P40145 (ADCY8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Adenylate cyclase type 8
EC=4.6.1.1

Alternative name(s):
ATP pyrophosphate-lyase 8
Adenylate cyclase type VIII
Adenylyl cyclase 8
Short name=AC8
Ca(2+)/calmodulin-activated adenylyl cyclase

Gene names

Name:

ADCY8

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	1251 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	This is a membrane-bound, calcium-stimulable adenylyl cyclase. May be involved in learning, in memory and in drug dependence By similarity.
Catalytic activity	ATP = 3',5'-cyclic AMP + diphosphate.
Cofactor	Binds 2 magnesium ions per subunit By similarity.
Enzyme regulation	Activated by calcium/calmodulin.
Subcellular location	Membrane; Multi-pass membrane protein.
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
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 learning or memory Traceable author statement Ref.1. Source: ProtInc long-term memory Inferred from electronic annotation. Source: Compara 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 plasma membrane Traceable author statement. Source: Reactome
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW calcium- and calmodulin-responsive adenylate cyclase activity Traceable author statement PubMed 8163524. Source: ProtInc 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 – 1251	1251	Adenylate cyclase type 8		PRO_0000195705
Regions
	Topological domain	1 – 182	182	Cytoplasmic Potential
	Transmembrane	183 – 203	21	Helical; Potential
	Transmembrane	212 – 232	21	Helical; Potential
	Transmembrane	247 – 267	21	Helical; Potential
	Transmembrane	274 – 294	21	Helical; Potential
	Transmembrane	296 – 316	21	Helical; Potential
	Transmembrane	321 – 341	21	Helical; Potential
	Topological domain	342 – 715	374	Cytoplasmic Potential
	Transmembrane	716 – 736	21	Helical; Potential
	Transmembrane	738 – 758	21	Helical; Potential
	Transmembrane	787 – 807	21	Helical; Potential
	Transmembrane	831 – 851	21	Helical; Potential
	Transmembrane	861 – 881	21	Helical; Potential
	Transmembrane	894 – 914	21	Helical; Potential
	Topological domain	915 – 1251	337	Cytoplasmic Potential
Sites
	Metal binding	419	1	Magnesium 1 By similarity
	Metal binding	419	1	Magnesium 2 By similarity
	Metal binding	420	1	Magnesium 2; via carbonyl oxygen By similarity
	Metal binding	463	1	Magnesium 1 By similarity
	Metal binding	463	1	Magnesium 2 By similarity
Amino acid modifications
	Glycosylation	817	1	N-linked (GlcNAc...) Potential
	Glycosylation	821	1	N-linked (GlcNAc...) Potential
	Glycosylation	888	1	N-linked (GlcNAc...) Potential
Natural variations
	Natural variant	80	1	A → T. Corresponds to variant rs2228949 [ dbSNP | Ensembl ].		VAR_029188
	Natural variant	881	1	F → L in a colorectal cancer sample; somatic mutation. Ref.4		VAR_036328

Sequences

	Sequence		Length	Mass (Da)
	P40145 [UniParc]. Last modified February 1, 1995. Version 1. Checksum: ABF25C40493E07C3	FASTA	1,251	140,122
	10 20 30 40 50 60 MELSDVRCLT GSEELYTIHP TPPAGDGRSA SRPQRLLWQT AVRHITEQRF IHGHRGGSGS 70 80 90 100 110 120 GSGGSGKASD PAGGGPNHHA PQLSGDSALP LYSLGPGERA HSTCGTKVFP ERSGSGSASG 130 140 150 160 170 180 SGGGGDLGFL HLDCAPSNSD FFLNGGYSYR GVIFPTLRNS FKSRDLERLY QRYFLGQRRK 190 200 210 220 230 240 SEVVMNVLDV LTKLTLLVLH LSLASAPMDP LKGILLGFFT GIEVVICALV VVRKDTTSHT 250 260 270 280 290 300 YLQYSGVVTW VAMTTQILAA GLGYGLLGDG IGYVLFTLFA TYSMLPLPLT WAILAGLGTS 310 320 330 340 350 360 LLQVILQVVI PRLAVISINQ VVAQAVLFMC MNTAGIFISY LSDRAQRQAF LETRRCVEAR 370 380 390 400 410 420 LRLETENQRQ ERLVLSVLPR FVVLEMINDM TNVEDEHLQH QFHRIYIHRY ENVSILFADV 430 440 450 460 470 480 KGFTNLSTTL SAQELVRMLN ELFARFDRLA HEHHCLRIKI LGDCYYCVSG LPEPRQDHAH 490 500 510 520 530 540 CCVEMGLSMI KTIRYVRSRT KHDVDMRIGI HSGSVLCGVL GLRKWQFDVW SWDVDIANKL 550 560 570 580 590 600 ESGGIPGRIH ISKATLDCLN GDYNVEEGHG KERNEFLRKH NIETYLIKQP EDSLLSLPED 610 620 630 640 650 660 IVKESVSSSD RRNSGATFTE GSWSPELPFD NIVGKQNTLA ALTRNSINLL PNHLAQALHV 670 680 690 700 710 720 QSGPEEINKR IEHTIDLRSG DKLRREHIKP FSLMFKDSSL EHKYSQMRDE VFKSNLVCAF 730 740 750 760 770 780 IVLLFITAIQ SLLPSSRVMP MTIQFSILIM LHSALVLITT AEDYKCLPLI LRKTCCWINE 790 800 810 820 830 840 TYLARNVIIF ASILINFLGA ILNILWCDFD KSIPLKNLTF NSSAVFTDIC SYPEYFVFTG 850 860 870 880 890 900 VLAMVTCAVF LRLNSVLKLA VLLIMIAIYA LLTETVYAGL FLRYDNLNHS GEDFLGTKEV 910 920 930 940 950 960 SLLLMAMFLL AVFYHGQQLE YTARLDFLWR VQAKEEINEM KELREHNENM LRNILPSHVA 970 980 990 1000 1010 1020 RHFLEKDRDN EELYSQSYDA VGVMFASIPG FADFYSQTEM NNQGVECLRL LNEIIADFDE 1030 1040 1050 1060 1070 1080 LLGEDRFQDI EKIKTIGSTY MAVSGLSPEK QQCEDKWGHL CALADFSLAL TESIQEINKH 1090 1100 1110 1120 1130 1140 SFNNFELRIG ISHGSVVAGV IGAKKPQYDI WGKTVNLASR MDSTGVSGRI QVPEETYLIL 1150 1160 1170 1180 1190 1200 KDQGFAFDYR GEIYVKGISE QEGKIKTYFL LGRVQPNPFI LPPRRLPGQY SLAAVVLGLV 1210 1220 1230 1240 1250 QSLNRQRQKQ LLNENNNTGI IKGHYNRRTL LSPSGTEPGA QAEGTDKSDL P

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of the human type VIII adenylyl cyclase." Defer N., Marinx O., Stengel D., Danisova A., Iourgenko V., Matsuoka I., Caput D., Hanoune J. FEBS Lett. 351:109-113(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain stem.
[2]	"Sequence of a human brain adenylyl cyclase partial cDNA: evidence for a consensus cyclase specific domain." Parma J., Stengel D., Gannage M.H., Poyard M., Barouki R., Hanoune J. Biochem. Biophys. Res. Commun. 179:455-462(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 577-1251. Tissue: Brain.
[3]	"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.
[4]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] LEU-881.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	Z35309 mRNA. Translation: CAA84552.1. M83533 mRNA. Translation: AAA35523.2.
IPI	IPI00027356.
PIR	PQ0227. S48687.
RefSeq	NP_001106.1. NM_001115.2.
UniGene	Hs.591859.
3D structure databases
ProteinModelPortal	P40145.
ModBase	Search...
Protein-protein interaction databases
IntAct	P40145. 1 interaction.
STRING	9606.ENSP00000286355.
PTM databases
PhosphoSite	P40145.
Polymorphism databases
DMDM	729242.
Proteomic databases
PaxDb	P40145.
PRIDE	P40145.
Protocols and materials databases
DNASU	114.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000286355; ENSP00000286355; ENSG00000155897.
GeneID	114.
KEGG	hsa:114.
UCSC	uc003ytd.4. human.
Organism-specific databases
CTD	114.
GeneCards	GC08M131861.
HGNC	HGNC:239. ADCY8.
HPA	CAB018652. HPA024291.
MIM	103070. gene.
neXtProt	NX_P40145.
PharmGKB	PA29.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2114.
HOGENOM	HOG000006941.
HOVERGEN	HBG050458.
InParanoid	P40145.
KO	K08048.
OMA	ERAHSTG.
PhylomeDB	P40145.
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	P40145.
Bgee	P40145.
CleanEx	HS_ADCY8.
Genevestigator	P40145.
GermOnline	ENSG00000155897. 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	P40145.
ChEMBL	CHEMBL2960.
ChiTaRS	ADCY8. human.
GenomeRNAi	114.
NextBio	441.
SOURCE	Search...

Entry information

Entry name

ADCY8_HUMAN

Accession

Primary (citable) accession number: P40145

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1995
Last sequence update:	February 1, 1995
Last modified:	May 1, 2013
This is version 120 of the entry and version 1 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.