PK2L1_HUMAN
ID PK2L1_HUMAN Reviewed; 805 AA.
AC Q9P0L9; O75972; Q5W039; Q9UP35; Q9UPA2;
DT 10-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Polycystic kidney disease 2-like 1 protein;
DE AltName: Full=Polycystin-2 homolog;
DE AltName: Full=Polycystin-2L1;
DE AltName: Full=Polycystin-L {ECO:0000303|PubMed:10517637, ECO:0000303|PubMed:9748274};
DE AltName: Full=Polycystin-L1;
GN Name=PKD2L1;
GN Synonyms=PKD2L, PKDL {ECO:0000303|PubMed:9748274},
GN TRPP3 {ECO:0000303|PubMed:23212381, ECO:0000303|PubMed:27754867};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND VARIANT
RP ILE-393.
RC TISSUE=Retina;
RX PubMed=9748274; DOI=10.1074/jbc.273.40.25967;
RA Nomura H., Turco A.E., Pei Y., Kalaydjieva L., Schiavello T.,
RA Weremowicz S., Ji W., Morton C.C., Meisler M., Reeders S.T., Zhou J.;
RT "Identification of PKDL, a novel polycystic kidney disease 2-like gene
RT whose murine homologue is deleted in mice with kidney and retinal
RT defects.";
RL J. Biol. Chem. 273:25967-25973(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1; 2; 3 AND 4).
RX PubMed=10602992; DOI=10.1007/s003350010009;
RA Guo L., Chen M., Basora N., Zhou J.;
RT "The human polycystic kidney disease 2-like (PKDL) gene: exon/intron
RT structure and evidence for a novel splicing mechanism.";
RL Mamm. Genome 11:46-50(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 96-805 (ISOFORM 1), AND TISSUE SPECIFICITY.
RC TISSUE=Retina;
RX PubMed=9878261; DOI=10.1006/geno.1998.5618;
RA Wu G., Hayashi T., Park J.-H., Dixit M., Reynolds D.M., Li L., Maeda Y.,
RA Cai Y., Coca-Prados M., Somlo S.;
RT "Identification of PKD2L, a human PKD2-related gene: tissue-specific
RT expression and mapping to chromosome 10q25.";
RL Genomics 54:564-568(1998).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 43-805 (ISOFORMS 1 AND 4).
RC TISSUE=Testis;
RX PubMed=10602361; DOI=10.1038/sj.ejhg.5200383;
RA Veldhuisen B., Spruit L., Dauwerse H.G., Breuning M.H., Peters D.J.M.;
RT "Genes homologous to the autosomal dominant polycystic kidney disease genes
RT (PKD1 and PKD2).";
RL Eur. J. Hum. Genet. 7:860-872(1999).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10517637; DOI=10.1038/43907;
RA Chen X.-Z., Vassilev P.M., Basora N., Peng J.-B., Nomura H., Segal Y.,
RA Brown E.M., Reeders S.T., Hediger M.A., Zhou J.;
RT "Polycystin-L is a calcium-regulated cation channel permeable to calcium
RT ions.";
RL Nature 401:383-386(1999).
RN [9]
RP ALTERNATIVE SPLICING (ISOFORMS 2 AND 5), FUNCTION, SUBCELLULAR LOCATION,
RP AND DOMAIN.
RX PubMed=11959145; DOI=10.1016/s0014-5793(02)02513-9;
RA Li Q., Liu Y., Zhao W., Chen X.Z.;
RT "The calcium-binding EF-hand in polycystin-L is not a domain for channel
RT activation and ensuing inactivation.";
RL FEBS Lett. 516:270-278(2002).
RN [10]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=19812697; DOI=10.1371/journal.pone.0007347;
RA Huque T., Cowart B.J., Dankulich-Nagrudny L., Pribitkin E.A., Bayley D.L.,
RA Spielman A.I., Feldman R.S., Mackler S.A., Brand J.G.;
RT "Sour ageusia in two individuals implicates ion channels of the ASIC and
RT PKD families in human sour taste perception at the anterior tongue.";
RL PLoS ONE 4:E7347-E7347(2009).
RN [11]
RP DOMAIN, AND CALCIUM-BINDING.
RX PubMed=20408813; DOI=10.1042/bj20091843;
RA Molland K.L., Narayanan A., Burgner J.W., Yernool D.A.;
RT "Identification of the structural motif responsible for trimeric assembly
RT of the C-terminal regulatory domains of polycystin channels PKD2L1 and
RT PKD2.";
RL Biochem. J. 429:171-183(2010).
RN [12]
RP INTERACTION WITH RACK1.
RX PubMed=22174419; DOI=10.1074/jbc.m111.305854;
RA Yang J., Wang Q., Zheng W., Tuli J., Li Q., Wu Y., Hussein S., Dai X.Q.,
RA Shafiei S., Li X.G., Shen P.Y., Tu J.C., Chen X.Z.;
RT "Receptor for activated C kinase 1 (RACK1) inhibits function of transient
RT receptor potential (TRP)-type channel Pkd2L1 through physical
RT interaction.";
RL J. Biol. Chem. 287:6551-6561(2012).
RN [13]
RP FUNCTION, SUBUNIT, INTERACTION WITH PKD1L1, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF 523-GLU--GLU-525.
RX PubMed=24336289; DOI=10.1038/nature12832;
RA DeCaen P.G., Delling M., Vien T.N., Clapham D.E.;
RT "Direct recording and molecular identification of the calcium channel of
RT primary cilia.";
RL Nature 504:315-318(2013).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, INTERACTION WITH PKD1L3, AND
RP MUTAGENESIS OF 2-ASN--TYR-96; 566-GLU--SER-805; 581-SER--SER-805 AND
RP 622-THR--SER-805.
RX PubMed=25820328; DOI=10.1038/srep09460;
RA Zheng W., Hussein S., Yang J., Huang J., Zhang F., Hernandez-Anzaldo S.,
RA Fernandez-Patron C., Cao Y., Zeng H., Tang J., Chen X.Z.;
RT "A novel PKD2L1 C-terminal domain critical for trimerization and channel
RT function.";
RL Sci. Rep. 5:9460-9460(2015).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, PALMITOYLATION AT CYS-38, AND MUTAGENESIS
RP OF 2-ASN--ARG-36; 2-ASN--CYS-38; CYS-38; THR-39; 594-ARG--LYS-599; ARG-594;
RP ARG-596; ARG-598 AND LYS-599.
RX PubMed=27754867; DOI=10.1074/jbc.m116.756544;
RA Zheng W., Yang J., Beauchamp E., Cai R., Hussein S., Hofmann L., Li Q.,
RA Flockerzi V., Berthiaume L.G., Tang J., Chen X.Z.;
RT "Regulation of TRPP3 Channel Function by N-terminal Domain Palmitoylation
RT and Phosphorylation.";
RL J. Biol. Chem. 291:25678-25691(2016).
RN [16]
RP FUNCTION, DOMAIN, ACTIVITY REGULATION, AND MUTAGENESIS OF 81-TRP--LEU-95;
RP TRP-81 AND LYS-568.
RX PubMed=29425510; DOI=10.1016/j.celrep.2018.01.042;
RA Zheng W., Cai R., Hofmann L., Nesin V., Hu Q., Long W., Fatehi M., Liu X.,
RA Hussein S., Kong T., Li J., Light P.E., Tang J., Flockerzi V., Tsiokas L.,
RA Chen X.Z.;
RT "Direct Binding between Pre-S1 and TRP-like Domains in TRPP Channels
RT Mediates Gating and Functional Regulation by PIP2.";
RL Cell Rep. 22:1560-1573(2018).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.69 ANGSTROMS) OF 699-737, SUBUNIT,
RP CALCIUM-BINDING, AND MUTAGENESIS OF LEU-710; VAL-714; LEU-717; ILE-728;
RP VAL-731 AND LEU-735.
RX PubMed=22193359; DOI=10.1016/j.bbapap.2011.12.002;
RA Molland K.L., Paul L.N., Yernool D.A.;
RT "Crystal structure and characterization of coiled-coil domain of the
RT transient receptor potential channel PKD2L1.";
RL Biochim. Biophys. Acta 1824:413-421(2012).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 699-743, FUNCTION, ACTIVITY
RP REGULATION, SUBUNIT, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-523 AND
RP ASP-525.
RX PubMed=23212381; DOI=10.1038/ncomms2257;
RA Yu Y., Ulbrich M.H., Li M.H., Dobbins S., Zhang W.K., Tong L.,
RA Isacoff E.Y., Yang J.;
RT "Molecular mechanism of the assembly of an acid-sensing receptor ion
RT channel complex.";
RL Nat. Commun. 3:1252-1252(2012).
RN [19] {ECO:0007744|PDB:6DU8}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.11 ANGSTROMS), FUNCTION, SUBUNIT,
RP TOPOLOGY, GLYCOSYLATION AT ASN-207, AND DISULFIDE BOND.
RX PubMed=30004384; DOI=10.7554/elife.36931;
RA Hulse R.E., Li Z., Huang R.K., Zhang J., Clapham D.E.;
RT "Cryo-EM structure of the polycystin 2-l1 ion channel.";
RL Elife 7:0-0(2018).
CC -!- FUNCTION: Pore-forming subunit of a heterotetrameric, non-selective
CC cation channel that is permeable to Ca(2+) (PubMed:10517637,
CC PubMed:11959145, PubMed:25820328, PubMed:27754867, PubMed:29425510,
CC PubMed:23212381, PubMed:30004384). Pore-forming subunit of a calcium-
CC permeant ion channel formed by PKD1L2 and PKD1L1 in primary cilia,
CC where it controls cilium calcium concentration, but does not affect
CC cytoplasmic calcium concentration (PubMed:24336289). The channel formed
CC by PKD1L2 and PKD1L1 in primary cilia regulates sonic hedgehog/SHH
CC signaling and GLI2 transcription (PubMed:24336289). Pore-forming
CC subunit of a channel formed by PKD1L2 and PKD1L3 that contributes to
CC sour taste perception in gustatory cells (PubMed:19812697). The
CC heteromeric channel formed by PKD1L2 and PKD1L3 is activated by low pH,
CC but opens only when the extracellular pH rises again (PubMed:23212381).
CC May play a role in the perception of carbonation taste (By similarity).
CC May play a role in the sensory perception of water, via a mechanism
CC that activates the channel in response to dilution of salivary
CC bicarbonate and changes in salivary pH (By similarity).
CC {ECO:0000250|UniProtKB:A2A259, ECO:0000269|PubMed:10517637,
CC ECO:0000269|PubMed:11959145, ECO:0000269|PubMed:19812697,
CC ECO:0000269|PubMed:23212381, ECO:0000269|PubMed:24336289,
CC ECO:0000269|PubMed:25820328, ECO:0000269|PubMed:27754867,
CC ECO:0000269|PubMed:29425510, ECO:0000269|PubMed:30004384}.
CC -!- ACTIVITY REGULATION: The cation channel is gated following an off-
CC response property by acid: gated open after the removal of acid
CC stimulus, but not during acid application (PubMed:23212381). Channel
CC activity is inhibited by phosphatidylinositol-4,5-bisphosphate (PIP2)
CC (PubMed:29425510). {ECO:0000269|PubMed:23212381,
CC ECO:0000269|PubMed:29425510}.
CC -!- SUBUNIT: Homotetramer (PubMed:25820328, PubMed:30004384).
CC Heterotetramer with either PKD1L1, PKD1L3 or PKD1; the heterotetrameric
CC complex probably contains three PKD1L2 chains plus one chain from
CC another family member (PubMed:25820328, PubMed:23212381). Interacts
CC with PKD1L1, forming a ciliary calcium channel (PubMed:24336289).
CC Interacts with PKD1L3, forming a cation channel that is activated by
CC low extracellular pH (PubMed:25820328, PubMed:23212381). Interacts with
CC PKD1 (By similarity). Interacts with RACK1; inhibits the channel
CC activity possibly by impairing localization to the cell membrane
CC (PubMed:22174419). {ECO:0000250|UniProtKB:A2A259,
CC ECO:0000269|PubMed:22174419, ECO:0000269|PubMed:22193359,
CC ECO:0000269|PubMed:23212381, ECO:0000269|PubMed:24336289,
CC ECO:0000269|PubMed:25820328, ECO:0000269|PubMed:30004384}.
CC -!- INTERACTION:
CC Q9P0L9; Q8N6F1-2: CLDN19; NbExp=3; IntAct=EBI-7956847, EBI-12256978;
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium membrane
CC {ECO:0000269|PubMed:24336289}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:30004384}. Cell membrane
CC {ECO:0000269|PubMed:10517637, ECO:0000269|PubMed:11959145,
CC ECO:0000269|PubMed:23212381, ECO:0000269|PubMed:25820328,
CC ECO:0000269|PubMed:27754867, ECO:0000269|PubMed:29425510}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:30004384}. Cytoplasmic vesicle
CC {ECO:0000250|UniProtKB:A2A259}. Note=Interaction with PKD1 or PKD1L3 is
CC required for localization to the cell membrane.
CC {ECO:0000250|UniProtKB:A2A259}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=Q9P0L9-1; Sequence=Displayed;
CC Name=2; Synonyms=PKDLdel15, PCL-TS, Testis isoform;
CC IsoId=Q9P0L9-2; Sequence=VSP_004730, VSP_004731;
CC Name=3; Synonyms=PKDLdel5;
CC IsoId=Q9P0L9-3; Sequence=VSP_004729;
CC Name=4; Synonyms=PKDLdel456;
CC IsoId=Q9P0L9-4; Sequence=VSP_004728;
CC Name=5; Synonyms=PCL-LV, Liver isoform;
CC IsoId=Q9P0L9-5; Sequence=VSP_053718;
CC -!- TISSUE SPECIFICITY: Detected in taste bud cells in fungiform papillae
CC (at protein level) (PubMed:19812697). Ubiquitous (PubMed:9748274).
CC Expressed in adult heart, skeletal muscle, brain, spleen, testis,
CC retina and liver (PubMed:9748274, PubMed:9878261). Isoform 4 appears to
CC be expressed only in transformed lymphoblasts.
CC {ECO:0000269|PubMed:19812697, ECO:0000269|PubMed:9748274,
CC ECO:0000269|PubMed:9878261}.
CC -!- DOMAIN: The EF-hand domain probably mediates calcium-binding. It is not
CC required for channel activation (PubMed:11959145).
CC {ECO:0000269|PubMed:11959145, ECO:0000269|PubMed:20408813}.
CC -!- DOMAIN: Interaction of the cytoplasmic N- and C-terminal domains is
CC important for channel activity. {ECO:0000269|PubMed:29425510}.
CC -!- PTM: Palmitoylation is important for expression at the cell membrane
CC and for channel activity. {ECO:0000269|PubMed:27754867}.
CC -!- MISCELLANEOUS: [Isoform 4]: Unusual intron exon spliced junction.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the polycystin family. {ECO:0000305}.
CC -!- CAUTION: The active channel complex is an obligate tetramer
CC (PubMed:25820328, PubMed:30004384). In contrast, the isolated
CC cytoplasmic C-terminal domain forms homotrimers in vitro
CC (PubMed:20408813, PubMed:25820328, PubMed:23212381). Likewise,
CC photobleaching experiments suggest formation of homotrimers in the
CC membrane (PubMed:23212381). {ECO:0000269|PubMed:20408813,
CC ECO:0000269|PubMed:23212381, ECO:0000269|PubMed:25820328,
CC ECO:0000269|PubMed:30004384}.
CC -!- CAUTION: PKD1L3 and PKD2L1 have been defined as sour taste receptor in
CC gustatory cells based on a number of indirect evidences in mouse. Some
CC data confirm this hypothesis in human: in 2 patients with sour ageusia
CC that are unresponsive to sour stimuli, but show normal responses to
CC bitter, sweet, and salty stimuli, expression of PKD1L3 and PKD2L1 is
CC absent in the anterior part of the tongue (PubMed:19812697). However, a
CC number of experiments have recently shown that the sour taste receptor
CC activity is probably indirect. {ECO:0000305|PubMed:19812697}.
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DR EMBL; AF073481; AAD41638.1; -; mRNA.
DR EMBL; AF153474; AAF28108.1; -; Genomic_DNA.
DR EMBL; AF153459; AAF28108.1; JOINED; Genomic_DNA.
DR EMBL; AF153460; AAF28108.1; JOINED; Genomic_DNA.
DR EMBL; AF153461; AAF28108.1; JOINED; Genomic_DNA.
DR EMBL; AF153462; AAF28108.1; JOINED; Genomic_DNA.
DR EMBL; AF153463; AAF28108.1; JOINED; Genomic_DNA.
DR EMBL; AF153464; AAF28108.1; JOINED; Genomic_DNA.
DR EMBL; AF153465; AAF28108.1; JOINED; Genomic_DNA.
DR EMBL; AF153466; AAF28108.1; JOINED; Genomic_DNA.
DR EMBL; AF153467; AAF28108.1; JOINED; Genomic_DNA.
DR EMBL; AF153468; AAF28108.1; JOINED; Genomic_DNA.
DR EMBL; AF153469; AAF28108.1; JOINED; Genomic_DNA.
DR EMBL; AF153470; AAF28108.1; JOINED; Genomic_DNA.
DR EMBL; AF153471; AAF28108.1; JOINED; Genomic_DNA.
DR EMBL; AF153472; AAF28108.1; JOINED; Genomic_DNA.
DR EMBL; AF153473; AAF28108.1; JOINED; Genomic_DNA.
DR EMBL; AL139819; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471066; EAW49833.1; -; Genomic_DNA.
DR EMBL; BC025665; AAH25665.1; -; mRNA.
DR EMBL; AF094827; AAD08695.1; -; mRNA.
DR EMBL; AF053316; AAD51859.1; -; mRNA.
DR CCDS; CCDS7492.1; -. [Q9P0L9-1]
DR RefSeq; NP_001240766.1; NM_001253837.1.
DR RefSeq; NP_057196.2; NM_016112.2. [Q9P0L9-1]
DR PDB; 3TE3; X-ray; 2.69 A; A/B/C/D/E/F=699-737.
DR PDB; 4GIF; X-ray; 2.80 A; A=699-743.
DR PDB; 6DU8; EM; 3.11 A; A/B/C/D=1-805.
DR PDBsum; 3TE3; -.
DR PDBsum; 4GIF; -.
DR PDBsum; 6DU8; -.
DR AlphaFoldDB; Q9P0L9; -.
DR SMR; Q9P0L9; -.
DR BioGRID; 114499; 3.
DR IntAct; Q9P0L9; 2.
DR MINT; Q9P0L9; -.
DR STRING; 9606.ENSP00000325296; -.
DR DrugBank; DB11093; Calcium citrate.
DR DrugBank; DB11348; Calcium Phosphate.
DR DrugBank; DB14481; Calcium phosphate dihydrate.
DR GuidetoPHARMACOLOGY; 505; -.
DR TCDB; 1.A.5.1.3; the polycystin cation channel (pcc) family.
DR GlyGen; Q9P0L9; 4 sites.
DR iPTMnet; Q9P0L9; -.
DR PhosphoSitePlus; Q9P0L9; -.
DR SwissPalm; Q9P0L9; -.
DR BioMuta; PKD2L1; -.
DR DMDM; 23821938; -.
DR MassIVE; Q9P0L9; -.
DR PaxDb; Q9P0L9; -.
DR PeptideAtlas; Q9P0L9; -.
DR PRIDE; Q9P0L9; -.
DR ProteomicsDB; 83574; -. [Q9P0L9-1]
DR ProteomicsDB; 83576; -. [Q9P0L9-3]
DR ProteomicsDB; 83577; -. [Q9P0L9-4]
DR Antibodypedia; 31169; 140 antibodies from 22 providers.
DR DNASU; 9033; -.
DR Ensembl; ENST00000318222.4; ENSP00000325296.3; ENSG00000107593.17. [Q9P0L9-1]
DR GeneID; 9033; -.
DR KEGG; hsa:9033; -.
DR MANE-Select; ENST00000318222.4; ENSP00000325296.3; NM_016112.3; NP_057196.2.
DR UCSC; uc001kqx.2; human. [Q9P0L9-1]
DR CTD; 9033; -.
DR DisGeNET; 9033; -.
DR GeneCards; PKD2L1; -.
DR HGNC; HGNC:9011; PKD2L1.
DR HPA; ENSG00000107593; Group enriched (brain, choroid plexus, lymphoid tissue, retina).
DR MIM; 604532; gene.
DR neXtProt; NX_Q9P0L9; -.
DR OpenTargets; ENSG00000107593; -.
DR PharmGKB; PA33344; -.
DR VEuPathDB; HostDB:ENSG00000107593; -.
DR eggNOG; KOG3599; Eukaryota.
DR GeneTree; ENSGT00940000157274; -.
DR HOGENOM; CLU_012097_0_0_1; -.
DR InParanoid; Q9P0L9; -.
DR OMA; PDPWGVQ; -.
DR OrthoDB; 426073at2759; -.
DR PhylomeDB; Q9P0L9; -.
DR TreeFam; TF316484; -.
DR PathwayCommons; Q9P0L9; -.
DR SignaLink; Q9P0L9; -.
DR BioGRID-ORCS; 9033; 13 hits in 1071 CRISPR screens.
DR ChiTaRS; PKD2L1; human.
DR GeneWiki; PKD2L1; -.
DR GenomeRNAi; 9033; -.
DR Pharos; Q9P0L9; Tchem.
DR PRO; PR:Q9P0L9; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q9P0L9; protein.
DR Bgee; ENSG00000107593; Expressed in spleen and 127 other tissues.
DR ExpressionAtlas; Q9P0L9; baseline and differential.
DR Genevisible; Q9P0L9; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0034704; C:calcium channel complex; IDA:UniProtKB.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0060170; C:ciliary membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:BHF-UCL.
DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; IEA:Ensembl.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:BHF-UCL.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0097730; C:non-motile cilium; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0043235; C:receptor complex; ISS:BHF-UCL.
DR GO; GO:0051393; F:alpha-actinin binding; IPI:BHF-UCL.
DR GO; GO:0005227; F:calcium activated cation channel activity; IDA:BHF-UCL.
DR GO; GO:0005262; F:calcium channel activity; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0015269; F:calcium-activated potassium channel activity; IDA:BHF-UCL.
DR GO; GO:0005261; F:cation channel activity; IDA:UniProtKB.
DR GO; GO:0008092; F:cytoskeletal protein binding; IPI:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISS:BHF-UCL.
DR GO; GO:0051371; F:muscle alpha-actinin binding; IPI:BHF-UCL.
DR GO; GO:0005272; F:sodium channel activity; IDA:BHF-UCL.
DR GO; GO:0033040; F:sour taste receptor activity; IEA:Ensembl.
DR GO; GO:0006812; P:cation transport; ISS:BHF-UCL.
DR GO; GO:0071468; P:cellular response to acidic pH; ISS:BHF-UCL.
DR GO; GO:0001581; P:detection of chemical stimulus involved in sensory perception of sour taste; ISS:BHF-UCL.
DR GO; GO:0050912; P:detection of chemical stimulus involved in sensory perception of taste; ISS:UniProtKB.
DR GO; GO:0050982; P:detection of mechanical stimulus; IBA:GO_Central.
DR GO; GO:0098662; P:inorganic cation transmembrane transport; IDA:UniProtKB.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:BHF-UCL.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR GO; GO:0009415; P:response to water; IEA:Ensembl.
DR GO; GO:0050915; P:sensory perception of sour taste; IMP:UniProtKB.
DR GO; GO:0007224; P:smoothened signaling pathway; ISS:UniProtKB.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IDA:BHF-UCL.
DR Gene3D; 1.20.120.350; -; 1.
DR InterPro; IPR013122; PKD1_2_channel.
DR InterPro; IPR003915; PKD_2.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR Pfam; PF08016; PKD_channel; 1.
DR PRINTS; PR01433; POLYCYSTIN2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Calcium channel;
KW Calcium transport; Cell membrane; Cell projection; Cilium; Coiled coil;
KW Cytoplasmic vesicle; Disulfide bond; Glycoprotein; Ion channel;
KW Ion transport; Lipoprotein; Membrane; Metal-binding; Palmitate;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..805
FT /note="Polycystic kidney disease 2-like 1 protein"
FT /id="PRO_0000164360"
FT TOPO_DOM 1..103
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:30004384"
FT TRANSMEM 104..124
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:30004384"
FT TOPO_DOM 125..356
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:30004384"
FT TRANSMEM 357..376
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:30004384"
FT TOPO_DOM 377..384
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:30004384"
FT TRANSMEM 385..405
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:30004384"
FT TOPO_DOM 406..433
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:30004384"
FT TRANSMEM 434..454
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:30004384"
FT TOPO_DOM 455..479
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:30004384"
FT TRANSMEM 480..499
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:30004384"
FT TOPO_DOM 500..511
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:30004384"
FT INTRAMEM 512..526
FT /note="Pore-forming"
FT /evidence="ECO:0000305|PubMed:30004384"
FT TOPO_DOM 527..536
FT /note="Extracellular"
FT /evidence="ECO:0000305|PubMed:30004384"
FT TRANSMEM 537..557
FT /note="Helical"
FT /evidence="ECO:0000305|PubMed:30004384"
FT TOPO_DOM 558..805
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:30004384"
FT DOMAIN 633..668
FT /note="EF-hand"
FT /evidence="ECO:0000255"
FT REGION 1..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 704..763
FT /note="Required for homooligomerization"
FT REGION 759..805
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 650..686
FT /evidence="ECO:0000255"
FT COILED 700..740
FT /evidence="ECO:0000269|PubMed:22193359,
FT ECO:0000269|PubMed:23212381"
FT COMPBIAS 779..799
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 646
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000305"
FT BINDING 648
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000305"
FT BINDING 650
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000305"
FT BINDING 657
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000305"
FT LIPID 38
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:27754867"
FT CARBOHYD 177
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 207
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:30004384,
FT ECO:0007744|PDB:6DU8"
FT CARBOHYD 241
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 505
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 210..223
FT /evidence="ECO:0000305|PubMed:30004384,
FT ECO:0007744|PDB:6DU8"
FT VAR_SEQ 225..344
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:10602361"
FT /id="VSP_004728"
FT VAR_SEQ 245..319
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_004729"
FT VAR_SEQ 638..666
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_053718"
FT VAR_SEQ 751..760
FT /note="KEQAIWKHPQ -> RFPIKEKRKP (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_004730"
FT VAR_SEQ 761..805
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_004731"
FT VARIANT 278
FT /note="R -> Q (in dbSNP:rs17112895)"
FT /id="VAR_050555"
FT VARIANT 378
FT /note="R -> W (in dbSNP:rs7909153)"
FT /id="VAR_050556"
FT VARIANT 393
FT /note="V -> I (in dbSNP:rs2278842)"
FT /evidence="ECO:0000269|PubMed:9748274"
FT /id="VAR_024569"
FT VARIANT 681
FT /note="R -> L (in dbSNP:rs6584356)"
FT /id="VAR_024570"
FT VARIANT 788
FT /note="A -> D (in dbSNP:rs12782963)"
FT /id="VAR_050557"
FT MUTAGEN 2..96
FT /note="Missing: Loss of channel activity. No effect on
FT expression at the cell membrane."
FT /evidence="ECO:0000269|PubMed:25820328"
FT MUTAGEN 2..38
FT /note="Missing: Loss of channel activity."
FT /evidence="ECO:0000269|PubMed:27754867"
FT MUTAGEN 2..36
FT /note="Missing: No effect on channel activity."
FT /evidence="ECO:0000269|PubMed:27754867"
FT MUTAGEN 38
FT /note="C->A: Strongly decreased channel activity. No effect
FT on expression at the cell membrane. Loss of
FT palmitoylation."
FT /evidence="ECO:0000269|PubMed:27754867"
FT MUTAGEN 39
FT /note="T->D,E: Decreased channel activity."
FT /evidence="ECO:0000269|PubMed:27754867"
FT MUTAGEN 81..95
FT /note="Missing: Loss of channel activity."
FT /evidence="ECO:0000269|PubMed:29425510"
FT MUTAGEN 81
FT /note="W->A,K,L,R: Loss of channel activity. No effect on
FT expression at the cell membrane."
FT /evidence="ECO:0000269|PubMed:29425510"
FT MUTAGEN 523..525
FT /note="DFD->AFA: Abolishes ion channel activity."
FT /evidence="ECO:0000269|PubMed:24336289"
FT MUTAGEN 523
FT /note="D->Q: Increased permeability of dimethylamine and
FT trimethylamine and decreased permeability of magnesium."
FT /evidence="ECO:0000269|PubMed:23212381"
FT MUTAGEN 525
FT /note="D->K: Increased permeability of dimethylamine and
FT trimethylamine and decreased permeability of magnesium."
FT /evidence="ECO:0000269|PubMed:23212381"
FT MUTAGEN 530
FT /note="D->A: Does not affect ion channel activity."
FT MUTAGEN 566..805
FT /note="Missing: Loss of channel activity. No effect on
FT expression at the cell membrane."
FT /evidence="ECO:0000269|PubMed:25820328"
FT MUTAGEN 568
FT /note="K->A,D,E: Loss of channel activity."
FT /evidence="ECO:0000269|PubMed:29425510"
FT MUTAGEN 581..805
FT /note="Missing: Loss of channel activity. No effect on
FT expression at the cell membrane."
FT /evidence="ECO:0000269|PubMed:25820328"
FT MUTAGEN 594..599
FT /note="Missing: Loss of phosphatidylinositol-4,5-
FT bisphosphate binding."
FT /evidence="ECO:0000269|PubMed:29425510"
FT MUTAGEN 594
FT /note="R->Q: Increased channel activity."
FT /evidence="ECO:0000269|PubMed:29425510"
FT MUTAGEN 596
FT /note="R->Q: Increased channel activity."
FT /evidence="ECO:0000269|PubMed:29425510"
FT MUTAGEN 598
FT /note="R->Q: Mildly increased channel activity."
FT /evidence="ECO:0000269|PubMed:29425510"
FT MUTAGEN 599
FT /note="K->Q: Mildly increased channel activity."
FT /evidence="ECO:0000269|PubMed:29425510"
FT MUTAGEN 622..805
FT /note="Missing: No effect on channel activity. No effect on
FT expression at the cell membrane."
FT /evidence="ECO:0000269|PubMed:25820328"
FT MUTAGEN 710
FT /note="L->A: Abolishes homooligomer formation; when
FT associated with A-714; A-717; A-728; A-731 and A-735."
FT /evidence="ECO:0000269|PubMed:22193359"
FT MUTAGEN 714
FT /note="V->A: Abolishes homooligomer formation; when
FT associated with A-710; A-717; A-728; A-731 and A-735."
FT /evidence="ECO:0000269|PubMed:22193359"
FT MUTAGEN 717
FT /note="L->A: Abolishes homooligomer formation; when
FT associated with A-710; A-714; A-728; A-731 and A-735."
FT /evidence="ECO:0000269|PubMed:22193359"
FT MUTAGEN 728
FT /note="I->A: Abolishes homooligomer formation; when
FT associated with A-710; A-714; A-717; A-731 and A-735."
FT /evidence="ECO:0000269|PubMed:22193359"
FT MUTAGEN 731
FT /note="V->A: Abolishes homooligomer formation; when
FT associated with A-710; A-714; A-717; A-728 and A-735."
FT /evidence="ECO:0000269|PubMed:22193359"
FT MUTAGEN 735
FT /note="L->A: Abolishes homooligomer formation; when
FT associated with A-710; A-714; A-717; A-728 and A-731."
FT /evidence="ECO:0000269|PubMed:22193359"
FT CONFLICT 13
FT /note="Q -> H (in Ref. 1; AAD41638)"
FT /evidence="ECO:0000305"
FT TURN 102..104
FT /evidence="ECO:0007829|PDB:6DU8"
FT HELIX 105..118
FT /evidence="ECO:0007829|PDB:6DU8"
FT TURN 119..121
FT /evidence="ECO:0007829|PDB:6DU8"
FT HELIX 127..137
FT /evidence="ECO:0007829|PDB:6DU8"
FT HELIX 148..150
FT /evidence="ECO:0007829|PDB:6DU8"
FT HELIX 157..160
FT /evidence="ECO:0007829|PDB:6DU8"
FT TURN 164..169
FT /evidence="ECO:0007829|PDB:6DU8"
FT STRAND 183..185
FT /evidence="ECO:0007829|PDB:6DU8"
FT STRAND 188..194
FT /evidence="ECO:0007829|PDB:6DU8"
FT STRAND 202..205
FT /evidence="ECO:0007829|PDB:6DU8"
FT STRAND 207..210
FT /evidence="ECO:0007829|PDB:6DU8"
FT STRAND 229..232
FT /evidence="ECO:0007829|PDB:6DU8"
FT STRAND 238..240
FT /evidence="ECO:0007829|PDB:6DU8"
FT STRAND 243..246
FT /evidence="ECO:0007829|PDB:6DU8"
FT HELIX 250..253
FT /evidence="ECO:0007829|PDB:6DU8"
FT STRAND 261..264
FT /evidence="ECO:0007829|PDB:6DU8"
FT HELIX 278..290
FT /evidence="ECO:0007829|PDB:6DU8"
FT STRAND 298..309
FT /evidence="ECO:0007829|PDB:6DU8"
FT TURN 310..313
FT /evidence="ECO:0007829|PDB:6DU8"
FT STRAND 314..323
FT /evidence="ECO:0007829|PDB:6DU8"
FT STRAND 333..339
FT /evidence="ECO:0007829|PDB:6DU8"
FT HELIX 356..375
FT /evidence="ECO:0007829|PDB:6DU8"
FT HELIX 385..419
FT /evidence="ECO:0007829|PDB:6DU8"
FT HELIX 429..451
FT /evidence="ECO:0007829|PDB:6DU8"
FT HELIX 452..454
FT /evidence="ECO:0007829|PDB:6DU8"
FT HELIX 482..498
FT /evidence="ECO:0007829|PDB:6DU8"
FT STRAND 499..502
FT /evidence="ECO:0007829|PDB:6DU8"
FT STRAND 504..506
FT /evidence="ECO:0007829|PDB:6DU8"
FT HELIX 511..521
FT /evidence="ECO:0007829|PDB:6DU8"
FT TURN 526..532
FT /evidence="ECO:0007829|PDB:6DU8"
FT STRAND 534..536
FT /evidence="ECO:0007829|PDB:6DU8"
FT HELIX 537..559
FT /evidence="ECO:0007829|PDB:6DU8"
FT HELIX 704..731
FT /evidence="ECO:0007829|PDB:3TE3"
FT HELIX 734..741
FT /evidence="ECO:0007829|PDB:4GIF"
SQ SEQUENCE 805 AA; 91982 MW; 3714C07F4B71F9C6 CRC64;
MNAVGSPEGQ ELQKLGSGAW DNPAYSGPPS PHGTLRVCTI SSTGPLQPQP KKPEDEPQET
AYRTQVSSCC LHICQGIRGL WGTTLTENTA ENRELYIKTT LRELLVYIVF LVDICLLTYG
MTSSSAYYYT KVMSELFLHT PSDTGVSFQA ISSMADFWDF AQGPLLDSLY WTKWYNNQSL
GHGSHSFIYY ENMLLGVPRL RQLKVRNDSC VVHEDFREDI LSCYDVYSPD KEEQLPFGPF
NGTAWTYHSQ DELGGFSHWG RLTSYSGGGY YLDLPGSRQG SAEALRALQE GLWLDRGTRV
VFIDFSVYNA NINLFCVLRL VVEFPATGGA IPSWQIRTVK LIRYVSNWDF FIVGCEVIFC
VFIFYYVVEE ILELHIHRLR YLSSIWNILD LVVILLSIVA VGFHIFRTLE VNRLMGKLLQ
QPNTYADFEF LAFWQTQYNN MNAVNLFFAW IKIFKYISFN KTMTQLSSTL ARCAKDILGF
AVMFFIVFFA YAQLGYLLFG TQVENFSTFI KCIFTQFRII LGDFDYNAID NANRILGPAY
FVTYVFFVFF VLLNMFLAII NDTYSEVKEE LAGQKDELQL SDLLKQGYNK TLLRLRLRKE
RVSDVQKVLQ GGEQEIQFED FTNTLRELGH AEHEITELTA TFTKFDRDGN RILDEKEQEK
MRQDLEEERV ALNTEIEKLG RSIVSSPQGK SGPEAARAGG WVSGEEFYML TRRVLQLETV
LEGVVSQIDA VGSKLKMLER KGWLAPSPGV KEQAIWKHPQ PAPAVTPDPW GVQGGQESEV
PYKREEEALE ERRLSRGEIP TLQRS
