FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1990249568> ?p ?o ?g. }

• W1990249568 endingPage "R588" @default.
• W1990249568 startingPage "R585" @default.
• W1990249568 abstract "Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disorder (incidence of 1 in 1,000), the cardinal manifestations of which are renal and liver cysts and intracranial aneurysm. The gene defective in the most common and severest form of ADPKD, PKD1, is broadly expressed and encodes a 4,302 amino acid plasma-membrane protein, polycystin-1 (PKD1) [1The International Kidney Disease ConsortiumPolycystic kidney disease: the complete structure of the PKD1 gene and its protein.Cell. 1995; 81: 289-298PubMed Google Scholar, 2The European Polycystic Kidney Disease ConsortiumThe polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16.Cell. 1995; 77: 881-894Abstract Full Text PDF Scopus (734) Google Scholar, 3Hughes J Ward CJ Peral B Aspinwall R Clark K San Millan J The polycystic kidney disease 1 (PKD1) gene encodes a novel protein with multiple cell recognition domains.Nat Genet. 1995; 10: 151-159Crossref PubMed Scopus (739) Google Scholar]. Despite detailed knowledge of the domain architecture for the majority of the PKD1 sequence (Figure 1), little is known of PKD1 function. Identification of PKD1 mutations has been hampered by the presence of numerous PKD1 homologues elsewhere on chromosome 16 [[2]The European Polycystic Kidney Disease ConsortiumThe polycystic kidney disease 1 gene encodes a 14 kb transcript and lies within a duplicated region on chromosome 16.Cell. 1995; 77: 881-894Abstract Full Text PDF Scopus (734) Google Scholar] and in vitro expression of full-length PKD1 is yet to be reported. Here, we report the identification of three previously unrecognised domains in PKD1 that are likely to possess distinct carbohydrate-, lipid- and protein-binding functions. These domains were identified using PSI-BLAST database searches [4Altschul SF Madden TL Shaffer AA Zhang J Zhang Z Miller W Lipman DJ Gapped BLAST and PSI-BLAST: a new generation of protein database search programs.Nucleic Acids Res. 1997; 25: 3389-3402Crossref PubMed Scopus (57590) Google Scholar, 5Altschul SF Koonin EV Iterated profile searches with PSI-BLAST – a tool for discovery in protein databases.Trends Biochem Sci. 1998; 23: 444-447Abstract Full Text Full Text PDF PubMed Scopus (534) Google Scholar] with an expect-value (E-value) inclusion threshold of E < 0.01. Independent evidence was provided using a generalised profile analysis method [[6]Bucher P Karplus K Moeri N Hofmann K A flexible search technique based on generalized profiles.Comput Chem. 1996; 20: 3-24Crossref PubMed Scopus (254) Google Scholar], in which the significances of findings were better than p < 0.01 in all cases. An extracellular region lying between the leucine-rich repeats (LRRs) and the amino-terminal PKD domain was found to contain a WSC domain that is also present in tandem in a fungal β-1,3-exoglucanase [[7]Cohen-Kupiec R Broglie KE Friesem D Broglie RM Chet I Molecular characterization of a novel β-1,3-exoglucanase related to mycoparasitism of Trichoderma harzianum.Gene. 1999; 226: 147-154Crossref PubMed Scopus (81) Google Scholar] and in Saccharomyces cerevisiae cell-wall integrity and stress-response component proteins [[8]Verna J Lodder A Lee K Vagts A Ballester R A family of genes required for maintenance of cell wall integrity and for the stress response in Saccharomyces cerevisiae.Proc Natl Acad Sci USA. 1997; 94: 13804-13809Crossref PubMed Scopus (305) Google Scholar]. An intracellular region between the first two transmembrane regions of PKD1 was found to contain a β-barrel LH2 domain homologous to a non-catalytic domain of lipoxygenases [[9]Gillmor SA Villasenor A Fletterick R Sigal E Browner MF The structure of mammalian 15-lipoxygenase reveals similarity to the lipases and the determinants of substrate specificity.Nat Struct Biol. 1997; 4: 1003-1009Crossref PubMed Scopus (383) Google Scholar]. This domain has been proposed to facilitate binding of lipase and lipoxygenase substrates to the enzymes’ active sites [[9]Gillmor SA Villasenor A Fletterick R Sigal E Browner MF The structure of mammalian 15-lipoxygenase reveals similarity to the lipases and the determinants of substrate specificity.Nat Struct Biol. 1997; 4: 1003-1009Crossref PubMed Scopus (383) Google Scholar]. This indicates that the PKD1 LH2 domain is likely to possess a lipid-binding function. Multiple alignments and information relating to these domains may be found in the Supplementary material, and are available from the SMART database [10Schultz J Milpetz F Bork P Ponting CP SMART, a simple modular architecture research tool: identification of signalling domains.Proc Natl Acad Sci USA. 1998; 95: 5857-5864Crossref PubMed Scopus (2929) Google Scholar, 11SMART database http://coot.embl-heidelberg.de/SMART/Google Scholar]. The third novel domain of PKD1 was found to be a member of a family that was recently identified in G-protein-coupled receptors (GPCRs) including the Ca2+-independent α-latrotoxin receptor (latrophilin or CL-1) and in other membrane-associated proteins such as the sea urchin receptor for egg jelly protein, REJ [12Sugita S Ichchenko K Khvotchev M Südhof TC α-Latrotoxin receptor CIRL/latrophilin 1 (CL1) defines an unusual family of ubiquitous G-protein-linked receptors.J Biol Chem. 1998; 273: 32715-32724Crossref PubMed Scopus (139) Google Scholar, 13Krasnoperov V Bittner MA Holz RW Chepurny O Petrenko AG Structural requirements for α-latrotoxin binding and α-latrotoxin-stimulated secretion.J Biol Chem. 1999; 274: 3590-3596Crossref PubMed Scopus (74) Google Scholar]. A PSI-BLAST search with the sequence of this domain from REJ (residues 1,353–1,401) demonstrates significant similarity with PKD1 (residues 3,002–3,050) within one iteration using an E-value threshold of 0.01 (Figure 2). Latrophilin/CL-1 is known to be cleaved within this domain [[14]Krasnoperov V Bittner MA Beavis R Kuang Y Salnikow KV Chepurny OG Little AR Plotnikov AN Wu D Holz RW et al.α-Latrotoxin stimulates exocytosis by the interaction with a neuronal G-protein-coupled receptor.Neuron. 1997; 18: 925-937Abstract Full Text Full Text PDF PubMed Scopus (269) Google Scholar], so it has been termed the GPCR proteolytic site (GPS) domain [[15]Ichtchenko K Bittner MA Krasnoperov V Little AR Chepurny O Holz RW Petrenko AG A novel ubiquitously expressed α-latrotoxin receptor is a member of the CIRL family of G-protein-coupled receptors.J Biol Chem. 1999; 274: 5491-5498Crossref PubMed Scopus (83) Google Scholar]. GPS domains in human, Fugu and Caenorhabditis elegans PKD1 proteins contain only one of the two putative disulphide bridges found in CL-1; the second disulphide bridge appears to be missing in GPS domains of C. elegans proteins F31D5.4 and F31D5.5 (Figure 2). Others have pointed out that CL-1 and three other GPS-domain-containing proteins, CL-2, CL-3 and CD97, are all proteolytically processed endogenously [[14]Krasnoperov V Bittner MA Beavis R Kuang Y Salnikow KV Chepurny OG Little AR Plotnikov AN Wu D Holz RW et al.α-Latrotoxin stimulates exocytosis by the interaction with a neuronal G-protein-coupled receptor.Neuron. 1997; 18: 925-937Abstract Full Text Full Text PDF PubMed Scopus (269) Google Scholar][[16]Gray JX Haino M Roth MJ Maguire JE Jensen PN Yarme A Stetler-Stevenson MA Siebenlist U Kelly K CD97 is a processed, seven-transmembrane, heterodimeric receptor associated with inflammation.J Immunol. 1996; 157: 5438-5447PubMed Google Scholar] and that the amino acids surrounding the putative cleavage site are highly conserved among GPS domain sequences [12Sugita S Ichchenko K Khvotchev M Südhof TC α-Latrotoxin receptor CIRL/latrophilin 1 (CL1) defines an unusual family of ubiquitous G-protein-linked receptors.J Biol Chem. 1998; 273: 32715-32724Crossref PubMed Scopus (139) Google Scholar, 15Ichtchenko K Bittner MA Krasnoperov V Little AR Chepurny O Holz RW Petrenko AG A novel ubiquitously expressed α-latrotoxin receptor is a member of the CIRL family of G-protein-coupled receptors.J Biol Chem. 1999; 274: 5491-5498Crossref PubMed Scopus (83) Google Scholar]. The cleavage site in the CL-1 GPS domain is highly conserved in PKD1 orthologues: rat CL-1 is cleaved at the Leu–Thr peptide bond of the sequence His836-Leu-Thr-Asn839[[14]Krasnoperov V Bittner MA Beavis R Kuang Y Salnikow KV Chepurny OG Little AR Plotnikov AN Wu D Holz RW et al.α-Latrotoxin stimulates exocytosis by the interaction with a neuronal G-protein-coupled receptor.Neuron. 1997; 18: 925-937Abstract Full Text Full Text PDF PubMed Scopus (269) Google Scholar], which corresponds to His3047-Leu-Thr-Ala3050 in human PKD1. Consequently, we predict that PKD1 is endogenously cleaved to produce an amino-terminal chain of 3,048 amino acids and a carboxy-terminal chain of 1,255 amino acids. By analogy, the PKD1 amino-terminal chain is unlikely to be released after cleavage, as the two subunits of cleaved rat CL-1 have unexpectedly been shown to be strongly associated [[14]Krasnoperov V Bittner MA Beavis R Kuang Y Salnikow KV Chepurny OG Little AR Plotnikov AN Wu D Holz RW et al.α-Latrotoxin stimulates exocytosis by the interaction with a neuronal G-protein-coupled receptor.Neuron. 1997; 18: 925-937Abstract Full Text Full Text PDF PubMed Scopus (269) Google Scholar]. The exogenous ligand for CL-1, α-latrotoxin, requires both the GPS domain and the hormone receptor domain of CL-1 (the latter is also in secretin receptors) for binding [[12]Sugita S Ichchenko K Khvotchev M Südhof TC α-Latrotoxin receptor CIRL/latrophilin 1 (CL1) defines an unusual family of ubiquitous G-protein-linked receptors.J Biol Chem. 1998; 273: 32715-32724Crossref PubMed Scopus (139) Google Scholar]. Unfortunately, the endogenous ligand of CL-1 remains unknown. Given that homologous molecules often bind homologous receptors, however, the as-yet-unknown ligands for PKD1 and CL-1 may yet prove to be homologues. It may be significant that a single base-pair change resulting in substitution of Val3008 with Leu, just amino-terminal to the GPS domain, has been observed in a patient with ADPKD, although it is unproven whether this mutation causes ADPKD [[17]Watnick TJ Piontek KB Cordal TM Weber H Gandolph MA Qian F Lens XM Neumann HPH Germino GG An unusual pattern of mutation in the duplicated portion of PKD1 is revealed by use of a novel strategy for mutation detection.Hum Mol Genet. 1997; 6: 1473-1481Crossref PubMed Scopus (85) Google Scholar]. PKD1, CL-1 and REJ possess functional similarities that are likely to be due to their common GPS domains and transmembrane regions. Each of these molecules is suggested to mediate transmembrane influx of Ca2+[13Krasnoperov V Bittner MA Holz RW Chepurny O Petrenko AG Structural requirements for α-latrotoxin binding and α-latrotoxin-stimulated secretion.J Biol Chem. 1999; 274: 3590-3596Crossref PubMed Scopus (74) Google Scholar, 18Sandford R Sgotto B Aparicio S Brenner S Vaudin M Wilson RK Chissoe S Pepin K Bateman A Chothia C et al.Comparative analysis of the polycystic kidney disease 1 (PKD1) gene reveals an integral membrane glycoprotein with multiple evolutionary conserved domains.Hum Mol Genet. 1997; 6: 1483-1489Crossref PubMed Scopus (137) Google Scholar, 19Moy GW Mendoza LM Schultz JR Swanson WJ Glabe CG Vacquier VD The sea urchin sperm receptor for egg jelly is a modular protein with extensive homology to the human polycystic kidney disease protein, PKD1.J Cell Biol. 1996; 133: 809-817Crossref PubMed Scopus (212) Google Scholar]. However, this function of PKD1 has been ascribed to its carboxy-terminal PKD2-like and voltage-gated Ca2+ channel-like region [[17]Watnick TJ Piontek KB Cordal TM Weber H Gandolph MA Qian F Lens XM Neumann HPH Germino GG An unusual pattern of mutation in the duplicated portion of PKD1 is revealed by use of a novel strategy for mutation detection.Hum Mol Genet. 1997; 6: 1473-1481Crossref PubMed Scopus (85) Google Scholar], which is lacking in CL-1 and REJ. It is notable that REJ, which contains a single transmembrane region, and a CL-1 truncation variant containing only its GPS-domain-containing extracellular region and the single amino-terminal transmembrane region, both support Ca2+ influx [13Krasnoperov V Bittner MA Holz RW Chepurny O Petrenko AG Structural requirements for α-latrotoxin binding and α-latrotoxin-stimulated secretion.J Biol Chem. 1999; 274: 3590-3596Crossref PubMed Scopus (74) Google Scholar, 20Trimmer JS Schackmann RW Vacquier VD Monoclonal antibodies increase intracellular Ca2+ in sea urchin spermatozoa.Proc Natl Acad Sci USA. 1986; 83: 9055-9059Crossref PubMed Scopus (59) Google Scholar]. Consequently, we predict that the PKD1 transmembrane region 1 functions similarly in supporting Ca2+ influx. In conclusion, the three previously unrecognised WSC, GPS and LH2 domains in human PKD1 are tentatively suggested to bind three different ligand types, namely carbohydrate, protein and lipid, respectively. Most of the amino-terminal region (amino acids 1–3,466) of human PKD1 has now been assigned domain homologues. However, mice heterozygous for a PKD1 mutation that results in a protein that lacks its carboxy-terminal region (amino acids 3,497–4,293) and yet retains all the newly identified domains have been shown to possess kidney and pancreas defects [[21]Lu W Peissel B Babakhanlou H Pavlova A Geng L Fan X Larson C Brent G Zhou J Perinatal lethality with kidney and pancreas defects in mice with a targetted Pkd1 mutation.Nat Genet. 1997; 17: 179-181Crossref PubMed Scopus (363) Google Scholar]. This demonstrates that further experiments are required to determine the functions of different regions and domains of this large and complex molecule. Supplementary material including multiple alignments and descriptions of the three domains is available at http://current-biology.com/supmat/supmatin.htm. C.P.P. is a National Research Council Senior Associate. Download .pdf (.06 MB) Help with pdf files Supplementary material CP Ponting, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda Maryland 20894, USA. E-mail: [email protected] K Hofmann, MEMOREC Stoffel GmbH, Stöckheimer Weg 1, D-50829 Köln, Germany. P Bork, European Molecular Biology Laboratory, Meyerhofstrasse 1, D-69012 Heidelberg, Max-Delbrück-Center for Molecular Medicine, D-13125 Berlin-Buch, Germany." @default.
• W1990249568 created "2016-06-24" @default.
• W1990249568 creator A5015519563 @default.
• W1990249568 creator A5021151726 @default.
• W1990249568 creator A5074309419 @default.
• W1990249568 date "1999-08-01" @default.
• W1990249568 modified "2023-10-17" @default.
• W1990249568 title "A latrophilin/CL-1-like GPS domain in polycystin-1" @default.
• W1990249568 cites W1583577648 @default.
• W1990249568 cites W1966354110 @default.
• W1990249568 cites W1966685035 @default.
• W1990249568 cites W1975207791 @default.
• W1990249568 cites W1977922844 @default.
• W1990249568 cites W1984615286 @default.
• W1990249568 cites W1985818354 @default.
• W1990249568 cites W1997199912 @default.
• W1990249568 cites W2005026678 @default.
• W1990249568 cites W2010726206 @default.
• W1990249568 cites W2021312899 @default.
• W1990249568 cites W2040518083 @default.
• W1990249568 cites W2056379655 @default.
• W1990249568 cites W2081659168 @default.
• W1990249568 cites W2087924977 @default.
• W1990249568 cites W2091583365 @default.
• W1990249568 cites W2113588019 @default.
• W1990249568 cites W2117852779 @default.
• W1990249568 cites W2134880511 @default.
• W1990249568 cites W2139780190 @default.
• W1990249568 cites W2147210417 @default.
• W1990249568 cites W2158714788 @default.
• W1990249568 cites W2223063733 @default.
• W1990249568 doi "https://doi.org/10.1016/s0960-9822(99)80379-0" @default.
• W1990249568 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/10469603" @default.
• W1990249568 hasPublicationYear "1999" @default.
• W1990249568 type Work @default.
• W1990249568 sameAs 1990249568 @default.
• W1990249568 citedByCount "133" @default.
• W1990249568 countsByYear W19902495682012 @default.
• W1990249568 countsByYear W19902495682013 @default.
• W1990249568 countsByYear W19902495682014 @default.
• W1990249568 countsByYear W19902495682015 @default.
• W1990249568 countsByYear W19902495682016 @default.
• W1990249568 countsByYear W19902495682017 @default.
• W1990249568 countsByYear W19902495682018 @default.
• W1990249568 countsByYear W19902495682019 @default.
• W1990249568 countsByYear W19902495682020 @default.
• W1990249568 countsByYear W19902495682021 @default.
• W1990249568 countsByYear W19902495682022 @default.
• W1990249568 countsByYear W19902495682023 @default.
• W1990249568 crossrefType "journal-article" @default.
• W1990249568 hasAuthorship W1990249568A5015519563 @default.
• W1990249568 hasAuthorship W1990249568A5021151726 @default.
• W1990249568 hasAuthorship W1990249568A5074309419 @default.
• W1990249568 hasBestOaLocation W19902495681 @default.
• W1990249568 hasConcept C134306372 @default.
• W1990249568 hasConcept C33923547 @default.
• W1990249568 hasConcept C36503486 @default.
• W1990249568 hasConcept C41008148 @default.
• W1990249568 hasConcept C60229501 @default.
• W1990249568 hasConcept C70721500 @default.
• W1990249568 hasConcept C76155785 @default.
• W1990249568 hasConcept C78458016 @default.
• W1990249568 hasConcept C86803240 @default.
• W1990249568 hasConcept C95444343 @default.
• W1990249568 hasConceptScore W1990249568C134306372 @default.
• W1990249568 hasConceptScore W1990249568C33923547 @default.
• W1990249568 hasConceptScore W1990249568C36503486 @default.
• W1990249568 hasConceptScore W1990249568C41008148 @default.
• W1990249568 hasConceptScore W1990249568C60229501 @default.
• W1990249568 hasConceptScore W1990249568C70721500 @default.
• W1990249568 hasConceptScore W1990249568C76155785 @default.
• W1990249568 hasConceptScore W1990249568C78458016 @default.
• W1990249568 hasConceptScore W1990249568C86803240 @default.
• W1990249568 hasConceptScore W1990249568C95444343 @default.
• W1990249568 hasIssue "16" @default.
• W1990249568 hasLocation W19902495681 @default.
• W1990249568 hasLocation W19902495682 @default.
• W1990249568 hasOpenAccess W1990249568 @default.
• W1990249568 hasPrimaryLocation W19902495681 @default.
• W1990249568 hasRelatedWork W1997770566 @default.
• W1990249568 hasRelatedWork W2006264290 @default.
• W1990249568 hasRelatedWork W2034736453 @default.
• W1990249568 hasRelatedWork W2055925137 @default.
• W1990249568 hasRelatedWork W2061542922 @default.
• W1990249568 hasRelatedWork W2422215742 @default.
• W1990249568 hasRelatedWork W4235748225 @default.
• W1990249568 hasRelatedWork W4236969087 @default.
• W1990249568 hasRelatedWork W4250751887 @default.
• W1990249568 hasRelatedWork W4250812939 @default.
• W1990249568 hasVolume "9" @default.
• W1990249568 isParatext "false" @default.
• W1990249568 isRetracted "false" @default.
• W1990249568 magId "1990249568" @default.
• W1990249568 workType "article" @default.