Polycystic kidney disease 2-like 1 protein

Details

Name
Polycystic kidney disease 2-like 1 protein
Synonyms
  • PKD2L
  • PKDL
  • Polycystin-2 homolog
  • Polycystin-2L1
  • Polycystin-L
  • Polycystin-L1
  • TRPP3
Gene Name
PKD2L1
Organism
Humans
Amino acid sequence
>lcl|BSEQ0049525|Polycystic kidney disease 2-like 1 protein
MNAVGSPEGQELQKLGSGAWDNPAYSGPPSPHGTLRVCTISSTGPLQPQPKKPEDEPQET
AYRTQVSSCCLHICQGIRGLWGTTLTENTAENRELYIKTTLRELLVYIVFLVDICLLTYG
MTSSSAYYYTKVMSELFLHTPSDTGVSFQAISSMADFWDFAQGPLLDSLYWTKWYNNQSL
GHGSHSFIYYENMLLGVPRLRQLKVRNDSCVVHEDFREDILSCYDVYSPDKEEQLPFGPF
NGTAWTYHSQDELGGFSHWGRLTSYSGGGYYLDLPGSRQGSAEALRALQEGLWLDRGTRV
VFIDFSVYNANINLFCVLRLVVEFPATGGAIPSWQIRTVKLIRYVSNWDFFIVGCEVIFC
VFIFYYVVEEILELHIHRLRYLSSIWNILDLVVILLSIVAVGFHIFRTLEVNRLMGKLLQ
QPNTYADFEFLAFWQTQYNNMNAVNLFFAWIKIFKYISFNKTMTQLSSTLARCAKDILGF
AVMFFIVFFAYAQLGYLLFGTQVENFSTFIKCIFTQFRIILGDFDYNAIDNANRILGPAY
FVTYVFFVFFVLLNMFLAIINDTYSEVKEELAGQKDELQLSDLLKQGYNKTLLRLRLRKE
RVSDVQKVLQGGEQEIQFEDFTNTLRELGHAEHEITELTATFTKFDRDGNRILDEKEQEK
MRQDLEEERVALNTEIEKLGRSIVSSPQGKSGPEAARAGGWVSGEEFYMLTRRVLQLETV
LEGVVSQIDAVGSKLKMLERKGWLAPSPGVKEQAIWKHPQPAPAVTPDPWGVQGGQESEV
PYKREEEALEERRLSRGEIPTLQRS
Number of residues
805
Molecular Weight
91981.23
Theoretical pI
Not Available
GO Classification
Functions
alpha-actinin binding / calcium activated cation channel activity / calcium channel activity / calcium ion binding / calcium-activated potassium channel activity / cation channel activity / cytoskeletal protein binding / identical protein binding / muscle alpha-actinin binding / sodium channel activity / sour taste receptor activity
Processes
cation transport / cellular response to acidic pH / detection of chemical stimulus involved in sensory perception of sour taste / detection of mechanical stimulus / potassium ion transmembrane transport / protein homotrimerization / sensory perception of sour taste / smoothened signaling pathway / sodium ion transmembrane transport
Components
calcium channel complex / cell surface / ciliary membrane / endoplasmic reticulum / integral component of membrane / intracellular membrane-bounded organelle / membrane / non-motile cilium / plasma membrane / receptor complex
General Function
Pore-forming subunit of a ciliary calcium channel that controls calcium concentration within primary cilia without affecting cytoplasmic calcium concentration. Forms a heterodimer with PKD1L1 in primary cilia and forms a calcium-permeant ciliary channel that regulates sonic hedgehog/SHH signaling and GLI2 transcription. May act as a sour taste receptor by forming a calcium channel with PKD1L3 in gustatory cells; however, its contribution to sour taste perception is unclear in vivo and may be indirect.
Specific Function
Alpha-actinin binding
Pfam Domain Function
Transmembrane Regions
104-124 314-334 348-368 385-405 477-497 540-560
Cellular Location
Cell projection
Gene sequence
>lcl|BSEQ0049526|Polycystic kidney disease 2-like 1 protein (PKD2L1)
ATGAATGCTGTGGGAAGTCCTGAGGGGCAGGAGCTGCAAAAGCTGGGGAGTGGAGCCTGG
GACAACCCCGCCTACAGTGGTCCCCCTTCCCCACACGGGACGCTGAGAGTCTGCACCATC
TCCAGCACGGGGCCTCTCCAGCCCCAACCCAAGAAGCCTGAAGATGAACCCCAGGAGACG
GCATACAGGACCCAGGTGTCCAGCTGCTGCCTCCATATCTGTCAAGGCATCAGAGGACTT
TGGGGAACAACCCTGACTGAGAACACAGCTGAGAACCGGGAACTTTATATCAAGACCACC
CTGAGGGAGCTGTTGGTATATATTGTGTTCCTGGTGGACATCTGTCTACTGACCTATGGA
ATGACAAGCTCCAGTGCTTATTACTACACCAAAGTGATGTCTGAGCTCTTCTTACATACT
CCATCAGACACTGGAGTCTCCTTTCAGGCCATCAGCAGCATGGCGGACTTCTGGGATTTT
GCCCAGGGCCCACTACTGGACAGTTTGTATTGGACCAAATGGTACAACAACCAGAGCCTG
GGCCATGGCTCCCACTCCTTCATCTACTATGAGAACATGCTGCTGGGGGTTCCGAGGCTG
CGGCAGCTAAAGGTCCGCAATGACTCCTGTGTGGTGCATGAAGACTTCCGGGAGGACATT
CTGAGCTGCTATGATGTCTACTCTCCAGACAAAGAAGAACAACTCCCCTTTGGGCCCTTC
AATGGCACAGCGTGGACATACCACTCGCAGGATGAGTTGGGGGGCTTCTCCCACTGGGGC
AGGCTCACAAGCTACAGCGGAGGTGGCTACTACCTGGACCTTCCAGGATCCCGACAGGGT
AGTGCAGAGGCTCTCCGGGCCCTTCAGGAGGGGCTGTGGCTGGACAGGGGCACTCGAGTG
GTGTTCATCGACTTCTCAGTCTACAATGCCAATATCAATCTTTTCTGTGTCCTGAGGCTG
GTGGTGGAGTTTCCAGCTACAGGAGGTGCCATCCCATCCTGGCAAATCCGCACAGTCAAG
CTGATCCGCTATGTCAGCAACTGGGACTTCTTTATCGTTGGCTGTGAGGTCATCTTCTGC
GTCTTCATCTTCTACTATGTGGTGGAAGAGATCCTGGAGCTCCACATTCACCGGCTTCGC
TACCTCAGCAGCATCTGGAACATACTGGACCTGGTGGTCATCTTGCTCTCCATTGTGGCT
GTGGGCTTCCACATATTCCGAACCCTCGAGGTGAATCGGCTCATGGGGAAGCTCCTGCAG
CAGCCAAACACGTATGCAGACTTTGAGTTCCTCGCCTTCTGGCAGACACAGTACAACAAC
ATGAATGCTGTCAACCTCTTCTTCGCCTGGATCAAGATATTCAAGTACATCAGCTTCAAC
AAAACCATGACCCAGCTCTCCTCCACGCTGGCCCGCTGTGCCAAGGACATCCTGGGCTTC
GCCGTCATGTTCTTCATTGTTTTCTTCGCCTATGCCCAACTCGGCTACCTGCTTTTCGGG
ACCCAAGTGGAAAACTTTAGCACTTTCATCAAGTGCATTTTCACTCAGTTCCGGATAATC
CTCGGGGACTTTGACTACAATGCTATCGACAATGCCAACCGCATCCTGGGCCCTGCCTAC
TTTGTCACCTATGTCTTCTTCGTCTTCTTCGTGCTCCTGAACATGTTCCTGGCCATCATC
AATGACACATATTCAGAGGTCAAGGAGGAGCTGGCTGGACAGAAGGATGAGCTGCAACTT
TCTGACCTCCTGAAACAGGGCTACAACAAGACCCTACTAAGACTGCGTCTGAGGAAGGAG
AGGGTTTCGGATGTGCAGAAGGTCCTGCAGGGTGGGGAGCAGGAGATCCAGTTTGAGGAT
TTCACCAACACCTTAAGGGAACTGGGACACGCAGAGCATGAAATCACTGAGCTCACGGCC
ACCTTCACCAAGTTTGACAGAGATGGGAATCGTATTCTGGATGAGAAGGAACAGGAAAAA
ATGCGACAGGACCTGGAGGAAGAGAGGGTGGCCCTCAACACTGAGATTGAGAAACTAGGC
CGATCTATTGTGAGCAGCCCACAAGGCAAATCGGGTCCAGAGGCTGCCAGAGCAGGAGGC
TGGGTTTCAGGAGAAGAATTCTACATGCTCACAAGGAGAGTTCTGCAGCTGGAGACTGTC
CTGGAAGGAGTAGTGTCCCAGATTGATGCTGTAGGCTCAAAGCTGAAAATGCTGGAGAGG
AAGGGGTGGCTGGCTCCCTCCCCAGGCGTGAAGGAACAAGCTATTTGGAAGCACCCGCAG
CCAGCCCCAGCTGTGACCCCAGACCCCTGGGGAGTCCAGGGTGGGCAGGAGAGTGAGGTT
CCCTATAAAAGAGAAGAGGAAGCCTTAGAGGAGAGGAGACTCTCCCGTGGTGAGATTCCA
ACGTTGCAGAGGAGTTAA
Chromosome Location
10
Locus
10q24.31
External Identifiers
ResourceLink
UniProtKB IDQ9P0L9
UniProtKB Entry NamePK2L1_HUMAN
HGNC IDHGNC:9011
General References
  1. Nomura H, Turco AE, Pei Y, Kalaydjieva L, Schiavello T, Weremowicz S, Ji W, Morton CC, Meisler M, Reeders ST, Zhou J: Identification of PKDL, a novel polycystic kidney disease 2-like gene whose murine homologue is deleted in mice with kidney and retinal defects. J Biol Chem. 1998 Oct 2;273(40):25967-73. [Article]
  2. Guo L, Chen M, Basora N, Zhou J: The human polycystic kidney disease 2-like (PKDL) gene: exon/intron structure and evidence for a novel splicing mechanism. Mamm Genome. 2000 Jan;11(1):46-50. [Article]
  3. Deloukas P, Earthrowl ME, Grafham DV, Rubenfield M, French L, Steward CA, Sims SK, Jones MC, Searle S, Scott C, Howe K, Hunt SE, Andrews TD, Gilbert JG, Swarbreck D, Ashurst JL, Taylor A, Battles J, Bird CP, Ainscough R, Almeida JP, Ashwell RI, Ambrose KD, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Bates K, Beasley H, Bray-Allen S, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Cahill P, Camire D, Carter NP, Chapman JC, Clark SY, Clarke G, Clee CM, Clegg S, Corby N, Coulson A, Dhami P, Dutta I, Dunn M, Faulkner L, Frankish A, Frankland JA, Garner P, Garnett J, Gribble S, Griffiths C, Grocock R, Gustafson E, Hammond S, Harley JL, Hart E, Heath PD, Ho TP, Hopkins B, Horne J, Howden PJ, Huckle E, Hynds C, Johnson C, Johnson D, Kana A, Kay M, Kimberley AM, Kershaw JK, Kokkinaki M, Laird GK, Lawlor S, Lee HM, Leongamornlert DA, Laird G, Lloyd C, Lloyd DM, Loveland J, Lovell J, McLaren S, McLay KE, McMurray A, Mashreghi-Mohammadi M, Matthews L, Milne S, Nickerson T, Nguyen M, Overton-Larty E, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter K, Rice CM, Rogosin A, Ross MT, Sarafidou T, Sehra HK, Shownkeen R, Skuce CD, Smith M, Standring L, Sycamore N, Tester J, Thorpe A, Torcasso W, Tracey A, Tromans A, Tsolas J, Wall M, Walsh J, Wang H, Weinstock K, West AP, Willey DL, Whitehead SL, Wilming L, Wray PW, Young L, Chen Y, Lovering RC, Moschonas NK, Siebert R, Fechtel K, Bentley D, Durbin R, Hubbard T, Doucette-Stamm L, Beck S, Smith DR, Rogers J: The DNA sequence and comparative analysis of human chromosome 10. Nature. 2004 May 27;429(6990):375-81. [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. Wu G, Hayashi T, Park JH, Dixit M, Reynolds DM, Li L, Maeda Y, Cai Y, Coca-Prados M, Somlo S: Identification of PKD2L, a human PKD2-related gene: tissue-specific expression and mapping to chromosome 10q25. Genomics. 1998 Dec 15;54(3):564-8. [Article]
  6. Veldhuisen B, Spruit L, Dauwerse HG, Breuning MH, Peters DJ: Genes homologous to the autosomal dominant polycystic kidney disease genes (PKD1 and PKD2). Eur J Hum Genet. 1999 Dec;7(8):860-72. [Article]
  7. Chen XZ, Vassilev PM, Basora N, Peng JB, Nomura H, Segal Y, Brown EM, Reeders ST, Hediger MA, Zhou J: Polycystin-L is a calcium-regulated cation channel permeable to calcium ions. Nature. 1999 Sep 23;401(6751):383-6. [Article]
  8. Stayner C, Zhou J: Polycystin channels and kidney disease. Trends Pharmacol Sci. 2001 Nov;22(11):543-6. [Article]
  9. Li Q, Liu Y, Zhao W, Chen XZ: The calcium-binding EF-hand in polycystin-L is not a domain for channel activation and ensuing inactivation. FEBS Lett. 2002 Apr 10;516(1-3):270-8. [Article]
  10. Inada H, Kawabata F, Ishimaru Y, Fushiki T, Matsunami H, Tominaga M: Off-response property of an acid-activated cation channel complex PKD1L3-PKD2L1. EMBO Rep. 2008 Jul;9(7):690-7. doi: 10.1038/embor.2008.89. Epub 2008 Jun 6. [Article]
  11. Ishii S, Misaka T, Kishi M, Kaga T, Ishimaru Y, Abe K: Acetic acid activates PKD1L3-PKD2L1 channel--a candidate sour taste receptor. Biochem Biophys Res Commun. 2009 Jul 31;385(3):346-50. doi: 10.1016/j.bbrc.2009.05.069. Epub 2009 May 21. [Article]
  12. Huque T, Cowart BJ, Dankulich-Nagrudny L, Pribitkin EA, Bayley DL, Spielman AI, Feldman RS, Mackler SA, Brand JG: Sour ageusia in two individuals implicates ion channels of the ASIC and PKD families in human sour taste perception at the anterior tongue. PLoS One. 2009 Oct 8;4(10):e7347. doi: 10.1371/journal.pone.0007347. [Article]
  13. Molland KL, Narayanan A, Burgner JW, Yernool DA: Identification of the structural motif responsible for trimeric assembly of the C-terminal regulatory domains of polycystin channels PKD2L1 and PKD2. Biochem J. 2010 Jul 1;429(1):171-83. doi: 10.1042/BJ20091843. [Article]
  14. Ishimaru Y, Katano Y, Yamamoto K, Akiba M, Misaka T, Roberts RW, Asakura T, Matsunami H, Abe K: Interaction between PKD1L3 and PKD2L1 through their transmembrane domains is required for localization of PKD2L1 at taste pores in taste cells of circumvallate and foliate papillae. FASEB J. 2010 Oct;24(10):4058-67. doi: 10.1096/fj.10-162925. Epub 2010 Jun 10. [Article]
  15. Ishii S, Kurokawa A, Kishi M, Yamagami K, Okada S, Ishimaru Y, Misaka T: The response of PKD1L3/PKD2L1 to acid stimuli is inhibited by capsaicin and its pungent analogs. FEBS J. 2012 May;279(10):1857-70. doi: 10.1111/j.1742-4658.2012.08566.x. Epub 2012 Apr 16. [Article]
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  17. DeCaen PG, Delling M, Vien TN, Clapham DE: Direct recording and molecular identification of the calcium channel of primary cilia. Nature. 2013 Dec 12;504(7479):315-8. doi: 10.1038/nature12832. [Article]
  18. Molland KL, Paul LN, Yernool DA: Crystal structure and characterization of coiled-coil domain of the transient receptor potential channel PKD2L1. Biochim Biophys Acta. 2012 Mar;1824(3):413-21. doi: 10.1016/j.bbapap.2011.12.002. Epub 2011 Dec 13. [Article]
  19. Yu Y, Ulbrich MH, Li MH, Dobbins S, Zhang WK, Tong L, Isacoff EY, Yang J: Molecular mechanism of the assembly of an acid-sensing receptor ion channel complex. Nat Commun. 2012;3:1252. doi: 10.1038/ncomms2257. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB11093Calcium citrateapproved, investigationalunknownsubstrateDetails
DB11348Calcium PhosphateapprovedunknownsubstrateDetails
DB14481Calcium phosphate dihydrateapprovedunknownDetails