ID PKD2_HUMAN Reviewed; 968 AA.
AC Q13563; O60441; Q15764; Q2M1Q3; Q2M1Q5;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 27-MAR-2024, entry version 226.
DE RecName: Full=Polycystin-2 {ECO:0000305};
DE Short=PC2 {ECO:0000303|PubMed:27991905};
DE AltName: Full=Autosomal dominant polycystic kidney disease type II protein;
DE AltName: Full=Polycystic kidney disease 2 protein;
DE AltName: Full=Polycystwin {ECO:0000303|PubMed:8954772};
DE AltName: Full=R48321;
DE AltName: Full=Transient receptor potential cation channel subfamily P member 2 {ECO:0000303|PubMed:19556541, ECO:0000312|HGNC:HGNC:9009};
GN Name=PKD2 {ECO:0000312|HGNC:HGNC:9009};
GN Synonyms=TRPP2 {ECO:0000303|PubMed:19556541, ECO:0000312|HGNC:HGNC:9009};
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), AND TISSUE SPECIFICITY.
RX PubMed=8650545; DOI=10.1126/science.272.5266.1339;
RA Mochizuki T., Wu G., Hayashi T., Xenophontos S.L., Veldhuisen B.,
RA Saris J.J., Reynolds D.M., Cai Y., Gabow P.A., Pierides A.,
RA Kimberling W.J., Breuning M.H., Deltas C.C., Peters D.J.M., Somlo S.;
RT "PKD2, a gene for polycystic kidney disease that encodes an integral
RT membrane protein.";
RL Science 272:1339-1342(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9286709; DOI=10.1006/geno.1997.4851;
RA Hayashi T., Mochizuki T., Reynolds D.M., Wu G., Cai Y., Somlo S.;
RT "Characterization of the exon structure of the polycystic kidney disease 2
RT gene (PKD2).";
RL Genomics 44:131-136(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT PRO-28.
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 361-968 (ISOFORM 1).
RC TISSUE=Mammary gland;
RX PubMed=8954772; DOI=10.1006/geno.1996.0584;
RA Schneider M.C., Rodriguez A., Nomura H., Zhou J., Morton C.C.,
RA Reeders S.T., Weremowicz S.;
RT "A gene similar to PKD1 maps to chromosome 4q22: a candidate gene for
RT PKD2.";
RL Genomics 38:1-4(1996).
RN [5]
RP TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=10770959; DOI=10.1681/asn.v115814;
RA Foggensteiner L., Bevan A.P., Thomas R., Coleman N., Boulter C.,
RA Bradley J., Ibraghimov-Beskrovnaya O., Klinger K., Sandford R.;
RT "Cellular and subcellular distribution of polycystin-2, the protein product
RT of the PKD2 gene.";
RL J. Am. Soc. Nephrol. 11:814-827(2000).
RN [6]
RP INTERACTION WITH CD2AP, AND SUBCELLULAR LOCATION.
RX PubMed=10913159; DOI=10.1074/jbc.m006624200;
RA Lehtonen S., Ora A., Olkkonen V.M., Geng L., Zerial M., Somlo S.,
RA Lehtonen E.;
RT "In vivo interaction of the adapter protein CD2-associated protein with the
RT type 2 polycystic kidney disease protein, polycystin-2.";
RL J. Biol. Chem. 275:32888-32893(2000).
RN [7]
RP INTERACTION WITH HAX1, AND SUBCELLULAR LOCATION.
RX PubMed=10760273; DOI=10.1073/pnas.97.8.4017;
RA Gallagher A.R., Cedzich A., Gretz N., Somlo S., Witzgall R.;
RT "The polycystic kidney disease protein PKD2 interacts with Hax-1, a protein
RT associated with the actin cytoskeleton.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:4017-4022(2000).
RN [8]
RP REVIEW.
RX PubMed=11698076; DOI=10.1016/s0165-6147(00)01832-0;
RA Stayner C., Zhou J.;
RT "Polycystin channels and kidney disease.";
RL Trends Pharmacol. Sci. 22:543-546(2001).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND CHARACTERIZATION OF VARIANT PKD2
RP VAL-511.
RX PubMed=11854751; DOI=10.1038/ncb754;
RA Koulen P., Cai Y., Geng L., Maeda Y., Nishimura S., Witzgall R.,
RA Ehrlich B.E., Somlo S.;
RT "Polycystin-2 is an intracellular calcium release channel.";
RL Nat. Cell Biol. 4:191-197(2002).
RN [10]
RP ALTERNATIVE SPLICING (ISOFORMS 2; 3; 4 AND 5).
RX PubMed=16192288; DOI=10.1093/hmg/ddi356;
RA Hackmann K., Markoff A., Qian F., Bogdanova N., Germino G.G., Pennekamp P.,
RA Dworniczak B., Horst J., Gerke V.;
RT "A splice form of polycystin-2, lacking exon 7, does not interact with
RT polycystin-1.";
RL Hum. Mol. Genet. 14:3249-3262(2005).
RN [11]
RP FUNCTION, INTERACTION WITH PACS1 AND PACS2, SUBCELLULAR LOCATION,
RP PHOSPHORYLATION AT SER-812, AND MUTAGENESIS OF SER-812 AND
RP 815-ASP--ASP-817.
RX PubMed=15692563; DOI=10.1038/sj.emboj.7600566;
RA Koettgen M., Benzing T., Simmen T., Tauber R., Buchholz B.,
RA Feliciangeli S., Huber T.B., Schermer B., Kramer-Zucker A., Hoepker K.,
RA Simmen K.C., Tschucke C.C., Sandford R., Kim E., Thomas G., Walz G.;
RT "Trafficking of TRPP2 by PACS proteins represents a novel mechanism of ion
RT channel regulation.";
RL EMBO J. 24:705-716(2005).
RN [12]
RP FUNCTION, ACTIVITY REGULATION, PHOSPHORYLATION AT SER-76; SER-80 AND
RP SER-812, AND MUTAGENESIS OF SER-76; SER-80; THR-721; SER-801; SER-812;
RP SER-831 AND SER-943.
RX PubMed=16551655; DOI=10.1093/hmg/ddl070;
RA Streets A.J., Moon D.J., Kane M.E., Obara T., Ong A.C.;
RT "Identification of an N-terminal glycogen synthase kinase 3 phosphorylation
RT site which regulates the functional localization of polycystin-2 in vivo
RT and in vitro.";
RL Hum. Mol. Genet. 15:1465-1473(2006).
RN [13]
RP FUNCTION, INTERACTION WITH TRPV4, AND SUBCELLULAR LOCATION.
RX PubMed=18695040; DOI=10.1083/jcb.200805124;
RA Kottgen M., Buchholz B., Garcia-Gonzalez M.A., Kotsis F., Fu X.,
RA Doerken M., Boehlke C., Steffl D., Tauber R., Wegierski T., Nitschke R.,
RA Suzuki M., Kramer-Zucker A., Germino G.G., Watnick T., Prenen J.,
RA Nilius B., Kuehn E.W., Walz G.;
RT "TRPP2 and TRPV4 form a polymodal sensory channel complex.";
RL J. Cell Biol. 182:437-447(2008).
RN [14]
RP GLYCOSYLATION AT ASN-328.
RX PubMed=19139490; DOI=10.1074/mcp.m800504-mcp200;
RA Jia W., Lu Z., Fu Y., Wang H.P., Wang L.H., Chi H., Yuan Z.F., Zheng Z.B.,
RA Song L.N., Han H.H., Liang Y.M., Wang J.L., Cai Y., Zhang Y.K., Deng Y.L.,
RA Ying W.T., He S.M., Qian X.H.;
RT "A strategy for precise and large scale identification of core fucosylated
RT glycoproteins.";
RL Mol. Cell. Proteomics 8:913-923(2009).
RN [15]
RP FUNCTION, ACTIVITY REGULATION, PHOSPHORYLATION AT SER-801, MUTAGENESIS OF
RP SER-801 AND SER-804, SUBCELLULAR LOCATION, SUBUNIT, AND INTERACTION WITH
RP PKD1.
RX PubMed=20881056; DOI=10.1091/mbc.e10-04-0377;
RA Streets A.J., Needham A.J., Gill S.K., Ong A.C.;
RT "Protein kinase D-mediated phosphorylation of polycystin-2 (TRPP2) is
RT essential for its effects on cell growth and calcium channel activity.";
RL Mol. Biol. Cell 21:3853-3865(2010).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-812, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-812, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [18]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT
RP SER-829, TISSUE SPECIFICITY, AND MUTAGENESIS OF SER-829.
RX PubMed=26269590; DOI=10.1074/jbc.m115.661082;
RA del Rocio Cantero M., Velazquez I.F., Streets A.J., Ong A.C.M.,
RA Cantiello H.F.;
RT "The cAMP Signaling Pathway and Direct Protein Kinase A Phosphorylation
RT Regulate Polycystin-2 (TRPP2) Channel Function.";
RL J. Biol. Chem. 290:23888-23896(2015).
RN [19]
RP SUBCELLULAR LOCATION.
RX PubMed=27259053; DOI=10.1016/j.ajhg.2016.05.004;
RG Genkyst Study Group, HALT Progression of Polycystic Kidney Disease Group;
RG Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease;
RA Porath B., Gainullin V.G., Cornec-Le Gall E., Dillinger E.K., Heyer C.M.,
RA Hopp K., Edwards M.E., Madsen C.D., Mauritz S.R., Banks C.J., Baheti S.,
RA Reddy B., Herrero J.I., Banales J.M., Hogan M.C., Tasic V., Watnick T.J.,
RA Chapman A.B., Vigneau C., Lavainne F., Audrezet M.P., Ferec C., Le Meur Y.,
RA Torres V.E., Harris P.C.;
RT "Mutations in GANAB, encoding the glucosidase IIalpha subunit, cause
RT autosomal-dominant polycystic kidney and liver disease.";
RL Am. J. Hum. Genet. 98:1193-1207(2016).
RN [20]
RP FUNCTION, INTERACTION WITH PKD1, SUBCELLULAR LOCATION, AND CHARACTERIZATION
RP OF VARIANT PKD2 VAL-511.
RX PubMed=27214281; DOI=10.1038/ncb3363;
RA Kim S., Nie H., Nesin V., Tran U., Outeda P., Bai C.X., Keeling J.,
RA Maskey D., Watnick T., Wessely O., Tsiokas L.;
RT "The polycystin complex mediates Wnt/Ca(2+) signalling.";
RL Nat. Cell Biol. 18:752-764(2016).
RN [21]
RP FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF PHE-604; PHE-605 AND
RP 736-LEU-ASN-737, AND CHARACTERIZATION OF VARIANTS PKD2 GLY-414; GLY-420 AND
RP VAL-511.
RX PubMed=27071085; DOI=10.1073/pnas.1517066113;
RA Arif Pavel M., Lv C., Ng C., Yang L., Kashyap P., Lam C., Valentino V.,
RA Fung H.Y., Campbell T., Moeller S.G., Zenisek D., Holtzman N.G., Yu Y.;
RT "Function and regulation of TRPP2 ion channel revealed by a gain-of-
RT function mutant.";
RL Proc. Natl. Acad. Sci. U.S.A. 113:E2363-E2372(2016).
RN [22]
RP SUBCELLULAR LOCATION.
RX PubMed=37681898; DOI=10.3390/cells12172166;
RA Lea W.A., Winklhofer T., Zelenchuk L., Sharma M., Rossol-Allison J.,
RA Fields T.A., Reif G., Calvet J.P., Bakeberg J.L., Wallace D.P., Ward C.J.;
RT "Polycystin-1 Interacting Protein-1 (CU062) Interacts with the Ectodomain
RT of Polycystin-1 (PC1).";
RL Cells 12:0-0(2023).
RN [23]
RP 3D-STRUCTURE MODELING, PROTEIN SEQUENCE OF 711-715; 720-724; 804-808 AND
RP 823-827, IDENTIFICATION BY MASS SPECTROMETRY, DOMAIN, CALCIUM-BINDING,
RP CIRCULAR DICHROISM, SUBUNIT, AND MUTAGENESIS OF THR-771; GLU-774; LEU-842;
RP VAL-846; MET-849; ILE-853; ILE-856 AND VAL-863.
RX PubMed=18694932; DOI=10.1074/jbc.m802743200;
RA Celic A., Petri E.T., Demeler B., Ehrlich B.E., Boggon T.J.;
RT "Domain mapping of the polycystin-2 C-terminal tail using de novo molecular
RT modeling and biophysical analysis.";
RL J. Biol. Chem. 283:28305-28312(2008).
RN [24] {ECO:0007744|PDB:3HRN, ECO:0007744|PDB:3HRO}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 833-872, COILED COIL, SUBCELLULAR
RP LOCATION, SUBUNIT, AND MUTAGENESIS OF LEU-842; VAL-846; MET-849; ILE-860;
RP VAL-863 AND LEU-867.
RX PubMed=19556541; DOI=10.1073/pnas.0903684106;
RA Yu Y., Ulbrich M.H., Li M.H., Buraei Z., Chen X.Z., Ong A.C., Tong L.,
RA Isacoff E.Y., Yang J.;
RT "Structural and molecular basis of the assembly of the TRPP2/PKD1
RT complex.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:11558-11563(2009).
RN [25] {ECO:0007744|PDB:2KQ6}
RP STRUCTURE BY NMR OF 720-797.
RX PubMed=20439752; DOI=10.1073/pnas.0912295107;
RA Petri E.T., Celic A., Kennedy S.D., Ehrlich B.E., Boggon T.J.,
RA Hodsdon M.E.;
RT "Structure of the EF-hand domain of polycystin-2 suggests a mechanism for
RT Ca2+-dependent regulation of polycystin-2 channel activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:9176-9181(2010).
RN [26] {ECO:0007744|PDB:2Y4Q}
RP STRUCTURE BY NMR OF 717-792 IN COMPLEX WITH CALCIUM, DOMAIN, AND
RP MUTAGENESIS OF GLN-768 AND GLU-774.
RX PubMed=24990821; DOI=10.1002/pro.2513;
RA Allen M.D., Qamar S., Vadivelu M.K., Sandford R.N., Bycroft M.;
RT "A high-resolution structure of the EF-hand domain of human polycystin-2.";
RL Protein Sci. 23:1301-1308(2014).
RN [27] {ECO:0007744|PDB:5T4D}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.00 ANGSTROMS) OF 198-702, SUBUNIT,
RP SUBCELLULAR LOCATION, TOPOLOGY, GLYCOSYLATION AT ASN-328; ASN-362 AND
RP ASN-375, AND DISULFIDE BONDS.
RX PubMed=27768895; DOI=10.1016/j.cell.2016.09.048;
RA Shen P.S., Yang X., DeCaen P.G., Liu X., Bulkley D., Clapham D.E., Cao E.;
RT "The structure of the polycystic kidney disease channel PKD2 in lipid
RT nanodiscs.";
RL Cell 167:763-773(2016).
RN [28] {ECO:0007744|PDB:5K47}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.20 ANGSTROMS) OF 185-723, FUNCTION,
RP SUBUNIT, TOPOLOGY, AND GLYCOSYLATION AT ASN-328; ASN-362 AND ASN-375.
RX PubMed=27991905; DOI=10.1038/nsmb.3343;
RA Grieben M., Pike A.C., Shintre C.A., Venturi E., El-Ajouz S., Tessitore A.,
RA Shrestha L., Mukhopadhyay S., Mahajan P., Chalk R., Burgess-Brown N.A.,
RA Sitsapesan R., Huiskonen J.T., Carpenter E.P.;
RT "Structure of the polycystic kidney disease TRP channel polycystin-2
RT (PC2).";
RL Nat. Struct. Mol. Biol. 24:114-122(2017).
RN [29] {ECO:0007744|PDB:5MKE, ECO:0007744|PDB:5MKF}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.20 ANGSTROMS) IN COMPLEX WITH CALCIUM
RP AND LIPIDS, SUBUNIT, SUBCELLULAR LOCATION, TOPOLOGY, GLYCOSYLATION AT
RP ASN-299; ASN-305; ASN-328; ASN-362 AND ASN-375, AND DISULFIDE BONDS.
RX PubMed=28092368; DOI=10.1038/nsmb.3357;
RA Wilkes M., Madej M.G., Kreuter L., Rhinow D., Heinz V., De Sanctis S.,
RA Ruppel S., Richter R.M., Joos F., Grieben M., Pike A.C., Huiskonen J.T.,
RA Carpenter E.P., Kuhlbrandt W., Witzgall R., Ziegler C.;
RT "Molecular insights into lipid-assisted Ca2+ regulation of the TRP channel
RT polycystin-2.";
RL Nat. Struct. Mol. Biol. 24:123-130(2017).
RN [30] {ECO:0007744|PDB:6D1W}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.54 ANGSTROMS) OF 53-792 OF MUTANT
RP PRO-604, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, TOPOLOGY, MUTAGENESIS OF
RP TRP-201; PHE-604; LEU-677; TYR-684 AND LYS-688, CHARACTERIZATION OF VARIANT
RP PKD2 VAL-511 AND TYR-684 DEL, AND DISULFIDE BONDS.
RX PubMed=29899465; DOI=10.1038/s41467-018-04586-x;
RA Zheng W., Yang X., Hu R., Cai R., Hofmann L., Wang Z., Hu Q., Liu X.,
RA Bulkey D., Yu Y., Tang J., Flockerzi V., Cao Y., Cao E., Chen X.Z.;
RT "Hydrophobic pore gates regulate ion permeation in polycystic kidney
RT disease 2 and 2L1 channels.";
RL Nat. Commun. 9:2302-2302(2018).
RN [31] {ECO:0007744|PDB:6A70}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) OF 185-723 IN COMPLEX
RP WITH PKD1, SUBUNIT, SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=30093605; DOI=10.1126/science.aat9819;
RA Su Q., Hu F., Ge X., Lei J., Yu S., Wang T., Zhou Q., Mei C., Shi Y.;
RT "Structure of the human PKD1-PKD2 complex.";
RL Science 361:0-0(2018).
RN [32]
RP VARIANT PKD2 GLY-414.
RX PubMed=9326320; DOI=10.1086/515497;
RA Veldhuisen B., Saris J.J., de Haij S., Hayashi T., Reynolds D.M.,
RA Mochizuki T., Elles R., Fossdal R., Bogdanova N., van Dijk M.A., Coto E.,
RA Ravine D., Noerby S., Verellen-Dumoulin C., Breuning M.H., Somlo S.,
RA Peters D.J.M.;
RT "A spectrum of mutations in the second gene for autosomal dominant
RT polycystic kidney disease (PKD2).";
RL Am. J. Hum. Genet. 61:547-555(1997).
RN [33]
RP VARIANT PKD2 VAL-511.
RX PubMed=10541293; DOI=10.1681/asn.v10112342;
RA Reynolds D.M., Hayashi T., Cai Y., Veldhuisen B., Watnick T.J., Lens X.M.,
RA Mochizuki T., Qian F., Maeda Y., Li L., Fossdal R., Coto E., Wu G.,
RA Breuning M.H., Germino G.G., Peters D.J.M., Somlo S.;
RT "Aberrant splicing in the PKD2 gene as a cause of polycystic kidney
RT disease.";
RL J. Am. Soc. Nephrol. 10:2342-2351(1999).
RN [34]
RP VARIANT PKD2 PRO-356, AND VARIANT PRO-28.
RX PubMed=10411676; DOI=10.1046/j.1523-1755.1999.00534.x;
RA Torra R., Viribay M., Telleria D., Badenas C., Watson M., Harris P.C.,
RA Darnell A., San Millan J.L.;
RT "Seven novel mutations of the PKD2 gene in families with autosomal dominant
RT polycystic kidney disease.";
RL Kidney Int. 56:28-33(1999).
RN [35]
RP VARIANTS PKD2 ILE-479 DEL; 504-ARG--VAL-512 DEL AND TYR-684 DEL.
RX PubMed=10835625; DOI=10.1038/75981;
RA Watnick T.J., He N., Wang K., Liang Y., Parfrey P., Hefferton D.,
RA St George-Hyslop P.H., Germino G.G., Pei Y.;
RT "Mutations of PKD1 in ADPKD2 cysts suggest a pathogenic effect of trans-
RT heterozygous mutations.";
RL Nat. Genet. 25:143-144(2000).
RN [36]
RP VARIANT PKD2 TRP-322, AND VARIANTS LEU-24; PRO-28 AND LEU-800.
RX PubMed=11968093; DOI=10.1002/humu.9035;
RA Reiterova J., Stekrova J., Peters D.J.M., Kapras J., Kohoutova M.,
RA Merta M., Zidovska J.;
RT "Four novel mutations of the PKD2 gene in Czech families with autosomal
RT dominant polycystic kidney disease.";
RL Hum. Mutat. 19:573-573(2002).
RN [37]
RP VARIANTS PKD2 PRO-356; GLY-414; ARG-632 AND GLN-807.
RX PubMed=12707387; DOI=10.1097/01.asn.0000061774.90975.25;
RA Magistroni R., He N., Wang K., Andrew R., Johnson A., Gabow P., Dicks E.,
RA Parfrey P., Torra R., San-Millan J.L., Coto E., Van Dijk M., Breuning M.,
RA Peters D., Bogdanova N., Ligabue G., Albertazzi A., Hateboer N.,
RA Demetriou K., Pierides A., Deltas C., St George-Hyslop P., Ravine D.,
RA Pei Y.;
RT "Genotype-renal function correlation in type 2 autosomal dominant
RT polycystic kidney disease.";
RL J. Am. Soc. Nephrol. 14:1164-1174(2003).
RN [38]
RP VARIANTS PKD2 GLN-306 AND GLY-420, AND VARIANT PRO-28.
RX PubMed=14993477; DOI=10.1093/ndt/gfh083;
RA Stekrova J., Reiterova J., Merta M., Damborsky J., Zidovska J.,
RA Kebrdlova V., Kohoutova M.;
RT "PKD2 mutations in a Czech population with autosomal dominant polycystic
RT kidney disease.";
RL Nephrol. Dial. Transplant. 19:1116-1122(2004).
RN [39]
RP VARIANT PKD2 GLN-322.
RX PubMed=15772804; DOI=10.1007/s00109-005-0644-6;
RA Peltola P., Lumiaho A., Miettinen R., Pihlajamaeki J., Sandford R.,
RA Laakso M.;
RT "Genetics and phenotypic characteristics of autosomal dominant polycystic
RT kidney disease in Finns.";
RL J. Mol. Med. 83:638-646(2005).
RN [40]
RP VARIANTS PRO-28; THR-190 AND CYS-482.
RX PubMed=18837007; DOI=10.1002/humu.20842;
RA Tan Y.-C., Blumenfeld J.D., Anghel R., Donahue S., Belenkaya R., Balina M.,
RA Parker T., Levine D., Leonard D.G.B., Rennert H.;
RT "Novel method for genomic analysis of PKD1 and PKD2 mutations in autosomal
RT dominant polycystic kidney disease.";
RL Hum. Mutat. 30:264-273(2009).
RN [41]
RP VARIANT PKD2 PRO-384.
RX PubMed=21115670; DOI=10.1093/ndt/gfq720;
RA Hoefele J., Mayer K., Scholz M., Klein H.G.;
RT "Novel PKD1 and PKD2 mutations in autosomal dominant polycystic kidney
RT disease (ADPKD).";
RL Nephrol. Dial. Transplant. 26:2181-2188(2011).
CC -!- FUNCTION: Component of a heteromeric calcium-permeable ion channel
CC formed by PKD1 and PKD2 that is activated by interaction between PKD1
CC and a Wnt family member, such as WNT3A and WNT9B (PubMed:27214281). Can
CC also form a functional, homotetrameric ion channel (PubMed:29899465).
CC Functions as a cation channel involved in fluid-flow mechanosensation
CC by the primary cilium in renal epithelium (PubMed:18695040). Functions
CC as outward-rectifying K(+) channel, but is also permeable to Ca(2+),
CC and to a much lesser degree also to Na(+) (PubMed:11854751,
CC PubMed:15692563, PubMed:27071085, PubMed:27991905). May contribute to
CC the release of Ca(2+) stores from the endoplasmic reticulum
CC (PubMed:11854751, PubMed:20881056). Together with TRPV4, forms
CC mechano- and thermosensitive channels in cilium (PubMed:18695040). PKD1
CC and PKD2 may function through a common signaling pathway that is
CC necessary to maintain the normal, differentiated state of renal tubule
CC cells. Acts as a regulator of cilium length, together with PKD1. The
CC dynamic control of cilium length is essential in the regulation of
CC mechanotransductive signaling. The cilium length response creates a
CC negative feedback loop whereby fluid shear-mediated deflection of the
CC primary cilium, which decreases intracellular cAMP, leads to cilium
CC shortening and thus decreases flow-induced signaling. Also involved in
CC left-right axis specification via its role in sensing nodal flow; forms
CC a complex with PKD1L1 in cilia to facilitate flow detection in left-
CC right patterning. Detection of asymmetric nodal flow gives rise to a
CC Ca(2+) signal that is required for normal, asymmetric expression of
CC genes involved in the specification of body left-right laterality (By
CC similarity). {ECO:0000250|UniProtKB:O35245,
CC ECO:0000269|PubMed:11854751, ECO:0000269|PubMed:15692563,
CC ECO:0000269|PubMed:16551655, ECO:0000269|PubMed:18695040,
CC ECO:0000269|PubMed:20881056, ECO:0000269|PubMed:27214281,
CC ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:29899465, ECO:0000305}.
CC -!- ACTIVITY REGULATION: Channel activity is regulated by phosphorylation
CC (PubMed:16551655, PubMed:20881056, PubMed:26269590). Channel activity
CC is regulated by intracellular Ca(2+) (PubMed:11854751).
CC {ECO:0000269|PubMed:11854751, ECO:0000269|PubMed:16551655,
CC ECO:0000269|PubMed:20881056, ECO:0000269|PubMed:26269590}.
CC -!- SUBUNIT: Component of the heterotetrameric polycystin channel complex
CC with PKD1; the tetramer contains one PKD1 chain and three PKD2 chains
CC (PubMed:20881056, PubMed:19556541, PubMed:27214281, PubMed:30093605).
CC Interaction with PKD1 is required for ciliary localization (By
CC similarity). Homotetramer (PubMed:20881056, PubMed:27768895,
CC PubMed:27991905, PubMed:28092368, PubMed:29899465). Isoform 1 interacts
CC with PKD1 while isoform 3 does not (By similarity). Interacts with
CC PKD1L1. Interacts with CD2AP (PubMed:10913159). Interacts with HAX1
CC (PubMed:10760273). Interacts with NEK8 (By similarity). Part of a
CC complex containing AKAP5, ADCY5, ADCY6 and PDE4C (By similarity).
CC Interacts (via C-terminus) with TRPV4 (via C-terminus)
CC (PubMed:18695040). Interacts (via C-terminal acidic region) with PACS1
CC and PACS2; these interactions retain the protein in the endoplasmic
CC reticulum and prevent trafficking to the cell membrane
CC (PubMed:15692563). Interacts with TMEM33 (By similarity).
CC {ECO:0000250|UniProtKB:O35245, ECO:0000269|PubMed:10760273,
CC ECO:0000269|PubMed:10913159, ECO:0000269|PubMed:15692563,
CC ECO:0000269|PubMed:18695040, ECO:0000269|PubMed:19556541,
CC ECO:0000269|PubMed:20881056, ECO:0000269|PubMed:27768895,
CC ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368}.
CC -!- INTERACTION:
CC Q13563; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-7813714, EBI-3867333;
CC Q13563; O75031: HSF2BP; NbExp=3; IntAct=EBI-7813714, EBI-7116203;
CC Q13563; Q02363: ID2; NbExp=7; IntAct=EBI-7813714, EBI-713450;
CC Q13563; Q6A162: KRT40; NbExp=3; IntAct=EBI-7813714, EBI-10171697;
CC Q13563; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-7813714, EBI-10171774;
CC Q13563; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-7813714, EBI-11962084;
CC Q13563; P43361: MAGEA8; NbExp=4; IntAct=EBI-7813714, EBI-10182930;
CC Q13563; Q99750: MDFI; NbExp=3; IntAct=EBI-7813714, EBI-724076;
CC Q13563; P98161: PKD1; NbExp=8; IntAct=EBI-7813714, EBI-1752013;
CC Q13563; P98161-1: PKD1; NbExp=4; IntAct=EBI-7813714, EBI-1951183;
CC Q13563; Q13563: PKD2; NbExp=11; IntAct=EBI-7813714, EBI-7813714;
CC Q13563; O15162: PLSCR1; NbExp=3; IntAct=EBI-7813714, EBI-740019;
CC Q13563; P48995: TRPC1; NbExp=12; IntAct=EBI-7813714, EBI-929665;
CC Q13563; P48995-2: TRPC1; NbExp=4; IntAct=EBI-7813714, EBI-9830970;
CC Q13563; O35387: Hax1; Xeno; NbExp=3; IntAct=EBI-7813714, EBI-642449;
CC Q13563; Q91908: itpr1.S; Xeno; NbExp=2; IntAct=EBI-7813714, EBI-9633447;
CC Q13563; Q9QZC1: Trpc3; Xeno; NbExp=3; IntAct=EBI-7813714, EBI-10051366;
CC Q13563; Q9EPK8: Trpv4; Xeno; NbExp=11; IntAct=EBI-7813714, EBI-7091763;
CC Q13563-1; P98161: PKD1; NbExp=5; IntAct=EBI-9837017, EBI-1752013;
CC Q13563-1; P98161-3: PKD1; NbExp=4; IntAct=EBI-9837017, EBI-15930070;
CC Q13563-1; Q13563-1: PKD2; NbExp=12; IntAct=EBI-9837017, EBI-9837017;
CC Q13563-1; O08852: Pkd1; Xeno; NbExp=2; IntAct=EBI-9837017, EBI-6666305;
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium membrane
CC {ECO:0000269|PubMed:18695040, ECO:0000269|PubMed:20881056,
CC ECO:0000269|PubMed:27259053}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:27768895, ECO:0000269|PubMed:27991905,
CC ECO:0000269|PubMed:28092368, ECO:0000269|PubMed:29899465,
CC ECO:0000269|PubMed:30093605}. Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:10760273, ECO:0000269|PubMed:11854751,
CC ECO:0000269|PubMed:15692563, ECO:0000269|PubMed:20881056,
CC ECO:0000269|PubMed:28092368, ECO:0000305|PubMed:10913159}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:27768895,
CC ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368,
CC ECO:0000269|PubMed:29899465, ECO:0000269|PubMed:30093605}. Cell
CC membrane {ECO:0000269|PubMed:15692563, ECO:0000269|PubMed:19556541,
CC ECO:0000269|PubMed:26269590, ECO:0000269|PubMed:27071085,
CC ECO:0000269|PubMed:27214281, ECO:0000269|PubMed:27259053,
CC ECO:0000269|PubMed:28092368, ECO:0000269|PubMed:29899465,
CC ECO:0000269|PubMed:30093605}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:27768895, ECO:0000269|PubMed:27991905,
CC ECO:0000269|PubMed:28092368, ECO:0000269|PubMed:29899465,
CC ECO:0000269|PubMed:30093605}. Basolateral cell membrane
CC {ECO:0000269|PubMed:10770959}. Cytoplasmic vesicle membrane
CC {ECO:0000269|PubMed:10770959}. Golgi apparatus
CC {ECO:0000250|UniProtKB:O35245}. Vesicle {ECO:0000269|PubMed:37681898}.
CC Secreted, extracellular exosome {ECO:0000269|PubMed:37681898}.
CC Note=PKD2 localization to the plasma and ciliary membranes requires
CC PKD1. PKD1:PKD2 interaction is required to reach the Golgi apparatus
CC form endoplasmic reticulum and then traffic to the cilia (By
CC similarity). Retained in the endoplasmic reticulum by interaction with
CC PACS1 and PACS2 (PubMed:15692563). Detected on kidney tubule
CC basolateral membranes and basal cytoplasmic vesicles (PubMed:10770959).
CC Cell surface and cilium localization requires GANAB (PubMed:27259053).
CC Detected on migrasomes and on extracellular exosomes in urine
CC (PubMed:21406692). {ECO:0000250|UniProtKB:O35245,
CC ECO:0000269|PubMed:15692563, ECO:0000269|PubMed:21406692,
CC ECO:0000269|PubMed:27259053}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Name=1;
CC IsoId=Q13563-1; Sequence=Displayed;
CC Name=2; Synonyms=delta6;
CC IsoId=Q13563-2; Sequence=VSP_042479, VSP_042480;
CC Name=3; Synonyms=delta7;
CC IsoId=Q13563-3; Sequence=VSP_042481;
CC Name=4; Synonyms=delta9;
CC IsoId=Q13563-4; Sequence=VSP_042482, VSP_042483;
CC Name=5; Synonyms=delta12/13;
CC IsoId=Q13563-5; Sequence=VSP_042484;
CC -!- TISSUE SPECIFICITY: Detected in fetal and adult kidney
CC (PubMed:10770959). Detected at the thick ascending limb of the loop of
CC Henle, at distal tubules, including the distal convoluted tubule and
CC cortical collecting tubules, with weak staining of the collecting duct
CC (PubMed:10770959). Detected on placenta syncytiotrophoblasts (at
CC protein level) (PubMed:26269590). Strongly expressed in ovary, fetal
CC and adult kidney, testis, and small intestine. Not detected in
CC peripheral leukocytes. {ECO:0000269|PubMed:10770959,
CC ECO:0000269|PubMed:26269590, ECO:0000269|PubMed:8650545}.
CC -!- DOMAIN: The C-terminal coiled-coil domain is involved in
CC oligomerization and the interaction with PKD1 (PubMed:18694932,
CC PubMed:19556541). The isolated coiled-coil domain forms a homotrimer in
CC vitro; the homotrimer interacts with a single PKD1 chain
CC (PubMed:19556541). The coiled-coil domain binds calcium and undergoes a
CC calcium-induced conformation change (in vitro) (PubMed:18694932).
CC {ECO:0000269|PubMed:18694932, ECO:0000269|PubMed:19556541}.
CC -!- PTM: Phosphorylated. Phosphorylation is important for protein function;
CC a mutant that lacks the N-terminal phosphorylation sites cannot
CC complement a zebrafish pkd2-deficient mutant (PubMed:16551655). PKD-
CC mediated phosphorylation at the C-terminus regulates its function in
CC the release of Ca(2+) stores from the endoplasmic reticulum
CC (PubMed:20881056). PKA-mediated phosphorylation at a C-terminal site
CC strongly increases the open probability of the channel, but does not
CC increase single channel conductance (PubMed:26269590).
CC {ECO:0000269|PubMed:16551655, ECO:0000269|PubMed:20881056,
CC ECO:0000269|PubMed:26269590}.
CC -!- PTM: N-glycosylated. The four subunits in a tetramer probably differ in
CC the extent of glycosylation; simultaneous glycosylation of all
CC experimentally validated sites would probably create steric hindrance.
CC Thus, glycosylation at Asn-305 is not compatible with glycosylation at
CC Asn-328; only one of these two residues is glycosylated at a given
CC time. {ECO:0000269|PubMed:28092368}.
CC -!- DISEASE: Polycystic kidney disease 2 with or without polycystic liver
CC disease (PKD2) [MIM:613095]: An autosomal dominant disorder
CC characterized by progressive formation and enlargement of cysts in both
CC kidneys, typically leading to end-stage renal disease in adult life.
CC Cysts also occurs in the liver and other organs. It represents
CC approximately 15% of the cases of autosomal dominant polycystic kidney
CC disease. PKD2 is clinically milder than PKD1 but it has a deleterious
CC impact on overall life expectancy. {ECO:0000269|PubMed:10411676,
CC ECO:0000269|PubMed:10541293, ECO:0000269|PubMed:10835625,
CC ECO:0000269|PubMed:11854751, ECO:0000269|PubMed:11968093,
CC ECO:0000269|PubMed:12707387, ECO:0000269|PubMed:14993477,
CC ECO:0000269|PubMed:15772804, ECO:0000269|PubMed:21115670,
CC ECO:0000269|PubMed:27071085, ECO:0000269|PubMed:27214281,
CC ECO:0000269|PubMed:29899465, ECO:0000269|PubMed:9326320}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: The mechanisms that govern channel opening are complex
CC and still under debate; heterologous expression of PKD2 by itself or
CC together with PKD1 gives rise to very low or undetectable spontaneous
CC ion channel activity, in spite of its presence at the cell membrane.
CC {ECO:0000269|PubMed:19556541, ECO:0000269|PubMed:27768895}.
CC -!- MISCELLANEOUS: [Isoform 5]: Minor isoform. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the polycystin family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding;
CC Note=Polycystin 2 - Not a C-type lectin;
CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_Ctlect_205";
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DR EMBL; U50928; AAC50520.1; -; mRNA.
DR EMBL; AF004873; AAC16004.1; -; Genomic_DNA.
DR EMBL; AF004859; AAC16004.1; JOINED; Genomic_DNA.
DR EMBL; AF004860; AAC16004.1; JOINED; Genomic_DNA.
DR EMBL; AF004861; AAC16004.1; JOINED; Genomic_DNA.
DR EMBL; AF004862; AAC16004.1; JOINED; Genomic_DNA.
DR EMBL; AF004863; AAC16004.1; JOINED; Genomic_DNA.
DR EMBL; AF004864; AAC16004.1; JOINED; Genomic_DNA.
DR EMBL; AF004865; AAC16004.1; JOINED; Genomic_DNA.
DR EMBL; AF004866; AAC16004.1; JOINED; Genomic_DNA.
DR EMBL; AF004867; AAC16004.1; JOINED; Genomic_DNA.
DR EMBL; AF004868; AAC16004.1; JOINED; Genomic_DNA.
DR EMBL; AF004869; AAC16004.1; JOINED; Genomic_DNA.
DR EMBL; AF004870; AAC16004.1; JOINED; Genomic_DNA.
DR EMBL; AF004871; AAC16004.1; JOINED; Genomic_DNA.
DR EMBL; AF004872; AAC16004.1; JOINED; Genomic_DNA.
DR EMBL; BC112261; AAI12262.1; -; mRNA.
DR EMBL; BC112263; AAI12264.1; -; mRNA.
DR EMBL; U56813; AAC50933.1; -; mRNA.
DR CCDS; CCDS3627.1; -. [Q13563-1]
DR PIR; G02640; G02640.
DR RefSeq; NP_000288.1; NM_000297.3. [Q13563-1]
DR PDB; 2KLD; NMR; -; A=680-796.
DR PDB; 2KLE; NMR; -; A=680-796.
DR PDB; 2KQ6; NMR; -; A=720-797.
DR PDB; 2Y4Q; NMR; -; A=717-792.
DR PDB; 3HRN; X-ray; 1.90 A; A=833-895.
DR PDB; 3HRO; X-ray; 1.90 A; A=833-872.
DR PDB; 5K47; EM; 4.20 A; A/B/C/D=185-723.
DR PDB; 5MKE; EM; 4.30 A; A/B/C/D=1-968.
DR PDB; 5MKF; EM; 4.20 A; A/B/C/D=1-968.
DR PDB; 5T4D; EM; 3.00 A; A/B/C/D=198-702.
DR PDB; 6A70; EM; 3.60 A; A/F/G=185-723.
DR PDB; 6D1W; EM; 3.54 A; A/B/C/D=53-792.
DR PDB; 6T9N; EM; 2.96 A; A/B/C/D=185-723.
DR PDB; 6T9O; EM; 3.39 A; A/B/C/D=185-723.
DR PDB; 6WB8; EM; 3.24 A; A/B/C/D=41-792.
DR PDBsum; 2KLD; -.
DR PDBsum; 2KLE; -.
DR PDBsum; 2KQ6; -.
DR PDBsum; 2Y4Q; -.
DR PDBsum; 3HRN; -.
DR PDBsum; 3HRO; -.
DR PDBsum; 5K47; -.
DR PDBsum; 5MKE; -.
DR PDBsum; 5MKF; -.
DR PDBsum; 5T4D; -.
DR PDBsum; 6A70; -.
DR PDBsum; 6D1W; -.
DR PDBsum; 6T9N; -.
DR PDBsum; 6T9O; -.
DR PDBsum; 6WB8; -.
DR AlphaFoldDB; Q13563; -.
DR BMRB; Q13563; -.
DR EMDB; EMD-10418; -.
DR EMDB; EMD-10419; -.
DR EMDB; EMD-21586; -.
DR EMDB; EMD-3523; -.
DR EMDB; EMD-3524; -.
DR EMDB; EMD-6991; -.
DR EMDB; EMD-6992; -.
DR EMDB; EMD-7786; -.
DR EMDB; EMD-8200; -.
DR EMDB; EMD-8354; -.
DR EMDB; EMD-8355; -.
DR EMDB; EMD-8356; -.
DR SMR; Q13563; -.
DR BioGRID; 111328; 88.
DR ComplexPortal; CPX-4001; PKD1-PKD2 Polycystin complex.
DR CORUM; Q13563; -.
DR DIP; DIP-47455N; -.
DR ELM; Q13563; -.
DR IntAct; Q13563; 46.
DR MINT; Q13563; -.
DR STRING; 9606.ENSP00000237596; -.
DR BindingDB; Q13563; -.
DR ChEMBL; CHEMBL5465; -.
DR GuidetoPHARMACOLOGY; 504; -.
DR TCDB; 1.A.5.2.1; the polycystin cation channel (pcc) family.
DR GlyCosmos; Q13563; 5 sites, No reported glycans.
DR GlyGen; Q13563; 7 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q13563; -.
DR PhosphoSitePlus; Q13563; -.
DR BioMuta; PKD2; -.
DR DMDM; 116242717; -.
DR EPD; Q13563; -.
DR jPOST; Q13563; -.
DR MassIVE; Q13563; -.
DR MaxQB; Q13563; -.
DR PaxDb; 9606-ENSP00000237596; -.
DR PeptideAtlas; Q13563; -.
DR ProteomicsDB; 59562; -. [Q13563-1]
DR ProteomicsDB; 59563; -. [Q13563-2]
DR ProteomicsDB; 59564; -. [Q13563-3]
DR ProteomicsDB; 59565; -. [Q13563-4]
DR ProteomicsDB; 59566; -. [Q13563-5]
DR Antibodypedia; 3871; 389 antibodies from 36 providers.
DR DNASU; 5311; -.
DR Ensembl; ENST00000237596.7; ENSP00000237596.2; ENSG00000118762.8. [Q13563-1]
DR GeneID; 5311; -.
DR KEGG; hsa:5311; -.
DR MANE-Select; ENST00000237596.7; ENSP00000237596.2; NM_000297.4; NP_000288.1.
DR UCSC; uc003hre.4; human. [Q13563-1]
DR AGR; HGNC:9009; -.
DR CTD; 5311; -.
DR DisGeNET; 5311; -.
DR GeneCards; PKD2; -.
DR GeneReviews; PKD2; -.
DR HGNC; HGNC:9009; PKD2.
DR HPA; ENSG00000118762; Low tissue specificity.
DR MalaCards; PKD2; -.
DR MIM; 173910; gene.
DR MIM; 613095; phenotype.
DR neXtProt; NX_Q13563; -.
DR OpenTargets; ENSG00000118762; -.
DR Orphanet; 730; Autosomal dominant polycystic kidney disease.
DR PharmGKB; PA33343; -.
DR VEuPathDB; HostDB:ENSG00000118762; -.
DR eggNOG; KOG3599; Eukaryota.
DR GeneTree; ENSGT00940000159025; -.
DR HOGENOM; CLU_012097_0_0_1; -.
DR InParanoid; Q13563; -.
DR OMA; RHEHRSC; -.
DR OrthoDB; 56358at2759; -.
DR PhylomeDB; Q13563; -.
DR TreeFam; TF316484; -.
DR PathwayCommons; Q13563; -.
DR Reactome; R-HSA-5620916; VxPx cargo-targeting to cilium.
DR SignaLink; Q13563; -.
DR SIGNOR; Q13563; -.
DR BioGRID-ORCS; 5311; 8 hits in 1152 CRISPR screens.
DR ChiTaRS; PKD2; human.
DR EvolutionaryTrace; Q13563; -.
DR GeneWiki; Polycystic_kidney_disease_2; -.
DR GenomeRNAi; 5311; -.
DR Pharos; Q13563; Tchem.
DR PRO; PR:Q13563; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q13563; Protein.
DR Bgee; ENSG00000118762; Expressed in blood vessel layer and 208 other cell types or tissues.
DR ExpressionAtlas; Q13563; baseline and differential.
DR Genevisible; Q13563; HS.
DR GO; GO:0045180; C:basal cortex; IDA:BHF-UCL.
DR GO; GO:0009925; C:basal plasma membrane; IDA:BHF-UCL.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0034703; C:cation channel complex; IDA:UniProtKB.
DR GO; GO:0005911; C:cell-cell junction; IEA:Ensembl.
DR GO; GO:0036064; C:ciliary basal body; IDA:MGI.
DR GO; GO:0060170; C:ciliary membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005929; C:cilium; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0098554; C:cytoplasmic side of endoplasmic reticulum membrane; IDA:BHF-UCL.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:BHF-UCL.
DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IDA:BHF-UCL.
DR GO; GO:0098553; C:lumenal side of endoplasmic reticulum membrane; IDA:BHF-UCL.
DR GO; GO:0016020; C:membrane; IDA:ComplexPortal.
DR GO; GO:0140494; C:migrasome; IDA:UniProtKB.
DR GO; GO:0072686; C:mitotic spindle; IDA:BHF-UCL.
DR GO; GO:0031514; C:motile cilium; ISS:BHF-UCL.
DR GO; GO:0097730; C:non-motile cilium; ISS:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0002133; C:polycystin complex; IPI:ComplexPortal.
DR GO; GO:0042805; F:actinin binding; IDA:BHF-UCL.
DR GO; GO:0051117; F:ATPase binding; ISS:BHF-UCL.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0048763; F:calcium-induced calcium release activity; IDA:BHF-UCL.
DR GO; GO:0008092; F:cytoskeletal protein binding; IDA:BHF-UCL.
DR GO; GO:0043398; F:HLH domain binding; IPI:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005261; F:monoatomic cation channel activity; IMP:UniProtKB.
DR GO; GO:0051371; F:muscle alpha-actinin binding; IBA:GO_Central.
DR GO; GO:0015271; F:outward rectifier potassium channel activity; ISS:UniProtKB.
DR GO; GO:0051219; F:phosphoprotein binding; IPI:UniProtKB.
DR GO; GO:0005267; F:potassium channel activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:BHF-UCL.
DR GO; GO:0005102; F:signaling receptor binding; IPI:BHF-UCL.
DR GO; GO:0140416; F:transcription regulator inhibitor activity; IPI:BHF-UCL.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:BHF-UCL.
DR GO; GO:0005245; F:voltage-gated calcium channel activity; IDA:BHF-UCL.
DR GO; GO:0022843; F:voltage-gated monoatomic cation channel activity; IDA:BHF-UCL.
DR GO; GO:0005244; F:voltage-gated monoatomic ion channel activity; IDA:BHF-UCL.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IMP:UniProtKB.
DR GO; GO:0005248; F:voltage-gated sodium channel activity; IDA:BHF-UCL.
DR GO; GO:0035904; P:aorta development; IEP:UniProtKB.
DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IEP:UniProtKB.
DR GO; GO:0070588; P:calcium ion transmembrane transport; IDA:BHF-UCL.
DR GO; GO:0006816; P:calcium ion transport; IDA:BHF-UCL.
DR GO; GO:0198738; P:cell-cell signaling by wnt; IDA:UniProtKB.
DR GO; GO:0071277; P:cellular response to calcium ion; ISS:UniProtKB.
DR GO; GO:0071320; P:cellular response to cAMP; IMP:UniProtKB.
DR GO; GO:0071498; P:cellular response to fluid shear stress; IMP:BHF-UCL.
DR GO; GO:0071464; P:cellular response to hydrostatic pressure; IDA:BHF-UCL.
DR GO; GO:0071470; P:cellular response to osmotic stress; IDA:BHF-UCL.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; NAS:BHF-UCL.
DR GO; GO:0051298; P:centrosome duplication; NAS:BHF-UCL.
DR GO; GO:0044782; P:cilium organization; IMP:MGI.
DR GO; GO:0050982; P:detection of mechanical stimulus; ISS:BHF-UCL.
DR GO; GO:0003127; P:detection of nodal flow; ISS:BHF-UCL.
DR GO; GO:0007368; P:determination of left/right symmetry; ISS:BHF-UCL.
DR GO; GO:0071910; P:determination of liver left/right asymmetry; IMP:BHF-UCL.
DR GO; GO:0001892; P:embryonic placenta development; ISS:BHF-UCL.
DR GO; GO:0051649; P:establishment of localization in cell; IEA:Ensembl.
DR GO; GO:0007507; P:heart development; IEP:UniProtKB.
DR GO; GO:0001947; P:heart looping; IMP:BHF-UCL.
DR GO; GO:0098662; P:inorganic cation transmembrane transport; IMP:UniProtKB.
DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IEA:Ensembl.
DR GO; GO:0001889; P:liver development; IEP:UniProtKB.
DR GO; GO:0072177; P:mesonephric duct development; IEP:UniProtKB.
DR GO; GO:0072164; P:mesonephric tubule development; IEP:UniProtKB.
DR GO; GO:0072218; P:metanephric ascending thin limb development; IEP:UniProtKB.
DR GO; GO:0072214; P:metanephric cortex development; IEP:UniProtKB.
DR GO; GO:0072219; P:metanephric cortical collecting duct development; IEP:UniProtKB.
DR GO; GO:0072235; P:metanephric distal tubule development; IEP:UniProtKB.
DR GO; GO:0072075; P:metanephric mesenchyme development; IEP:UniProtKB.
DR GO; GO:0035502; P:metanephric part of ureteric bud development; IEP:UniProtKB.
DR GO; GO:0072284; P:metanephric S-shaped body morphogenesis; IEP:UniProtKB.
DR GO; GO:0072208; P:metanephric smooth muscle tissue development; IEP:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; NAS:BHF-UCL.
DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; IMP:BHF-UCL.
DR GO; GO:0060315; P:negative regulation of ryanodine-sensitive calcium-release channel activity; ISS:BHF-UCL.
DR GO; GO:0021915; P:neural tube development; IEP:UniProtKB.
DR GO; GO:0060674; P:placenta blood vessel development; ISS:BHF-UCL.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0031587; P:positive regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity; IMP:BHF-UCL.
DR GO; GO:0045429; P:positive regulation of nitric oxide biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:UniProtKB.
DR GO; GO:0051290; P:protein heterotetramerization; IDA:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR GO; GO:0051262; P:protein tetramerization; IDA:UniProtKB.
DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; ISS:BHF-UCL.
DR GO; GO:0090279; P:regulation of calcium ion import; IDA:BHF-UCL.
DR GO; GO:0051726; P:regulation of cell cycle; ISS:BHF-UCL.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:BHF-UCL.
DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IDA:BHF-UCL.
DR GO; GO:0061441; P:renal artery morphogenesis; IEP:UniProtKB.
DR GO; GO:0061333; P:renal tubule morphogenesis; ISS:BHF-UCL.
DR GO; GO:0035725; P:sodium ion transmembrane transport; IDA:BHF-UCL.
DR GO; GO:0021510; P:spinal cord development; IEP:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR DisProt; DP02758; -.
DR Gene3D; 1.10.287.70; -; 1.
DR Gene3D; 1.20.5.340; -; 1.
DR Gene3D; 1.10.238.10; EF-hand; 1.
DR Gene3D; 1.20.120.350; Voltage-gated potassium channels. Chain C; 1.
DR InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR013122; PKD1_2_channel.
DR InterPro; IPR003915; PKD_2.
DR InterPro; IPR046791; Polycystin_dom.
DR InterPro; IPR027359; Volt_channel_dom_sf.
DR PANTHER; PTHR10877; POLYCYSTIN FAMILY MEMBER; 1.
DR PANTHER; PTHR10877:SF114; POLYCYSTIN-2; 1.
DR Pfam; PF18109; Fer4_24; 1.
DR Pfam; PF08016; PKD_channel; 1.
DR Pfam; PF20519; Polycystin_dom; 1.
DR PRINTS; PR01433; POLYCYSTIN2.
DR SUPFAM; SSF47473; EF-hand; 1.
DR SUPFAM; SSF81324; Voltage-gated potassium channels; 1.
DR PROSITE; PS50222; EF_HAND_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Calcium; Calcium channel;
KW Calcium transport; Cell membrane; Cell projection; Ciliopathy; Cilium;
KW Coiled coil; Cytoplasmic vesicle; Direct protein sequencing;
KW Disease variant; Disulfide bond; Endoplasmic reticulum; Glycoprotein;
KW Golgi apparatus; Ion channel; Ion transport; Membrane; Metal-binding;
KW Methylation; Phosphoprotein; Potassium; Potassium channel;
KW Potassium transport; Reference proteome; Secreted; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel;
KW Wnt signaling pathway.
FT CHAIN 1..968
FT /note="Polycystin-2"
FT /id="PRO_0000164356"
FT TOPO_DOM 1..219
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:27768895,
FT ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368"
FT TRANSMEM 220..241
FT /note="Helical; Name=S1"
FT /evidence="ECO:0000269|PubMed:27768895,
FT ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368"
FT TOPO_DOM 242..468
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:27768895,
FT ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368"
FT TRANSMEM 469..489
FT /note="Helical; Name=S2"
FT /evidence="ECO:0000269|PubMed:27768895,
FT ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368"
FT TOPO_DOM 490..505
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:27768895,
FT ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368"
FT TRANSMEM 506..526
FT /note="Helical; Name=S3"
FT /evidence="ECO:0000269|PubMed:27768895,
FT ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368"
FT TOPO_DOM 527..552
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:27768895,
FT ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368"
FT TRANSMEM 553..573
FT /note="Helical; Name=S4"
FT /evidence="ECO:0000269|PubMed:27768895,
FT ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368"
FT TOPO_DOM 574..597
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:27768895,
FT ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368"
FT TRANSMEM 598..619
FT /note="Helical; Name=5"
FT /evidence="ECO:0000269|PubMed:27768895,
FT ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368"
FT TOPO_DOM 620..631
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:27768895,
FT ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368"
FT INTRAMEM 632..646
FT /note="Pore-forming"
FT /evidence="ECO:0000269|PubMed:27768895,
FT ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368"
FT TOPO_DOM 647..654
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:27768895,
FT ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368"
FT TRANSMEM 655..675
FT /note="Helical; Name=S6"
FT /evidence="ECO:0000269|PubMed:27768895,
FT ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368"
FT TOPO_DOM 676..968
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:27768895,
FT ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368"
FT DOMAIN 750..785
FT /note="EF-hand"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448,
FT ECO:0000269|PubMed:18694932, ECO:0000269|PubMed:24990821"
FT REGION 1..28
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 58..181
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 764..831
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 803..822
FT /note="Linker"
FT /evidence="ECO:0000305|PubMed:18694932"
FT REGION 810..821
FT /note="Important for interaction with PACS1 and PACS2"
FT /evidence="ECO:0000269|PubMed:15692563"
FT REGION 917..968
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 833..872
FT /evidence="ECO:0000269|PubMed:19556541,
FT ECO:0000305|PubMed:18694932"
FT MOTIF 641..643
FT /note="Selectivity filter"
FT /evidence="ECO:0000305|PubMed:28092368"
FT COMPBIAS 94..111
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 764..794
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 937..968
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 763
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:24990821,
FT ECO:0007744|PDB:2Y4Q"
FT BINDING 765
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:24990821,
FT ECO:0007744|PDB:2Y4Q"
FT BINDING 767
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:24990821,
FT ECO:0007744|PDB:2Y4Q"
FT BINDING 769
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:24990821,
FT ECO:0007744|PDB:2Y4Q"
FT BINDING 774
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /evidence="ECO:0000269|PubMed:24990821,
FT ECO:0007744|PDB:2Y4Q"
FT MOD_RES 76
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16551655"
FT MOD_RES 80
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:16551655"
FT MOD_RES 137
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:O35245"
FT MOD_RES 801
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:20881056,
FT ECO:0000305|PubMed:16551655"
FT MOD_RES 808
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O35245"
FT MOD_RES 812
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:15692563,
FT ECO:0000305|PubMed:16551655, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 829
FT /note="Phosphoserine"
FT /evidence="ECO:0000305|PubMed:26269590"
FT CARBOHYD 299
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:28092368"
FT CARBOHYD 305
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:28092368"
FT CARBOHYD 328
FT /note="N-linked (GlcNAc...) (complex) asparagine"
FT /evidence="ECO:0000269|PubMed:19139490,
FT ECO:0000269|PubMed:27768895, ECO:0000269|PubMed:27991905,
FT ECO:0000269|PubMed:28092368"
FT CARBOHYD 362
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:27768895,
FT ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368"
FT CARBOHYD 375
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:27768895,
FT ECO:0000269|PubMed:27991905, ECO:0000269|PubMed:28092368"
FT DISULFID 331..344
FT /evidence="ECO:0000269|PubMed:27768895,
FT ECO:0000269|PubMed:28092368, ECO:0007744|PDB:5MKF,
FT ECO:0007744|PDB:5T4D"
FT VAR_SEQ 476..483
FT /note="CEIIFCFF -> FICSSYGD (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_042479"
FT VAR_SEQ 484..968
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_042480"
FT VAR_SEQ 517..572
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_042481"
FT VAR_SEQ 633..646
FT /note="IFTQFRIILGDINF -> IICSWRSSMIRTLK (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_042482"
FT VAR_SEQ 647..968
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_042483"
FT VAR_SEQ 748..841
FT /note="Missing (in isoform 5)"
FT /evidence="ECO:0000305"
FT /id="VSP_042484"
FT VARIANT 24
FT /note="P -> L (in dbSNP:rs1004860210)"
FT /evidence="ECO:0000269|PubMed:11968093"
FT /id="VAR_058820"
FT VARIANT 28
FT /note="R -> P (in dbSNP:rs1805044)"
FT /evidence="ECO:0000269|PubMed:10411676,
FT ECO:0000269|PubMed:11968093, ECO:0000269|PubMed:14993477,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:18837007"
FT /id="VAR_011072"
FT VARIANT 190
FT /note="A -> T (in dbSNP:rs117078377)"
FT /evidence="ECO:0000269|PubMed:18837007"
FT /id="VAR_058821"
FT VARIANT 306
FT /note="R -> Q (in PKD2; dbSNP:rs990932947)"
FT /evidence="ECO:0000269|PubMed:14993477"
FT /id="VAR_058822"
FT VARIANT 322
FT /note="R -> Q (in PKD2; dbSNP:rs145877597)"
FT /evidence="ECO:0000269|PubMed:15772804"
FT /id="VAR_058823"
FT VARIANT 322
FT /note="R -> W (in PKD2; dbSNP:rs1553925453)"
FT /evidence="ECO:0000269|PubMed:11968093"
FT /id="VAR_058824"
FT VARIANT 356
FT /note="A -> P (in PKD2)"
FT /evidence="ECO:0000269|PubMed:10411676,
FT ECO:0000269|PubMed:12707387"
FT /id="VAR_011073"
FT VARIANT 384
FT /note="A -> P (in PKD2)"
FT /evidence="ECO:0000269|PubMed:21115670"
FT /id="VAR_064394"
FT VARIANT 414
FT /note="W -> G (in PKD2; affects channel activity as it is
FT able to abolish channel currents induced by the gain-of-
FT function artificial mutant P-604)"
FT /evidence="ECO:0000269|PubMed:12707387,
FT ECO:0000269|PubMed:27071085, ECO:0000269|PubMed:9326320"
FT /id="VAR_009195"
FT VARIANT 420
FT /note="R -> G (in PKD2; affects channel activity as it is
FT able to abolish channel currents induced by the gain-of-
FT function artificial mutant P-604)"
FT /evidence="ECO:0000269|PubMed:14993477,
FT ECO:0000269|PubMed:27071085"
FT /id="VAR_058825"
FT VARIANT 452
FT /note="I -> V (in dbSNP:rs1801612)"
FT /id="VAR_014919"
FT VARIANT 479
FT /note="Missing (in PKD2; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:10835625"
FT /id="VAR_011074"
FT VARIANT 482
FT /note="F -> C (in dbSNP:rs75762896)"
FT /evidence="ECO:0000269|PubMed:18837007"
FT /id="VAR_058826"
FT VARIANT 504..512
FT /note="Missing (in PKD2; somatic mutation)"
FT /evidence="ECO:0000269|PubMed:10835625"
FT /id="VAR_011075"
FT VARIANT 511
FT /note="D -> V (in PKD2; loss of function in the release of
FT Ca(2+) stores from the endoplasmic reticulum; no effect on
FT location at the endoplasmic reticulum; affects channel
FT activity as it is able to abolish channel currents induced
FT by the gain-of-function artificial mutant P-604;
FT dbSNP:rs121918043)"
FT /evidence="ECO:0000269|PubMed:10541293,
FT ECO:0000269|PubMed:11854751, ECO:0000269|PubMed:27071085,
FT ECO:0000269|PubMed:27214281, ECO:0000269|PubMed:29899465"
FT /id="VAR_058827"
FT VARIANT 632
FT /note="C -> R (in PKD2)"
FT /evidence="ECO:0000269|PubMed:12707387"
FT /id="VAR_058828"
FT VARIANT 684
FT /note="Missing (in PKD2; somatic mutation; abolishes
FT channel currents induced by the gain-of-function artificial
FT mutant P-604; dbSNP:rs1578144872)"
FT /evidence="ECO:0000269|PubMed:10835625"
FT /id="VAR_011076"
FT VARIANT 800
FT /note="M -> L (in dbSNP:rs2234917)"
FT /evidence="ECO:0000269|PubMed:11968093"
FT /id="VAR_058829"
FT VARIANT 807
FT /note="R -> Q (in PKD2; dbSNP:rs147654263)"
FT /evidence="ECO:0000269|PubMed:12707387"
FT /id="VAR_058830"
FT MUTAGEN 76
FT /note="S->A: Abolishes phosphorylation of the N-terminal
FT domain. Abolishes the ability to complement a pkd2-
FT deficient zebrafish mutant; when associated with A-80."
FT /evidence="ECO:0000269|PubMed:16551655"
FT MUTAGEN 80
FT /note="S->A: Decreases phosphorylation of the N-terminal
FT domain. Abolishes the ability to complement a pkd2-
FT deficient zebrafish mutant; when associated with A-76."
FT /evidence="ECO:0000269|PubMed:16551655"
FT MUTAGEN 201
FT /note="W->A: Abolishes increased channel activity due to a
FT gain of function mutation; when associated with P-604."
FT /evidence="ECO:0000269|PubMed:29899465"
FT MUTAGEN 604
FT /note="F->A,I: No effect on channel activation."
FT /evidence="ECO:0000269|PubMed:27071085"
FT MUTAGEN 604
FT /note="F->P: Gain-of-function mutation resulting in
FT increased channel activity. Absence of gain of function;
FT when associated with F-605 DEL; when associated with A-201;
FT when associated with V-511; when associated with G-414;
FT when associated with G-420; when associated with Y-684 DEL;
FT when associated with A-684. Increased channel activity;
FT when associated with 736-L-N-737 DEL."
FT /evidence="ECO:0000269|PubMed:27071085,
FT ECO:0000269|PubMed:29899465"
FT MUTAGEN 605
FT /note="Missing: Abolishes increased channel activity due to
FT a gain of function mutation; when associated with P-604."
FT /evidence="ECO:0000269|PubMed:27071085"
FT MUTAGEN 677
FT /note="L->N: Gain of function mutation."
FT /evidence="ECO:0000269|PubMed:29899465"
FT MUTAGEN 684
FT /note="Y->A: Abolishes increased channel activity due to a
FT gain of function mutation; when associated with P-604."
FT /evidence="ECO:0000269|PubMed:29899465"
FT MUTAGEN 688
FT /note="K->A: Abolishes increased channel activity due to a
FT gain of function mutation; when associated with P-604."
FT /evidence="ECO:0000269|PubMed:29899465"
FT MUTAGEN 721
FT /note="T->A: Decreases phosphorylation; when associated
FT with A-801; A-812; A-831 and A-943."
FT /evidence="ECO:0000269|PubMed:16551655"
FT MUTAGEN 736..737
FT /note="Missing: Increased channel activity; when associated
FT with P-604."
FT /evidence="ECO:0000269|PubMed:27071085"
FT MUTAGEN 768
FT /note="Q->G: Strongly increases calcium binding affinity."
FT /evidence="ECO:0000269|PubMed:24990821"
FT MUTAGEN 771
FT /note="T->A: Loss of calcium-binding site; when associated
FT with A-774."
FT /evidence="ECO:0000269|PubMed:18694932"
FT MUTAGEN 774
FT /note="E->A: Loss of calcium-binding site; when associated
FT with A-771."
FT /evidence="ECO:0000269|PubMed:18694932"
FT MUTAGEN 774
FT /note="E->Q: Abolishes calcium binding via the EF-hand."
FT /evidence="ECO:0000269|PubMed:24990821"
FT MUTAGEN 801
FT /note="S->A: Decreases phosphorylation; when associated
FT with A-721; A-812; A-831 and A-943."
FT /evidence="ECO:0000269|PubMed:16551655"
FT MUTAGEN 801
FT /note="S->D: Phosphomimetic mutant. No effect on release of
FT Ca(2+) stores from the endoplasmic reticulum."
FT /evidence="ECO:0000269|PubMed:20881056"
FT MUTAGEN 801
FT /note="S->G: Loss of phosphorylation at this site. Impairs
FT release of Ca(2+) stores from the endoplasmic reticulum."
FT /evidence="ECO:0000269|PubMed:20881056"
FT MUTAGEN 804
FT /note="S->N: Loss of phosphorylation at Ser-801."
FT /evidence="ECO:0000269|PubMed:20881056"
FT MUTAGEN 812
FT /note="S->A: Decreases interaction with PACS1 and enhances
FT expression at the cell membrane. Decreases phosphorylation;
FT when associated with A-721; A-801; A-831 and A-943."
FT /evidence="ECO:0000269|PubMed:15692563,
FT ECO:0000269|PubMed:16551655"
FT MUTAGEN 812
FT /note="S->D: No effect on interaction with PACS1."
FT /evidence="ECO:0000269|PubMed:15692563"
FT MUTAGEN 815..817
FT /note="DDD->AAA: Strongly decreases interaction with PACS1
FT and enhances expression at the cell membrane."
FT /evidence="ECO:0000269|PubMed:15692563"
FT MUTAGEN 829
FT /note="S->A: Abolishes increased channel opening in
FT response to cAMP and phosphorylation by PKA."
FT /evidence="ECO:0000269|PubMed:26269590"
FT MUTAGEN 831
FT /note="S->A: Decreases phosphorylation; when associated
FT with A-721; A-801; A-812 and A-943."
FT /evidence="ECO:0000269|PubMed:16551655"
FT MUTAGEN 842
FT /note="L->A: Abolishes oligomerization and interaction with
FT PKD1; when associated with A-846; A-849; A-860; A-863 and
FT A-867."
FT /evidence="ECO:0000269|PubMed:19556541"
FT MUTAGEN 842
FT /note="L->P: Loss of protein solubility."
FT /evidence="ECO:0000269|PubMed:18694932"
FT MUTAGEN 846
FT /note="V->A: Abolishes oligomerization and interaction with
FT PKD1; when associated with A-842; A-849; A-860; A-863 and
FT A-867."
FT /evidence="ECO:0000269|PubMed:19556541"
FT MUTAGEN 846
FT /note="V->E: Loss of protein solubility."
FT /evidence="ECO:0000269|PubMed:18694932"
FT MUTAGEN 849
FT /note="M->A: Abolishes oligomerization and interaction with
FT PKD1; when associated with A-842; A-846; A-860; A-863 and
FT A-867."
FT /evidence="ECO:0000269|PubMed:19556541"
FT MUTAGEN 849
FT /note="M->K: Loss of protein solubility."
FT /evidence="ECO:0000269|PubMed:18694932"
FT MUTAGEN 853
FT /note="I->P: Loss of protein solubility."
FT /evidence="ECO:0000269|PubMed:18694932"
FT MUTAGEN 856
FT /note="I->K: Loss of protein solubility."
FT /evidence="ECO:0000269|PubMed:18694932"
FT MUTAGEN 860
FT /note="I->A: Abolishes oligomerization and interaction with
FT PKD1; when associated with A-842; A-846; A-849; A-863 and
FT A-867."
FT /evidence="ECO:0000269|PubMed:19556541"
FT MUTAGEN 863
FT /note="V->A: Abolishes oligomerization and interaction with
FT PKD1; when associated with A-842; A-846; A-849; A-860 and
FT A-867."
FT /evidence="ECO:0000269|PubMed:19556541"
FT MUTAGEN 863
FT /note="V->E: Loss of protein solubility; when associated
FT with K-849."
FT /evidence="ECO:0000269|PubMed:18694932"
FT MUTAGEN 867
FT /note="L->A: Abolishes oligomerization and interaction with
FT PKD1; when associated with A-842; A-846; A-849; A-860 and
FT A-863."
FT /evidence="ECO:0000269|PubMed:19556541"
FT MUTAGEN 943
FT /note="S->A: Decreases phosphorylation; when associated
FT with A-721; A-801; A-812 and A-831."
FT /evidence="ECO:0000269|PubMed:16551655"
FT CONFLICT 45
FT /note="G -> R (in Ref. 2; AAC16004)"
FT /evidence="ECO:0000305"
FT CONFLICT 449
FT /note="G -> V (in Ref. 4; AAC50933)"
FT /evidence="ECO:0000305"
FT HELIX 214..241
FT /evidence="ECO:0007829|PDB:6T9N"
FT HELIX 247..257
FT /evidence="ECO:0007829|PDB:6T9N"
FT HELIX 270..272
FT /evidence="ECO:0007829|PDB:6WB8"
FT HELIX 276..284
FT /evidence="ECO:0007829|PDB:6T9N"
FT HELIX 286..291
FT /evidence="ECO:0007829|PDB:6T9N"
FT STRAND 304..306
FT /evidence="ECO:0007829|PDB:5T4D"
FT TURN 310..312
FT /evidence="ECO:0007829|PDB:6T9N"
FT STRAND 313..315
FT /evidence="ECO:0007829|PDB:6T9N"
FT STRAND 320..326
FT /evidence="ECO:0007829|PDB:6T9N"
FT HELIX 328..330
FT /evidence="ECO:0007829|PDB:5T4D"
FT HELIX 335..337
FT /evidence="ECO:0007829|PDB:6T9N"
FT TURN 338..340
FT /evidence="ECO:0007829|PDB:6T9N"
FT TURN 350..352
FT /evidence="ECO:0007829|PDB:5T4D"
FT STRAND 363..367
FT /evidence="ECO:0007829|PDB:6T9N"
FT TURN 371..375
FT /evidence="ECO:0007829|PDB:6T9N"
FT STRAND 382..386
FT /evidence="ECO:0007829|PDB:6T9O"
FT STRAND 390..394
FT /evidence="ECO:0007829|PDB:6T9N"
FT HELIX 399..411
FT /evidence="ECO:0007829|PDB:6T9N"
FT STRAND 419..430
FT /evidence="ECO:0007829|PDB:6T9N"
FT TURN 431..434
FT /evidence="ECO:0007829|PDB:6T9N"
FT STRAND 435..444
FT /evidence="ECO:0007829|PDB:6T9N"
FT STRAND 452..460
FT /evidence="ECO:0007829|PDB:6T9N"
FT HELIX 468..495
FT /evidence="ECO:0007829|PDB:6T9N"
FT TURN 500..503
FT /evidence="ECO:0007829|PDB:6T9N"
FT STRAND 504..506
FT /evidence="ECO:0007829|PDB:6T9N"
FT HELIX 507..527
FT /evidence="ECO:0007829|PDB:6T9N"
FT TURN 528..530
FT /evidence="ECO:0007829|PDB:6T9N"
FT HELIX 533..538
FT /evidence="ECO:0007829|PDB:6T9N"
FT HELIX 549..572
FT /evidence="ECO:0007829|PDB:6T9N"
FT HELIX 573..575
FT /evidence="ECO:0007829|PDB:6T9N"
FT HELIX 581..619
FT /evidence="ECO:0007829|PDB:6T9N"
FT TURN 620..622
FT /evidence="ECO:0007829|PDB:6T9N"
FT HELIX 624..626
FT /evidence="ECO:0007829|PDB:6T9N"
FT HELIX 629..641
FT /evidence="ECO:0007829|PDB:6T9N"
FT HELIX 646..652
FT /evidence="ECO:0007829|PDB:6T9N"
FT HELIX 656..667
FT /evidence="ECO:0007829|PDB:6T9N"
FT HELIX 668..672
FT /evidence="ECO:0007829|PDB:6T9N"
FT HELIX 673..697
FT /evidence="ECO:0007829|PDB:6T9N"
FT TURN 730..734
FT /evidence="ECO:0007829|PDB:2KLD"
FT HELIX 738..744
FT /evidence="ECO:0007829|PDB:2KLD"
FT TURN 745..747
FT /evidence="ECO:0007829|PDB:2KLD"
FT HELIX 752..762
FT /evidence="ECO:0007829|PDB:2KLD"
FT STRAND 763..766
FT /evidence="ECO:0007829|PDB:2KLD"
FT STRAND 767..771
FT /evidence="ECO:0007829|PDB:2Y4Q"
FT HELIX 773..777
FT /evidence="ECO:0007829|PDB:2KLD"
FT TURN 781..783
FT /evidence="ECO:0007829|PDB:2KLD"
FT STRAND 793..795
FT /evidence="ECO:0007829|PDB:2KQ6"
FT HELIX 836..894
FT /evidence="ECO:0007829|PDB:3HRN"
SQ SEQUENCE 968 AA; 109691 MW; F8D2E760EBEA8B47 CRC64;
MVNSSRVQPQ QPGDAKRPPA PRAPDPGRLM AGCAAVGASL AAPGGLCEQR GLEIEMQRIR
QAAARDPPAG AAASPSPPLS SCSRQAWSRD NPGFEAEEEE EEVEGEEGGM VVEMDVEWRP
GSRRSAASSA VSSVGARSRG LGGYHGAGHP SGRRRRREDQ GPPCPSPVGG GDPLHRHLPL
EGQPPRVAWA ERLVRGLRGL WGTRLMEESS TNREKYLKSV LRELVTYLLF LIVLCILTYG
MMSSNVYYYT RMMSQLFLDT PVSKTEKTNF KTLSSMEDFW KFTEGSLLDG LYWKMQPSNQ
TEADNRSFIF YENLLLGVPR IRQLRVRNGS CSIPQDLRDE IKECYDVYSV SSEDRAPFGP
RNGTAWIYTS EKDLNGSSHW GIIATYSGAG YYLDLSRTRE ETAAQVASLK KNVWLDRGTR
ATFIDFSVYN ANINLFCVVR LLVEFPATGG VIPSWQFQPL KLIRYVTTFD FFLAACEIIF
CFFIFYYVVE EILEIRIHKL HYFRSFWNCL DVVIVVLSVV AIGINIYRTS NVEVLLQFLE
DQNTFPNFEH LAYWQIQFNN IAAVTVFFVW IKLFKFINFN RTMSQLSTTM SRCAKDLFGF
AIMFFIIFLA YAQLAYLVFG TQVDDFSTFQ ECIFTQFRII LGDINFAEIE EANRVLGPIY
FTTFVFFMFF ILLNMFLAII NDTYSEVKSD LAQQKAEMEL SDLIRKGYHK ALVKLKLKKN
TVDDISESLR QGGGKLNFDE LRQDLKGKGH TDAEIEAIFT KYDQDGDQEL TEHEHQQMRD
DLEKEREDLD LDHSSLPRPM SSRSFPRSLD DSEEDDDEDS GHSSRRRGSI SSGVSYEEFQ
VLVRRVDRME HSIGSIVSKI DAVIVKLEIM ERAKLKRREV LGRLLDGVAE DERLGRDSEI
HREQMERLVR EELERWESDD AASQISHGLG TPVGLNGQPR PRSSRPSSSQ STEGMEGAGG
NGSSNVHV
//
