Reviewed, UniProtKB/Swiss-Prot Q03100 (CYAA_DICDI)

Names and origin

Protein names

Recommended name:
    Adenylate cyclase, aggregation specific
    EC=4.6.1.1
Alternative name(s):
    ATP pyrophosphate-lyase
    Adenylyl cyclase

Gene names

Name:	acaA
Synonyms:	aca
ORF Names:	DDB_G0281545

Organism

Dictyostelium discoideum (Slime mold) [Complete proteome]

Taxonomic identifier

44689 [NCBI]

Taxonomic lineage

Eukaryota › Amoebozoa › Mycetozoa › Dictyosteliida › Dictyostelium

Protein attributes

Sequence length	1407 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Coordinates cell aggregation by synthesizing the cAMP that influences differentiation and morphogenesis of cells within a developing multicellular structure. Ref.1 Ref.3 Ref.4 Ref.6 Ref.9 Ref.11
Catalytic activity	ATP = 3',5'-cyclic AMP + diphosphate. Ref.1 Ref.4
Cofactor	Binds 2 magnesium ions per subunit. Ref.4
Enzyme regulation	Regulated by cyclic AMP receptor 1 through a guanine nucleotide binding protein and protein CRAC. Both positively and negatively regulated by extracellular cAMP; this regulation is part of the mechanism that establishes the oscillatory cAMP waves during aggregation. Ref.1 Ref.4 Ref.10 Ref.13
Subcellular location	Membrane; Multi-pass membrane protein. Cell projection › uropodium. Note: In non-polarized cells ACA is uniformly distributed at the membrane but upon polarization it becomes highly enriched at the uropodium. Ref.9
Tissue specificity	Expressed throughout the structure in the tipped mound and finger. Expressed primarily in the prestalk region of the slug. In the early culminant expression is increased in the posterior prespore and anterior-most regions and expands into the developing stalk. In the mid and late culminant it is expressed throughout the stalk. Ref.7 Ref.8
Developmental stage	Expressed during development. First detected at 3 hours of development. Levels increase during aggregation and peak at 6 hours. Levels decrease after tight aggregate formation. Ref.1 Ref.7 Ref.8 Ref.12
Disruption phenotype	No cAMP synthesis. Cells are unable to aggregate, stimulation with cAMP pulses restores aggregation but slug and fruiting body formation remains very inefficient. When placed in a cAMP gradient mutants lacking ACA acquire polarity and migrate along the gradient but fail to align in a head to tail fashion and form streams. They are also unable to suppress lateral pseudopod formation, resulting in abnormal turns and inefficient chemotaxis. Transfer of the temperature-sensitive mutant tsaca2 to a temperature of 28 degrees Celsius leads to developmental arrest that is reversible when the temperature is shifted down to 22 degrees Celsius. In mutants with a constitutively active ACA, localization to the uropodium in polarized cells is reduced and these mutants fail to stream in a cAMP gradient. Ref.1 Ref.3 Ref.9 Ref.11 Ref.5
Sequence similarities	Belongs to the adenylyl cyclase class-4/guanylyl cyclase family. Contains 2 guanylate cyclase domains.
Biophysicochemical properties	Kinetic parameters: KM=0.2 mM for cAMP Vmax=20 pmol/min/mg enzyme

Ontologies

Keywords
Biological process	cAMP biosynthesis
Cellular component	Cell projection Membrane
Domain	Repeat Transmembrane
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Lyase
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	cAMP biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW intracellular signaling cascade Inferred from electronic annotation. Source: InterPro
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell uropod Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW adenylate cyclase activity Inferred from electronic annotation. Source: EC magnesium 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 – 1407	1407	Adenylate cyclase, aggregation specific		PRO_0000195714
Regions
	Topological domain	1 – 219	219	Cytoplasmic Potential
	Transmembrane	220 – 240	21	Potential
	Transmembrane	244 – 264	21	Potential
	Transmembrane	276 – 296	21	Potential
	Transmembrane	304 – 324	21	Potential
	Transmembrane	325 – 345	21	Potential
	Transmembrane	353 – 373	21	Potential
	Topological domain	374 – 962	589	Cytoplasmic Potential
	Transmembrane	963 – 979	17	Potential
	Transmembrane	992 – 1012	21	Potential
	Transmembrane	1018 – 1038	21	Potential
	Transmembrane	1071 – 1091	21	Potential
	Transmembrane	1105 – 1125	21	Potential
	Transmembrane	1378 – 1398	21	Potential
	Topological domain	1399 – 1407	9	Cytoplasmic Potential
	Domain	438 – 661	224	Guanylate cyclase 1
	Domain	1189 – 1311	123	Guanylate cyclase 2
	Compositional bias	65 – 74	10	Poly-Gly
	Compositional bias	88 – 113	26	Asn-rich
	Compositional bias	532 – 576	45	Asn-rich
	Compositional bias	535 – 576	42	Asn-rich
	Compositional bias	753 – 872	120	Asn-rich
	Compositional bias	753 – 785	33	Poly-Asn
	Compositional bias	847 – 864	18	Poly-Asn
Sites
	Metal binding	443	1	Magnesium 1 By similarity
	Metal binding	443	1	Magnesium 2 By similarity
	Metal binding	444	1	Magnesium 2; via carbonyl oxygen By similarity
	Metal binding	488	1	Magnesium 1 By similarity
	Metal binding	488	1	Magnesium 2 By similarity
Experimental info
	Mutagenesis	306	1	F → L in temperature-sensitive mutant tsaca2. Ref.6
	Mutagenesis	394	1	L → S: Constitutive activity. Ref.4
	Mutagenesis	498	1	S → G in temperature-sensitive mutant tsaca2. Ref.6
	Mutagenesis	504	1	K → E in temperature-sensitive mutant tsaca2. Ref.6
	Mutagenesis	593	1	E → V in temperature-sensitive mutant tsaca2. Ref.6
	Mutagenesis	649	1	I → T in temperature-sensitive mutant tsaca2. Ref.6
	Sequence conflict	567 – 568	2	NN → TT in AAA33163. Ref.1
	Sequence conflict	578 – 579	2	NN → TT in AAA33163. Ref.1
	Sequence conflict	940	1	L → Y in AAA33163. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q03100-1 [UniParc]. Last modified May 15, 2007. Version 2. Checksum: C7A115B4AE417007	FASTA	1,407	159,702
	10 20 30 40 50 60 MASSSPMFND HAIARSKYAL NSVLQQTNEL HDGNGGGGYT PSSPHLGGVS LNKSQNQPYT 70 80 90 100 110 120 QYNNGGGGGG GGGGHINPMH LNLNSITNNH NNHHNHHPNT LSTPHNNNHN NNNHSTSHHP 130 140 150 160 170 180 HSNSVANGGH LSQSITQQRG GLADLANAVI NRKNRSDSVQ TKMKPTDSAS NIESWAKVEK 190 200 210 220 230 240 FSSSIFDSEK SKKSNIFQKY TLRLKNSYEK GYLHQHYNSQ IMLLRITNLI GIVAVSYGFT 250 260 270 280 290 300 KEAIFMLIAI RILCFNLFAF SIFLSFLRNR ELYKKLFHPL FLFSFTTFFI TILLEYKTTT 310 320 330 340 350 360 TTLILFLYVV IFCCLYALGC LLFIWMVMCN LMNAICFIIF IFLESTLDRN NLISFVIYIL 370 380 390 400 410 420 TMFLVGASHL YVLEKFRKES FIAEKKLIKE SNILKNEKEK SSKLLNNILP DFIIENIVYD 430 440 450 460 470 480 FEKRDIVIPE PEEYKSCSIL CFDIVQFTNM SAKLDSPSRL VDLLTQVFRE FDTVVLRNGC 490 500 510 520 530 540 QKIKTDGDAY ICACGLKSKK KAKKQMPNSK STPLLQSTSS TSVNNIDLDK DNKDNNNNNN 550 560 570 580 590 600 NNKNSNNNFK NKNNIINNNN NSNSNNNNNN NSNNNNINNS GNDDDDEEIE DSELEHFEKL 610 620 630 640 650 660 IDVAIEIMNL DVLKETGNTE GIQVQFRCGI AAGSVYGGVI GSQKYQFDIW GDTIARSHTL 670 680 690 700 710 720 EQLGQPGKVH VGETIMTHKN WLKKWQYNYN IVSNSECKDQ EHDYEFHKAH GECITSYFVD 730 740 750 760 770 780 WKDDYREKKK KDLSCDFSIN KVLNAETIES KSNNNNYNNN NYNNNNYNNN YNNNNLNNNS 790 800 810 820 830 840 NNNNNEYGSS SSSSSVLGEA VTEQIDCNNT NPPLQHKKSQ SILTNNENDI VSPSLTSNSP 850 860 870 880 890 900 ILDTTVNNNN NNNNTNNNNK NQNNIYGNNN NNEEDFKIKS KSNSSFEIEM SNIKKPKSRF 910 920 930 940 950 960 IDRVMGILHH VKISNDKIDK EIIQIDEDFV KVTKLRKYFL FFENLTTEKF FHKYVIINNV 970 980 990 1000 1010 1020 VETKFFLVIG LILHLMFYLD DHIMDSAPYF NSNVIYLVMG IAFLVYIGLS FTRIFRTPLV 1030 1040 1050 1060 1070 1080 YQIAFFILLC AFGVCTVLEL IRFQNPLARS SLTRVCATLF YLNVFHSLNF LSVLFLNLFI 1090 1100 1110 1120 1130 1140 FSFFIICSIL ISPTLTNHLY ETDYIGFVIV LLIQICSSYG MKLAMRKAWV VNCKINFKTI 1150 1160 1170 1180 1190 1200 SVNKEKDKFN FLLKSIFPQS ALTKLRDMID TPNIETKGIV YVQPHQDVSI MFIQIAGFQE 1210 1220 1230 1240 1250 1260 YDEPKDLIKK LNDIFSFFDG LLNQKYGGTV EKIKTIGNTY MAVSGLDGSP SFLEKMSDFA 1270 1280 1290 1300 1310 1320 LDVKAYTNSV AISRVVRIGI SHGPLVAGCI GISRAKFDVW GDTANTASRM QSNAQDNEIM 1330 1340 1350 1360 1370 1380 VTHSVYERLN KLFYFDDEKE ILVKGKGKMV THVLKGKKDL EQTNKWFTKP PEVWEVNATP 1390 1400 AGIASPLSGT LLGEIGSFTT PRFHLSS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structurally distinct and stage-specific adenylyl cyclase genes play different roles in Dictyostelium development." Pitt G.S., Milona N., Borleis J., Lin K.C., Reed R.R., Devreotes P.N. Cell 69:305-315(1992) [PubMed: 1348970] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
[2]	"The genome of the social amoeba Dictyostelium discoideum." Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R., Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B., Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T., Lehmann R., Hamlin N. , Davies R., Gaudet P., Fey P., Pilcher K., Chen G., Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N., Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E., Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N., Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D., Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T., Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D., Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A., Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M., Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A., Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y., Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C., Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R., Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A. Nature 435:43-57(2005) [PubMed: 15875012] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: AX4.
[3]	"Extracellular cAMP is sufficient to restore developmental gene expression and morphogenesis in Dictyostelium cells lacking the aggregation adenylyl cyclase (ACA)." Pitt G.S., Brandt R., Lin K.C., Devreotes P.N., Schaap P. Genes Dev. 7:2172-2180(1993) [PubMed: 8224844] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[4]	"Constitutively active adenylyl cyclase mutant requires neither G proteins nor cytosolic regulators." Parent C.A., Devreotes P.N. J. Biol. Chem. 271:18333-18336(1996) [PubMed: 8702473] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF LEU-394.
[5]	"A novel adenylyl cyclase detected in rapidly developing mutants of Dictyostelium." Kim H.-J., Chang W.-T., Meima M., Gross J.D., Schaap P. J. Biol. Chem. 273:30859-30862(1998) [PubMed: 9812977] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[6]	"A temperature-sensitive adenylyl cyclase mutant of Dictyostelium." Patel H., Guo K., Parent C., Gross J., Devreotes P.N., Weijer C.J. EMBO J. 19:2247-2256(2000) [PubMed: 10811616] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF PHE-306; SER-498; LYS-504; GLU-593 AND ILE-649.
[7]	"Adenylyl cyclase A expression is tip-specific in Dictyostelium slugs and directs StatA nuclear translocation and CudA gene expression." Verkerke-van Wijk I., Fukuzawa M., Devreotes P.N., Schaap P. Dev. Biol. 234:151-160(2001) [PubMed: 11356026] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[8]	"Spatial expression patterns of genes involved in cyclic AMP responses in Dictyostelium discoideum development." Tsujioka M., Yokoyama M., Nishio K., Kuwayama H., Morio T., Katoh M., Urushihara H., Saito T., Ochiai H., Tanaka Y., Takeuchi I., Maeda M. Dev. Growth Differ. 43:275-283(2001) [PubMed: 11422293] [Abstract] Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
[9]	"Adenylyl cyclase localization regulates streaming during chemotaxis." Kriebel P.W., Barr V.A., Parent C.A. Cell 112:549-560(2003) [PubMed: 12600317] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, CONSTITUTIVELY ACTIVE MUTANT, DISRUPTION PHENOTYPE.
[10]	"The PI3K-mediated activation of CRAC independently regulates adenylyl cyclase activation and chemotaxis." Comer F.I., Lippincott C.K., Masbad J.J., Parent C.A. Curr. Biol. 15:134-139(2005) [PubMed: 15668169] [Abstract] Cited for: ENZYME REGULATION.
[11]	"Intracellular role of adenylyl cyclase in regulation of lateral pseudopod formation during Dictyostelium chemotaxis." Stepanovic V., Wessels D., Daniels K., Loomis W.F., Soll D.R. Eukaryot. Cell 4:775-786(2005) [PubMed: 15821137] [Abstract] Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[12]	"The C-module DNA-binding factor mediates expression of the dictyostelium aggregation-specific adenylyl cyclase ACA." Siol O., Dingermann T., Winckler T. Eukaryot. Cell 5:658-664(2006) [PubMed: 16607013] [Abstract] Cited for: DEVELOPMENTAL STAGE.
[13]	"Phosphoinositide 3-kinase activity controls the chemoattractant-mediated activation and adaptation of adenylyl cyclase." Comer F.I., Parent C.A. Mol. Biol. Cell 17:357-366(2006) [PubMed: 16267269] [Abstract] Cited for: ENZYME REGULATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	L05499 , L05496, L05497, L05498 Genomic DNA. Translation: AAA33163.1. AAFI02000042 Genomic DNA. Translation: EAL66534.2.
PIR	B42239.
RefSeq	XP_640636.2.
3D structure databases
HSSP	HSSP built from PDB template 1CJK based on UniProtKB P26769.
ModBase	Search...
Genome annotation databases
GeneID	3391609.
GenomeReviews	Gene locus acaA in contig CM000152_GR.
KEGG	ddi:DDB_0214814.
Organism-specific databases
dictyBase	DDB_G0281545. acaA.
Enzyme and pathway databases
BRENDA	4.6.1.1. 424.
Family and domain databases
InterPro	IPR001054. A/G_cyclase. IPR018297. A/G_cyclase_CS. [Graphical view]
Pfam	PF00211. Guanylate_cyc. 2 hits. [Graphical view]
SMART	SM00044. CYCc. 2 hits. [Graphical view]
PROSITE	PS00452. GUANYLATE_CYCLASE_1. 1 hit. PS50125. GUANYLATE_CYCLASE_2. 2 hits. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

CYAA_DICDI

Accession

Primary (citable) accession number: Q03100
Secondary accession number(s): Q54TF5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	May 15, 2007
Last modified:	October 13, 2009
This is version 70 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)