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, GN 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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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 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. DR Genevisible; Q13563; HS. 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 FT gain-of-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 FT gain-of-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 FT pkd2-deficient zebrafish mutant; when associated with FT 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 FT pkd2-deficient zebrafish mutant; when associated with FT 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 //