GUC2C_HUMAN
ID GUC2C_HUMAN Reviewed; 1073 AA.
AC P25092; B2RMY6;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 2.
DT 03-AUG-2022, entry version 208.
DE RecName: Full=Guanylyl cyclase C {ECO:0000303|PubMed:11950846};
DE Short=GC-C {ECO:0000303|PubMed:11950846};
DE EC=4.6.1.2 {ECO:0000269|PubMed:11950846, ECO:0000269|PubMed:23269669, ECO:0000305|PubMed:1718270};
DE AltName: Full=Heat-stable enterotoxin receptor {ECO:0000303|PubMed:1718270};
DE Short=STA receptor {ECO:0000303|PubMed:1718270};
DE Short=hSTAR {ECO:0000303|PubMed:1718270};
DE AltName: Full=Intestinal guanylate cyclase;
DE Flags: Precursor;
GN Name=GUCY2C {ECO:0000303|PubMed:22521417, ECO:0000312|HGNC:HGNC:4688};
GN Synonyms=GUC2C, STAR {ECO:0000303|PubMed:1718270};
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], FUNCTION, CATALYTIC ACTIVITY, AND VARIANT
RP LEU-281.
RX PubMed=1718270; DOI=10.1016/0006-291x(91)91736-v;
RA Singh S., Singh G., Heim J.-M., Gerzer R.;
RT "Isolation and expression of a guanylate cyclase-coupled heat stable
RT enterotoxin receptor cDNA from a human colonic cell line.";
RL Biochem. Biophys. Res. Commun. 179:1455-1463(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND VARIANT LEU-281.
RX PubMed=1680854; DOI=10.1016/s0021-9258(18)55214-5;
RA de Sauvage F.J., Camerato T.R., Goeddel D.V.;
RT "Primary structure and functional expression of the human receptor for
RT Escherichia coli heat-stable enterotoxin.";
RL J. Biol. Chem. 266:17912-17918(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT LEU-281.
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-281.
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-72.
RC TISSUE=Placenta;
RX PubMed=8605253; DOI=10.1016/0167-4781(95)00190-5;
RA Mann E.A., Jump M.L., Giannella R.A.;
RT "Cell line-specific transcriptional activation of the promoter of the human
RT guanylyl cyclase C/heat-stable enterotoxin receptor gene.";
RL Biochim. Biophys. Acta 1305:7-10(1996).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 24-1073, FUNCTION, AND VARIANT
RP LEU-281.
RC TISSUE=Colon carcinoma;
RX PubMed=8381596; DOI=10.1152/ajpgi.1993.264.1.g172;
RA Mann E.A., Cohen M.B., Giannella R.A.;
RT "Comparison of receptors for Escherichia coli heat-stable enterotoxin:
RT novel receptor present in IEC-6 cells.";
RL Am. J. Physiol. 264:G172-G178(1993).
RN [8]
RP SUBUNIT.
RX PubMed=11123935; DOI=10.1021/bi0013849;
RA Vijayachandra K., Guruprasad M., Bhandari R., Manjunath U.H., Somesh B.P.,
RA Srinivasan N., Suguna K., Visweswariah S.S.;
RT "Biochemical characterization of the intracellular domain of the human
RT guanylyl cyclase C receptor provides evidence for a catalytically active
RT homotrimer.";
RL Biochemistry 39:16075-16083(2000).
RN [9]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH PDZK2.
RX PubMed=11950846; DOI=10.1074/jbc.m202434200;
RA Scott R.O., Thelin W.R., Milgram S.L.;
RT "A novel PDZ protein regulates the activity of guanylyl cyclase C, the
RT heat-stable enterotoxin receptor.";
RL J. Biol. Chem. 277:22934-22941(2002).
RN [10]
RP GLYCOSYLATION AT ASN-32; ASN-75; ASN-79; ASN-195; ASN-284; ASN-307; ASN-345
RP AND ASN-402, LACK OF GLYCOSYLATION AT ASN-357, FUNCTION, CATALYTIC
RP ACTIVITY, INTERACTION WITH VIP36, AND SUBCELLULAR LOCATION.
RX PubMed=23269669; DOI=10.1074/jbc.m112.413906;
RA Arshad N., Ballal S., Visweswariah S.S.;
RT "Site-specific N-linked glycosylation of receptor guanylyl cyclase C
RT regulates ligand binding, ligand-mediated activation and interaction with
RT vesicular integral membrane protein 36, VIP36.";
RL J. Biol. Chem. 288:3907-3917(2013).
RN [11]
RP VARIANT MECIL GLY-387, FUNCTION, AND CHARACTERIZATION OF VARIANT MECIL
RP GLY-387.
RX PubMed=22521417; DOI=10.1016/j.ajhg.2012.03.022;
RA Romi H., Cohen I., Landau D., Alkrinawi S., Yerushalmi B., Hershkovitz R.,
RA Newman-Heiman N., Cutting G.R., Ofir R., Sivan S., Birk O.S.;
RT "Meconium ileus caused by mutations in GUCY2C, encoding the CFTR-activating
RT guanylate cyclase 2C.";
RL Am. J. Hum. Genet. 90:893-899(2012).
RN [12]
RP VARIANT DIAR6 ILE-840, FUNCTION, AND CHARACTERIZATION OF VARIANT DIAR6
RP ILE-840.
RX PubMed=22436048; DOI=10.1056/nejmoa1110132;
RA Fiskerstrand T., Arshad N., Haukanes B.I., Tronstad R.R., Pham K.D.,
RA Johansson S., Havik B., Tonder S.L., Levy S.E., Brackman D., Boman H.,
RA Biswas K.H., Apold J., Hovdenak N., Visweswariah S.S., Knappskog P.M.;
RT "Familial diarrhea syndrome caused by an activating GUCY2C mutation.";
RL N. Engl. J. Med. 366:1586-1595(2012).
RN [13]
RP VARIANTS [LARGE SCALE ANALYSIS] ARG-30; ARG-61; GLN-114; LEU-464; LYS-610;
RP VAL-859; ARG-1045 AND CYS-1072.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Guanylyl cyclase that catalyzes synthesis of cyclic GMP
CC (cGMP) from GTP (PubMed:1718270, PubMed:11950846, PubMed:23269669,
CC PubMed:22521417, PubMed:22436048). Receptor for the E.coli heat-stable
CC enterotoxin; E.coli enterotoxin markedly stimulates the accumulation of
CC cGMP in mammalian cells expressing GUCY2C (PubMed:1718270,
CC PubMed:1680854). Also activated by the endogenous peptides guanylin and
CC uroguanylin (PubMed:8381596). {ECO:0000269|PubMed:11950846,
CC ECO:0000269|PubMed:1680854, ECO:0000269|PubMed:1718270,
CC ECO:0000269|PubMed:22436048, ECO:0000269|PubMed:22521417,
CC ECO:0000269|PubMed:23269669, ECO:0000269|PubMed:8381596}.
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:11950846, ECO:0000269|PubMed:23269669,
CC ECO:0000305|PubMed:1718270};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13666;
CC Evidence={ECO:0000269|PubMed:11950846, ECO:0000305|PubMed:1718270};
CC -!- SUBUNIT: Homotrimer (PubMed:11123935). Interacts via its C-terminal
CC region with PDZK2 (PubMed:11950846). Interacts with the lectin
CC chaperone VIP36 (PubMed:23269669). {ECO:0000269|PubMed:11123935,
CC ECO:0000269|PubMed:11950846, ECO:0000269|PubMed:23269669}.
CC -!- INTERACTION:
CC P25092; Q86UT5-2: PDZD3; NbExp=4; IntAct=EBI-2816795, EBI-8299496;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23269669};
CC Single-pass type I membrane protein {ECO:0000269|PubMed:23269669}.
CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:23269669}; Single-
CC pass type I membrane protein {ECO:0000269|PubMed:23269669}. Note=The
CC 145 kDa plasma membrane form of GUCY2C contains sialic acid and
CC galactose residues, while a differencially glycosylated 130 Kda form is
CC a high mannose form that is resident in the endoplasmic reticulum and
CC may serve as the precursor for the cell surface form.
CC {ECO:0000269|PubMed:23269669}.
CC -!- DOMAIN: The protein kinase domain is predicted to be catalytically
CC inactive.
CC -!- PTM: Glycosylation at Asn-75 and/or Asn-79 is required for interaction
CC with VIP36 while glycosylation at Asn-345 and Asn-402 modulates ligand-
CC mediated GUCY2C activation. {ECO:0000269|PubMed:23269669}.
CC -!- DISEASE: Diarrhea 6 (DIAR6) [MIM:614616]: A relatively mild, early-
CC onset chronic diarrhea that may be associated with increased
CC susceptibility to inflammatory bowel disease, small bowel obstruction,
CC and esophagitis. {ECO:0000269|PubMed:22436048}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Meconium ileus (MECIL) [MIM:614665]: A condition characterized
CC by intestinal obstruction due to inspissated meconium in the distal
CC ileum and cecum, which develops in utero and presents shortly after
CC birth as a failure to pass meconium. Meconium ileus is a known clinical
CC manifestation of cystic fibrosis. {ECO:0000269|PubMed:22521417}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/GUCY2CID43303ch12p13.html";
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DR EMBL; S57551; AAB19934.2; -; mRNA.
DR EMBL; M73489; AAA36655.1; -; mRNA.
DR EMBL; AC007545; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC010168; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471094; EAW96324.1; -; Genomic_DNA.
DR EMBL; BC136544; AAI36545.1; -; mRNA.
DR EMBL; BC136545; AAI36546.1; -; mRNA.
DR EMBL; U20230; AAC50381.1; -; Genomic_DNA.
DR CCDS; CCDS8664.1; -.
DR PIR; A40940; OYHUHX.
DR RefSeq; NP_004954.2; NM_004963.3.
DR AlphaFoldDB; P25092; -.
DR SMR; P25092; -.
DR BioGRID; 109239; 2.
DR IntAct; P25092; 3.
DR MINT; P25092; -.
DR STRING; 9606.ENSP00000261170; -.
DR ChEMBL; CHEMBL1795197; -.
DR DrugBank; DB08890; Linaclotide.
DR DrugCentral; P25092; -.
DR GuidetoPHARMACOLOGY; 1750; -.
DR TCDB; 8.A.85.1.1; the guanylate cyclase (gc) family.
DR GlyGen; P25092; 8 sites.
DR iPTMnet; P25092; -.
DR PhosphoSitePlus; P25092; -.
DR BioMuta; GUCY2C; -.
DR DMDM; 311033390; -.
DR jPOST; P25092; -.
DR MassIVE; P25092; -.
DR MaxQB; P25092; -.
DR PaxDb; P25092; -.
DR PeptideAtlas; P25092; -.
DR PRIDE; P25092; -.
DR ProteomicsDB; 54253; -.
DR ABCD; P25092; 1 sequenced antibody.
DR Antibodypedia; 12046; 294 antibodies from 25 providers.
DR DNASU; 2984; -.
DR Ensembl; ENST00000261170.5; ENSP00000261170.3; ENSG00000070019.5.
DR GeneID; 2984; -.
DR KEGG; hsa:2984; -.
DR MANE-Select; ENST00000261170.5; ENSP00000261170.3; NM_004963.4; NP_004954.2.
DR UCSC; uc001rcd.4; human.
DR CTD; 2984; -.
DR DisGeNET; 2984; -.
DR GeneCards; GUCY2C; -.
DR HGNC; HGNC:4688; GUCY2C.
DR HPA; ENSG00000070019; Tissue enriched (intestine).
DR MalaCards; GUCY2C; -.
DR MIM; 601330; gene.
DR MIM; 614616; phenotype.
DR MIM; 614665; phenotype.
DR neXtProt; NX_P25092; -.
DR OpenTargets; ENSG00000070019; -.
DR Orphanet; 314373; Chronic infantile diarrhea due to guanylate cyclase 2C overactivity.
DR Orphanet; 103908; Congenital sodium diarrhea.
DR Orphanet; 314376; Intestinal obstruction in the newborn due to guanylate cyclase 2C deficiency.
DR PharmGKB; PA29069; -.
DR VEuPathDB; HostDB:ENSG00000070019; -.
DR eggNOG; KOG1023; Eukaryota.
DR GeneTree; ENSGT00940000155955; -.
DR HOGENOM; CLU_001072_1_3_1; -.
DR InParanoid; P25092; -.
DR OMA; VMCGGPE; -.
DR OrthoDB; 229634at2759; -.
DR PhylomeDB; P25092; -.
DR BRENDA; 4.6.1.2; 2681.
DR PathwayCommons; P25092; -.
DR Reactome; R-HSA-8935690; Digestion.
DR Reactome; R-HSA-8942233; Intestinal infectious diseases.
DR SignaLink; P25092; -.
DR SIGNOR; P25092; -.
DR BioGRID-ORCS; 2984; 6 hits in 1077 CRISPR screens.
DR ChiTaRS; GUCY2C; human.
DR GeneWiki; Guanylate_cyclase_2C; -.
DR GenomeRNAi; 2984; -.
DR Pharos; P25092; Tclin.
DR PRO; PR:P25092; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P25092; protein.
DR Bgee; ENSG00000070019; Expressed in jejunal mucosa and 59 other tissues.
DR Genevisible; P25092; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0004383; F:guanylate cyclase activity; IDA:UniProtKB.
DR GO; GO:0016941; F:natriuretic peptide receptor activity; IBA:GO_Central.
DR GO; GO:0017046; F:peptide hormone binding; IBA:GO_Central.
DR GO; GO:0001653; F:peptide receptor activity; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; IEA:InterPro.
DR GO; GO:0015643; F:toxic substance binding; IEA:Ensembl.
DR GO; GO:0006182; P:cGMP biosynthetic process; IBA:GO_Central.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0007168; P:receptor guanylyl cyclase signaling pathway; IBA:GO_Central.
DR GO; GO:0042127; P:regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd07302; CHD; 1.
DR CDD; cd14044; PK_GC-C; 1.
DR Gene3D; 3.30.70.1230; -; 1.
DR InterPro; IPR001054; A/G_cyclase.
DR InterPro; IPR018297; A/G_cyclase_CS.
DR InterPro; IPR042822; GC-C_PK.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR029787; Nucleotide_cyclase.
DR InterPro; IPR028082; Peripla_BP_I.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR Pfam; PF00211; Guanylate_cyc; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR SMART; SM00044; CYCc; 1.
DR SUPFAM; SSF53822; SSF53822; 1.
DR SUPFAM; SSF55073; SSF55073; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00452; GUANYLATE_CYCLASE_1; 1.
DR PROSITE; PS50125; GUANYLATE_CYCLASE_2; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW Cell membrane; cGMP biosynthesis; Disease variant; Endoplasmic reticulum;
KW Glycoprotein; GTP-binding; Lyase; Membrane; Nucleotide-binding; Receptor;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..1073
FT /note="Guanylyl cyclase C"
FT /id="PRO_0000012376"
FT TOPO_DOM 24..430
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 431..454
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 455..1073
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 489..749
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 824..954
FT /note="Guanylate cyclase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT SITE 357
FT /note="Not glycosylated"
FT /evidence="ECO:0000269|PubMed:23269669"
FT CARBOHYD 32
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23269669"
FT CARBOHYD 75
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23269669"
FT CARBOHYD 79
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23269669"
FT CARBOHYD 195
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23269669"
FT CARBOHYD 284
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23269669"
FT CARBOHYD 307
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23269669"
FT CARBOHYD 345
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23269669"
FT CARBOHYD 402
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:23269669"
FT VARIANT 30
FT /note="C -> R (in dbSNP:rs56142849)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042221"
FT VARIANT 61
FT /note="G -> R (in a metastatic melanoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042222"
FT VARIANT 114
FT /note="R -> Q (in dbSNP:rs56275235)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042223"
FT VARIANT 281
FT /note="F -> L (in dbSNP:rs1420635)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:1680854, ECO:0000269|PubMed:1718270,
FT ECO:0000269|PubMed:8381596, ECO:0000269|Ref.4"
FT /id="VAR_049253"
FT VARIANT 387
FT /note="D -> G (in MECIL; activation of guanylate cyclase
FT activity is 60% lower than in wild-type;
FT dbSNP:rs587776905)"
FT /evidence="ECO:0000269|PubMed:22521417"
FT /id="VAR_068174"
FT VARIANT 464
FT /note="R -> L (in dbSNP:rs55684775)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042224"
FT VARIANT 610
FT /note="E -> K (in dbSNP:rs55897626)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042225"
FT VARIANT 840
FT /note="S -> I (in DIAR6; activating mutation; exposure of
FT the mutant receptor to its ligands results in markedly
FT increased production of cyclic guanosine monophosphate;
FT dbSNP:rs587776871)"
FT /evidence="ECO:0000269|PubMed:22436048"
FT /id="VAR_067724"
FT VARIANT 859
FT /note="I -> V (in dbSNP:rs34890806)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042226"
FT VARIANT 1045
FT /note="Q -> R (in dbSNP:rs35617837)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042227"
FT VARIANT 1072
FT /note="Y -> C (in dbSNP:rs35179392)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042228"
FT CONFLICT 322
FT /note="A -> R (in Ref. 1; AAB19934)"
FT /evidence="ECO:0000305"
FT CONFLICT 331
FT /note="L -> V (in Ref. 1; AAB19934)"
FT /evidence="ECO:0000305"
FT CONFLICT 509
FT /note="D -> V (in Ref. 1; AAB19934)"
FT /evidence="ECO:0000305"
FT CONFLICT 543
FT /note="N -> T (in Ref. 1; AAB19934)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1073 AA; 123403 MW; 486A4DE6F9097E22 CRC64;
MKTLLLDLAL WSLLFQPGWL SFSSQVSQNC HNGSYEISVL MMGNSAFAEP LKNLEDAVNE
GLEIVRGRLQ NAGLNVTVNA TFMYSDGLIH NSGDCRSSTC EGLDLLRKIS NAQRMGCVLI
GPSCTYSTFQ MYLDTELSYP MISAGSFGLS CDYKETLTRL MSPARKLMYF LVNFWKTNDL
PFKTYSWSTS YVYKNGTETE DCFWYLNALE ASVSYFSHEL GFKVVLRQDK EFQDILMDHN
RKSNVIIMCG GPEFLYKLKG DRAVAEDIVI ILVDLFNDQY FEDNVTAPDY MKNVLVLTLS
PGNSLLNSSF SRNLSPTKRD FALAYLNGIL LFGHMLKIFL ENGENITTPK FAHAFRNLTF
EGYDGPVTLD DWGDVDSTMV LLYTSVDTKK YKVLLTYDTH VNKTYPVDMS PTFTWKNSKL
PNDITGRGPQ ILMIAVFTLT GAVVLLLLVA LLMLRKYRKD YELRQKKWSH IPPENIFPLE
TNETNHVSLK IDDDKRRDTI QRLRQCKYDK KRVILKDLKH NDGNFTEKQK IELNKLLQID
YYNLTKFYGT VKLDTMIFGV IEYCERGSLR EVLNDTISYP DGTFMDWEFK ISVLYDIAKG
MSYLHSSKTE VHGRLKSTNC VVDSRMVVKI TDFGCNSILP PKKDLWTAPE HLRQANISQK
GDVYSYGIIA QEIILRKETF YTLSCRDRNE KIFRVENSNG MKPFRPDLFL ETAEEKELEV
YLLVKNCWEE DPEKRPDFKK IETTLAKIFG LFHDQKNESY MDTLIRRLQL YSRNLEHLVE
ERTQLYKAER DRADRLNFML LPRLVVKSLK EKGFVEPELY EEVTIYFSDI VGFTTICKYS
TPMEVVDMLN DIYKSFDHIV DHHDVYKVET IGDAYMVASG LPKRNGNRHA IDIAKMALEI
LSFMGTFELE HLPGLPIWIR IGVHSGPCAA GVVGIKMPRY CLFGDTVNTA SRMESTGLPL
RIHVSGSTIA ILKRTECQFL YEVRGETYLK GRGNETTYWL TGMKDQKFNL PTPPTVENQQ
RLQAEFSDMI ANSLQKRQAA GIRSQKPRRV ASYKKGTLEY LQLNTTDKES TYF
