Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O95622 (ADCY5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 127. 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·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Adenylate cyclase type 5

EC=4.6.1.1
Alternative name(s):
ATP pyrophosphate-lyase 5
Adenylate cyclase type V
Adenylyl cyclase 5
Gene names
Name:ADCY5
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1261 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

This is a membrane-bound, calcium-inhibitable adenylyl cyclase.

Catalytic activity

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

Cofactor

Binds 2 magnesium ions per subunit By similarity.

Enzyme regulation

Inhibition by calcium in the submicromolar concentration range By similarity. Phosphorylation by RAF1 results in its activation. Ref.5

Subunit structure

Part of a complex containing AKAP5, ADCY6, PDE4C and PKD2 By similarity. Interacts with RAF1. Ref.5

Subcellular location

Membrane; Multi-pass membrane protein. Cell projectioncilium By similarity.

Post-translational modification

Phosphorylated by RAF1. Ref.5

Involvement in disease

Dyskinesia, familial, with facial myokymia (FDFM) [MIM:606703]: A disorder characterized by predominantly perioral and periorbital myokymia, and face, neck and upper limb dystonic/choreic movements. Initially paroxysmal and worsened by stress, the dyskinetic episodes become nearly constant by the end of the third decade of life, but in some individuals, they may diminish in frequency and severity at older ages.
Note: The disease is caused by mutations affecting the gene represented in this entry. 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 componentCell projection
Cilium
Membrane
   Coding sequence diversityAlternative splicing
   DiseaseDisease mutation
   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

adenosine receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

adenylate cyclase-activating G-protein coupled receptor signaling pathway

Traceable author statement. Source: Reactome

adenylate cyclase-activating dopamine receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

Traceable author statement. Source: Reactome

adenylate cyclase-inhibiting dopamine receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

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

locomotory behavior

Inferred from electronic annotation. Source: Ensembl

neuromuscular process controlling balance

Inferred from electronic annotation. Source: Ensembl

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_componentintegral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

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

primary cilium

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

adenylate cyclase activity

Inferred from electronic annotation. Source: UniProtKB-EC

adenylate cyclase binding

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

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...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O95622-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O95622-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-28: MSGSKSVSPPGYAAQKTAAPAPRGGPEH → MKSQKEGCCSRGDLSIQTGPGGEWAPRR
     29-378: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12611261Adenylate cyclase type 5
PRO_0000195694

Regions

Topological domain1 – 195195Cytoplasmic Potential
Transmembrane196 – 21621Helical; Potential
Transmembrane242 – 26221Helical; Potential
Transmembrane268 – 28821Helical; Potential
Transmembrane299 – 31921Helical; Potential
Transmembrane325 – 34521Helical; Potential
Transmembrane374 – 39421Helical; Potential
Topological domain395 – 769375Cytoplasmic Potential
Transmembrane770 – 79021Helical; Potential
Transmembrane792 – 81221Helical; Potential
Transmembrane836 – 85621Helical; Potential
Topological domain857 – 90953Extracellular Potential
Transmembrane910 – 93021Helical; Potential
Transmembrane935 – 95521Helical; Potential
Transmembrane984 – 100421Helical; Potential
Topological domain1005 – 1261257Cytoplasmic Potential
Domain469 – 596128Guanylate cyclase 1
Domain1071 – 1210140Guanylate cyclase 2

Sites

Metal binding4741Magnesium 1 By similarity
Metal binding4741Magnesium 2 By similarity
Metal binding4751Magnesium 2; via carbonyl oxygen By similarity
Metal binding5181Magnesium 1 By similarity
Metal binding5181Magnesium 2 By similarity

Amino acid modifications

Glycosylation8701N-linked (GlcNAc...) Potential
Glycosylation8871N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence1 – 2828MSGSK…GGPEH → MKSQKEGCCSRGDLSIQTGP GGEWAPRR in isoform 2.
VSP_042914
Alternative sequence29 – 378350Missing in isoform 2.
VSP_042915
Natural variant7261A → T in FDFM. Ref.6
VAR_068821

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 28, 2006. Version 3.
Checksum: C50492A0B053694F

FASTA1,261138,908
        10         20         30         40         50         60 
MSGSKSVSPP GYAAQKTAAP APRGGPEHRS AWGEADSRAN GYPHAPGGSA RGSTKKPGGA 

        70         80         90        100        110        120 
VTPQQQQRLA SRWRSDDDDD PPLSGDDPLA GGFGFSFRSK SAWQERGGDD CGRGSRRQRR 

       130        140        150        160        170        180 
GAASGGSTRA PPAGGGGGSA AAAASAGGTE VRPRSVEVGL EERRGKGRAA DELEAGAVEG 

       190        200        210        220        230        240 
GEGSGDGGSS ADSGSGAGPG AVLSLGACCL ALLQIFRSKK FPSDKLERLY QRYFFRLNQS 

       250        260        270        280        290        300 
SLTMLMAVLV LVCLVMLAFH AARPPLQLPY LAVLAAAVGV ILIMAVLCNR AAFHQDHMGL 

       310        320        330        340        350        360 
ACYALIAVVL AVQVVGLLLP QPRSASEGIW WTVFFIYTIY TLLPVRMRAA VLSGVLLSAL 

       370        380        390        400        410        420 
HLAIALRTNA QDQFLLKQLV SNVLIFSCTN IVGVCTHYPA EVSQRQAFQE TRECIQARLH 

       430        440        450        460        470        480 
SQRENQQQER LLLSVLPRHV AMEMKADINA KQEDMMFHKI YIQKHDNVSI LFADIEGFTS 

       490        500        510        520        530        540 
LASQCTAQEL VMTLNELFAR FDKLAAENHC LRIKILGDCY YCVSGLPEAR ADHAHCCVEM 

       550        560        570        580        590        600 
GMDMIEAISL VREVTGVNVN MRVGIHSGRV HCGVLGLRKW QFDVWSNDVT LANHMEAGGK 

       610        620        630        640        650        660 
AGRIHITKAT LNYLNGDYEV EPGCGGERNA YLKEHSIETF LILRCTQKRK EEKAMIAKMN 

       670        680        690        700        710        720 
RQRTNSIGHN PPHWGAERPF YNHLGGNQVS KEMKRMGFED PKDKNAQESA NPEDEVDEFL 

       730        740        750        760        770        780 
GRAIDARSID RLRSEHVRKF LLTFREPDLE KKYSKQVDDR FGAYVACASL VFLFICFVQI 

       790        800        810        820        830        840 
TIVPHSIFML SFYLTCSLLL TLVVFVSVIY SCVKLFPSPL QTLSRKIVRS KMNSTLVGVF 

       850        860        870        880        890        900 
TITLVFLAAF VNMFTCNSRD LLGCLAQEHN ISASQVNACH VAESAVNYSL GDEQGFCGSP 

       910        920        930        940        950        960 
WPNCNFPEYF TYSVLLSLLA CSVFLQISCI GKLVLMLAIE LIYVLIVEVP GVTLFDNADL 

       970        980        990       1000       1010       1020 
LVTANAIDFF NNGTSQCPEH ATKVALKVVT PIIISVFVLA LYLHAQQVES TARLDFLWKL 

      1030       1040       1050       1060       1070       1080 
QATEEKEEME ELQAYNRRLL HNILPKDVAA HFLARERRND ELYYQSCECV AVMFASIANF 

      1090       1100       1110       1120       1130       1140 
SEFYVELEAN NEGVECLRLL NEIIADFDEI ISEDRFRQLE KIKTIGSTYM AASGLNDSTY 

      1150       1160       1170       1180       1190       1200 
DKVGKTHIKA LADFAMKLMD QMKYINEHSF NNFQMKIGLN IGPVVAGVIG ARKPQYDIWG 

      1210       1220       1230       1240       1250       1260 
NTVNVASRMD STGVPDRIQV TTDMYQVLAA NTYQLECRGV VKVKGKGEMM TYFLNGGPPL 


S 

« Hide

Isoform 2 [UniParc].

Checksum: CA9E766B744A6222
Show »

FASTA911102,606

References

« Hide 'large scale' references
[1]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Testis.
[2]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"Characterization of the human adenylyl cyclase gene family: cDNA, gene structure, and tissue distribution of the nine isoforms."
Ludwig M.G., Seuwen K.
J. Recept. Signal Transduct. 22:79-110(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 368-1261 (ISOFORM 1).
Tissue: Heart.
[4]"Cloning and sequence of partial cDNAs encoding the human type V and VI adenylyl cyclases and subsequent RNA-quantification in various tissues."
Raimundo S., Giray J., Volff J.-N., Schwab M., Altenbuchner J., Ratge D., Wisser H.
Clin. Chim. Acta 285:155-161(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 560-664 (ISOFORM 1).
Tissue: Heart muscle.
[5]"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.
[6]"Autosomal dominant familial dyskinesia and facial myokymia: single exome sequencing identifies a mutation in adenylyl cyclase 5."
Chen Y.Z., Matsushita M.M., Robertson P., Rieder M., Girirajan S., Antonacci F., Lipe H., Eichler E.E., Nickerson D.A., Bird T.D., Raskind W.H.
Arch. Neurol. 69:630-635(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT FDFM THR-726.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK303070 mRNA. Translation: BAH13892.1.
AC025571 Genomic DNA. No translation available.
AC112503 Genomic DNA. No translation available.
AF497517 mRNA. Translation: AAM94374.1.
U65473 mRNA. Translation: AAD00121.1.
BK000371 mRNA. Translation: DAA00057.1.
RefSeqNP_001186571.1. NM_001199642.1.
NP_899200.1. NM_183357.2.
UniGeneHs.593292.

3D structure databases

ProteinModelPortalO95622.
SMRO95622. Positions 454-643, 1064-1255.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106624. 14 interactions.
STRING9606.ENSP00000419361.

Chemistry

BindingDBO95622.
ChEMBLCHEMBL2097167.
GuidetoPHARMACOLOGY1282.

PTM databases

PhosphoSiteO95622.

Proteomic databases

PaxDbO95622.
PRIDEO95622.

Protocols and materials databases

DNASU111.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000309879; ENSP00000308685; ENSG00000173175. [O95622-2]
ENST00000462833; ENSP00000419361; ENSG00000173175. [O95622-1]
GeneID111.
KEGGhsa:111.
UCSCuc003egh.2. human. [O95622-1]
uc003egi.1. human. [O95622-2]

Organism-specific databases

CTD111.
GeneCardsGC03M122949.
H-InvDBHIX0003612.
HGNCHGNC:236. ADCY5.
HPAHPA017730.
MIM600293. gene.
606703. phenotype.
neXtProtNX_O95622.
Orphanet324588. Familial dyskinesia and facial myokymia.
PharmGKBPA24563.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2114.
HOGENOMHOG000006941.
HOVERGENHBG050458.
InParanoidO95622.
KOK08045.
OMAVRSKMNS.
OrthoDBEOG7B8S30.
PhylomeDBO95622.
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

ArrayExpressO95622.
BgeeO95622.
CleanExHS_ADCY5.
GenevestigatorO95622.

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

ChiTaRSADCY5. human.
GeneWikiADCY5.
GenomeRNAi111.
NextBio427.
PROO95622.
SOURCESearch...

Entry information

Entry nameADCY5_HUMAN
AccessionPrimary (citable) accession number: O95622
Secondary accession number(s): B7Z8A6, Q7RTV7, Q8NFM3
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: November 28, 2006
Last modified: April 16, 2014
This is version 127 of the entry and version 3 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 3

Human chromosome 3: entries, gene names and cross-references to MIM