ID   GCYB2_HUMAN             Reviewed;         617 AA.
AC   O75343; Q9NZ64;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   11-JUL-2001, sequence version 2.
DT   03-AUG-2022, entry version 156.
DE   RecName: Full=Guanylate cyclase soluble subunit beta-2;
DE            Short=GCS-beta-2;
DE            EC=4.6.1.2;
GN   Name=GUCY1B2;
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 [GENOMIC DNA], SEQUENCE REVISION TO 175, AND TISSUE
RP   SPECIFICITY.
RC   TISSUE=Kidney;
RX   PubMed=10777682; DOI=10.1006/bbrc.2000.2596;
RA   Behrends S., Vehse K.;
RT   "The beta(2) subunit of soluble guanylyl cyclase contains a human-specific
RT   frameshift and is expressed in gastric carcinoma.";
RL   Biochem. Biophys. Res. Commun. 271:64-69(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 95-257.
RC   TISSUE=Heart;
RX   PubMed=9889008; DOI=10.1006/geno.1998.5613;
RA   Behrends S., Kazmierczak B., Steenpa A., Knauf B., Bullerdiek J.,
RA   Scholz H., Eiberg H.;
RT   "Assignment of GUCY1B2, the gene coding for the beta2 subunit of human
RT   guanylyl cyclase to chromosomal band 13q14.3 between markers D13S168 and
RT   D13S155.";
RL   Genomics 55:126-127(1999).
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   -!- COFACTOR:
CC       Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC       Note=Binds 1 or 2 heme groups per heterodimer. {ECO:0000250};
CC   -!- ACTIVITY REGULATION: Activated by nitric oxide in the presence of
CC       magnesium or manganese ions.
CC   -!- SUBUNIT: Heterodimer of an alpha and a beta chain.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm.
CC   -!- TISSUE SPECIFICITY: Expressed in gastric signet ring cell carcinoma,
CC       but not in the normal stomach. {ECO:0000269|PubMed:10777682}.
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   -!- CAUTION: Could be the product of a pseudogene. {ECO:0000305}.
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; AF038499; AAD09440.2; -; mRNA.
DR   EMBL; AF218383; AAF66105.1; -; Genomic_DNA.
DR   AlphaFoldDB; O75343; -.
DR   SMR; O75343; -.
DR   IntAct; O75343; 2.
DR   ChEMBL; CHEMBL2111348; -.
DR   DrugBank; DB09401; Isosorbide.
DR   DrugCentral; O75343; -.
DR   iPTMnet; O75343; -.
DR   PhosphoSitePlus; O75343; -.
DR   BioMuta; HGNC:4686; -.
DR   jPOST; O75343; -.
DR   MassIVE; O75343; -.
DR   MaxQB; O75343; -.
DR   PeptideAtlas; O75343; -.
DR   PRIDE; O75343; -.
DR   ProteomicsDB; 49911; -.
DR   GeneCards; GUCY1B2; -.
DR   HGNC; HGNC:4686; GUCY1B2.
DR   MIM; 603695; gene.
DR   neXtProt; NX_O75343; -.
DR   InParanoid; O75343; -.
DR   PhylomeDB; O75343; -.
DR   BRENDA; 4.6.1.2; 2681.
DR   PathwayCommons; O75343; -.
DR   Reactome; R-HSA-392154; Nitric oxide stimulates guanylate cyclase.
DR   Reactome; R-HSA-445355; Smooth Muscle Contraction.
DR   SignaLink; O75343; -.
DR   SIGNOR; O75343; -.
DR   ChiTaRS; GUCY1B2; human.
DR   Pharos; O75343; Tclin.
DR   PRO; PR:O75343; -.
DR   Proteomes; UP000005640; Unplaced.
DR   RNAct; O75343; protein.
DR   GO; GO:0008074; C:guanylate cyclase complex, soluble; IBA:GO_Central.
DR   GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR   GO; GO:0004383; F:guanylate cyclase activity; IBA:GO_Central.
DR   GO; GO:0020037; F:heme binding; IEA:InterPro.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0019934; P:cGMP-mediated signaling; IBA:GO_Central.
DR   GO; GO:0070482; P:response to oxygen levels; IBA:GO_Central.
DR   CDD; cd07302; CHD; 1.
DR   Gene3D; 3.30.450.260; -; 1.
DR   Gene3D; 3.30.70.1230; -; 1.
DR   Gene3D; 3.90.1520.10; -; 1.
DR   InterPro; IPR001054; A/G_cyclase.
DR   InterPro; IPR018297; A/G_cyclase_CS.
DR   InterPro; IPR038158; H-NOX_domain_sf.
DR   InterPro; IPR011644; Heme_NO-bd.
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   Pfam; PF00211; Guanylate_cyc; 1.
DR   Pfam; PF07700; HNOB; 1.
DR   Pfam; PF07701; HNOBA; 1.
DR   SMART; SM00044; CYCc; 1.
DR   SUPFAM; SSF111126; SSF111126; 1.
DR   SUPFAM; SSF55073; SSF55073; 1.
DR   PROSITE; PS00452; GUANYLATE_CYCLASE_1; 1.
DR   PROSITE; PS50125; GUANYLATE_CYCLASE_2; 1.
PE   5: Uncertain;
KW   cGMP biosynthesis; Cytoplasm; GTP-binding; Heme; Iron; Lyase;
KW   Metal-binding; Nucleotide-binding; Reference proteome.
FT   CHAIN           1..617
FT                   /note="Guanylate cyclase soluble subunit beta-2"
FT                   /id="PRO_0000074119"
FT   DOMAIN          391..519
FT                   /note="Guanylate cyclase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT   REGION          577..605
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        585..605
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         26
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="proximal binding residue"
FT                   /evidence="ECO:0000250"
FT   VARIANT         55
FT                   /note="Y -> C (in dbSNP:rs9568497)"
FT                   /id="VAR_024469"
FT   VARIANT         128
FT                   /note="M -> I (in dbSNP:rs11841997)"
FT                   /id="VAR_024470"
FT   VARIANT         316
FT                   /note="N -> H (in dbSNP:rs1328361)"
FT                   /id="VAR_022131"
SQ   SEQUENCE   617 AA;  70368 MW;  1B6C965CAB9A5E3E CRC64;
     MSGYDRMLRT LGGNLMEFIE NLDALHSYLA LSYQEMNAPS FRVERGADGK MFLHYYSDRS
     GLCHIVPGII EAVAKDFFDI DVIMDILDMN EEVERTGKKE HVVFLIVQKA HRKMRKTKPK
     RLQDSQGMER DQEALQAAFL KMKEKYLNVS ACPVKKSHWD VVRSIVMFGK GHLMNTFEPI
     YPERLWIEEK TFCNAFPFHI VFDESLQVKQ ARVNIQKYVP GLQTQNIQLD EYFSIIHPQV
     TFNIFSIRRF INSQFVLKTR REMMPVAWQS RTTLKLQGQM IWMESMWCMV YLCSPKLRSL
     QELEELNMHL SDIAPNDTTR DLILLNQQRL AEIELSNQLE RKKEELQVLS KHLAIEKKKT
     ETLLYAMLPK HVANQLREGK KVAAGEFKSC TILFSDVVTF TNICTACEPI QIVNVLNSMY
     SKFDRLTSVH AVYKVETIGD AYMVVGGVPV PIGNHAQRVA NFALGMRISA KEVTNPVTGE
     PIQLRVGIHT GPVLADVVGD KMPRYCLFGD TVNTASRMES HGLPNKVHLS PTAYRALKNQ
     GFKIIERGEI EVKGKGRMTT YFLIQNLNAT EDEIMGRSKT PVDHKGSTQK ASLPTTKLQG
     SVQPSCPEHS SLASWLL