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Protein

Heat-stable enterotoxin receptor

Gene

GUCY2C

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Receptor for the E.coli heat-stable enterotoxin (E.coli enterotoxin markedly stimulates the accumulation of cGMP in mammalian cells expressing GC-C). Also activated by the endogenous peptides guanylin and uroguanylin.

Catalytic activityi

GTP = 3',5'-cyclic GMP + diphosphate.

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionLyase, Receptor
Biological processcGMP biosynthesis
LigandGTP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi4.6.1.2 2681
ReactomeiR-HSA-8935690 Digestion
R-HSA-8942233 Intestinal infectious diseases
SIGNORiP25092

Protein family/group databases

TCDBi8.A.85.1.1 the guanylate cyclase (gc) family

Names & Taxonomyi

Protein namesi
Recommended name:
Heat-stable enterotoxin receptor (EC:4.6.1.2)
Short name:
STA receptor
Short name:
hSTAR
Alternative name(s):
Guanylyl cyclase C
Short name:
GC-C
Intestinal guanylate cyclase
Gene namesi
Name:GUCY2C
Synonyms:GUC2C, STAR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000070019.4
HGNCiHGNC:4688 GUCY2C
MIMi601330 gene
neXtProtiNX_P25092

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini24 – 430ExtracellularSequence analysisAdd BLAST407
Transmembranei431 – 454HelicalSequence analysisAdd BLAST24
Topological domaini455 – 1073CytoplasmicSequence analysisAdd BLAST619

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Diarrhea 6 (DIAR6)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA relatively mild, early-onset chronic diarrhea that may be associated with increased susceptibility to inflammatory bowel disease, small bowel obstruction, and esophagitis.
See also OMIM:614616
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067724840S → I in DIAR6; activating mutation; exposure of the mutant receptor to its ligands results in markedly increased production of cyclic guanosine monophosphate. 1 PublicationCorresponds to variant dbSNP:rs587776871EnsemblClinVar.1
Meconium ileus (MECIL)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA condition characterized by a intestinal obstruction due to inspissated meconium in the distal ileum and cecum, which develops in utero and presents shortly after birth as a failure to pass meconium. Meconium ileus is a known clinical manifestation of cystic fibrosis.
See also OMIM:614665
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_068174387D → G in MECIL; activation of guanylate cyclase activity is 60% lower than in wild-type. 1 PublicationCorresponds to variant dbSNP:rs587776905EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi2984
MalaCardsiGUCY2C
MIMi614616 phenotype
614665 phenotype
OpenTargetsiENSG00000070019
Orphaneti314373 Chronic diarrhea due to guanylate cyclase 2C overactivity
314376 Intestinal obstruction in the newborn due to guanylate cyclase 2C deficiency
PharmGKBiPA29069

Chemistry databases

ChEMBLiCHEMBL1795197
DrugBankiDB08890 Linaclotide
GuidetoPHARMACOLOGYi1750

Polymorphism and mutation databases

BioMutaiGUCY2C
DMDMi311033390

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
ChainiPRO_000001237624 – 1073Heat-stable enterotoxin receptorAdd BLAST1050

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi32N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi75N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi79N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi195N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi284N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi307N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi345N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi402N-linked (GlcNAc...) asparagine1 Publication1

Post-translational modificationi

Glycosylation at Asn-75 and/or Asn-79 is required for interaction with VIP36 while glycosylation at Asn-345 and Asn-402 modulates ligand-mediated GC-C activation.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei357Not glycosylated1 Publication1

Keywords - PTMi

Glycoprotein

Proteomic databases

MaxQBiP25092
PaxDbiP25092
PeptideAtlasiP25092
PRIDEiP25092
ProteomicsDBi54253

PTM databases

GlyConnecti1304
iPTMnetiP25092
PhosphoSitePlusiP25092

Expressioni

Gene expression databases

BgeeiENSG00000070019 Expressed in 65 organ(s), highest expression level in jejunal mucosa
CleanExiHS_GUCY2C
HS_STAR
GenevisibleiP25092 HS

Organism-specific databases

HPAiHPA037655
HPA073759

Interactioni

Subunit structurei

Homotrimer. Interacts via its C-terminal region with PDZK2. Interacts with the lectin chaperone VIP36.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PDZD3Q86UT5-24EBI-2816795,EBI-8299496

Protein-protein interaction databases

BioGridi109239, 2 interactors
IntActiP25092, 3 interactors
MINTiP25092
STRINGi9606.ENSP00000261170

Structurei

3D structure databases

ProteinModelPortaliP25092
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini489 – 749Protein kinasePROSITE-ProRule annotationAdd BLAST261
Domaini824 – 954Guanylate cyclasePROSITE-ProRule annotationAdd BLAST131

Domaini

The protein kinase domain is predicted to be catalytically inactive.

Sequence similaritiesi

Belongs to the adenylyl cyclase class-4/guanylyl cyclase family.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1023 Eukaryota
COG2114 LUCA
GeneTreeiENSGT00760000118959
HOGENOMiHOG000112833
HOVERGENiHBG106967
InParanoidiP25092
KOiK12320
OMAiMGCVLMG
OrthoDBiEOG091G01F8
PhylomeDBiP25092

Family and domain databases

Gene3Di3.30.70.1230, 1 hit
InterProiView protein in InterPro
IPR001054 A/G_cyclase
IPR018297 A/G_cyclase_CS
IPR011009 Kinase-like_dom_sf
IPR029787 Nucleotide_cyclase
IPR028082 Peripla_BP_I
IPR000719 Prot_kinase_dom
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
PfamiView protein in Pfam
PF00211 Guanylate_cyc, 1 hit
PF07714 Pkinase_Tyr, 1 hit
SMARTiView protein in SMART
SM00044 CYCc, 1 hit
SUPFAMiSSF53822 SSF53822, 1 hit
SSF55073 SSF55073, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00452 GUANYLATE_CYCLASE_1, 1 hit
PS50125 GUANYLATE_CYCLASE_2, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P25092-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MKTLLLDLAL WSLLFQPGWL SFSSQVSQNC HNGSYEISVL MMGNSAFAEP
60 70 80 90 100
LKNLEDAVNE GLEIVRGRLQ NAGLNVTVNA TFMYSDGLIH NSGDCRSSTC
110 120 130 140 150
EGLDLLRKIS NAQRMGCVLI GPSCTYSTFQ MYLDTELSYP MISAGSFGLS
160 170 180 190 200
CDYKETLTRL MSPARKLMYF LVNFWKTNDL PFKTYSWSTS YVYKNGTETE
210 220 230 240 250
DCFWYLNALE ASVSYFSHEL GFKVVLRQDK EFQDILMDHN RKSNVIIMCG
260 270 280 290 300
GPEFLYKLKG DRAVAEDIVI ILVDLFNDQY FEDNVTAPDY MKNVLVLTLS
310 320 330 340 350
PGNSLLNSSF SRNLSPTKRD FALAYLNGIL LFGHMLKIFL ENGENITTPK
360 370 380 390 400
FAHAFRNLTF EGYDGPVTLD DWGDVDSTMV LLYTSVDTKK YKVLLTYDTH
410 420 430 440 450
VNKTYPVDMS PTFTWKNSKL PNDITGRGPQ ILMIAVFTLT GAVVLLLLVA
460 470 480 490 500
LLMLRKYRKD YELRQKKWSH IPPENIFPLE TNETNHVSLK IDDDKRRDTI
510 520 530 540 550
QRLRQCKYDK KRVILKDLKH NDGNFTEKQK IELNKLLQID YYNLTKFYGT
560 570 580 590 600
VKLDTMIFGV IEYCERGSLR EVLNDTISYP DGTFMDWEFK ISVLYDIAKG
610 620 630 640 650
MSYLHSSKTE VHGRLKSTNC VVDSRMVVKI TDFGCNSILP PKKDLWTAPE
660 670 680 690 700
HLRQANISQK GDVYSYGIIA QEIILRKETF YTLSCRDRNE KIFRVENSNG
710 720 730 740 750
MKPFRPDLFL ETAEEKELEV YLLVKNCWEE DPEKRPDFKK IETTLAKIFG
760 770 780 790 800
LFHDQKNESY MDTLIRRLQL YSRNLEHLVE ERTQLYKAER DRADRLNFML
810 820 830 840 850
LPRLVVKSLK EKGFVEPELY EEVTIYFSDI VGFTTICKYS TPMEVVDMLN
860 870 880 890 900
DIYKSFDHIV DHHDVYKVET IGDAYMVASG LPKRNGNRHA IDIAKMALEI
910 920 930 940 950
LSFMGTFELE HLPGLPIWIR IGVHSGPCAA GVVGIKMPRY CLFGDTVNTA
960 970 980 990 1000
SRMESTGLPL RIHVSGSTIA ILKRTECQFL YEVRGETYLK GRGNETTYWL
1010 1020 1030 1040 1050
TGMKDQKFNL PTPPTVENQQ RLQAEFSDMI ANSLQKRQAA GIRSQKPRRV
1060 1070
ASYKKGTLEY LQLNTTDKES TYF
Length:1,073
Mass (Da):123,403
Last modified:November 2, 2010 - v2
Checksum:i486A4DE6F9097E22
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti322A → R in AAB19934 (PubMed:1718270).Curated1
Sequence conflicti331L → V in AAB19934 (PubMed:1718270).Curated1
Sequence conflicti509D → V in AAB19934 (PubMed:1718270).Curated1
Sequence conflicti543N → T in AAB19934 (PubMed:1718270).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04222130C → R1 PublicationCorresponds to variant dbSNP:rs56142849Ensembl.1
Natural variantiVAR_04222261G → R in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_042223114R → Q1 PublicationCorresponds to variant dbSNP:rs56275235Ensembl.1
Natural variantiVAR_049253281F → L5 PublicationsCorresponds to variant dbSNP:rs1420635Ensembl.1
Natural variantiVAR_068174387D → G in MECIL; activation of guanylate cyclase activity is 60% lower than in wild-type. 1 PublicationCorresponds to variant dbSNP:rs587776905EnsemblClinVar.1
Natural variantiVAR_042224464R → L1 PublicationCorresponds to variant dbSNP:rs55684775Ensembl.1
Natural variantiVAR_042225610E → K1 PublicationCorresponds to variant dbSNP:rs55897626Ensembl.1
Natural variantiVAR_067724840S → I in DIAR6; activating mutation; exposure of the mutant receptor to its ligands results in markedly increased production of cyclic guanosine monophosphate. 1 PublicationCorresponds to variant dbSNP:rs587776871EnsemblClinVar.1
Natural variantiVAR_042226859I → V1 PublicationCorresponds to variant dbSNP:rs34890806Ensembl.1
Natural variantiVAR_0422271045Q → R1 PublicationCorresponds to variant dbSNP:rs35617837Ensembl.1
Natural variantiVAR_0422281072Y → C1 PublicationCorresponds to variant dbSNP:rs35179392Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S57551 mRNA Translation: AAB19934.2
M73489 mRNA Translation: AAA36655.1
AC007545 Genomic DNA No translation available.
AC010168 Genomic DNA No translation available.
CH471094 Genomic DNA Translation: EAW96324.1
BC136544 mRNA Translation: AAI36545.1
BC136545 mRNA Translation: AAI36546.1
U20230 Genomic DNA Translation: AAC50381.1
CCDSiCCDS8664.1
PIRiA40940 OYHUHX
RefSeqiNP_004954.2, NM_004963.3
UniGeneiHs.524278

Genome annotation databases

EnsembliENST00000261170; ENSP00000261170; ENSG00000070019
GeneIDi2984
KEGGihsa:2984
UCSCiuc001rcd.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
S57551 mRNA Translation: AAB19934.2
M73489 mRNA Translation: AAA36655.1
AC007545 Genomic DNA No translation available.
AC010168 Genomic DNA No translation available.
CH471094 Genomic DNA Translation: EAW96324.1
BC136544 mRNA Translation: AAI36545.1
BC136545 mRNA Translation: AAI36546.1
U20230 Genomic DNA Translation: AAC50381.1
CCDSiCCDS8664.1
PIRiA40940 OYHUHX
RefSeqiNP_004954.2, NM_004963.3
UniGeneiHs.524278

3D structure databases

ProteinModelPortaliP25092
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109239, 2 interactors
IntActiP25092, 3 interactors
MINTiP25092
STRINGi9606.ENSP00000261170

Chemistry databases

ChEMBLiCHEMBL1795197
DrugBankiDB08890 Linaclotide
GuidetoPHARMACOLOGYi1750

Protein family/group databases

TCDBi8.A.85.1.1 the guanylate cyclase (gc) family

PTM databases

GlyConnecti1304
iPTMnetiP25092
PhosphoSitePlusiP25092

Polymorphism and mutation databases

BioMutaiGUCY2C
DMDMi311033390

Proteomic databases

MaxQBiP25092
PaxDbiP25092
PeptideAtlasiP25092
PRIDEiP25092
ProteomicsDBi54253

Protocols and materials databases

DNASUi2984
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261170; ENSP00000261170; ENSG00000070019
GeneIDi2984
KEGGihsa:2984
UCSCiuc001rcd.4 human

Organism-specific databases

CTDi2984
DisGeNETi2984
EuPathDBiHostDB:ENSG00000070019.4
GeneCardsiGUCY2C
H-InvDBiHIX0036867
HGNCiHGNC:4688 GUCY2C
HPAiHPA037655
HPA073759
MalaCardsiGUCY2C
MIMi601330 gene
614616 phenotype
614665 phenotype
neXtProtiNX_P25092
OpenTargetsiENSG00000070019
Orphaneti314373 Chronic diarrhea due to guanylate cyclase 2C overactivity
314376 Intestinal obstruction in the newborn due to guanylate cyclase 2C deficiency
PharmGKBiPA29069
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1023 Eukaryota
COG2114 LUCA
GeneTreeiENSGT00760000118959
HOGENOMiHOG000112833
HOVERGENiHBG106967
InParanoidiP25092
KOiK12320
OMAiMGCVLMG
OrthoDBiEOG091G01F8
PhylomeDBiP25092

Enzyme and pathway databases

BRENDAi4.6.1.2 2681
ReactomeiR-HSA-8935690 Digestion
R-HSA-8942233 Intestinal infectious diseases
SIGNORiP25092

Miscellaneous databases

ChiTaRSiGUCY2C human
GeneWikiiGuanylate_cyclase_2C
GenomeRNAii2984
PROiPR:P25092
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000070019 Expressed in 65 organ(s), highest expression level in jejunal mucosa
CleanExiHS_GUCY2C
HS_STAR
GenevisibleiP25092 HS

Family and domain databases

Gene3Di3.30.70.1230, 1 hit
InterProiView protein in InterPro
IPR001054 A/G_cyclase
IPR018297 A/G_cyclase_CS
IPR011009 Kinase-like_dom_sf
IPR029787 Nucleotide_cyclase
IPR028082 Peripla_BP_I
IPR000719 Prot_kinase_dom
IPR001245 Ser-Thr/Tyr_kinase_cat_dom
PfamiView protein in Pfam
PF00211 Guanylate_cyc, 1 hit
PF07714 Pkinase_Tyr, 1 hit
SMARTiView protein in SMART
SM00044 CYCc, 1 hit
SUPFAMiSSF53822 SSF53822, 1 hit
SSF55073 SSF55073, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00452 GUANYLATE_CYCLASE_1, 1 hit
PS50125 GUANYLATE_CYCLASE_2, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiGUC2C_HUMAN
AccessioniPrimary (citable) accession number: P25092
Secondary accession number(s): B2RMY6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: November 2, 2010
Last modified: November 7, 2018
This is version 185 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
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Main funding by: National Institutes of Health

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