GUC2C_RAT
ID GUC2C_RAT Reviewed; 1072 AA.
AC P23897;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 2.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Guanylyl cyclase C;
DE Short=GC-C;
DE EC=4.6.1.2 {ECO:0000269|PubMed:1701694};
DE AltName: Full=Heat-stable enterotoxin receptor;
DE Short=STA receptor;
DE AltName: Full=Intestinal guanylate cyclase;
DE Flags: Precursor;
GN Name=Gucy2c; Synonyms=Guc2c;
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], FUNCTION, CATALYTIC ACTIVITY, AND TISSUE
RP SPECIFICITY.
RC STRAIN=Sprague-Dawley; TISSUE=Small intestine;
RX PubMed=1701694; DOI=10.1016/0092-8674(90)90497-3;
RA Schulz S., Green C.K., Yuen P.S.T., Garbers D.L.;
RT "Guanylyl cyclase is a heat-stable enterotoxin receptor.";
RL Cell 63:941-948(1990).
CC -!- FUNCTION: Guanylyl cyclase that catalyzes synthesis of cyclic GMP
CC (cGMP) from GTP (PubMed:1701694). 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:1701694).
CC {ECO:0000269|PubMed:1701694}.
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:1701694};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13666;
CC Evidence={ECO:0000305|PubMed:1701694};
CC -!- SUBUNIT: Homotrimer. Interacts via its C-terminal region with PDZK2.
CC Interacts with the lectin chaperone VIP36.
CC {ECO:0000250|UniProtKB:P25092}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P25092};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:P25092}.
CC Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:P25092}; Single-
CC pass type I membrane protein {ECO:0000250|UniProtKB:P25092}. 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:0000250|UniProtKB:P25092}.
CC -!- DOMAIN: The protein kinase domain is predicted to be catalytically
CC inactive. {ECO:0000305}.
CC -!- PTM: Glycosylation at Asn-74 and/or Asn-78 is required for interaction
CC with VIP36 while glycosylation at Asn-401 modulates ligand-mediated GC-
CC C activation. {ECO:0000250|UniProtKB:P25092}.
CC -!- SIMILARITY: Belongs to the adenylyl cyclase class-4/guanylyl cyclase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00099}.
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DR EMBL; M55636; AAA41201.1; -; mRNA.
DR PIR; A36292; OYRTHX.
DR RefSeq; NP_037302.1; NM_013170.1.
DR AlphaFoldDB; P23897; -.
DR SMR; P23897; -.
DR STRING; 10116.ENSRNOP00000012212; -.
DR DrugCentral; P23897; -.
DR GuidetoPHARMACOLOGY; 1750; -.
DR GlyGen; P23897; 7 sites.
DR PhosphoSitePlus; P23897; -.
DR PaxDb; P23897; -.
DR PRIDE; P23897; -.
DR Ensembl; ENSRNOT00000012212; ENSRNOP00000012212; ENSRNOG00000009031.
DR GeneID; 25711; -.
DR KEGG; rno:25711; -.
DR UCSC; RGD:2771; rat.
DR CTD; 2984; -.
DR RGD; 2771; Gucy2c.
DR eggNOG; KOG1023; Eukaryota.
DR GeneTree; ENSGT00940000155955; -.
DR HOGENOM; CLU_001072_1_3_1; -.
DR InParanoid; P23897; -.
DR OMA; VMCGGPE; -.
DR OrthoDB; 229634at2759; -.
DR PhylomeDB; P23897; -.
DR Reactome; R-RNO-8935690; Digestion.
DR PRO; PR:P23897; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000009031; Expressed in jejunum and 9 other tissues.
DR Genevisible; P23897; RN.
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:RGD.
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; IDA:RGD.
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; ISO:RGD.
DR GO; GO:0009636; P:response to toxic substance; ISO:RGD.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd07302; CHD; 1.
DR Gene3D; 3.30.70.1230; -; 1.
DR InterPro; IPR001054; A/G_cyclase.
DR InterPro; IPR018297; A/G_cyclase_CS.
DR InterPro; IPR001828; ANF_lig-bd_rcpt.
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; PF01094; ANF_receptor; 1.
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; Endoplasmic reticulum; Glycoprotein;
KW GTP-binding; Lyase; Membrane; Nucleotide-binding; Receptor;
KW Reference proteome; Signal; Transmembrane; Transmembrane helix.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..1072
FT /note="Guanylyl cyclase C"
FT /id="PRO_0000012378"
FT TOPO_DOM 23..429
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 430..453
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 454..1072
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 488..748
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 823..953
FT /note="Guanylate cyclase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00099"
FT CARBOHYD 31
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 78
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 187
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 194
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 306
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 401
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 1072 AA; 123467 MW; EBA8656B2948C211 CRC64;
MTSLLGLAVR LLLFQPTLMF WASQVRQKCH NGTYEISVLM MDNSAYKEPL QNLRDAVEEG
LDIVRKRLRE AELNVTVNAT FIYSDGLIHK SGDCRSSTCE GLDLLREITR DRKMGCVLMG
PSCTYSTFQM YLDTELNYPM ISAGSFGLSC DYKETLTRIL PPARKLMYFL VDFWKVNNAP
FKTFSWNSSY VYKNGSEPED CFWYLNALEA GVSYFSEVLS FKDVLRRSEQ FQEILMGRNR
KSNVIVMCGT PETFYNVKGD LKVADDTVVI LVDLFSNHYF EDDTRAPEYM DNVLVLTLPP
EKFIANASVS GRFPSERSDF SLAYLEGTLL FGHMLQTFLE NGESVTTPKF ARAFRNLTFQ
GLEGPVTLDD SGDIDNIMCL LYVSLDTRKY KVLMAYDTHK NQTIPVATSP NFIWKNHRLP
NDVPGLGPQI LMIAVFTLTG IVVVLLLIAL LVLRKYRRDH ELRQKKWSHI PSENIFPLET
NETNHVSLKI DDDRRRDTIQ RVRQCKYDKK KVILKDLKHC DGNFSEKQKI ELNKLLQSDY
YNLTKFYGTV KLDTRIFGVV EYCERGSLRE VLNDTISYPD GTFMDWEFKI SVLNDIAKGM
SYLHSSKIEV HGRLKSTNCV VDSRMVVKIT DFGCNSILPP KKDLWTAPEH LRQATISQKG
DVYSFSIIAQ EIILRKETFY TLSCRDQNEK IFRVENSYGT KPFRPDLFLE TADEKELEVY
LLVKSCWEED PEKRPDFKKI ESTLAKIFGL FHDQKNESYM DTLIRRLQLY SRNLEHLVEE
RTQLYKAERD RADHLNFMLL PRLVVKSLKE KGIVEPELYE EVTIYFSDIV GFTTICKYST
PMEVVDMLND IYKSFDQIVD HHDVYKVETI GDAYVVASGL PMRNGNRHAV DISKMALDIL
SFMGTFELEH LPGLPVWIRI GVHSGPCAAG VVGIKMPRYC LFGDTVNTAS RMESTGLPLR
IHMSSSTIAI LRRTDCQFLY EVRGETYLKG RGTETTYWLT GMKDQEYNLP TPPTVENQQR
LQTEFSDMIV SALQKRQASG VKSRRPTRVA SYKKGFLEYM QLNNSDHDST YF
