LOCUS       NP_000846                732 aa            linear   PRI 29-APR-2025
DEFINITION  guanylate cyclase soluble subunit alpha-2 isoform 2 [Homo sapiens].
ACCESSION   NP_000846
VERSION     NP_000846.1
DBSOURCE    REFSEQ: accession NM_000855.3
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 732)
  AUTHORS   Zhao,D., Dong,Y., Duan,M., He,D., Xie,Q., Peng,W., Cui,W.,
            Jiang,J., Cheng,Y., Zhang,H., Tang,F., Zhang,C., Gao,Y. and Duan,C.
  TITLE     Circadian gene ARNTL initiates circGUCY1A2 transcription to
            suppress non-small cell lung cancer progression via
            miR-200c-3p/PTEN signaling
  JOURNAL   J Exp Clin Cancer Res 42 (1), 229 (2023)
   PUBMED   37667322
  REMARK    GeneRIF: Circadian gene ARNTL initiates circGUCY1A2 transcription
            to suppress non-small cell lung cancer progression via
            miR-200c-3p/PTEN signaling.
            Publication Status: Online-Only
REFERENCE   2  (residues 1 to 732)
  AUTHORS   Luck,K., Kim,D.K., Lambourne,L., Spirohn,K., Begg,B.E., Bian,W.,
            Brignall,R., Cafarelli,T., Campos-Laborie,F.J., Charloteaux,B.,
            Choi,D., Cote,A.G., Daley,M., Deimling,S., Desbuleux,A., Dricot,A.,
            Gebbia,M., Hardy,M.F., Kishore,N., Knapp,J.J., Kovacs,I.A.,
            Lemmens,I., Mee,M.W., Mellor,J.C., Pollis,C., Pons,C.,
            Richardson,A.D., Schlabach,S., Teeking,B., Yadav,A., Babor,M.,
            Balcha,D., Basha,O., Bowman-Colin,C., Chin,S.F., Choi,S.G.,
            Colabella,C., Coppin,G., D'Amata,C., De Ridder,D., De Rouck,S.,
            Duran-Frigola,M., Ennajdaoui,H., Goebels,F., Goehring,L., Gopal,A.,
            Haddad,G., Hatchi,E., Helmy,M., Jacob,Y., Kassa,Y., Landini,S.,
            Li,R., van Lieshout,N., MacWilliams,A., Markey,D., Paulson,J.N.,
            Rangarajan,S., Rasla,J., Rayhan,A., Rolland,T., San-Miguel,A.,
            Shen,Y., Sheykhkarimli,D., Sheynkman,G.M., Simonovsky,E., Tasan,M.,
            Tejeda,A., Tropepe,V., Twizere,J.C., Wang,Y., Weatheritt,R.J.,
            Weile,J., Xia,Y., Yang,X., Yeger-Lotem,E., Zhong,Q., Aloy,P.,
            Bader,G.D., De Las Rivas,J., Gaudet,S., Hao,T., Rak,J.,
            Tavernier,J., Hill,D.E., Vidal,M., Roth,F.P. and Calderwood,M.A.
  TITLE     A reference map of the human binary protein interactome
  JOURNAL   Nature 580 (7803), 402-408 (2020)
   PUBMED   32296183
REFERENCE   3  (residues 1 to 732)
  AUTHORS   Sundell,G.N., Arnold,R., Ali,M., Naksukpaiboon,P., Orts,J.,
            Guntert,P., Chi,C.N. and Ivarsson,Y.
  TITLE     Proteome-wide analysis of phospho-regulated PDZ domain interactions
  JOURNAL   Mol Syst Biol 14 (8), e8129 (2018)
   PUBMED   30126976
  REMARK    Publication Status: Online-Only
REFERENCE   4  (residues 1 to 732)
  AUTHORS   Otowa,T., Maher,B.S., Aggen,S.H., McClay,J.L., van den Oord,E.J.
            and Hettema,J.M.
  TITLE     Genome-wide and gene-based association studies of anxiety disorders
            in European and African American samples
  JOURNAL   PLoS One 9 (11), e112559 (2014)
   PUBMED   25390645
  REMARK    Publication Status: Online-Only
REFERENCE   5  (residues 1 to 732)
  AUTHORS   Seeger,F., Quintyn,R., Tanimoto,A., Williams,G.J., Tainer,J.A.,
            Wysocki,V.H. and Garcin,E.D.
  TITLE     Interfacial residues promote an optimal alignment of the catalytic
            center in human soluble guanylate cyclase: heterodimerization is
            required but not sufficient for activity
  JOURNAL   Biochemistry 53 (13), 2153-2165 (2014)
   PUBMED   24669844
  REMARK    GeneRIF: The data support a novel regulatory mechanism whereby sGC
            activity is tuned by distinct domain interactions that either
            promote or inhibit catalytic activity.
REFERENCE   6  (residues 1 to 732)
  AUTHORS   Bamberger,A.M., Koglin,M., Kempfert,J., Loning,T., Scholz,H. and
            Behrends,S.
  TITLE     Expression and tissue localization of soluble guanylyl cyclase in
            the human placenta using novel antibodies directed against the
            alpha(2) subunit
  JOURNAL   J Clin Endocrinol Metab 86 (2), 909-912 (2001)
   PUBMED   11158065
REFERENCE   7  (residues 1 to 732)
  AUTHORS   Budworth,J., Meillerais,S., Charles,I. and Powell,K.
  TITLE     Tissue distribution of the human soluble guanylate cyclases
  JOURNAL   Biochem Biophys Res Commun 263 (3), 696-701 (1999)
   PUBMED   10512742
REFERENCE   8  (residues 1 to 732)
  AUTHORS   Yu,F., Warburton,D., Wellington,S. and Danziger,R.S.
  TITLE     Assignment of GUCIA2, the gene coding for the alpha 2 subunit of
            soluble guanylyl cyclase, to position 11q21-q22 on human chromosome
            11
  JOURNAL   Genomics 33 (2), 334-336 (1996)
   PUBMED   8660992
REFERENCE   9  (residues 1 to 732)
  AUTHORS   Behrends,S., Harteneck,C., Schultz,G. and Koesling,D.
  TITLE     A variant of the alpha 2 subunit of soluble guanylyl cyclase
            contains an insert homologous to a region within adenylyl cyclases
            and functions as a dominant negative protein
  JOURNAL   J Biol Chem 270 (36), 21109-21113 (1995)
   PUBMED   7673142
REFERENCE   10 (residues 1 to 732)
  AUTHORS   Harteneck,C., Wedel,B., Koesling,D., Malkewitz,J., Bohme,E. and
            Schultz,G.
  TITLE     Molecular cloning and expression of a new alpha-subunit of soluble
            guanylyl cyclase. Interchangeability of the alpha-subunits of the
            enzyme
  JOURNAL   FEBS Lett 292 (1-2), 217-222 (1991)
   PUBMED   1683630
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from AP003078.2, X63282.1,
            AP005014.3 and CA774108.1.
            
            Summary: Soluble guanylate cyclases are heterodimeric proteins that
            catalyze the conversion of GTP to 3',5'-cyclic GMP and
            pyrophosphate. The protein encoded by this gene is an alpha subunit
            of this complex and it interacts with a beta subunit to form the
            guanylate cyclase enzyme, which is activated by nitric oxide. Two
            transcript variants encoding different isoforms have been found for
            this gene. [provided by RefSeq, Jan 2012].
            
            Transcript Variant: This variant (2) lacks an alternate in-frame
            exon compared to variant 1. The resulting isoform (2) has the same
            N- and C-termini but is shorter compared to isoform 1.
            
            Sequence Note: This RefSeq record was created from transcript and
            genomic sequence data to make the sequence consistent with the
            reference genome assembly. The genomic coordinates used for the
            transcript record were based on transcript alignments.
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: X63282.1, BC130488.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000526355.7/ ENSP00000431245.2
            RefSeq Select criteria :: based on manual assertion, conservation,
                                      expression
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..732
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="11"
                     /map="11q22.3"
     Protein         1..732
                     /product="guanylate cyclase soluble subunit alpha-2
                     isoform 2"
                     /EC_number="4.6.1.2"
                     /note="guanylate cyclase soluble subunit alpha-2;
                     GCS-alpha-2; guanylate cyclase 1, soluble, alpha 2"
                     /calculated_mol_wt=81619
     Region          1..58
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (P33402.1)"
     Region          <159..270
                     /region_name="HNOB"
                     /note="Haem-NO-binding; pfam07700"
                     /db_xref="CDD:462233"
     Region          316..503
                     /region_name="HNOBA"
                     /note="Heme NO binding associated; pfam07701"
                     /db_xref="CDD:462234"
     Region          514..698
                     /region_name="Guanylate_cyc"
                     /note="Adenylate and Guanylate cyclase catalytic domain;
                     pfam00211"
                     /db_xref="CDD:425528"
     Site            order(524,526..531,566,568..570,573,635..637,641..642,
                     645..646,683)
                     /site_type="active"
                     /note="nucleotidyl binding site [active]"
                     /db_xref="CDD:143636"
     Site            order(526,570)
                     /site_type="metal-binding"
                     /note="metal binding site [ion binding]"
                     /db_xref="CDD:143636"
     Site            order(531,543,546..547,550,554,566..567,623,626,636..639,
                     642,683)
                     /site_type="other"
                     /note="dimer interface [polypeptide binding]"
                     /db_xref="CDD:143636"
     CDS             1..732
                     /gene="GUCY1A2"
                     /gene_synonym="GC-SA2; GUC1A2"
                     /coded_by="NM_000855.3:422..2620"
                     /note="isoform 2 is encoded by transcript variant 2"
                     /db_xref="CCDS:CCDS8335.1"
                     /db_xref="GeneID:2977"
                     /db_xref="HGNC:HGNC:4684"
                     /db_xref="MIM:601244"
ORIGIN      
        1 msrrkisses fsslgsdyle tspeeegecp lsrlcwngsr sppgplepsp aaaaaaaapa
       61 ptpaasaaaa aatagarrvq rrrrvnldsl gesisrltap spqtiqqtlk rtlqyyehqv
      121 igyrdaeknf hnisnrcsya dhsnkeeied vsgilqctan ilglkfeeiq krfgeeffni
      181 cfhenervlr avggtlqdff ngfdallehi rtsfgkqatl espsflckel pegtlmlhyf
      241 hphhivgfam lgmikaagkk iyrldveveq vaneklcsdv snpgncsclt flikecentn
      301 imknlpqgts qvpadlrisi ntfcrafpfh lmfdpsmsvl qlgeglrkql rcdthkvlkf
      361 edcfeivspk vnatfervll rlstpfvirt kpeasgsenk dkvmevkgqm ihvpesnsil
      421 flgspcvdkl delmgrglhl sdipihdatr dvilvgeqak aqdglkkrmd klkatlerth
      481 qaleeekkkt vdllysifpg dvaqqlwqgq qvqarkfddv tmlfsdivgf taicaqctpm
      541 qvismlnely trfdhqcgfl diykvetigd aycvaaglhr kslchakpia lmalkmmels
      601 eevltpdgrp iqmrigihsg svlagvvgvr mpryclfgnn vtlaskfesg shprrinvsp
      661 ttyqllkree sftfiprsre elpdnfpkei pgicyflevr tgpkppkpsl sssrikkvsy
      721 nigtmflret sl
//
