O43306 (ADCY6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Adenylate cyclase type 6
EC=4.6.1.1

Alternative name(s):
ATP pyrophosphate-lyase 6
Adenylate cyclase type VI
Adenylyl cyclase 6
Ca(2+)-inhibitable adenylyl cyclase

Gene names

Name:	ADCY6
Synonyms:	KIAA0422

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	1168 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Membrane-bound, calcium-inhibitable adenylyl cyclase By similarity.
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.6
Subunit structure	Part of a complex containing AKAP5, ADCY5, PDE4C and PKD2 By similarity. Interacts with RAF1. Ref.6
Subcellular location	Membrane; Multi-pass membrane protein. Cell projection › cilium By similarity.
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.
Sequence caution	The sequence BAA24852.2 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	cAMP biosynthesis
Cellular component	Cell projection Cilium Membrane
Coding sequence diversity	Alternative splicing 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 catecholamine stimulus Inferred from direct assay PubMed 18403039. Source: BHF-UCL cellular response to glucagon stimulus Traceable author statement. Source: Reactome cellular response to prostaglandin E stimulus Inferred from direct assay PubMed 18403039. Source: BHF-UCL dopamine receptor signaling pathway Inferred from direct assay PubMed 18403039. Source: BHF-UCL 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	cilium Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW adenylate cyclase activity Inferred from direct assay PubMed 18403039. Source: BHF-UCL metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein kinase binding 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: O43306-1)

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: O43306-2)

The sequence of this isoform differs from the canonical sequence as follows:
     762-814: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1168	1168	Adenylate cyclase type 6		PRO_0000195699
Regions
	Topological domain	1 – 151	151	Cytoplasmic Potential
	Transmembrane	152 – 168	17	Helical; Potential
	Transmembrane	181 – 197	17	Helical; Potential
	Transmembrane	214 – 230	17	Helical; Potential
	Transmembrane	239 – 255	17	Helical; Potential
	Transmembrane	259 – 275	17	Helical; Potential
	Transmembrane	289 – 305	17	Helical; Potential
	Topological domain	306 – 673	368	Cytoplasmic Potential
	Transmembrane	674 – 691	18	Helical; Potential
	Transmembrane	702 – 718	17	Helical; Potential
	Transmembrane	743 – 759	17	Helical; Potential
	Topological domain	760 – 819	60	Extracellular Potential
	Transmembrane	820 – 836	17	Helical; Potential
	Transmembrane	839 – 855	17	Helical; Potential
	Transmembrane	897 – 913	17	Helical; Potential
	Topological domain	914 – 1168	255	Cytoplasmic Potential
Sites
	Metal binding	384	1	Magnesium 1 By similarity
	Metal binding	384	1	Magnesium 2 By similarity
	Metal binding	385	1	Magnesium 2; via carbonyl oxygen By similarity
	Metal binding	428	1	Magnesium 1 By similarity
	Metal binding	428	1	Magnesium 2 By similarity
Amino acid modifications
	Modified residue	556	1	Phosphoserine By similarity
	Modified residue	576	1	Phosphoserine Ref.7
	Modified residue	662	1	Phosphoserine By similarity
	Modified residue	919	1	Phosphothreonine By similarity
	Glycosylation	793	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	762 – 814	53	Missing in isoform 2.		VSP_000244
	Natural variant	674	1	A → S. Corresponds to variant rs3730071 [ dbSNP | Ensembl ].		VAR_048249

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 11, 2001. Version 2. Checksum: 127BB6E67F73AA61	FASTA	1,168	130,615
	10 20 30 40 50 60 MSWFSGLLVP KVDERKTAWG ERNGQKRSRR RGTRAGGFCT PRYMSCLRDA EPPSPTPAGP 70 80 90 100 110 120 PRCPWQDDAF IRRGGPGKGK ELGLRAVALG FEDTEVTTTA GGTAEVAPDA VPRSGRSCWR 130 140 150 160 170 180 RLVQVFQSKQ FRSAKLERLY QRYFFQMNQS SLTLLMAVLV LLTAVLLAFH AAPARPQPAY 190 200 210 220 230 240 VALLACAAAL FVGLMVVCNR HSFRQDSMWV VSYVVLGILA AVQVGGALAA DPRSPSAGLW 250 260 270 280 290 300 CPVFFVYIAY TLLPIRMRAA VLSGLGLSTL HLILAWQLNR GDAFLWKQLG ANVLLFLCTN 310 320 330 340 350 360 VIGICTHYPA EVSQRQAFQE TRGYIQARLH LQHENRQQER LLLSVLPQHV AMEMKEDINT 370 380 390 400 410 420 KKEDMMFHKI YIQKHDNVSI LFADIEGFTS LASQCTAQEL VMTLNELFAR FDKLAAENHC 430 440 450 460 470 480 LRIKILGDCY YCVSGLPEAR ADHAHCCVEM GVDMIEAISL VREVTGVNVN MRVGIHSGRV 490 500 510 520 530 540 HCGVLGLRKW QFDVWSNDVT LANHMEAGGR AGRIHITRAT LQYLNGDYEV EPGRGGERNA 550 560 570 580 590 600 YLKEQHIETF LILGASQKRK EEKAMLAKLQ RTRANSMEGL MPRWVPDRAF SRTKDSKAFR 610 620 630 640 650 660 QMGIDDSSKD NRGTQDALNP EDEVDEFLSR AIDARSIDQL RKDHVRRFLL TFQREDLEKK 670 680 690 700 710 720 YSRKVDPRFG AYVACALLVF CFICFIQLLI FPHSTLMLGI YASIFLLLLI TVLICAVYSC 730 740 750 760 770 780 GSLFPKALQR LSRSIVRSRA HSTAVGIFSV LLVFTSAIAN MFTCNHTPIR SCAARMLNLT 790 800 810 820 830 840 PADITACHLQ QLNYSLGLDA PLCEGTMPTC SFPEYFIGNM LLSLLASSVF LHISSIGKLA 850 860 870 880 890 900 MIFVLGLIYL VLLLLGPPAT IFDNYDLLLG VHGLASSNET FDGLDCPAAG RVALKYMTPV 910 920 930 940 950 960 ILLVFALALY LHAQQVESTA RLDFLWKLQA TGEKEEMEEL QAYNRRLLHN ILPKDVAAHF 970 980 990 1000 1010 1020 LARERRNDEL YYQSCECVAV MFASIANFSE FYVELEANNE GVECLRLLNE IIADFDEIIS 1030 1040 1050 1060 1070 1080 EERFRQLEKI KTIGSTYMAA SGLNASTYDQ VGRSHITALA DYAMRLMEQM KHINEHSFNN 1090 1100 1110 1120 1130 1140 FQMKIGLNMG PVVAGVIGAR KPQYDIWGNT VNVSSRMDST GVPDRIQVTT DLYQVLAAKG 1150 1160 YQLECRGVVK VKGKGEMTTY FLNGGPSS
	Isoform 2 [UniParc]. Checksum: D1D26C1E15FAC0B0	FASTA	1,115	124,865
	10 20 30 40 50 60 MSWFSGLLVP KVDERKTAWG ERNGQKRSRR RGTRAGGFCT PRYMSCLRDA EPPSPTPAGP 70 80 90 100 110 120 PRCPWQDDAF IRRGGPGKGK ELGLRAVALG FEDTEVTTTA GGTAEVAPDA VPRSGRSCWR 130 140 150 160 170 180 RLVQVFQSKQ FRSAKLERLY QRYFFQMNQS SLTLLMAVLV LLTAVLLAFH AAPARPQPAY 190 200 210 220 230 240 VALLACAAAL FVGLMVVCNR HSFRQDSMWV VSYVVLGILA AVQVGGALAA DPRSPSAGLW 250 260 270 280 290 300 CPVFFVYIAY TLLPIRMRAA VLSGLGLSTL HLILAWQLNR GDAFLWKQLG ANVLLFLCTN 310 320 330 340 350 360 VIGICTHYPA EVSQRQAFQE TRGYIQARLH LQHENRQQER LLLSVLPQHV AMEMKEDINT 370 380 390 400 410 420 KKEDMMFHKI YIQKHDNVSI LFADIEGFTS LASQCTAQEL VMTLNELFAR FDKLAAENHC 430 440 450 460 470 480 LRIKILGDCY YCVSGLPEAR ADHAHCCVEM GVDMIEAISL VREVTGVNVN MRVGIHSGRV 490 500 510 520 530 540 HCGVLGLRKW QFDVWSNDVT LANHMEAGGR AGRIHITRAT LQYLNGDYEV EPGRGGERNA 550 560 570 580 590 600 YLKEQHIETF LILGASQKRK EEKAMLAKLQ RTRANSMEGL MPRWVPDRAF SRTKDSKAFR 610 620 630 640 650 660 QMGIDDSSKD NRGTQDALNP EDEVDEFLSR AIDARSIDQL RKDHVRRFLL TFQREDLEKK 670 680 690 700 710 720 YSRKVDPRFG AYVACALLVF CFICFIQLLI FPHSTLMLGI YASIFLLLLI TVLICAVYSC 730 740 750 760 770 780 GSLFPKALQR LSRSIVRSRA HSTAVGIFSV LLVFTSAIAN MYFIGNMLLS LLASSVFLHI 790 800 810 820 830 840 SSIGKLAMIF VLGLIYLVLL LLGPPATIFD NYDLLLGVHG LASSNETFDG LDCPAAGRVA 850 860 870 880 890 900 LKYMTPVILL VFALALYLHA QQVESTARLD FLWKLQATGE KEEMEELQAY NRRLLHNILP 910 920 930 940 950 960 KDVAAHFLAR ERRNDELYYQ SCECVAVMFA SIANFSEFYV ELEANNEGVE CLRLLNEIIA 970 980 990 1000 1010 1020 DFDEIISEER FRQLEKIKTI GSTYMAASGL NASTYDQVGR SHITALADYA MRLMEQMKHI 1030 1040 1050 1060 1070 1080 NEHSFNNFQM KIGLNMGPVV AGVIGARKPQ YDIWGNTVNV SSRMDSTGVP DRIQVTTDLY 1090 1100 1110 QVLAAKGYQL ECRGVVKVKG KGEMTTYFLN GGPSS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and expression of human adenylyl cyclase type VI in normal thyroid tissues." Wicker R., Catalan A.G., Cailleux A.-F., Starenki D., Stengel D., Sarasin A., Suarez H.G. Biochim. Biophys. Acta 1493:279-283(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Thyroid.
[2]	"Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro." Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 4:307-313(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Brain.
[3]	"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.
[4]	"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] (ISOFORM 1). Tissue: Retina.
[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 1040-1103.
[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.
[7]	"Phosphoproteome of resting human platelets." Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A. J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-576, MASS SPECTROMETRY. Tissue: Platelet.
[8]	"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF250226 mRNA. Translation: AAF82478.1. AB007882 mRNA. Translation: BAA24852.2. Different initiation. BC064923 mRNA. No translation available.
IPI	IPI00011938. IPI00220444.
RefSeq	NP_056085.1. NM_015270.3. NP_066193.1. NM_020983.2.
UniGene	Hs.525401. Hs.694408.
3D structure databases
ProteinModelPortal	O43306.
ModBase	Search...
Protein-protein interaction databases
IntAct	O43306. 1 interaction.
MINT	MINT-2856766.
STRING	9606.ENSP00000311405.
PTM databases
PhosphoSite	O43306.
Proteomic databases
PaxDb	O43306.
PRIDE	O43306.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000307885; ENSP00000311405; ENSG00000174233. ENST00000357869; ENSP00000350536; ENSG00000174233. ENST00000550422; ENSP00000446730; ENSG00000174233.
GeneID	112.
KEGG	hsa:112.
UCSC	uc001rsh.4. human. uc001rsi.4. human.
Organism-specific databases
CTD	112.
GeneCards	GC12M049159.
HGNC	HGNC:237. ADCY6.
HPA	CAB018365.
MIM	600294. gene.
neXtProt	NX_O43306.
PharmGKB	PA27.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2114.
HOGENOM	HOG000006941.
HOVERGEN	HBG050458.
InParanoid	O43306.
KO	K08046.
OMA	RSCWRRL.
PhylomeDB	O43306.
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	O43306.
Bgee	O43306.
CleanEx	HS_ADCY6.
Genevestigator	O43306.
GermOnline	ENSG00000174233. 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	O43306.
ChEMBL	CHEMBL3221.
GenomeRNAi	112.
NextBio	431.
SOURCE	Search...

Entry information

Entry name

ADCY6_HUMAN

Accession

Primary (citable) accession number: O43306
Secondary accession number(s): Q9NR75, Q9UDB0

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	January 11, 2001
Last modified:	May 1, 2013
This is version 130 of the entry and version 2 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.