ADCYA_RAT
ID ADCYA_RAT Reviewed; 1608 AA.
AC Q9Z286;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Adenylate cyclase type 10;
DE EC=4.6.1.1 {ECO:0000269|PubMed:12609998, ECO:0000269|PubMed:9874775};
DE AltName: Full=Germ cell soluble adenylyl cyclase {ECO:0000303|PubMed:11423534};
DE Short=sAC;
DE AltName: Full=Testicular soluble adenylyl cyclase;
GN Name=Adcy10; Synonyms=Sac;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 60-67; 254-262 AND 402-409,
RP BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, TISSUE SPECIFICITY,
RP SUBCELLULAR LOCATION, DOMAIN, AND COFACTOR.
RC STRAIN=Sprague-Dawley; TISSUE=Testis;
RX PubMed=9874775; DOI=10.1073/pnas.96.1.79;
RA Buck J., Sinclair M.L., Schapal L., Cann M.J., Levin L.R.;
RT "Cytosolic adenylyl cyclase defines a unique signaling molecule in
RT mammals.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:79-84(1999).
RN [2]
RP ALTERNATIVE SPLICING.
RX PubMed=11423534; DOI=10.1074/jbc.m011698200;
RA Jaiswal B.S., Conti M.;
RT "Identification and functional analysis of splice variants of the germ cell
RT soluble adenylyl cyclase.";
RL J. Biol. Chem. 276:31698-31708(2001).
RN [3]
RP SUBCELLULAR LOCATION.
RX PubMed=12475901; DOI=10.1096/fj.02-0598fje;
RA Zippin J.H., Chen Y., Nahirney P., Kamenetsky M., Wuttke M.S.,
RA Fischman D.A., Levin L.R., Buck J.;
RT "Compartmentalization of bicarbonate-sensitive adenylyl cyclase in distinct
RT signaling microdomains.";
RL FASEB J. 17:82-84(2003).
RN [4]
RP CATALYTIC ACTIVITY, AND ACTIVITY REGULATION.
RX PubMed=12609998; DOI=10.1074/jbc.m212475200;
RA Litvin T.N., Kamenetsky M., Zarifyan A., Buck J., Levin L.R.;
RT "Kinetic properties of 'soluble' adenylyl cyclase. Synergism between
RT calcium and bicarbonate.";
RL J. Biol. Chem. 278:15922-15926(2003).
CC -!- FUNCTION: Catalyzes the formation of the signaling molecule cAMP
CC (PubMed:9874775). May function as sensor that mediates responses to
CC changes in cellular bicarbonate and CO(2) levels (By similarity). Has a
CC critical role in mammalian spermatogenesis by producing the cAMP which
CC regulates cAMP-responsive nuclear factors indispensable for sperm
CC maturation in the epididymis. Induces capacitation, the maturational
CC process that sperm undergo prior to fertilization (By similarity).
CC Involved in ciliary beat regulation (By similarity).
CC {ECO:0000250|UniProtKB:Q8C0T9, ECO:0000250|UniProtKB:Q96PN6,
CC ECO:0000269|PubMed:9874775}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP = 3',5'-cyclic AMP + diphosphate; Xref=Rhea:RHEA:15389,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:58165; EC=4.6.1.1;
CC Evidence={ECO:0000269|PubMed:12609998, ECO:0000269|PubMed:9874775};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000305|PubMed:9874775};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:9874775};
CC Note=Binds 2 magnesium ions per subunit (By similarity). Is also active
CC with manganese (in vitro) (PubMed:9874775).
CC {ECO:0000250|UniProtKB:Q96PN6, ECO:0000269|PubMed:9874775};
CC -!- ACTIVITY REGULATION: Activated by manganese or magnesium ions
CC (PubMed:9874775). In the presence of magnesium ions, the enzyme is
CC activated by bicarbonate (PubMed:12609998). Calcium mildly increases
CC the enzyme activity, also in the presence of magnesium ions.
CC {ECO:0000250|UniProtKB:Q96PN6, ECO:0000269|PubMed:12609998,
CC ECO:0000269|PubMed:9874775}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=1 mM for ATP-Mn(2+) {ECO:0000269|PubMed:9874775};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q96PN6};
CC Peripheral membrane protein {ECO:0000250|UniProtKB:Q96PN6}; Cytoplasmic
CC side {ECO:0000250|UniProtKB:Q96PN6}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q96PN6}. Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:Q96PN6}. Nucleus {ECO:0000269|PubMed:12475901}.
CC Cell projection, cilium {ECO:0000250|UniProtKB:Q96PN6}. Cytoplasm
CC {ECO:0000269|PubMed:9874775}. Mitochondrion
CC {ECO:0000269|PubMed:12475901}. Note=Distributed to subcellular
CC compartments containing cAMP targets. Found as a plasma membrane-
CC associated protein, protein concentrated in the perinuclear region and
CC protein colocalized with actin or tubulin.
CC {ECO:0000250|UniProtKB:Q96PN6}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=1;
CC Comment=A number of isoforms are produced.;
CC Name=1;
CC IsoId=Q9Z286-1; Sequence=Displayed;
CC -!- TISSUE SPECIFICITY: Detected in testis (at protein level).
CC Preferentially expressed in testis. {ECO:0000269|PubMed:9874775}.
CC -!- DOMAIN: The N-terminal guanylate cyclase domains are required for
CC enzyme activity. Fragments containing the first 470 amino acid residues
CC are fully active. {ECO:0000269|PubMed:9874775}.
CC -!- PTM: Cleavage may occur to generate the active 48 kDa form.
CC {ECO:0000305|PubMed:9874775}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF081941; AAD04035.1; -; mRNA.
DR PIR; T17201; T17201.
DR RefSeq; NP_067716.1; NM_021684.1. [Q9Z286-1]
DR RefSeq; XP_008767899.1; XM_008769677.2. [Q9Z286-1]
DR RefSeq; XP_008767900.1; XM_008769678.2. [Q9Z286-1]
DR RefSeq; XP_008767901.1; XM_008769679.2. [Q9Z286-1]
DR AlphaFoldDB; Q9Z286; -.
DR SMR; Q9Z286; -.
DR STRING; 10116.ENSRNOP00000004326; -.
DR PaxDb; Q9Z286; -.
DR PRIDE; Q9Z286; -.
DR Ensembl; ENSRNOT00000082677; ENSRNOP00000072356; ENSRNOG00000053410. [Q9Z286-1]
DR GeneID; 59320; -.
DR KEGG; rno:59320; -.
DR UCSC; RGD:708450; rat. [Q9Z286-1]
DR CTD; 55811; -.
DR RGD; 708450; Adcy10.
DR eggNOG; ENOG502QPPT; Eukaryota.
DR GeneTree; ENSGT00390000001322; -.
DR HOGENOM; CLU_004055_1_0_1; -.
DR InParanoid; Q9Z286; -.
DR OMA; TVDIRLN; -.
DR OrthoDB; 37924at2759; -.
DR PhylomeDB; Q9Z286; -.
DR BRENDA; 4.6.1.1; 5301.
DR Reactome; R-RNO-5610787; Hedgehog 'off' state.
DR SABIO-RK; Q9Z286; -.
DR PRO; PR:Q9Z286; -.
DR Proteomes; UP000002494; Chromosome 13.
DR Bgee; ENSRNOG00000053410; Expressed in testis and 7 other tissues.
DR Genevisible; Q9Z286; RN.
DR GO; GO:0045177; C:apical part of cell; IDA:RGD.
DR GO; GO:0016324; C:apical plasma membrane; ISO:RGD.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0045178; C:basal part of cell; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0005576; C:extracellular region; IEA:GOC.
DR GO; GO:0030426; C:growth cone; IDA:RGD.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0015630; C:microtubule cytoskeleton; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0031514; C:motile cilium; IEA:Ensembl.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0004016; F:adenylate cyclase activity; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0051117; F:ATPase binding; IPI:RGD.
DR GO; GO:0071890; F:bicarbonate binding; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0030145; F:manganese ion binding; IDA:RGD.
DR GO; GO:0006171; P:cAMP biosynthetic process; IDA:RGD.
DR GO; GO:0071241; P:cellular response to inorganic substance; ISS:UniProtKB.
DR GO; GO:0003351; P:epithelial cilium movement involved in extracellular fluid movement; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:RGD.
DR GO; GO:0007283; P:spermatogenesis; IEA:InterPro.
DR CDD; cd07302; CHD; 2.
DR Gene3D; 3.30.70.1230; -; 2.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR001054; A/G_cyclase.
DR InterPro; IPR016577; Adenylate_cyclase_typ10.
DR InterPro; IPR029787; Nucleotide_cyclase.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR Pfam; PF00211; Guanylate_cyc; 2.
DR PIRSF; PIRSF011131; Soluble_adenylyl_cyclase; 1.
DR SMART; SM00044; CYCc; 1.
DR SUPFAM; SSF48452; SSF48452; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF55073; SSF55073; 2.
DR PROSITE; PS50125; GUANYLATE_CYCLASE_2; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; cAMP biosynthesis; Cell membrane;
KW Cell projection; Cytoplasm; Cytoskeleton; Direct protein sequencing; Lyase;
KW Magnesium; Membrane; Metal-binding; Mitochondrion; Nucleotide-binding;
KW Nucleus; Reference proteome; Repeat.
FT CHAIN 1..1608
FT /note="Adenylate cyclase type 10"
FT /id="PRO_0000317104"
FT DOMAIN 42..179
FT /note="Guanylate cyclase 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT DOMAIN 293..418
FT /note="Guanylate cyclase 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 47..52
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q96PN6"
FT BINDING 47
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 47
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 48
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 95
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /evidence="ECO:0000250|UniProtKB:Q96PN6"
FT BINDING 99
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q96PN6"
FT BINDING 99
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 99
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT BINDING 144
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q96PN6"
FT BINDING 167
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /evidence="ECO:0000250|UniProtKB:Q96PN6"
FT BINDING 176
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /evidence="ECO:0000250|UniProtKB:Q96PN6"
FT BINDING 337
FT /ligand="hydrogencarbonate"
FT /ligand_id="ChEBI:CHEBI:17544"
FT /evidence="ECO:0000250|UniProtKB:Q96PN6"
FT BINDING 406
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q96PN6"
FT BINDING 412..416
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q96PN6"
SQ SEQUENCE 1608 AA; 185854 MW; BEF6D3F60A5D2556 CRC64;
MSARRQELQD RAIVKIAAHL PDLIVYGDFS PERPSVKCFD GVLMFVDISG FTAMTEKFST
AMYMDRGAEQ LVEILNYYIS AIVEKVLIFG GDILKFAGDA LLALWKVERK QLKNIITVVI
KCSLEIHGLF EAKEVEEGLD IRVKIGLAAG HITMLVFGDE TRNYFLVIGQ AVDDVRLAQN
MAQMNDVILS PNCWQLCDRS MIEIERIPDQ RAVKVSFLKP PPTFNFDEFF AKCMAFMDYY
PSGDHKNFLR LACMLESDPE LELSLQKYVM EIILKQIDDK QLRGYLSELR PVTIVFVNLM
FKEQDKAEVI GSAIQAACVH ITSVLKVFRG QINKVFMFDK GCSFLCVFGF PGEKAPDEIT
HALESAVDIF DFCSQVHKIR TVSIGVASGI VFCGIVGHTV RHEYTVIGQK VNIAARMMMY
YPGIVTCDSV TYDGSNLPAY FFKELPKKVM KGVADPGPVY QCLGLNEKVM FGMAYLICNR
YEGYPLLGRV REIDYFMSTM KDFLMTNCSR VLMYEGLPGY GKSQVLMEIE YLASQHENHR
AVAIALTKIS FHQNFYTIQI LMANVLGLDT CKHYKERQTN LQNRVKTLLD DKYHCLLNDI
FHVQFPVSRE MSRMSKIRKQ KQLEALFMKI LEQTVREERI IFIIDEAQFV DVASWAFIEK
LIRSMPIFIV MSLCPFPETP CAAANAIMKN RNTTYITLGT MQPQEIRDKV CVDLSVSSIP
RELDSYLVEG SCGIPYYCEE LLKNLDHHRI LIFQQAEAEE KTNVTWNNLF KYSVKPTEDM
YLYTSIAAGQ KEACYLTSGV RLKNLSPPAS LKEISLVQLD SMSLSHQMLV RCAAIIGLTF
TTELLFEILP CWNMKMMIKA LATLVESNVF DCFRSSKDLQ LALKQNVTTF EVHYRSLSLK
SKEGLAYSEE EQLREMEGEV IECRILRFCR PIMQKTAYEL WLKDQKKVLH LKCARFLEES
AHRCNHCRNR DFIPYHHFIA DIRLNTLDMD TVKKMVKSHG FKTEDEVIFS KSEIPRKFKF
PENISITETR EKILHFFDNV IIKMRTSQDD VIPLESCHCE ELLQIVILPL AQHFVALEEN
NKALYYFLEL ASAYLILGDN YNAYMYLGEG ERLLKSLTNE DSWSQTFEYA TFYSLKGEIC
FNMGQMVLAK KMLRKALKLL NRMFPCNLLS LTFQMHIEKN RLSHFMNQHT QEGSLPGKKL
AQLFLQSSCF SLLWKIYSLN FFFHYKYYGR LAAIMQMNTS LETQNNFQII KAFLDFSLYR
HLAGYEGVWF KYEILVMEQL LNLPLKGEAF EIMAYAADAL GHIKFLTGHL DLAIELGSRA
HKMWSLLRNP NKYHMVLCRL SKPLFLKSRY KHLVQVLGWL WDLSVTEEHI FSKAFFYFVC
LDIMLYSGFI YRTFEECLEF IHHNEDNRIL KFQSGLLLGL YSCIAVWYAR LQEWDNFYKF
SNRAKTLVTR RTPTVLYYEG ISRYMEGQVL HLQKQIEEQA ENAQDSGVEL LKALETLVAQ
NTTGPVFYPR LYHLMAYVCI LMGDGHSCDF FLNTALELSE TQGNLLEKCW LSMSKEWWYS
APELTGDQWL QTVLSLPSWD KIVSGNVTLQ DVQKNKFLMR VNILDNPF
