GUCY2C

Protein identityUniProt · HPA

UniProt accession

P25092

Gene

GUCY2C

Ensembl

ENSG00000070019

Chromosome

12

Canonical length

1073 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Predicted membrane proteins, Transporters

Subcellular location

Vesicles

Quaternary structure

Homotrimer

OverviewNCBI Gene

This gene encodes a transmembrane protein that functions as a receptor for endogenous peptides guanylin and uroguanylin, and the heat-stable E. coli enterotoxin. The encoded protein activates the cystic fibrosis transmembrane conductance regulator. Mutations in this gene are associated with familial diarrhea (autosomal dominant) and meconium ileus (autosomal recessive). [provided by RefSeq, Nov 2016]

Canonical amino-acid sequenceUniProt

1073 residues, UniProt reviewed canonical sequence.

>P25092|GUCY2C
     1  MKTLLLDLAL WSLLFQPGWL SFSSQVSQNC HNGSYEISVL MMGNSAFAEP LKNLEDAVNE
    61  GLEIVRGRLQ NAGLNVTVNA TFMYSDGLIH NSGDCRSSTC EGLDLLRKIS NAQRMGCVLI
   121  GPSCTYSTFQ MYLDTELSYP MISAGSFGLS CDYKETLTRL MSPARKLMYF LVNFWKTNDL
   181  PFKTYSWSTS YVYKNGTETE DCFWYLNALE ASVSYFSHEL GFKVVLRQDK EFQDILMDHN
   241  RKSNVIIMCG GPEFLYKLKG DRAVAEDIVI ILVDLFNDQY FEDNVTAPDY MKNVLVLTLS
   301  PGNSLLNSSF SRNLSPTKRD FALAYLNGIL LFGHMLKIFL ENGENITTPK FAHAFRNLTF
   361  EGYDGPVTLD DWGDVDSTMV LLYTSVDTKK YKVLLTYDTH VNKTYPVDMS PTFTWKNSKL
   421  PNDITGRGPQ ILMIAVFTLT GAVVLLLLVA LLMLRKYRKD YELRQKKWSH IPPENIFPLE
   481  TNETNHVSLK IDDDKRRDTI QRLRQCKYDK KRVILKDLKH NDGNFTEKQK IELNKLLQID
   541  YYNLTKFYGT VKLDTMIFGV IEYCERGSLR EVLNDTISYP DGTFMDWEFK ISVLYDIAKG
   601  MSYLHSSKTE VHGRLKSTNC VVDSRMVVKI TDFGCNSILP PKKDLWTAPE HLRQANISQK
   661  GDVYSYGIIA QEIILRKETF YTLSCRDRNE KIFRVENSNG MKPFRPDLFL ETAEEKELEV
   721  YLLVKNCWEE DPEKRPDFKK IETTLAKIFG LFHDQKNESY MDTLIRRLQL YSRNLEHLVE
   781  ERTQLYKAER DRADRLNFML LPRLVVKSLK EKGFVEPELY EEVTIYFSDI VGFTTICKYS
   841  TPMEVVDMLN DIYKSFDHIV DHHDVYKVET IGDAYMVASG LPKRNGNRHA IDIAKMALEI
   901  LSFMGTFELE HLPGLPIWIR IGVHSGPCAA GVVGIKMPRY CLFGDTVNTA SRMESTGLPL
   961  RIHVSGSTIA ILKRTECQFL YEVRGETYLK GRGNETTYWL TGMKDQKFNL PTPPTVENQQ
  1021  RLQAEFSDMI ANSLQKRQAA GIRSQKPRRV ASYKKGTLEY LQLNTTDKES TYF

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against GUCY2C can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.28

Highest tissue expression

64 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about GUCY2C.

Disease | AllUniProt

Conditions GUCY2C is implicated in, by any mechanism.

• Diarrhea 6 (DIAR6) MIM:614616
• Meconium ileus (MECIL) MIM:614665

Disease | GeneticClinVar

14 pathogenic / likely-pathogenic of 984 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Congenital diarrhea 6
• Meconium ileus
• Intestinal obstruction in the newborn due to guanylate cyclase 2C deficiency
• Abnormal biliary tract morphology
• Asplenia

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.08

gnomAD pLI

0

gnomAD missense Z

1.25

DepMap mean gene effect

-0.02

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cGMP biosynthetic process
• intracellular signal transduction
• receptor guanylyl cyclase signaling pathway
• regulation of cell population proliferation
• response to toxic substance

Molecular functions

• ATP binding
• GTP binding
• guanylate cyclase activity
• peptide receptor activity
• protein kinase activity
• toxic substance binding

Cellular components

• endoplasmic reticulum membrane
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Protein kinase domain
• Adenylyl cyclase class-3/4/guanylyl cyclase
• Serine-threonine/tyrosine-protein kinase, catalytic domain
• Protein kinase-like domain superfamily
• Adenylyl cyclase class-4/guanylyl cyclase, conserved site
• Periplasmic binding protein-like I
• Nucleotide cyclase
• Cyclic nucleotide synthase
• Adenylate and Guanylate cyclase catalytic domain
• Protein tyrosine and serine/threonine kinase
• Membrane Guanylate Cyclase receptor GC-C, pseudokinase domain

KeywordsUniProt

• Cell membrane
• cGMP biosynthesis
• Endoplasmic reticulum
• Glycoprotein
• GTP-binding
• Lyase
• Membrane
• Nucleotide-binding
• Receptor
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of GUCY2C in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• NHERF4