ID   GCYA1_HUMAN             Reviewed;         690 AA.
AC   Q02108; D3DP19; D6RDW3; O43843; Q8TAH3;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   30-MAY-2000, sequence version 2.
DT   28-JUN-2023, entry version 201.
DE   RecName: Full=Guanylate cyclase soluble subunit alpha-1 {ECO:0000305};
DE            Short=GCS-alpha-1;
DE            EC=4.6.1.2 {ECO:0000269|PubMed:23505436, ECO:0000269|PubMed:24669844, ECO:0000269|PubMed:9742212};
DE   AltName: Full=Guanylate cyclase soluble subunit alpha-3 {ECO:0000303|PubMed:1352257};
DE            Short=GCS-alpha-3;
DE   AltName: Full=Soluble guanylate cyclase large subunit;
GN   Name=GUCY1A1 {ECO:0000312|HGNC:HGNC:4685};
GN   Synonyms=GUC1A3, GUCSA3, GUCY1A3;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Brain;
RX   PubMed=1352257; DOI=10.1016/0014-5793(92)80594-7;
RA   Giuili G., Scholl U., Bulle F., Guellaeen G.;
RT   "Molecular cloning of the cDNAs coding for the two subunits of soluble
RT   guanylyl cyclase from human brain.";
RL   FEBS Lett. 304:83-88(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Kidney;
RA   Gansemans Y., Brouckaert P., Fiers W.;
RT   "Human soluble guanylate cyclase large subunit mRNA, alpha3-like.";
RL   Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CATALYTIC ACTIVITY, ACTIVITY
RP   REGULATION, SUBUNIT, INTERACTION WITH GUCY1B1, AND TISSUE SPECIFICITY.
RC   TISSUE=Brain;
RX   PubMed=9742212; DOI=10.1042/bj3350051;
RA   Zabel U., Weeger M., La M., Schmidt H.H.;
RT   "Human soluble guanylate cyclase: functional expression and revised
RT   isoenzyme family.";
RL   Biochem. J. 335:51-57(1998).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Placenta;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA   Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA   Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA   Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA   Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA   Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA   Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA   Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA   Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA   Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA   Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA   Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA   Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA   Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA   Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA   Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA   Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA   Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT   4.";
RL   Nature 434:724-731(2005).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [8] {ECO:0007744|PDB:3UVJ}
RP   X-RAY CRYSTALLOGRAPHY (2.08 ANGSTROMS) OF 468-690 IN COMPLEX WITH GUCY1B1,
RP   CATALYTIC ACTIVITY, ACTIVITY REGULATION, COFACTOR, AND INTERACTION WITH
RP   GUCY1B1.
RX   PubMed=23505436; DOI=10.1371/journal.pone.0057644;
RA   Allerston C.K., von Delft F., Gileadi O.;
RT   "Crystal structures of the catalytic domain of human soluble guanylate
RT   cyclase.";
RL   PLoS ONE 8:E57644-E57644(2013).
RN   [9]
RP   INVOLVEMENT IN MYMY6.
RX   PubMed=24581742; DOI=10.1016/j.ajhg.2014.01.018;
RA   Herve D., Philippi A., Belbouab R., Zerah M., Chabrier S.,
RA   Collardeau-Frachon S., Bergametti F., Essongue A., Berrou E., Krivosic V.,
RA   Sainte-Rose C., Houdart E., Adam F., Billiemaz K., Lebret M., Roman S.,
RA   Passemard S., Boulday G., Delaforge A., Guey S., Dray X., Chabriat H.,
RA   Brouckaert P., Bryckaert M., Tournier-Lasserve E.;
RT   "Loss of alpha1beta1 soluble guanylate cyclase, the major nitric oxide
RT   receptor, leads to moyamoya and achalasia.";
RL   Am. J. Hum. Genet. 94:385-394(2014).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 468-662 IN COMPLEX WITH GUCY1B1,
RP   INTERACTION WITH GUCY1B1, CATALYTIC ACTIVITY, AND COFACTOR.
RX   PubMed=24669844; DOI=10.1021/bi500129k;
RA   Seeger F., Quintyn R., Tanimoto A., Williams G.J., Tainer J.A.,
RA   Wysocki V.H., Garcin E.D.;
RT   "Interfacial residues promote an optimal alignment of the catalytic center
RT   in human soluble guanylate cyclase: heterodimerization is required but not
RT   sufficient for activity.";
RL   Biochemistry 53:2153-2165(2014).
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=GTP = 3',5'-cyclic GMP + diphosphate; Xref=Rhea:RHEA:13665,
CC         ChEBI:CHEBI:33019, ChEBI:CHEBI:37565, ChEBI:CHEBI:57746; EC=4.6.1.2;
CC         Evidence={ECO:0000269|PubMed:23505436, ECO:0000269|PubMed:24669844,
CC         ECO:0000269|PubMed:9742212};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC         Evidence={ECO:0000269|PubMed:23505436, ECO:0000269|PubMed:24669844};
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000269|PubMed:23505436, ECO:0000269|PubMed:24669844};
CC       Note=Has also activity with Mn(2+) (in vitro).
CC       {ECO:0000269|PubMed:23505436, ECO:0000269|PubMed:24669844};
CC   -!- ACTIVITY REGULATION: Activated by nitric oxide in the presence of
CC       magnesium or manganese ions. {ECO:0000269|PubMed:9742212}.
CC   -!- SUBUNIT: The active enzyme is formed by a heterodimer of an alpha and a
CC       beta subunit. Heterodimer with GUCY1B1 (PubMed:9742212,
CC       PubMed:23505436, PubMed:24669844). {ECO:0000269|PubMed:23505436,
CC       ECO:0000269|PubMed:24669844, ECO:0000269|PubMed:9742212}.
CC   -!- INTERACTION:
CC       Q02108; Q02153: GUCY1B1; NbExp=2; IntAct=EBI-3910037, EBI-6911707;
CC       Q02108-1; Q02153-1: GUCY1B1; NbExp=2; IntAct=EBI-25372173, EBI-25372164;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q02108-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q02108-2; Sequence=VSP_045477;
CC   -!- TISSUE SPECIFICITY: Detected in brain cortex and lung (at protein
CC       level). {ECO:0000269|PubMed:1352257}.
CC   -!- DISEASE: Moyamoya disease 6 with or without achalasia (MYMY6)
CC       [MIM:615750]: A form of Moyamoya disease, a progressive cerebral
CC       angiopathy characterized by bilateral intracranial carotid artery
CC       stenosis and telangiectatic vessels in the region of the basal ganglia.
CC       The abnormal vessels resemble a 'puff of smoke' (moyamoya) on cerebral
CC       angiogram. Affected individuals can develop transient ischemic attacks
CC       and/or cerebral infarction, and rupture of the collateral vessels can
CC       cause intracranial hemorrhage. Hemiplegia of sudden onset and epileptic
CC       seizures constitute the prevailing presentation in childhood, while
CC       subarachnoid bleeding occurs more frequently in adults. MYMY6 is
CC       characterized by severe cerebral angiopathy and onset of severe
CC       achalasia in infancy or early childhood. {ECO:0000269|PubMed:24581742}.
CC       Note=The disease is caused by variants affecting the gene represented
CC       in this entry.
CC   -!- MISCELLANEOUS: There are two types of guanylate cyclases: soluble forms
CC       and membrane-associated receptor forms.
CC   -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC       family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA47145.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; X66534; CAA47145.1; ALT_FRAME; mRNA.
DR   EMBL; U58855; AAB94794.1; -; mRNA.
DR   EMBL; Y15723; CAA75738.1; -; mRNA.
DR   EMBL; AK309950; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AC104083; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471056; EAX04892.1; -; Genomic_DNA.
DR   EMBL; CH471056; EAX04895.1; -; Genomic_DNA.
DR   EMBL; CH471056; EAX04896.1; -; Genomic_DNA.
DR   EMBL; CH471056; EAX04897.1; -; Genomic_DNA.
DR   EMBL; BC028384; AAH28384.1; -; mRNA.
DR   CCDS; CCDS34085.1; -. [Q02108-1]
DR   CCDS; CCDS54812.1; -. [Q02108-2]
DR   PIR; S23098; S23098.
DR   RefSeq; NP_000847.2; NM_000856.5. [Q02108-1]
DR   RefSeq; NP_001124154.1; NM_001130682.2. [Q02108-1]
DR   RefSeq; NP_001124155.1; NM_001130683.3. [Q02108-1]
DR   RefSeq; NP_001124156.1; NM_001130684.2. [Q02108-1]
DR   RefSeq; NP_001124159.1; NM_001130687.2. [Q02108-2]
DR   RefSeq; NP_001243378.1; NM_001256449.1. [Q02108-1]
DR   RefSeq; XP_005263012.1; XM_005262955.2.
DR   RefSeq; XP_006714259.1; XM_006714196.2.
DR   RefSeq; XP_006714260.1; XM_006714197.2.
DR   PDB; 3UVJ; X-ray; 2.08 A; A/C=468-690.
DR   PDB; 4NI2; X-ray; 1.90 A; A=468-662.
DR   PDB; 6JT0; EM; 4.00 A; A=1-690.
DR   PDB; 6JT1; EM; 3.90 A; A=1-690.
DR   PDB; 6JT2; EM; 3.80 A; A=1-690.
DR   PDB; 7D9R; EM; 3.30 A; A=1-690.
DR   PDB; 7D9S; EM; 3.40 A; A=1-690.
DR   PDB; 7D9T; EM; 4.10 A; A=1-690.
DR   PDB; 7D9U; EM; 3.80 A; A=1-690.
DR   PDBsum; 3UVJ; -.
DR   PDBsum; 4NI2; -.
DR   PDBsum; 6JT0; -.
DR   PDBsum; 6JT1; -.
DR   PDBsum; 6JT2; -.
DR   PDBsum; 7D9R; -.
DR   PDBsum; 7D9S; -.
DR   PDBsum; 7D9T; -.
DR   PDBsum; 7D9U; -.
DR   AlphaFoldDB; Q02108; -.
DR   SMR; Q02108; -.
DR   BioGRID; 109237; 44.
DR   ComplexPortal; CPX-928; Soluble guanylate cyclase complex, SGCalpha1-SGCbeta1 variant.
DR   CORUM; Q02108; -.
DR   IntAct; Q02108; 5.
DR   STRING; 9606.ENSP00000296518; -.
DR   BindingDB; Q02108; -.
DR   ChEMBL; CHEMBL3137281; -.
DR   DrugBank; DB09401; Isosorbide.
DR   DrugCentral; Q02108; -.
DR   GuidetoPHARMACOLOGY; 1288; -.
DR   iPTMnet; Q02108; -.
DR   PhosphoSitePlus; Q02108; -.
DR   BioMuta; GUCY1A3; -.
DR   DMDM; 7404351; -.
DR   jPOST; Q02108; -.
DR   MassIVE; Q02108; -.
DR   MaxQB; Q02108; -.
DR   PaxDb; Q02108; -.
DR   PeptideAtlas; Q02108; -.
DR   ProteomicsDB; 14181; -.
DR   ProteomicsDB; 58050; -. [Q02108-1]
DR   Antibodypedia; 4394; 334 antibodies from 35 providers.
DR   DNASU; 2982; -.
DR   Ensembl; ENST00000296518.11; ENSP00000296518.7; ENSG00000164116.17. [Q02108-1]
DR   Ensembl; ENST00000455639.6; ENSP00000412201.2; ENSG00000164116.17. [Q02108-1]
DR   Ensembl; ENST00000506455.6; ENSP00000424361.1; ENSG00000164116.17. [Q02108-1]
DR   Ensembl; ENST00000511108.5; ENSP00000421493.1; ENSG00000164116.17. [Q02108-1]
DR   Ensembl; ENST00000511507.5; ENSP00000426968.1; ENSG00000164116.17. [Q02108-2]
DR   Ensembl; ENST00000513574.1; ENSP00000426040.1; ENSG00000164116.17. [Q02108-1]
DR   GeneID; 2982; -.
DR   KEGG; hsa:2982; -.
DR   MANE-Select; ENST00000506455.6; ENSP00000424361.1; NM_001130682.3; NP_001124154.1.
DR   UCSC; uc003iov.4; human. [Q02108-1]
DR   AGR; HGNC:4685; -.
DR   CTD; 2982; -.
DR   DisGeNET; 2982; -.
DR   GeneCards; GUCY1A1; -.
DR   HGNC; HGNC:4685; GUCY1A1.
DR   HPA; ENSG00000164116; Low tissue specificity.
DR   MalaCards; GUCY1A1; -.
DR   MIM; 139396; gene.
DR   MIM; 615750; phenotype.
DR   neXtProt; NX_Q02108; -.
DR   OpenTargets; ENSG00000164116; -.
DR   Orphanet; 401945; Moyamoya disease with early-onset achalasia.
DR   PharmGKB; PA29067; -.
DR   VEuPathDB; HostDB:ENSG00000164116; -.
DR   eggNOG; KOG4171; Eukaryota.
DR   GeneTree; ENSGT00940000158285; -.
DR   HOGENOM; CLU_011614_5_0_1; -.
DR   InParanoid; Q02108; -.
DR   OMA; NANFFGE; -.
DR   OrthoDB; 2898719at2759; -.
DR   PhylomeDB; Q02108; -.
DR   TreeFam; TF351403; -.
DR   BRENDA; 4.6.1.2; 2681.
DR   PathwayCommons; Q02108; -.
DR   Reactome; R-HSA-392154; Nitric oxide stimulates guanylate cyclase.
DR   Reactome; R-HSA-445355; Smooth Muscle Contraction.
DR   SignaLink; Q02108; -.
DR   SIGNOR; Q02108; -.
DR   BioGRID-ORCS; 2982; 9 hits in 1146 CRISPR screens.
DR   ChiTaRS; GUCY1A3; human.
DR   GeneWiki; GUCY1A3; -.
DR   GenomeRNAi; 2982; -.
DR   Pharos; Q02108; Tclin.
DR   PRO; PR:Q02108; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   RNAct; Q02108; protein.
DR   Bgee; ENSG00000164116; Expressed in urethra and 204 other tissues.
DR   ExpressionAtlas; Q02108; baseline and differential.
DR   Genevisible; Q02108; HS.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl.
DR   GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR   GO; GO:0008074; C:guanylate cyclase complex, soluble; IDA:UniProtKB.
DR   GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004383; F:guanylate cyclase activity; IDA:UniProtKB.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0038023; F:signaling receptor activity; TAS:ProtInc.
DR   GO; GO:0008015; P:blood circulation; TAS:ProtInc.
DR   GO; GO:0006182; P:cGMP biosynthetic process; IDA:UniProtKB.
DR   GO; GO:0019934; P:cGMP-mediated signaling; IBA:GO_Central.
DR   GO; GO:0007263; P:nitric oxide mediated signal transduction; TAS:ProtInc.
DR   GO; GO:0038060; P:nitric oxide-cGMP-mediated signaling pathway; IDA:ComplexPortal.
DR   GO; GO:0010750; P:positive regulation of nitric oxide mediated signal transduction; IEA:Ensembl.
DR   GO; GO:0008217; P:regulation of blood pressure; IEA:Ensembl.
DR   GO; GO:0060087; P:relaxation of vascular associated smooth muscle; IEA:Ensembl.
DR   GO; GO:0070482; P:response to oxygen levels; IBA:GO_Central.
DR   GO; GO:0098925; P:retrograde trans-synaptic signaling by nitric oxide, modulating synaptic transmission; IEA:Ensembl.
DR   CDD; cd07302; CHD; 1.
DR   Gene3D; 6.10.250.780; -; 1.
DR   Gene3D; 3.90.1520.10; H-NOX domain; 1.
DR   Gene3D; 3.30.450.260; Haem NO binding associated domain; 1.
DR   Gene3D; 3.30.70.1230; Nucleotide cyclase; 1.
DR   InterPro; IPR001054; A/G_cyclase.
DR   InterPro; IPR018297; A/G_cyclase_CS.
DR   InterPro; IPR038158; H-NOX_domain_sf.
DR   InterPro; IPR011645; HNOB_dom_associated.
DR   InterPro; IPR042463; HNOB_dom_associated_sf.
DR   InterPro; IPR024096; NO_sig/Golgi_transp_ligand-bd.
DR   InterPro; IPR029787; Nucleotide_cyclase.
DR   PANTHER; PTHR45655:SF4; GUANYLATE CYCLASE SOLUBLE SUBUNIT ALPHA-1; 1.
DR   PANTHER; PTHR45655; GUANYLATE CYCLASE SOLUBLE SUBUNIT BETA-2; 1.
DR   Pfam; PF00211; Guanylate_cyc; 1.
DR   Pfam; PF07701; HNOBA; 1.
DR   SMART; SM00044; CYCc; 1.
DR   SUPFAM; SSF111126; Ligand-binding domain in the NO signalling and Golgi transport; 1.
DR   SUPFAM; SSF55073; Nucleotide cyclase; 1.
DR   PROSITE; PS00452; GUANYLATE_CYCLASE_1; 1.
DR   PROSITE; PS50125; GUANYLATE_CYCLASE_2; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; cGMP biosynthesis; Cytoplasm;
KW   GTP-binding; Lyase; Nucleotide-binding; Phosphoprotein; Reference proteome.
FT   CHAIN           1..690
FT                   /note="Guanylate cyclase soluble subunit alpha-1"
FT                   /id="PRO_0000074110"
FT   DOMAIN          481..608
FT                   /note="Guanylate cyclase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT   MOD_RES         267
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9ERL9"
FT   VAR_SEQ         625..690
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_045477"
FT   VARIANT         25
FT                   /note="V -> I (in dbSNP:rs2170646)"
FT                   /id="VAR_049257"
FT   CONFLICT        44
FT                   /note="V -> M (in Ref. 7; AAH28384)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        124..127
FT                   /note="AAGV -> QQS (in Ref. 1; CAA47145)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        322
FT                   /note="Missing (in Ref. 1; CAA47145)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        497
FT                   /note="C -> R (in Ref. 4; AK309950)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        554
FT                   /note="L -> V (in Ref. 7; AAH28384)"
FT                   /evidence="ECO:0000305"
FT   HELIX           71..82
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   HELIX           86..100
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   HELIX           115..125
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   HELIX           129..145
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   TURN            146..148
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   STRAND          149..153
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   HELIX           159..164
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   TURN            165..170
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   HELIX           211..225
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   HELIX           279..285
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   STRAND          287..293
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   HELIX           303..308
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   TURN            321..323
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   STRAND          324..326
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   HELIX           335..340
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   STRAND          342..344
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   STRAND          346..350
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   STRAND          364..373
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   TURN            374..377
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   STRAND          378..385
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   TURN            400..402
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   STRAND          405..408
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   HELIX           409..457
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   HELIX           460..467
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   STRAND          472..487
FT                   /evidence="ECO:0007829|PDB:4NI2"
FT   HELIX           490..496
FT                   /evidence="ECO:0007829|PDB:4NI2"
FT   HELIX           499..519
FT                   /evidence="ECO:0007829|PDB:4NI2"
FT   STRAND          523..525
FT                   /evidence="ECO:0007829|PDB:4NI2"
FT   STRAND          533..540
FT                   /evidence="ECO:0007829|PDB:4NI2"
FT   HELIX           545..560
FT                   /evidence="ECO:0007829|PDB:4NI2"
FT   STRAND          568..570
FT                   /evidence="ECO:0007829|PDB:4NI2"
FT   STRAND          573..587
FT                   /evidence="ECO:0007829|PDB:4NI2"
FT   STRAND          589..591
FT                   /evidence="ECO:0007829|PDB:4NI2"
FT   STRAND          593..598
FT                   /evidence="ECO:0007829|PDB:4NI2"
FT   HELIX           599..609
FT                   /evidence="ECO:0007829|PDB:4NI2"
FT   STRAND          616..618
FT                   /evidence="ECO:0007829|PDB:4NI2"
FT   HELIX           620..626
FT                   /evidence="ECO:0007829|PDB:4NI2"
FT   STRAND          632..636
FT                   /evidence="ECO:0007829|PDB:4NI2"
FT   HELIX           639..641
FT                   /evidence="ECO:0007829|PDB:7D9R"
FT   STRAND          655..660
FT                   /evidence="ECO:0007829|PDB:4NI2"
SQ   SEQUENCE   690 AA;  77452 MW;  DA1E14A5E11451CF CRC64;
     MFCTKLKDLK ITGECPFSLL APGQVPNESS EEAAGSSESC KATVPICQDI PEKNIQESLP
     QRKTSRSRVY LHTLAESICK LIFPEFERLN VALQRTLAKH KIKESRKSLE REDFEKTIAE
     QAVAAGVPVE VIKESLGEEV FKICYEEDEN ILGVVGGTLK DFLNSFSTLL KQSSHCQEAG
     KRGRLEDASI LCLDKEDDFL HVYYFFPKRT TSLILPGIIK AAAHVLYETE VEVSLMPPCF
     HNDCSEFVNQ PYLLYSVHMK STKPSLSPSK PQSSLVIPTS LFCKTFPFHF MFDKDMTILQ
     FGNGIRRLMN RRDFQGKPNF EEYFEILTPK INQTFSGIMT MLNMQFVVRV RRWDNSVKKS
     SRVMDLKGQM IYIVESSAIL FLGSPCVDRL EDFTGRGLYL SDIPIHNALR DVVLIGEQAR
     AQDGLKKRLG KLKATLEQAH QALEEEKKKT VDLLCSIFPC EVAQQLWQGQ VVQAKKFSNV
     TMLFSDIVGF TAICSQCSPL QVITMLNALY TRFDQQCGEL DVYKVETIGD AYCVAGGLHK
     ESDTHAVQIA LMALKMMELS DEVMSPHGEP IKMRIGLHSG SVFAGVVGVK MPRYCLFGNN
     VTLANKFESC SVPRKINVSP TTYRLLKDCP GFVFTPRSRE ELPPNFPSEI PGICHFLDAY
     QQGTNSKPCF QKKDVEDGNA NFLGKASGID
//