O95622 (ADCY5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1261 AA.
Sequence status	Complete.
Protein existence	Evidence 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.4
Subunit structure	Part of a complex containing AKAP5, ADCY6, PDE4C and PKD2 By similarity. Interacts with RAF1. Ref.4
Subcellular location	Membrane; Multi-pass membrane protein. Cell projection › cilium By similarity.
Post-translational modification	Phosphorylated by RAF1. Ref.4
Sequence similarities	Belongs to the adenylyl cyclase class-4/guanylyl cyclase family. Contains 2 guanylate cyclase domains.

Ontologies

Keywords
Biological process	cAMP biosynthesis
Cellular component	Cell projection Cilium Membrane
Domain	Repeat Transmembrane Transmembrane helix
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Lyase
PTM	Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	activation of phospholipase C activity Traceable author statement. Source: Reactome activation of protein kinase A activity Traceable author statement. Source: Reactome cellular response to glucagon stimulus Traceable author statement. Source: Reactome energy reserve metabolic process Traceable author statement. Source: Reactome nerve growth factor receptor signaling pathway 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 component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW primary cilium Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW GTPase activity Traceable author statement. Source: Reactome metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1261	1261	Adenylate cyclase type 5		PRO_0000195694
Regions
	Topological domain	1 – 195	195	Cytoplasmic Potential
	Transmembrane	196 – 216	21	Helical; Potential
	Transmembrane	242 – 262	21	Helical; Potential
	Transmembrane	268 – 288	21	Helical; Potential
	Transmembrane	299 – 319	21	Helical; Potential
	Transmembrane	325 – 345	21	Helical; Potential
	Transmembrane	374 – 394	21	Helical; Potential
	Topological domain	395 – 769	375	Cytoplasmic Potential
	Transmembrane	770 – 790	21	Helical; Potential
	Transmembrane	792 – 812	21	Helical; Potential
	Transmembrane	836 – 856	21	Helical; Potential
	Topological domain	857 – 909	53	Extracellular Potential
	Transmembrane	910 – 930	21	Helical; Potential
	Transmembrane	935 – 955	21	Helical; Potential
	Transmembrane	984 – 1004	21	Helical; Potential
	Topological domain	1005 – 1261	257	Cytoplasmic Potential
	Domain	469 – 596	128	Guanylate cyclase 1
	Domain	1071 – 1210	140	Guanylate cyclase 2
Sites
	Metal binding	474	1	Magnesium 1 By similarity
	Metal binding	474	1	Magnesium 2 By similarity
	Metal binding	475	1	Magnesium 2; via carbonyl oxygen By similarity
	Metal binding	518	1	Magnesium 1 By similarity
	Metal binding	518	1	Magnesium 2 By similarity
Amino acid modifications
	Modified residue	8	1	Phosphoserine By similarity
	Glycosylation	870	1	N-linked (GlcNAc...) Potential
	Glycosylation	887	1	N-linked (GlcNAc...) Potential

Sequences

	Sequence		Length	Mass (Da)
	O95622 [UniParc]. Last modified November 28, 2006. Version 3. Checksum: C50492A0B053694F	FASTA	1,261	138,908
	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

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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. , 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: 16641997] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[2]	"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: 12503609] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 368-1261. Tissue: Heart.
[3]	"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: 10481931] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 560-664. Tissue: Heart muscle.
[4]	"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: 15385642] [Abstract] Cited for: PHOSPHORYLATION BY RAF1, INTERACTION WITH RAF1, ENZYME REGULATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AC025571 Genomic DNA. No translation available. AF497517 mRNA. Translation: AAM94374.1. U65473 mRNA. Translation: AAD00121.1. BK000371 mRNA. Translation: DAA00057.1.
IPI	IPI00339214.
RefSeq	NP_899200.1. NM_183357.2.
UniGene	Hs.593292.
3D structure databases
ProteinModelPortal	O95622.
SMR	O95622. Positions 454-643, 1063-1255.
ModBase	Search...
Protein-protein interaction databases
STRING	O95622.
PTM databases
PhosphoSite	O95622.
Proteomic databases
PRIDE	O95622.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000462833; ENSP00000419361; ENSG00000173175.
GeneID	111.
KEGG	hsa:111.
UCSC	uc003egh.1. human.
Organism-specific databases
CTD	111.
GeneCards	GC03M122949.
H-InvDB	HIX0003612.
HGNC	HGNC:236. ADCY5.
HPA	HPA017730.
MIM	600293. gene.
neXtProt	NX_O95622.
PharmGKB	PA24563.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG17453.
GeneTree	ENSGT00590000082802.
HOGENOM	HBG445220.
HOVERGEN	HBG050458.
InParanoid	O95622.
OMA	GDEQGFC.
OrthoDB	EOG4255S0.
PhylomeDB	O95622.
Enzyme and pathway databases
BRENDA	4.6.1.1. 2681.
Pathway_Interaction_DB	endothelinpathway. Endothelins. lysophospholipid_pathway. LPA receptor mediated events. lpa4_pathway. LPA4-mediated signaling events.
Reactome	REACT_111102. Signal Transduction. REACT_111217. Metabolism. REACT_13685. Neuronal System. REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	O95622.
Bgee	O95622.
CleanEx	HS_ADCY5.
Genevestigator	O95622.
Family and domain databases
InterPro	IPR001054. A/G_cyclase. IPR018297. A/G_cyclase_CS. IPR009398. Adenylate_cyclase-like. [Graphical view]
Gene3D	G3DSA:3.30.70.1230. A/G_cyclase. 2 hits.
KO	K08045.
Pfam	PF06327. DUF1053. 1 hit. PF00211. Guanylate_cyc. 2 hits. [Graphical view]
SMART	SM00044. CYCc. 2 hits. [Graphical view]
SUPFAM	SSF55073. A/G_cyclase. 2 hits.
PROSITE	PS00452. GUANYLATE_CYCLASE_1. 2 hits. PS50125. GUANYLATE_CYCLASE_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	427.
SOURCE	Search...

Entry information

Entry name

ADCY5_HUMAN

Accession

Primary (citable) accession number: O95622
Secondary accession number(s): Q7RTV7, Q8NFM3

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	November 28, 2006
Last modified:	January 25, 2012
This is version 104 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.