Q08462 (ADCY2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1091 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	cAMP biosynthesis
Cellular component	Membrane
Coding sequence diversity	Polymorphism
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 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 intracellular signal transduction Inferred from electronic annotation. Source: InterPro 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	cytoplasm Inferred from direct assay PubMed 11549699. Source: UniProtKB dendrite Inferred from sequence or structural similarity. Source: UniProtKB integral to membrane Non-traceable author statement. 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: Compara
Molecular_function	ATP 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: Compara 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1091	1091	Adenylate cyclase type 2		PRO_0000195684
Regions
	Topological domain	1 – 45	45	Cytoplasmic Potential
	Transmembrane	46 – 66	21	Helical; Potential
	Transmembrane	76 – 96	21	Helical; Potential
	Transmembrane	108 – 128	21	Helical; Potential
	Transmembrane	133 – 153	21	Helical; Potential
	Transmembrane	159 – 179	21	Helical; Potential
	Transmembrane	187 – 207	21	Helical; Potential
	Topological domain	208 – 601	394	Cytoplasmic Potential
	Transmembrane	602 – 622	21	Helical; Potential
	Transmembrane	628 – 652	25	Helical; Potential
	Transmembrane	680 – 701	22	Helical; Potential
	Transmembrane	734 – 755	22	Helical; Potential
	Transmembrane	763 – 780	18	Helical; Potential
	Transmembrane	801 – 821	21	Helical; Potential
	Topological domain	822 – 1091	270	Cytoplasmic Potential
Sites
	Metal binding	295	1	Magnesium 1 By similarity
	Metal binding	295	1	Magnesium 2 By similarity
	Metal binding	296	1	Magnesium 2; via carbonyl oxygen By similarity
	Metal binding	339	1	Magnesium 1 By similarity
	Metal binding	339	1	Magnesium 2 By similarity
Amino acid modifications
	Glycosylation	713	1	N-linked (GlcNAc...) Potential
	Glycosylation	716	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	147	1	V → L. Ref.2 Corresponds to variant rs13166360 [ dbSNP | Ensembl ].		VAR_029012
	Natural variant	163	1	V → I. Corresponds to variant rs34043481 [ dbSNP | Ensembl ].		VAR_048247
Experimental info
	Sequence conflict	188 – 207	20	VWQIL…LAGAY → GLADPGQCDHFHLWEPGXTN in AAP97285. Ref.1
	Sequence conflict	675	1	R → Q in CAA52282. Ref.4
	Sequence conflict	675	1	R → Q in AAA64923. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Q08462 [UniParc]. Last modified November 28, 2006. Version 5. Checksum: 41FD8BC607C075D1	FASTA	1,091	123,603
	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

References

	« Hide 'large scale' referencesShow '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.
IPI	IPI00328273.
PIR	I37136.
RefSeq	NP_065433.2. NM_020546.2.
UniGene	Hs.481545.
3D structure databases
ProteinModelPortal	Q08462.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-422N.
STRING	9606.ENSP00000342952.
PTM databases
PhosphoSite	Q08462.
Polymorphism databases
DMDM	118572617.
Proteomic databases
PaxDb	Q08462.
PRIDE	Q08462.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000338316; ENSP00000342952; ENSG00000078295.
GeneID	108.
KEGG	hsa:108.
UCSC	uc003jdz.1. human.
Organism-specific databases
CTD	108.
GeneCards	GC05P007449.
HGNC	HGNC:233. ADCY2.
HPA	CAB031482. HPA038015. HPA038483.
MIM	103071. gene.
neXtProt	NX_Q08462.
PharmGKB	PA24561.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2114.
HOGENOM	HOG000006941.
HOVERGEN	HBG050458.
InParanoid	Q08462.
KO	K08042.
OMA	AGQMENT.
OrthoDB	EOG48D0TJ.
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_116125. Disease. REACT_13685. Neuronal System. REACT_15518. Transmembrane transport of small molecules. REACT_6900. Immune System.
Gene expression databases
ArrayExpress	Q08462.
Bgee	Q08462.
CleanEx	HS_ADCY2.
Genevestigator	Q08462.
GermOnline	ENSG00000078295. Homo sapiens.
Family and domain databases
Gene3D	3.30.70.1230. 2 hits.
InterPro	IPR001054. A/G_cyclase. IPR018297. A/G_cyclase_CS. IPR009398. Adenylate_cyclase-like. [Graphical view]
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
BindingDB	Q08462.
ChEMBL	CHEMBL3760.
ChiTaRS	ADCY2. human.
GenomeRNAi	108.
NextBio	419.
SOURCE	Search...

Entry information

Entry name

ADCY2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 128 of the entry and version 5 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.