Heat-stable enterotoxin receptor

Details

Name
Heat-stable enterotoxin receptor
Synonyms
  • 4.6.1.2
  • GC-C
  • Guanylyl cyclase C
  • GUC2C
  • Intestinal guanylate cyclase
  • STA receptor
  • STAR
Gene Name
GUCY2C
Organism
Humans
Amino acid sequence
>lcl|BSEQ0012440|Heat-stable enterotoxin receptor
MKTLLLDLALWSLLFQPGWLSFSSQVSQNCHNGSYEISVLMMGNSAFAEPLKNLEDAVNE
GLEIVRGRLQNAGLNVTVNATFMYSDGLIHNSGDCRSSTCEGLDLLRKISNAQRMGCVLI
GPSCTYSTFQMYLDTELSYPMISAGSFGLSCDYKETLTRLMSPARKLMYFLVNFWKTNDL
PFKTYSWSTSYVYKNGTETEDCFWYLNALEASVSYFSHELGFKVVLRQDKEFQDILMDHN
RKSNVIIMCGGPEFLYKLKGDRAVAEDIVIILVDLFNDQYFEDNVTAPDYMKNVLVLTLS
PGNSLLNSSFSRNLSPTKRDFALAYLNGILLFGHMLKIFLENGENITTPKFAHAFRNLTF
EGYDGPVTLDDWGDVDSTMVLLYTSVDTKKYKVLLTYDTHVNKTYPVDMSPTFTWKNSKL
PNDITGRGPQILMIAVFTLTGAVVLLLLVALLMLRKYRKDYELRQKKWSHIPPENIFPLE
TNETNHVSLKIDDDKRRDTIQRLRQCKYDKKRVILKDLKHNDGNFTEKQKIELNKLLQID
YYNLTKFYGTVKLDTMIFGVIEYCERGSLREVLNDTISYPDGTFMDWEFKISVLYDIAKG
MSYLHSSKTEVHGRLKSTNCVVDSRMVVKITDFGCNSILPPKKDLWTAPEHLRQANISQK
GDVYSYGIIAQEIILRKETFYTLSCRDRNEKIFRVENSNGMKPFRPDLFLETAEEKELEV
YLLVKNCWEEDPEKRPDFKKIETTLAKIFGLFHDQKNESYMDTLIRRLQLYSRNLEHLVE
ERTQLYKAERDRADRLNFMLLPRLVVKSLKEKGFVEPELYEEVTIYFSDIVGFTTICKYS
TPMEVVDMLNDIYKSFDHIVDHHDVYKVETIGDAYMVASGLPKRNGNRHAIDIAKMALEI
LSFMGTFELEHLPGLPIWIRIGVHSGPCAAGVVGIKMPRYCLFGDTVNTASRMESTGLPL
RIHVSGSTIAILKRTECQFLYEVRGETYLKGRGNETTYWLTGMKDQKFNLPTPPTVENQQ
RLQAEFSDMIANSLQKRQAAGIRSQKPRRVASYKKGTLEYLQLNTTDKESTYF
Number of residues
1073
Molecular Weight
123401.73
Theoretical pI
7.18
GO Classification
Functions
ATP binding / GTP binding / guanylate cyclase activity / protein kinase activity / toxic substance binding
Processes
cGMP biosynthetic process / intracellular signal transduction / receptor guanylyl cyclase signaling pathway / regulation of cell proliferation / response to toxic substance
Components
endoplasmic reticulum membrane / guanylate cyclase complex, soluble / integral component of membrane / plasma membrane
General Function
Toxic substance binding
Specific Function
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.
Pfam Domain Function
Transmembrane Regions
431-454
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0012441|Heat-stable enterotoxin receptor (GUCY2C)
ATGAAGACGTTGCTGTTGGACTTGGCTTTGTGGTCACTGCTCTTCCAGCCCGGGTGGCTG
TCCTTTAGTTCCCAGGTGAGTCAGAACTGCCACAATGGCAGCTATGAAATCAGCGTCCTG
ATGATGGGCAACTCAGCCTTTGCAGAGCCCCTGAAAAACTTGGAAGATGCGGTGAATGAG
GGGCTGGAAATAGTGAGAGGACGTCTGCAAAATGCTGGCCTAAATGTGACTGTGAACGCT
ACTTTCATGTATTCGGATGGTCTGATTCATAACTCAGGCGACTGCCGGAGTAGCACCTGT
GAAGGCCTCGACCTACTCAGGAAAATTTCAAATGCACAACGGATGGGCTGTGTCCTCATA
GGGCCCTCATGTACATACTCCACCTTCCAGATGTACCTTGACACAGAATTGAGCTACCCC
ATGATCTCAGCTGGAAGTTTTGGATTGTCATGTGACTATAAAGAAACCTTAACCAGGCTG
ATGTCTCCAGCTAGAAAGTTGATGTACTTCTTGGTTAACTTTTGGAAAACCAACGATCTG
CCCTTCAAAACTTATTCCTGGAGCACTTCGTATGTTTACAAGAATGGTACAGAAACTGAG
GACTGTTTCTGGTACCTTAATGCTCTGGAGGCTAGCGTTTCCTATTTCTCCCACGAACTC
GGCTTTAAGGTGGTGTTAAGACAAGATAAGGAGTTTCAGGATATCTTAATGGACCACAAC
AGGAAAAGCAATGTGATTATTATGTGTGGTGGTCCAGAGTTCCTCTACAAGCTGAAGGGT
GACCGAGCAGTGGCTGAAGACATTGTCATTATTCTAGTGGATCTTTTCAATGACCAGTAC
TTTGAGGACAATGTCACAGCCCCTGACTATATGAAAAATGTCCTTGTTCTGACGCTGTCT
CCTGGGAATTCCCTTCTAAATAGCTCTTTCTCCAGGAATCTATCACCAACAAAACGAGAC
TTTGCTCTTGCCTATTTGAATGGAATCCTGCTCTTTGGACATATGCTGAAGATATTTCTT
GAAAATGGAGAAAATATTACCACCCCCAAATTTGCTCATGCTTTCAGGAATCTCACTTTT
GAAGGGTATGACGGTCCAGTGACCTTGGATGACTGGGGGGATGTTGACAGTACCATGGTG
CTTCTGTATACCTCTGTGGACACCAAGAAATACAAGGTTCTTTTGACCTATGATACCCAC
GTAAATAAGACCTATCCTGTGGATATGAGCCCCACATTCACTTGGAAGAACTCTAAACTT
CCTAATGATATTACAGGCCGGGGCCCTCAGATCCTGATGATTGCAGTCTTCACCCTCACT
GGAGCTGTGGTGCTGCTCCTGCTCGTCGCTCTCCTGATGCTCAGAAAATATAGAAAAGAT
TATGAACTTCGTCAGAAAAAATGGTCCCACATTCCTCCTGAAAATATCTTTCCTCTGGAG
ACCAATGAGACCAATCATGTTAGCCTCAAGATCGATGATGACAAAAGACGAGATACAATC
CAGAGACTACGACAGTGCAAATACGACAAAAAGCGAGTGATTCTCAAAGATCTCAAGCAC
AATGATGGTAATTTCACTGAAAAACAGAAGATAGAATTGAACAAGTTGCTTCAGATTGAC
TATTACAACCTGACCAAGTTCTACGGCACAGTGAAACTTGATACCATGATCTTCGGGGTG
ATAGAATACTGTGAGAGAGGATCCCTCCGGGAAGTTTTAAATGACACAATTTCCTACCCT
GATGGCACATTCATGGATTGGGAGTTTAAGATCTCTGTCTTGTATGACATTGCTAAGGGA
ATGTCATATCTGCACTCCAGTAAGACAGAAGTCCATGGTCGTCTGAAATCTACCAACTGC
GTAGTGGACAGTAGAATGGTGGTGAAGATCACTGATTTTGGCTGCAATTCCATTTTACCT
CCAAAAAAGGACCTGTGGACAGCTCCAGAGCACCTCCGCCAAGCCAACATCTCTCAGAAA
GGAGATGTGTACAGCTATGGGATCATCGCACAGGAGATCATCCTGCGGAAAGAAACCTTC
TACACTTTGAGCTGTCGGGACCGGAATGAGAAGATTTTCAGAGTGGAAAATTCCAATGGA
ATGAAACCCTTCCGCCCAGATTTATTCTTGGAAACAGCAGAGGAAAAAGAGCTAGAAGTG
TACCTACTTGTAAAAAACTGTTGGGAGGAAGATCCAGAAAAGAGACCAGATTTCAAAAAA
ATTGAGACTACACTTGCCAAGATATTTGGACTTTTTCATGACCAAAAAAATGAAAGCTAT
ATGGATACCTTGATCCGACGTCTACAGCTATATTCTCGAAACCTGGAACATCTGGTAGAG
GAAAGGACACAGCTGTACAAGGCAGAGAGGGACAGGGCTGACAGACTTAACTTTATGTTG
CTTCCAAGGCTAGTGGTAAAGTCTCTGAAGGAGAAAGGCTTTGTGGAGCCGGAACTATAT
GAGGAAGTTACAATCTACTTCAGTGACATTGTAGGTTTCACTACTATCTGCAAATACAGC
ACCCCCATGGAAGTGGTGGACATGCTTAATGACATCTATAAGAGTTTTGACCACATTGTT
GATCATCATGATGTCTACAAGGTGGAAACCATCGGTGATGCGTACATGGTGGCTAGTGGT
TTGCCTAAGAGAAATGGCAATCGGCATGCAATAGACATTGCCAAGATGGCCTTGGAAATC
CTCAGCTTCATGGGGACCTTTGAGCTGGAGCATCTTCCTGGCCTCCCAATATGGATTCGC
ATTGGAGTTCACTCTGGTCCCTGTGCTGCTGGAGTTGTGGGAATCAAGATGCCTCGTTAT
TGTCTATTTGGAGATACGGTCAACACAGCCTCTAGGATGGAATCCACTGGCCTCCCTTTG
AGAATTCACGTGAGTGGCTCCACCATAGCCATCCTGAAGAGAACTGAGTGCCAGTTCCTT
TATGAAGTGAGAGGAGAAACATACTTAAAGGGAAGAGGAAATGAGACTACCTACTGGCTG
ACTGGGATGAAGGACCAGAAATTCAACCTGCCAACCCCTCCTACTGTGGAGAATCAACAG
CGTTTGCAAGCAGAATTTTCAGACATGATTGCCAACTCTTTACAGAAAAGACAGGCAGCA
GGGATAAGAAGCCAAAAACCCAGACGGGTAGCCAGCTATAAAAAAGGCACTCTGGAATAC
TTGCAGCTGAATACCACAGACAAGGAGAGCACCTATTTTTAA
Chromosome Location
12
Locus
Not Available
External Identifiers
ResourceLink
UniProtKB IDP25092
UniProtKB Entry NameGUC2C_HUMAN
GenBank Gene IDU20230
GenAtlas IDGUCY2C
HGNC IDHGNC:4688
General References
  1. Singh S, Singh G, Heim JM, Gerzer R: Isolation and expression of a guanylate cyclase-coupled heat stable enterotoxin receptor cDNA from a human colonic cell line. Biochem Biophys Res Commun. 1991 Sep 30;179(3):1455-63. [Article]
  2. de Sauvage FJ, Camerato TR, Goeddel DV: Primary structure and functional expression of the human receptor for Escherichia coli heat-stable enterotoxin. J Biol Chem. 1991 Sep 25;266(27):17912-8. [Article]
  3. Scherer SE, Muzny DM, Buhay CJ, Chen R, Cree A, Ding Y, Dugan-Rocha S, Gill R, Gunaratne P, Harris RA, Hawes AC, Hernandez J, Hodgson AV, Hume J, Jackson A, Khan ZM, Kovar-Smith C, Lewis LR, Lozado RJ, Metzker ML, Milosavljevic A, Miner GR, Montgomery KT, Morgan MB, Nazareth LV, Scott G, Sodergren E, Song XZ, Steffen D, Lovering RC, Wheeler DA, Worley KC, Yuan Y, Zhang Z, Adams CQ, Ansari-Lari MA, Ayele M, Brown MJ, Chen G, Chen Z, Clerc-Blankenburg KP, Davis C, Delgado O, Dinh HH, Draper H, Gonzalez-Garay ML, Havlak P, Jackson LR, Jacob LS, Kelly SH, Li L, Li Z, Liu J, Liu W, Lu J, Maheshwari M, Nguyen BV, Okwuonu GO, Pasternak S, Perez LM, Plopper FJ, Santibanez J, Shen H, Tabor PE, Verduzco D, Waldron L, Wang Q, Williams GA, Zhang J, Zhou J, Allen CC, Amin AG, Anyalebechi V, Bailey M, Barbaria JA, Bimage KE, Bryant NP, Burch PE, Burkett CE, Burrell KL, Calderon E, Cardenas V, Carter K, Casias K, Cavazos I, Cavazos SR, Ceasar H, Chacko J, Chan SN, Chavez D, Christopoulos C, Chu J, Cockrell R, Cox CD, Dang M, Dathorne SR, David R, Davis CM, Davy-Carroll L, Deshazo DR, Donlin JE, D'Souza L, Eaves KA, Egan A, Emery-Cohen AJ, Escotto M, Flagg N, Forbes LD, Gabisi AM, Garza M, Hamilton C, Henderson N, Hernandez O, Hines S, Hogues ME, Huang M, Idlebird DG, Johnson R, Jolivet A, Jones S, Kagan R, King LM, Leal B, Lebow H, Lee S, LeVan JM, Lewis LC, London P, Lorensuhewa LM, Loulseged H, Lovett DA, Lucier A, Lucier RL, Ma J, Madu RC, Mapua P, Martindale AD, Martinez E, Massey E, Mawhiney S, Meador MG, Mendez S, Mercado C, Mercado IC, Merritt CE, Miner ZL, Minja E, Mitchell T, Mohabbat F, Mohabbat K, Montgomery B, Moore N, Morris S, Munidasa M, Ngo RN, Nguyen NB, Nickerson E, Nwaokelemeh OO, Nwokenkwo S, Obregon M, Oguh M, Oragunye N, Oviedo RJ, Parish BJ, Parker DN, Parrish J, Parks KL, Paul HA, Payton BA, Perez A, Perrin W, Pickens A, Primus EL, Pu LL, Puazo M, Quiles MM, Quiroz JB, Rabata D, Reeves K, Ruiz SJ, Shao H, Sisson I, Sonaike T, Sorelle RP, Sutton AE, Svatek AF, Svetz LA, Tamerisa KS, Taylor TR, Teague B, Thomas N, Thorn RD, Trejos ZY, Trevino BK, Ukegbu ON, Urban JB, Vasquez LI, Vera VA, Villasana DM, Wang L, Ward-Moore S, Warren JT, Wei X, White F, Williamson AL, Wleczyk R, Wooden HS, Wooden SH, Yen J, Yoon L, Yoon V, Zorrilla SE, Nelson D, Kucherlapati R, Weinstock G, Gibbs RA: The finished DNA sequence of human chromosome 12. Nature. 2006 Mar 16;440(7082):346-51. [Article]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
  5. Mann EA, Jump ML, Glenella RA: Cell line-specific transcriptional activation of the promoter of the human guanylyl cyclase C/heat-stable enterotoxin/receptor gene. Biochim Biophys Acta. 1996 Feb 7;1305(1-2):7-10. [Article]
  6. Mann EA, Cohen MB, Giannella RA: Comparison of receptors for Escherichia coli heat-stable enterotoxin: novel receptor present in IEC-6 cells. Am J Physiol. 1993 Jan;264(1 Pt 1):G172-8. [Article]
  7. Vijayachandra K, Guruprasad M, Bhandari R, Manjunath UH, Somesh BP, Srinivasan N, Suguna K, Visweswariah SS: Biochemical characterization of the intracellular domain of the human guanylyl cyclase C receptor provides evidence for a catalytically active homotrimer. Biochemistry. 2000 Dec 26;39(51):16075-83. [Article]
  8. Scott RO, Thelin WR, Milgram SL: A novel PDZ protein regulates the activity of guanylyl cyclase C, the heat-stable enterotoxin receptor. J Biol Chem. 2002 Jun 21;277(25):22934-41. Epub 2002 Apr 11. [Article]
  9. Arshad N, Ballal S, Visweswariah SS: Site-specific N-linked glycosylation of receptor guanylyl cyclase C regulates ligand binding, ligand-mediated activation and interaction with vesicular integral membrane protein 36, VIP36. J Biol Chem. 2013 Feb 8;288(6):3907-17. doi: 10.1074/jbc.M112.413906. Epub 2012 Dec 26. [Article]
  10. Romi H, Cohen I, Landau D, Alkrinawi S, Yerushalmi B, Hershkovitz R, Newman-Heiman N, Cutting GR, Ofir R, Sivan S, Birk OS: Meconium ileus caused by mutations in GUCY2C, encoding the CFTR-activating guanylate cyclase 2C. Am J Hum Genet. 2012 May 4;90(5):893-9. doi: 10.1016/j.ajhg.2012.03.022. Epub 2012 Apr 19. [Article]
  11. Fiskerstrand T, Arshad N, Haukanes BI, Tronstad RR, Pham KD, Johansson S, Havik B, Tonder SL, Levy SE, Brackman D, Boman H, Biswas KH, Apold J, Hovdenak N, Visweswariah SS, Knappskog PM: Familial diarrhea syndrome caused by an activating GUCY2C mutation. N Engl J Med. 2012 Apr 26;366(17):1586-95. doi: 10.1056/NEJMoa1110132. Epub 2012 Mar 21. [Article]
  12. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB08890LinaclotideapprovedyesagonistDetails