GUC2C_MOUSE
ID GUC2C_MOUSE Reviewed; 1072 AA.
AC Q3UWA6; Q499D2; Q8JZQ6;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 11-OCT-2005, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Guanylyl cyclase C;
DE Short=GC-C;
DE EC=4.6.1.2 {ECO:0000250|UniProtKB:P25092};
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Cecum;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 319-1072 (ISOFORM 1).
RC STRAIN=FVB/N; TISSUE=Colon, and Pancreas;
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).
CC -!- FUNCTION: Guanylyl cyclase that catalyzes synthesis of cyclic GMP
CC (cGMP) from GTP. {ECO:0000250|UniProtKB:P25092}.
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:0000250|UniProtKB:P25092};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:13666;
CC Evidence={ECO:0000250|UniProtKB:P25092};
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q3UWA6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q3UWA6-2; Sequence=VSP_023652;
CC -!- DOMAIN: The protein kinase domain is predicted to be catalytically
CC inactive. {ECO:0000305}.
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 GC-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; AK136496; BAE23010.1; -; mRNA.
DR EMBL; BC034064; AAH34064.1; -; mRNA.
DR EMBL; BC099968; AAH99968.1; -; mRNA.
DR CCDS; CCDS20653.1; -. [Q3UWA6-2]
DR CCDS; CCDS51941.1; -. [Q3UWA6-1]
DR RefSeq; NP_001120790.1; NM_001127318.1. [Q3UWA6-1]
DR RefSeq; NP_659504.2; NM_145067.3. [Q3UWA6-2]
DR AlphaFoldDB; Q3UWA6; -.
DR SMR; Q3UWA6; -.
DR BioGRID; 200125; 6.
DR STRING; 10090.ENSMUSP00000032338; -.
DR GuidetoPHARMACOLOGY; 1750; -.
DR GlyGen; Q3UWA6; 10 sites.
DR iPTMnet; Q3UWA6; -.
DR PhosphoSitePlus; Q3UWA6; -.
DR MaxQB; Q3UWA6; -.
DR PaxDb; Q3UWA6; -.
DR PeptideAtlas; Q3UWA6; -.
DR PRIDE; Q3UWA6; -.
DR ProteomicsDB; 269847; -. [Q3UWA6-1]
DR ProteomicsDB; 270872; -. [Q3UWA6-2]
DR Antibodypedia; 12046; 294 antibodies from 25 providers.
DR DNASU; 14917; -.
DR Ensembl; ENSMUST00000032338; ENSMUSP00000032338; ENSMUSG00000042638. [Q3UWA6-1]
DR Ensembl; ENSMUST00000078095; ENSMUSP00000077236; ENSMUSG00000042638. [Q3UWA6-2]
DR GeneID; 14917; -.
DR KEGG; mmu:14917; -.
DR UCSC; uc009emb.2; mouse. [Q3UWA6-2]
DR UCSC; uc009emc.2; mouse. [Q3UWA6-1]
DR CTD; 2984; -.
DR MGI; MGI:106903; Gucy2c.
DR VEuPathDB; HostDB:ENSMUSG00000042638; -.
DR eggNOG; KOG1023; Eukaryota.
DR GeneTree; ENSGT00940000155955; -.
DR HOGENOM; CLU_001072_1_3_1; -.
DR InParanoid; Q3UWA6; -.
DR OMA; VMCGGPE; -.
DR OrthoDB; 229634at2759; -.
DR PhylomeDB; Q3UWA6; -.
DR TreeFam; TF106338; -.
DR BRENDA; 4.6.1.2; 3474.
DR Reactome; R-MMU-8935690; Digestion.
DR BioGRID-ORCS; 14917; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Gucy2c; mouse.
DR PRO; PR:Q3UWA6; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q3UWA6; protein.
DR Bgee; ENSMUSG00000042638; Expressed in jejunum and 38 other tissues.
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; IMP:MGI.
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; ISO:MGI.
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; IGI:MGI.
DR GO; GO:0009636; P:response to toxic substance; IMP:MGI.
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 2: Evidence at transcript level;
KW Alternative splicing; Cell membrane; cGMP biosynthesis;
KW Endoplasmic reticulum; Glycoprotein; GTP-binding; Lyase; Membrane;
KW Nucleotide-binding; Receptor; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..1072
FT /note="Guanylyl cyclase C"
FT /id="PRO_0000280396"
FT TOPO_DOM 20..433
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 434..454
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 455..1072
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 489..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 32
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 75
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 79
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 179
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 188
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 195
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 284
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 307
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 345
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 402
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 512..535
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023652"
FT CONFLICT 381
FT /note="L -> F (in Ref. 2; AAH34064)"
FT /evidence="ECO:0000305"
FT CONFLICT 969
FT /note="T -> A (in Ref. 2; AAH34064/AAH99968)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1072 AA; 123232 MW; 7129508166E7790A CRC64;
MTSLLGLAVR LLLFQPALMV FWASQVRQNC RNGSYEISVL MMDNSAYKEP MQNLREAVEE
GLDIVRKRLR EADLNVTVNA TFIYSDGLIH KSGDCRSSTC EGLDLLREIT RDHKMGCALM
GPSCTYSTFQ MYLDTELNYP MISAGSYGLS CDYKETLTRI LPPARKLMYF LVDFWKVNNA
SFKPFSWNSS YVYKNGSEPE DCFWYLNALE AGVSYFSEVL NFKDVLRRSE QFQEILTGHN
RKSNVIVMCG TPESFYDVKG DLQVAEDTVV ILVDLFSNHY FEENTTAPEY MDNVLVLTLP
SEQSTSNTSV AERFSSGRSD FSLAYLEGTL LFGHMLQTFL ENGENVTGPK FARAFRNLTF
QGFAGPVTLD DSGDIDNIMS LLYVSLDTRK YKVLMKYDTH KNKTIPVAEN PNFIWKNHKL
PNDVPGLGPQ ILMIAVFTLT GILVVLLLIA LLVLRKYRRD HALRQKKWSH IPSENIFPLE
TNETNHISLK IDDDRRRDTI QRVRQCKYDK KKVILKDLKH SDGNFSEKQK IDLNKLLQSD
YYNLTKFYGT VKLDTRIFGV VEYCERGSLR EVLNDTISYP DGTFMDWEFK ISVLNDIAKG
MSYLHSSKIE VHGRLKSTNC VVDSRMVVKI TDFGCNSILP PKKDLWTAPE HLRQATISQK
GDVYSFAIIA QEIILRKETF YTLSCRDHNE KIFRVENSYG KPFRPDLFLE TADEKELEVY
LLVKSCWEED PEKRPDFKKI ESTLAKIFGL FHDQKNESYM DTLIRRLQLY SRNLEHLVEE
RTQLYKAERD RADHLNFMLL PRLVVKSLKE KGIVEPELYE EVTIYFSDIV GFTTICKYST
PMEVVDMLND IYKSFDQIVD HHDVYKVETI GDAYVVASGL PMRNGNRHAV DISKMALDIL
SFIGTFELEH LPGLPVWIRI GVHSGPCAAG VVGIKMPRYC LFGDTVNTAS RMESTGLPLR
IHMSSSTITI LKRTDCQFLY EVRGETYLKG RGTETTYWLT GMKDQEYNLP SPPTVENQQR
LQTEFSDMIV SALQKRQASG KKSRRPTRVA SYKKGFLEYM QLNNSDHDST YF
