVD DFNNNMLWFN FKLRVGFNHG PLTAGVIGTT KLLYDIWGDT VNIASRMDTT 

      1210       1220       1230       1240       1250       1260 
GVECRIQVSE ESYRVLSKMG YDFDYRGTVN VKGKGQMKTY LYPKCTDHRV IPQHQLSISP 

      1270       1280       1290       1300       1310       1320 
DIRVQVDGSI GRSPTDEIAN LVPSVQYVDK TSLGSDSSTQ AKDAHLSPKR PWKEPVKAEE 

      1330       1340       1350 
RGRFGKAIEK DDCDETGIEE ANELTKLNVS KSV 

« Hide

References

« Hide 'large scale' references
[1]"Cloning, chromosomal mapping, and regulatory properties of the human type 9 adenylyl cyclase (ADCY9)."
Hacker B.M., Tomlinson J.E., Wayman G.A., Sultana R., Chan G., Villacres E., Disteche C., Storm D.R.
Genomics 50:97-104(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Heart.
[2]"An Ile to Met polymorphism in the catalytic domain of adenylyl cyclase type 9 confers reduced beta2-adrenergic receptor stimulation."
Small K.M., Brown K.M., Theiss C.T., Seman C.A., Weiss S.T., Liggett S.B.
Pharmacogenetics 13:535-541(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANT MET-772.
[3]"Molecular properties and pharmacogenetics of a polymorphism of adenylyl cyclase type 9 in asthma: interaction between beta-agonist and corticosteroid pathways."
Tantisira K.G., Small K.M., Litonjua A.A., Weiss S.T., Liggett S.B.
Hum. Mol. Genet. 14:1671-1677(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT MET-772.
[4]"Cloning and characterisation of human adenylyl cyclase IX: differential mRNA regulation and inhibition by Ca2+/calcineurin."
Paterson J.M., Smith S.M., Simpson J., Grace O.C., Bell J.E., Antoni F.A.
Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]"Mutation screening, case control study and transmission disequilibrium analysis of adenylate cyclase type 9 (ADCY9) gene in functional psychoses."
Toyota T., Yamada K., Meerabux J., Hattori E., Saito K., Yoshitsugu K., Shimizu H., Nankai M., Toru M., Detera-Wadleigh S.D., Yoshikawa T.
Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]"Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:31-39(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[7]"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION.
[8]Ohara O., Nagase T., Kikuno R., Ishikawa K.
Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[9]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]"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].
[11]"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1259, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1307, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF036927 mRNA. Translation: AAC24201.1. Frameshift.
DQ008441 mRNA. Translation: AAY27880.1.
DQ005545 mRNA. Translation: AAY21237.1.
AJ133123 mRNA. Translation: CAB65084.1.
AY028959 expand/collapse EMBL AC list , AY028949, AY028950, AY028951, AY028952, AY028953, AY028954, AY028955, AY028956, AY028957 Genomic DNA. Translation: AAK29464.1.
AB011092 mRNA. Translation: BAA25446.3. Different initiation.
CH471112 Genomic DNA. Translation: EAW85331.1.
CH471112 Genomic DNA. Translation: EAW85332.1.
BC136657 mRNA. Translation: AAI36658.1.
BC136658 mRNA. Translation: AAI36659.1.
BC151207 mRNA. Translation: AAI51208.1.
RefSeqNP_001107.2. NM_001116.3.
UniGeneHs.391860.
Hs.610484.

3D structure databases

ProteinModelPortalO60503.
SMRO60503. Positions 380-572, 1050-1241.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106628. 2 interactions.
STRING9606.ENSP00000294016.

Chemistry

BindingDBO60503.
ChEMBLCHEMBL2097167.

PTM databases

PhosphoSiteO60503.

Proteomic databases

PaxDbO60503.
PRIDEO60503.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000294016; ENSP00000294016; ENSG00000162104.
GeneID115.
KEGGhsa:115.
UCSCuc002cvx.3. human.

Organism-specific databases

CTD115.
GeneCardsGC16M004003.
HGNCHGNC:240. ADCY9.
HPAHPA041328.
HPA044225.
MIM603302. gene.
neXtProtNX_O60503.
PharmGKBPA30.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2114.
HOVERGENHBG050459.
InParanoidO60503.
KOK08049.
OMAIYFGVHM.
OrthoDBEOG7TF78Q.
PhylomeDBO60503.
TreeFamTF313845.

Enzyme and pathway databases

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

ArrayExpressO60503.
BgeeO60503.
CleanExHS_ADCY9.
GenevestigatorO60503.

Family and domain databases

Gene3D3.30.70.1230. 2 hits.
InterProIPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
[Graphical view]
PfamPF00211. 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

ChiTaRSADCY9. human.
GeneWikiADCY9.
GenomeRNAi115.
NextBio445.
PROO60503.
SOURCESearch...

Entry information

Entry nameADCY9_HUMAN
AccessionPrimary (citable) accession number: O60503
Secondary accession number(s): A7E2V5 expand/collapse secondary AC list , D3DUD1, O60273, Q4ZHT9, Q4ZIR5, Q9BWT4, Q9UGP2
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: December 13, 2002
Last modified: April 16, 2014
This is version 125 of the entry and version 4 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 16

Human chromosome 16: entries, gene names and cross-references to MIM