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Protein

Heat-stable enterotoxin receptor

Gene

Gucy2c

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript 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 peptide guanylin.

Catalytic activityi

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

GO - Molecular functioni

  1. ATP binding Source: InterPro
  2. GTP binding Source: UniProtKB-KW
  3. guanylate cyclase activity Source: RGD
  4. protein kinase activity Source: InterPro
  5. toxic substance binding Source: RGD

GO - Biological processi

  1. intracellular signal transduction Source: InterPro
  2. regulation of cell proliferation Source: Ensembl
  3. response to toxic substance Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Lyase, Receptor

Keywords - Biological processi

cGMP biosynthesis

Keywords - Ligandi

GTP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Heat-stable enterotoxin receptor (EC:4.6.1.2)
Short name:
STA receptor
Alternative name(s):
Guanylyl cyclase C
Short name:
GC-C
Intestinal guanylate cyclase
Gene namesi
Name:Gucy2c
Synonyms:Guc2c
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
ProteomesiUP000002494: Chromosome 4

Organism-specific databases

RGDi2771. Gucy2c.

Subcellular locationi

Cell membrane; Single-pass type I membrane protein. Endoplasmic reticulum membrane By similarity; Single-pass type I membrane protein
Note: The 145 kDa plasma membrane form of GC-C contains sialic acid and galactose residues, while a differencially glycosylated 130 Kda form is a high mannose form that is resident in the endoplasmic reticulum and may serve as the precursor for the cell surface form.By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini23 – 429407ExtracellularSequence AnalysisAdd
BLAST
Transmembranei430 – 45324HelicalSequence AnalysisAdd
BLAST
Topological domaini454 – 1072619CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. endoplasmic reticulum membrane Source: UniProtKB-SubCell
  2. integral component of membrane Source: UniProtKB-KW
  3. plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2222Sequence AnalysisAdd
BLAST
Chaini23 – 10721050Heat-stable enterotoxin receptorPRO_0000012378Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi31 – 311N-linked (GlcNAc...)Sequence Analysis
Glycosylationi74 – 741N-linked (GlcNAc...)Sequence Analysis
Glycosylationi78 – 781N-linked (GlcNAc...)Sequence Analysis
Glycosylationi187 – 1871N-linked (GlcNAc...)Sequence Analysis
Glycosylationi194 – 1941N-linked (GlcNAc...)Sequence Analysis
Glycosylationi306 – 3061N-linked (GlcNAc...)Sequence Analysis
Glycosylationi401 – 4011N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

Glycosylation at Asn-74 and/or Asn-78 is required for interaction with VIP36 while glycosylation at Asn-401 modulates ligand-mediated GC-C activation.By similarity

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiP23897.
PRIDEiP23897.

PTM databases

PhosphoSiteiP23897.

Expressioni

Tissue specificityi

Intestine and possibly at low levels in additional tissues.

Gene expression databases

GenevestigatoriP23897.

Interactioni

Subunit structurei

Homotrimer. Interacts via its C-terminal region with PDZK2. Interacts with the lectin chaperone VIP36 (By similarity).By similarity

Protein-protein interaction databases

MINTiMINT-4996544.
STRINGi10116.ENSRNOP00000012212.

Structurei

3D structure databases

ProteinModelPortaliP23897.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini488 – 748261Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini823 – 953131Guanylate cyclasePROSITE-ProRule annotationAdd
BLAST

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
Contains 1 guanylate cyclase domain.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG1023.
GeneTreeiENSGT00760000118959.
HOGENOMiHOG000112833.
HOVERGENiHBG106967.
InParanoidiP23897.
KOiK12320.
OMAiAYHDAVL.
OrthoDBiEOG72VH58.
PhylomeDBiP23897.

Family and domain databases

Gene3Di3.30.70.1230. 1 hit.
InterProiIPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
IPR001828. ANF_lig-bd_rcpt.
IPR011009. Kinase-like_dom.
IPR029787. Nucleotide_cyclase.
IPR028082. Peripla_BP_I.
IPR000719. Prot_kinase_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
[Graphical view]
PfamiPF01094. ANF_receptor. 1 hit.
PF00211. Guanylate_cyc. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
SMARTiSM00044. CYCc. 1 hit.
[Graphical view]
SUPFAMiSSF53822. SSF53822. 1 hit.
SSF55073. SSF55073. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00452. GUANYLATE_CYCLASE_1. 1 hit.
PS50125. GUANYLATE_CYCLASE_2. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P23897-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MTSLLGLAVR LLLFQPTLMF WASQVRQKCH NGTYEISVLM MDNSAYKEPL
60 70 80 90 100
QNLRDAVEEG LDIVRKRLRE AELNVTVNAT FIYSDGLIHK SGDCRSSTCE
110 120 130 140 150
GLDLLREITR DRKMGCVLMG PSCTYSTFQM YLDTELNYPM ISAGSFGLSC
160 170 180 190 200
DYKETLTRIL PPARKLMYFL VDFWKVNNAP FKTFSWNSSY VYKNGSEPED
210 220 230 240 250
CFWYLNALEA GVSYFSEVLS FKDVLRRSEQ FQEILMGRNR KSNVIVMCGT
260 270 280 290 300
PETFYNVKGD LKVADDTVVI LVDLFSNHYF EDDTRAPEYM DNVLVLTLPP
310 320 330 340 350
EKFIANASVS GRFPSERSDF SLAYLEGTLL FGHMLQTFLE NGESVTTPKF
360 370 380 390 400
ARAFRNLTFQ GLEGPVTLDD SGDIDNIMCL LYVSLDTRKY KVLMAYDTHK
410 420 430 440 450
NQTIPVATSP NFIWKNHRLP NDVPGLGPQI LMIAVFTLTG IVVVLLLIAL
460 470 480 490 500
LVLRKYRRDH ELRQKKWSHI PSENIFPLET NETNHVSLKI DDDRRRDTIQ
510 520 530 540 550
RVRQCKYDKK KVILKDLKHC DGNFSEKQKI ELNKLLQSDY YNLTKFYGTV
560 570 580 590 600
KLDTRIFGVV EYCERGSLRE VLNDTISYPD GTFMDWEFKI SVLNDIAKGM
610 620 630 640 650
SYLHSSKIEV HGRLKSTNCV VDSRMVVKIT DFGCNSILPP KKDLWTAPEH
660 670 680 690 700
LRQATISQKG DVYSFSIIAQ EIILRKETFY TLSCRDQNEK IFRVENSYGT
710 720 730 740 750
KPFRPDLFLE TADEKELEVY LLVKSCWEED PEKRPDFKKI ESTLAKIFGL
760 770 780 790 800
FHDQKNESYM DTLIRRLQLY SRNLEHLVEE RTQLYKAERD RADHLNFMLL
810 820 830 840 850
PRLVVKSLKE KGIVEPELYE EVTIYFSDIV GFTTICKYST PMEVVDMLND
860 870 880 890 900
IYKSFDQIVD HHDVYKVETI GDAYVVASGL PMRNGNRHAV DISKMALDIL
910 920 930 940 950
SFMGTFELEH LPGLPVWIRI GVHSGPCAAG VVGIKMPRYC LFGDTVNTAS
960 970 980 990 1000
RMESTGLPLR IHMSSSTIAI LRRTDCQFLY EVRGETYLKG RGTETTYWLT
1010 1020 1030 1040 1050
GMKDQEYNLP TPPTVENQQR LQTEFSDMIV SALQKRQASG VKSRRPTRVA
1060 1070
SYKKGFLEYM QLNNSDHDST YF
Length:1,072
Mass (Da):123,467
Last modified:February 1, 1996 - v2
Checksum:iEBA8656B2948C211
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M55636 mRNA. Translation: AAA41201.1.
PIRiA36292. OYRTHX.
RefSeqiNP_037302.1. NM_013170.1.
UniGeneiRn.10931.

Genome annotation databases

EnsembliENSRNOT00000012212; ENSRNOP00000012212; ENSRNOG00000009031.
GeneIDi25711.
KEGGirno:25711.
UCSCiRGD:2771. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M55636 mRNA. Translation: AAA41201.1.
PIRiA36292. OYRTHX.
RefSeqiNP_037302.1. NM_013170.1.
UniGeneiRn.10931.

3D structure databases

ProteinModelPortaliP23897.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

MINTiMINT-4996544.
STRINGi10116.ENSRNOP00000012212.

Chemistry

GuidetoPHARMACOLOGYi1750.

PTM databases

PhosphoSiteiP23897.

Proteomic databases

PaxDbiP23897.
PRIDEiP23897.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000012212; ENSRNOP00000012212; ENSRNOG00000009031.
GeneIDi25711.
KEGGirno:25711.
UCSCiRGD:2771. rat.

Organism-specific databases

CTDi2984.
RGDi2771. Gucy2c.

Phylogenomic databases

eggNOGiKOG1023.
GeneTreeiENSGT00760000118959.
HOGENOMiHOG000112833.
HOVERGENiHBG106967.
InParanoidiP23897.
KOiK12320.
OMAiAYHDAVL.
OrthoDBiEOG72VH58.
PhylomeDBiP23897.

Miscellaneous databases

NextBioi607775.

Gene expression databases

GenevestigatoriP23897.

Family and domain databases

Gene3Di3.30.70.1230. 1 hit.
InterProiIPR001054. A/G_cyclase.
IPR018297. A/G_cyclase_CS.
IPR001828. ANF_lig-bd_rcpt.
IPR011009. Kinase-like_dom.
IPR029787. Nucleotide_cyclase.
IPR028082. Peripla_BP_I.
IPR000719. Prot_kinase_dom.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
[Graphical view]
PfamiPF01094. ANF_receptor. 1 hit.
PF00211. Guanylate_cyc. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
SMARTiSM00044. CYCc. 1 hit.
[Graphical view]
SUPFAMiSSF53822. SSF53822. 1 hit.
SSF55073. SSF55073. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS00452. GUANYLATE_CYCLASE_1. 1 hit.
PS50125. GUANYLATE_CYCLASE_2. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "Guanylyl cyclase is a heat-stable enterotoxin receptor."
    Schulz S., Green C.K., Yuen P.S.T., Garbers D.L.
    Cell 63:941-948(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Sprague-Dawley.
    Tissue: Small intestine.

Entry informationi

Entry nameiGUC2C_RAT
AccessioniPrimary (citable) accession number: P23897
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: February 1, 1996
Last modified: January 7, 2015
This is version 133 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.