Q8NFM4 (ADCY4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Adenylate cyclase type 4
EC=4.6.1.1

Alternative name(s):
ATP pyrophosphate-lyase 4
Adenylate cyclase type IV
Adenylyl cyclase 4

Gene names

Name:

ADCY4

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	1077 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	This is a membrane-bound, calmodulin-insensitive adenylyl cyclase By similarity.
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.
Subcellular location	Membrane; Multi-pass membrane protein.
Sequence similarities	Belongs to the adenylyl cyclase class-4/guanylyl cyclase family. Contains 2 guanylate cyclase domains.
Sequence caution	The sequence BAB71270.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	cAMP biosynthesis
Cellular component	Membrane
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 adenylate cyclase activity by G-protein signaling pathway Traceable author statement. Source: Reactome 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 inhibition of adenylate cyclase activity by G-protein signaling pathway 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	cytoplasm Inferred from direct assay. Source: UniProtKB 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 GTPase activity Traceable author statement. Source: Reactome adenylate cyclase activity Traceable author statement. Source: Reactome metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1077	1077	Adenylate cyclase type 4		PRO_0000195690
Regions
	Topological domain	1 – 28	28	Cytoplasmic Potential
	Transmembrane	29 – 50	22	Helical; Potential
	Transmembrane	61 – 80	20	Helical; Potential
	Transmembrane	94 – 117	24	Helical; Potential
	Transmembrane	120 – 138	19	Helical; Potential
	Transmembrane	141 – 162	22	Helical; Potential
	Transmembrane	170 – 190	21	Helical; Potential
	Topological domain	191 – 585	395	Cytoplasmic Potential
	Transmembrane	586 – 607	22	Helical; Potential
	Transmembrane	611 – 633	23	Helical; Potential
	Transmembrane	664 – 687	24	Helical; Potential
	Topological domain	688 – 714	27	Extracellular Potential
	Transmembrane	715 – 736	22	Helical; Potential
	Transmembrane	744 – 764	21	Helical; Potential
	Transmembrane	791 – 807	17	Helical; Potential
	Topological domain	808 – 1077	270	Cytoplasmic Potential
Sites
	Metal binding	278	1	Magnesium 1 By similarity
	Metal binding	278	1	Magnesium 2 By similarity
	Metal binding	279	1	Magnesium 2; via carbonyl oxygen By similarity
	Metal binding	322	1	Magnesium 1 By similarity
	Metal binding	322	1	Magnesium 2 By similarity
Amino acid modifications
	Glycosylation	697	1	N-linked (GlcNAc...) Potential
	Glycosylation	704	1	N-linked (GlcNAc...) Potential
Experimental info
	Sequence conflict	571	1	E → G in BAB71270. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q8NFM4 [UniParc]. Last modified October 1, 2002. Version 1. Checksum: 24C0D5AE495CFD50	FASTA	1,077	119,794
	10 20 30 40 50 60 MARLFSPRPP PSEDLFYETY YSLSQQYPLL LLLLGIVLCA LAALLAVAWA SGRELTSDPS 70 80 90 100 110 120 FLTTVLCALG GFSLLLGLAS REQRLQRWTR PLSGLVWVAL LALGHAFLFT GGVVSAWDQV 130 140 150 160 170 180 SYFLFVIFTA YAMLPLGMRD AAVAGLASSL SHLLVLGLYL GPQPDSRPAL LPQLAANAVL 190 200 210 220 230 240 FLCGNVAGVY HKALMERALR ATFREALSSL HSRRRLDTEK KHQEHLLLSI LPAYLAREMK 250 260 270 280 290 300 AEIMARLQAG QGSRPESTNN FHSLYVKRHQ GVSVLYADIV GFTRLASECS PKELVLMLNE 310 320 330 340 350 360 LFGKFDQIAK EHECMRIKIL GDCYYCVSGL PLSLPDHAIN CVRMGLDMCR AIRKLRAATG 370 380 390 400 410 420 VDINMRVGVH SGSVLCGVIG LQKWQYDVWS HDVTLANHME AGGVPGRVHI TGATLALLAG 430 440 450 460 470 480 AYAVEDAGME HRDPYLRELG EPTYLVIDPR AEEEDEKGTA GGLLSSLEGL KMRPSLLMTR 490 500 510 520 530 540 YLESWGAAKP FAHLSHGDSP VSTSTPLPEK TLASFSTQWS LDRSRTPRGL DDELDTGDAK 550 560 570 580 590 600 FFQVIEQLNS QKQWKQSKDF NPLTLYFREK EMEKEYRLSA IPAFKYYEAC TFLVFLSNFI 610 620 630 640 650 660 IQMLVTNRPP ALAITYSITF LLFLLILFVC FSEDLMRCVL KGPKMLHWLP ALSGLVATRP 670 680 690 700 710 720 GLRIALGTAT ILLVFAMAIT SLFFFPTSSD CPFQAPNVSS MISNLSWELP GSLPLISVPY 730 740 750 760 770 780 SMHCCTLGFL SCSLFLHMSF ELKLLLLLLW LAASCSLFLH SHAWLSECLI VRLYLGPLDS 790 800 810 820 830 840 RPGVLKEPKL MGAISFFIFF FTLLVLARQN EYYCRLDFLW KKKLRQEREE TETMENLTRL 850 860 870 880 890 900 LLENVLPAHV APQFIGQNRR NEDLYHQSYE CVCVLFASVP DFKEFYSESN INHEGLECLR 910 920 930 940 950 960 LLNEIIADFD ELLSKPKFSG VEKIKTIGST YMAATGLNAT SGQDAQQDAE RSCSHLGTMV 970 980 990 1000 1010 1020 EFAVALGSKL DVINKHSFNN FRLRVGLNHG PVVAGVIGAQ KPQYDIWGNT VNVASRMEST 1030 1040 1050 1060 1070 GVLGKIQVTE ETAWALQSLG YTCYSRGVIK VKGKGQLCTY FLNTDLTRTG PPSATLG

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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]. Tissue: Spleen.
[2]	"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. , 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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta and Tongue.
[3]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF497516 mRNA. Translation: AAM94373.1. AK056745 mRNA. Translation: BAB71270.1. Different initiation. AK122714 mRNA. Translation: BAG53686.1. CH471078 Genomic DNA. Translation: EAW66023.1. CH471078 Genomic DNA. Translation: EAW66026.1. CH471078 Genomic DNA. Translation: EAW66027.1. BC117473 mRNA. Translation: AAI17474.1. BC117475 mRNA. Translation: AAI17476.1.
IPI	IPI00465156.
RefSeq	NP_001185497.1. NM_001198568.1. NP_001185521.1. NM_001198592.1. NP_640340.2. NM_139247.3.
UniGene	Hs.443428.
3D structure databases
ProteinModelPortal	Q8NFM4.
SMR	Q8NFM4. Positions 261-447, 864-1043.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8NFM4. 4 interactions.
STRING	Q8NFM4.
PTM databases
PhosphoSite	Q8NFM4.
Polymorphism databases
DMDM	25008336.
Proteomic databases
PRIDE	Q8NFM4.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000310677; ENSP00000312126; ENSG00000129467. ENST00000418030; ENSP00000393177; ENSG00000129467.
GeneID	196883.
KEGG	hsa:196883.
UCSC	uc001wov.1. human.
Organism-specific databases
CTD	196883.
GeneCards	GC14M024787.
H-InvDB	HIX0011571.
HGNC	HGNC:235. ADCY4.
HPA	CAB005070.
MIM	600292. gene.
neXtProt	NX_Q8NFM4.
PharmGKB	PA24562.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG08999.
HOVERGEN	HBG050458.
InParanoid	Q8NFM4.
OMA	SCSLFLH.
OrthoDB	EOG4H4631.
PhylomeDB	Q8NFM4.
Enzyme and pathway databases
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	Q8NFM4.
Bgee	Q8NFM4.
CleanEx	HS_ADCY4.
Genevestigator	Q8NFM4.
GermOnline	ENSG00000129467. Homo sapiens.
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	K08044.
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	89574.
SOURCE	Search...

Entry information

Entry name

ADCY4_HUMAN

Accession

Primary (citable) accession number: Q8NFM4
Secondary accession number(s): B3KV74 , D3DS75, Q17R40, Q96ML7

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 8, 2002
Last sequence update:	October 1, 2002
Last modified:	January 25, 2012
This is version 92 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.