ID PKD2_MOUSE Reviewed; 966 AA. AC O35245; C0KJK2; E9Q4F6; E9QQA3; Q8BPR6; Q9ES37; Q9QWP0; Q9Z193; Q9Z194; DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot. DT 27-JUL-2011, sequence version 2. DT 27-MAR-2024, entry version 199. DE RecName: Full=Polycystin-2; DE AltName: Full=Polycystic kidney disease 2 protein homolog; DE AltName: Full=Transient receptor potential cation channel subfamily P member 2 {ECO:0000312|MGI:MGI:1099818}; GN Name=Pkd2 {ECO:0000312|MGI:MGI:1099818}; GN Synonyms=TRPP2 {ECO:0000303|PubMed:27214281, GN ECO:0000312|MGI:MGI:1099818}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=9339380; DOI=10.1006/geno.1997.4920; RA Wu G.Q., Mochizuki T., Le T.C., Cai Y., Hayashi T., Reynolds D.M., RA Somlo S.; RT "Molecular cloning, cDNA sequence analysis, and chromosomal localization of RT mouse Pkd2."; RL Genomics 45:220-223(1997). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), AND TISSUE RP SPECIFICITY. RX PubMed=9716661; DOI=10.1007/s003359900857; RA Pennekamp P., Bogdanova N., Wilda M., Markoff A., Hameister H., Horst J., RA Dworniczak B.; RT "Characterization of the murine polycystic kidney disease (Pkd2) gene."; RL Mamm. Genome 9:749-752(1998). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), ALTERNATIVE SPLICING (ISOFORMS 2; RP 3; 4 AND 5), LACK OF INTERACTION OF ISOFORM 3 WITH PKD1, AND TISSUE RP SPECIFICITY. 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC STRAIN=C57BL/6J; TISSUE=Eye; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-95. RC STRAIN=129/Ola; RX PubMed=10873385; DOI=10.1006/geno.2000.6197; RA Park J.H., Li L., Cai Y., Hayashi T., Dong F., Maeda Y., Rubin C., RA Somlo S., Wu G.; RT "Cloning and characterization of the murine pkd2 promoter."; RL Genomics 66:305-312(2000). RN [7] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND RP FUNCTION. RX PubMed=9568711; DOI=10.1016/s0092-8674(00)81570-6; RA Wu G., D'Agati V., Cai Y., Markowitz G., Park J.H., Reynolds D.M., RA Maeda Y., Le T.C., Hou H. Jr., Kucherlapati R., Edelmann W., Somlo S.; RT "Somatic inactivation of Pkd2 results in polycystic kidney disease."; RL Cell 93:177-188(1998). RN [8] 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 [9] 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 [10] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=10615132; DOI=10.1038/71724; RA Wu G., Markowitz G.S., Li L., D'Agati V.D., Factor S.M., Geng L., RA Tibara S., Tuchman J., Cai Y., Park J.H., van Adelsberg J., Hou H. Jr., RA Kucherlapati R., Edelmann W., Somlo S.; RT "Cardiac defects and renal failure in mice with targeted mutations in RT Pkd2."; RL Nat. Genet. 24:75-78(2000). RN [11] RP INTERACTION WITH HAX1. 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 [12] RP DISRUPTION PHENOTYPE, AND FUNCTION. RX PubMed=12062060; DOI=10.1016/s0960-9822(02)00869-2; RA Pennekamp P., Karcher C., Fischer A., Schweickert A., Skryabin B., RA Horst J., Blum M., Dworniczak B.; RT "The ion channel polycystin-2 is required for left-right axis determination RT in mice."; RL Curr. Biol. 12:938-943(2002). RN [13] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND GLYCOSYLATION. 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 [14] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=12514735; DOI=10.1038/ng1076; RA Nauli S.M., Alenghat F.J., Luo Y., Williams E., Vassilev P., Li X., RA Elia A.E., Lu W., Brown E.M., Quinn S.J., Ingber D.E., Zhou J.; RT "Polycystins 1 and 2 mediate mechanosensation in the primary cilium of RT kidney cells."; RL Nat. Genet. 33:129-137(2003). RN [15] RP INTERACTION WITH PACS1. 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 [16] RP PHOSPHORYLATION, AND SUBCELLULAR LOCATION. 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 [17] RP INTERACTION WITH NEK8. RX PubMed=18235101; DOI=10.1681/asn.2006090985; RA Sohara E., Luo Y., Zhang J., Manning D.K., Beier D.R., Zhou J.; RT "Nek8 regulates the expression and localization of polycystin-1 and RT polycystin-2."; RL J. Am. Soc. Nephrol. 19:469-476(2008). RN [18] 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 [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-806; SER-810 AND SER-827, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brown adipose tissue, Kidney, Lung, Pancreas, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [20] RP FUNCTION AS REGULATOR OF CILIUM LENGTH. RX PubMed=20096584; DOI=10.1016/j.cub.2009.11.072; RA Besschetnova T.Y., Kolpakova-Hart E., Guan Y., Zhou J., Olsen B.R., RA Shah J.V.; RT "Identification of signaling pathways regulating primary cilium length and RT flow-mediated adaptation."; RL Curr. Biol. 20:182-187(2010). RN [21] RP INTERACTION WITH AKAP5; ADCY5; ADCY6 AND PDE4C. RX PubMed=21670265; DOI=10.1073/pnas.1016214108; RA Choi Y.H., Suzuki A., Hajarnis S., Ma Z., Chapin H.C., Caplan M.J., RA Pontoglio M., Somlo S., Igarashi P.; RT "Polycystin-2 and phosphodiesterase 4C are components of a ciliary A-kinase RT anchoring protein complex that is disrupted in cystic kidney diseases."; RL Proc. Natl. Acad. Sci. U.S.A. 108:10679-10684(2011). RN [22] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PKD1L1, MUTAGENESIS OF RP GLU-442, AND TISSUE SPECIFICITY. RX PubMed=21307093; DOI=10.1242/dev.058149; RA Field S., Riley K.L., Grimes D.T., Hilton H., Simon M., Powles-Glover N., RA Siggers P., Bogani D., Greenfield A., Norris D.P.; RT "Pkd1l1 establishes left-right asymmetry and physically interacts with RT Pkd2."; RL Development 138:1131-1142(2011). RN [23] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PKD1L1, MUTAGENESIS OF RP ARG-6; GLU-442; ASP-509 AND 819-GLY--ALA-966, AND DEVELOPMENTAL STAGE. RX PubMed=22983710; DOI=10.1126/science.1222538; RA Yoshiba S., Shiratori H., Kuo I.Y., Kawasumi A., Shinohara K., Nonaka S., RA Asai Y., Sasaki G., Belo J.A., Sasaki H., Nakai J., Dworniczak B., RA Ehrlich B.E., Pennekamp P., Hamada H.; RT "Cilia at the node of mouse embryos sense fluid flow for left-right RT determination via Pkd2."; RL Science 338:226-231(2012). RN [24] RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-135, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryo; RX PubMed=24129315; DOI=10.1074/mcp.o113.027870; RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M., RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V., RA Bedford M.T., Comb M.J.; RT "Immunoaffinity enrichment and mass spectrometry analysis of protein RT methylation."; RL Mol. Cell. Proteomics 13:372-387(2014). RN [25] RP SUBCELLULAR LOCATION, AND INTERACTION WITH PKD1. RX PubMed=25405894; DOI=10.1038/ncomms6482; RA Kim H., Xu H., Yao Q., Li W., Huang Q., Outeda P., Cebotaru V., RA Chiaravalli M., Boletta A., Piontek K., Germino G.G., Weinman E.J., RA Watnick T., Qian F.; RT "Ciliary membrane proteins traffic through the Golgi via a RT Rabep1/GGA1/Arl3-dependent mechanism."; RL Nat. Commun. 5:5482-5482(2014). RN [26] RP FUNCTION, AND SUBCELLULAR LOCATION. 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 [27] RP FUNCTION, SUBCELLULAR LOCATION, AND ACTIVITY REGULATION. RX PubMed=27760766; DOI=10.1152/ajprenal.00272.2016; RA Kleene S.J., Kleene N.K.; RT "The native TRPP2-dependent channel of murine renal primary cilia."; RL Am. J. Physiol. 312:F96-F108(2017). RN [28] RP FUNCTION, AND INTERACTION WITH TMEM33. RX PubMed=31048699; DOI=10.1038/s41467-019-10045-y; RA Arhatte M., Gunaratne G.S., El Boustany C., Kuo I.Y., Moro C., Duprat F., RA Plaisant M., Duval H., Li D., Picard N., Couvreux A., Duranton C., RA Rubera I., Pagnotta S., Lacas-Gervais S., Ehrlich B.E., Marchant J.S., RA Savage A.M., van Eeden F.J.M., Wilkinson R.N., Demolombe S., Honore E., RA Patel A.; RT "TMEM33 regulates intracellular calcium homeostasis in renal tubular RT epithelial cells."; RL Nat. Commun. 10:2024-2024(2019). 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. Can also form a CC functional, homotetrameric ion channel (PubMed:27214281). Functions as CC a cation channel involved in fluid-flow mechanosensation by the primary CC cilium in renal epithelium (PubMed:12514735, PubMed:18695040, CC PubMed:27760766, PubMed:31048699). Functions as outward-rectifying K(+) CC channel, but is also permeable to Ca(2+), and to a much lesser degree CC also to Na(+) (PubMed:27760766). May contribute to the release of CC Ca(2+) stores from the endoplasmic reticulum (By similarity). Together CC with TRPV4, forms mechano- and thermosensitive channels in cilium CC (PubMed:18695040). PKD1 and PKD2 may function through a common CC signaling pathway that is necessary to maintain the normal, CC differentiated state of renal tubule cells (PubMed:9568711, CC PubMed:10615132). Acts as a regulator of cilium length, together with CC PKD1. The dynamic control of cilium length is essential in the CC regulation of mechanotransductive signaling. The cilium length response CC creates a negative feedback loop whereby fluid shear-mediated CC deflection of the primary cilium, which decreases intracellular cAMP, CC leads to cilium shortening and thus decreases flow-induced signaling CC (PubMed:20096584). Also involved in left-right axis specification via CC its role in sensing nodal flow; forms a complex with PKD1L1 in cilia to CC facilitate flow detection in left-right patterning (PubMed:21307093, CC PubMed:22983710). 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 CC (PubMed:12062060, PubMed:21307093, PubMed:22983710). CC {ECO:0000250|UniProtKB:Q13563, ECO:0000269|PubMed:12062060, CC ECO:0000269|PubMed:12514735, ECO:0000269|PubMed:18695040, CC ECO:0000269|PubMed:20096584, ECO:0000269|PubMed:21307093, CC ECO:0000269|PubMed:22983710, ECO:0000269|PubMed:27214281, CC ECO:0000269|PubMed:27760766, ECO:0000269|PubMed:31048699, CC ECO:0000305|PubMed:10615132, ECO:0000305|PubMed:9568711}. CC -!- ACTIVITY REGULATION: Channel activity is regulated by phosphorylation CC (By similarity). The channel is activated by increased cytoplasmic CC Ca(2+) (in the uM range) and by membrane depolarization CC (PubMed:27760766). {ECO:0000250|UniProtKB:Q13563, CC ECO:0000269|PubMed:27760766}. CC -!- SUBUNIT: Component of the heterotetrameric polycystin channel complex CC with PKD1; the tetramer contains one PKD1 chain and three PKD2 chains CC (By similarity). Interaction with PKD1 is required for ciliary CC localization (PubMed:25405894). Homotetramer (By similarity). Isoform 1 CC interacts with PKD1 while isoform 3 does not (PubMed:16192288). CC Interacts with PKD1L1 (PubMed:21307093, PubMed:22983710). PKD1 requires CC the presence of PKD2 for stable expression (PubMed:16192288). Interacts CC with CD2AP (PubMed:10913159). Interacts with HAX1 (PubMed:10760273). CC Interacts with NEK8 (PubMed:18235101). Part of a complex containing CC AKAP5, ADCY5, ADCY6 and PDE4C (PubMed:21670265). Interacts (via C- CC terminus) with TRPV4 (via C-terminus) (PubMed:18695040). Interacts (via CC C-terminal acidic region) with PACS1 and PACS2; these interactions CC retain the protein in the endoplasmic reticulum and prevent trafficking CC to the cell membrane (PubMed:15692563). Interacts with TMEM33 CC (PubMed:31048699). {ECO:0000250|UniProtKB:Q13563, CC ECO:0000269|PubMed:10760273, ECO:0000269|PubMed:10913159, CC ECO:0000269|PubMed:15692563, ECO:0000269|PubMed:16192288, CC ECO:0000269|PubMed:18235101, ECO:0000269|PubMed:18695040, CC ECO:0000269|PubMed:21307093, ECO:0000269|PubMed:21670265, CC ECO:0000269|PubMed:25405894, ECO:0000269|PubMed:31048699}. CC -!- INTERACTION: CC O35245; E2JF22: Piezo1; NbExp=3; IntAct=EBI-9823400, EBI-9837938; CC -!- SUBCELLULAR LOCATION: Cell projection, cilium membrane CC {ECO:0000269|PubMed:12514735, ECO:0000269|PubMed:18695040, CC ECO:0000269|PubMed:21307093, ECO:0000269|PubMed:22983710, CC ECO:0000269|PubMed:25405894, ECO:0000269|PubMed:27760766}; Multi-pass CC membrane protein {ECO:0000250|UniProtKB:Q13563}. Cell membrane CC {ECO:0000269|PubMed:16551655, ECO:0000269|PubMed:27214281}; Multi-pass CC membrane protein {ECO:0000250|UniProtKB:Q13563}. Basolateral cell CC membrane {ECO:0000269|PubMed:10770959, ECO:0000269|PubMed:9568711}; CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q13563}. Cytoplasmic CC vesicle membrane {ECO:0000269|PubMed:10770959, CC ECO:0000269|PubMed:16551655, ECO:0000269|PubMed:9568711}. Endoplasmic CC reticulum membrane {ECO:0000269|PubMed:11854751, CC ECO:0000269|PubMed:25405894, ECO:0000305|PubMed:10913159}. Golgi CC apparatus {ECO:0000269|PubMed:25405894}. Vesicle CC {ECO:0000250|UniProtKB:Q13563}. Secreted, extracellular exosome CC {ECO:0000250|UniProtKB:Q13563}. Note=PKD2 localization to the plasma CC and ciliary membranes requires PKD1. PKD1:PKD2 interaction is required CC to reach the Golgi apparatus form endoplasmic reticulum and then CC traffic to the cilia (PubMed:25405894). Detected on kidney tubule CC basolateral membranes and basal cytoplasmic vesicles (PubMed:9568711, CC PubMed:10770959). Retained in the endoplasmic reticulum by interaction CC with PACS1 and PACS2. Cilium localization requires GANAB (By CC similarity). Detected on migrasomes and on extracellular exosomes in CC urine (By similarity). {ECO:0000250|UniProtKB:Q13563, CC ECO:0000269|PubMed:10770959, ECO:0000269|PubMed:25405894, CC ECO:0000269|PubMed:9568711}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=5; CC Name=1; CC IsoId=O35245-1; Sequence=Displayed; CC Name=2; Synonyms=delta6; CC IsoId=O35245-2; Sequence=VSP_042485, VSP_042486; CC Name=3; Synonyms=delta7; CC IsoId=O35245-3; Sequence=VSP_042487; CC Name=4; Synonyms=delta9; CC IsoId=O35245-4; Sequence=VSP_042488, VSP_042489; CC Name=5; Synonyms=delta12/13; CC IsoId=O35245-5; Sequence=VSP_042490; CC -!- TISSUE SPECIFICITY: Detected in kidney epithelium (at protein level) CC (PubMed:9568711, PubMed:10770959, PubMed:11854751). Highly expressed on CC basolateral membranes in distal convoluted tubules and medullary thick CC ascending limbs of Henle (PubMed:9568711). Detected at much lower CC levels in cortical and medullary collecting tubules, and not detected CC in the glomerular tuft, in thin limbs of Henle, interstitium and blood CC vessels (at protein level) (PubMed:9568711). Expressed in mesenchymally CC derived structures in the developing embryo at day 12.5. Isoform 1 is CC predominantly expressed in kidney at all developmental stages with high CC levels also detected in lung. Isoform 3 shows highest expression in CC brain with lower expression in kidney and lung, low levels in thymus CC and is hardly detectable in liver. {ECO:0000269|PubMed:10770959, CC ECO:0000269|PubMed:11854751, ECO:0000269|PubMed:16192288, CC ECO:0000269|PubMed:21307093, ECO:0000269|PubMed:9568711, CC ECO:0000269|PubMed:9716661}. CC -!- DEVELOPMENTAL STAGE: Ubiquitous in embryos at the early somite stage. CC {ECO:0000269|PubMed:22983710}. CC -!- DOMAIN: The C-terminal coiled-coil domain is involved in CC oligomerization and the interaction with PKD1. The isolated coiled-coil CC domain forms a homotrimer in vitro; the homotrimer interacts with a CC single PKD1 chain. The coiled-coil domain binds calcium and undergoes a CC calcium-induced conformation change (in vitro). CC {ECO:0000250|UniProtKB:Q13563}. CC -!- PTM: N-glycosylated (PubMed:11854751). The four subunits in a tetramer CC probably differ in the extent of glycosylation; simultaneous CC glycosylation of all experimentally validated sites would probably CC create steric hindrance (By similarity). {ECO:0000250|UniProtKB:Q13563, CC ECO:0000269|PubMed:11854751}. CC -!- PTM: Phosphorylated (PubMed:16551655). Phosphorylation is important for CC protein function; a mutant that lacks the N-terminal phosphorylation CC sites cannot complement a zebrafish pkd2-deficient mutant. PKD-mediated CC phosphorylation at the C-terminus regulates its function in the release CC of Ca(2+) stores from the endoplasmic reticulum. PKA-mediated CC phosphorylation at a C-terminal site strongly increases the open CC probability of the channel, but does not increase single channel CC conductance. {ECO:0000250|UniProtKB:Q13563, CC ECO:0000269|PubMed:16551655}. CC -!- DISRUPTION PHENOTYPE: Complete embryonic lethality, with most embryos CC surviving up to about 16.5 dpc (PubMed:9568711, PubMed:10615132, CC PubMed:12062060). Embryos lacking Pkd2 develop normally up to 13.5 dpc, CC but after that about half of them display total body edema and focal CC hemorrhages (PubMed:10615132). Mutant embryos display defects in left- CC right laterality, including abnormal heart looping (PubMed:12062060). CC After 13.5 dpc, all embryos display defects in heart development, with CC defective formation of the interventricular septum (PubMed:10615132, CC PubMed:12062060). Besides, many display defective formation of the CC atrial septum and pericardial effusions (PubMed:10615132). After 14.5 CC dpc, the embryos display progressive cystic dilatation of pancreatic CC ducts (PubMed:10615132). After 15.5 dpc, they display progressive CC kidney cyst formation (PubMed:10615132). In contrast, liver development CC is normal, without any cyst formation (PubMed:10615132). Heterozygous CC mice with one null allele and one instable allele that leads to somatic CC loss of Pkd2 expression due to intragenic recombination all display CC bilateral renal cysts at an age of about 11 weeks (PubMed:9568711). CC These cysts cover 25-75% of the cut surface area of each kidney CC (PubMed:9568711). Progressive cyst formation leads eventually to renal CC failure and shortened lifespan (PubMed:10615132). Besides, these mice CC all display liver cysts and half of them display also bile duct CC proliferation (PubMed:9568711). About half of the heterozygous mice CC with one null allele and one instable allele that leads to somatic loss CC of Pkd2 expression due to intragenic recombination display visible CC pancreas cysts at an age of three months (PubMed:10615132). Mice CC homozygous for an instable allele that leads to somatic loss of Pkd2 CC expression due to intragenic recombination develop renal cysts that CC arise from cells that have lost Pkd2 expression (PubMed:9568711). CC Heterozygous mice that bear one null allele also have a reduced CC lifespan, but this is not due to kidney failure (PubMed:10615132). CC {ECO:0000269|PubMed:10615132, ECO:0000269|PubMed:12062060, CC ECO:0000269|PubMed:9568711}. CC -!- MISCELLANEOUS: [Isoform 5]: Minor isoform. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the polycystin family. {ECO:0000305}. 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; AF014010; AAC53388.1; -; mRNA. DR EMBL; Y13278; CAA73727.1; -; mRNA. DR EMBL; Y14105; CAA74551.1; -; Genomic_DNA. DR EMBL; Y14106; CAA74551.1; JOINED; Genomic_DNA. DR EMBL; Y14107; CAA74551.1; JOINED; Genomic_DNA. DR EMBL; Y14108; CAA74551.1; JOINED; Genomic_DNA. DR EMBL; Y14109; CAA74551.1; JOINED; Genomic_DNA. DR EMBL; Y14110; CAA74551.1; JOINED; Genomic_DNA. DR EMBL; Y14111; CAA74551.1; JOINED; Genomic_DNA. DR EMBL; Y14112; CAA74551.1; JOINED; Genomic_DNA. DR EMBL; Y14113; CAA74551.1; JOINED; Genomic_DNA. DR EMBL; Y14114; CAA74551.1; JOINED; Genomic_DNA. DR EMBL; Y14115; CAA74551.1; JOINED; Genomic_DNA. DR EMBL; Y14116; CAA74551.1; JOINED; Genomic_DNA. DR EMBL; Y14117; CAA74551.1; JOINED; Genomic_DNA. DR EMBL; Y14118; CAA74551.1; JOINED; Genomic_DNA. DR EMBL; Y14119; CAA74551.1; JOINED; Genomic_DNA. DR EMBL; Y14120; CAA74552.1; -; mRNA. DR EMBL; FJ609779; ACN11624.1; -; mRNA. DR EMBL; AK053502; BAC35407.1; -; mRNA. DR EMBL; AC123687; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC124106; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AF242389; AAG13267.1; -; Genomic_DNA. DR CCDS; CCDS19487.1; -. [O35245-1] DR RefSeq; NP_032887.3; NM_008861.3. [O35245-1] DR RefSeq; XP_006534878.1; XM_006534815.3. [O35245-3] DR AlphaFoldDB; O35245; -. DR SMR; O35245; -. DR BioGRID; 202205; 17. DR ComplexPortal; CPX-4041; PKD1-PKD2 Polycystin complex. DR CORUM; O35245; -. DR DIP; DIP-60904N; -. DR IntAct; O35245; 5. DR MINT; O35245; -. DR STRING; 10090.ENSMUSP00000084041; -. DR GlyCosmos; O35245; 5 sites, No reported glycans. DR GlyGen; O35245; 5 sites. DR iPTMnet; O35245; -. DR PhosphoSitePlus; O35245; -. DR MaxQB; O35245; -. DR PaxDb; 10090-ENSMUSP00000084041; -. DR PeptideAtlas; O35245; -. DR ProteomicsDB; 288216; -. [O35245-1] DR ProteomicsDB; 288217; -. [O35245-2] DR ProteomicsDB; 288218; -. [O35245-3] DR ProteomicsDB; 288219; -. [O35245-4] DR ProteomicsDB; 288220; -. [O35245-5] DR Pumba; O35245; -. DR Antibodypedia; 3871; 389 antibodies from 36 providers. DR DNASU; 18764; -. DR Ensembl; ENSMUST00000086831.4; ENSMUSP00000084041.4; ENSMUSG00000034462.10. [O35245-1] DR GeneID; 18764; -. DR KEGG; mmu:18764; -. DR UCSC; uc012eab.1; mouse. [O35245-1] DR UCSC; uc012eac.1; mouse. [O35245-3] DR AGR; MGI:1099818; -. DR CTD; 5311; -. DR MGI; MGI:1099818; Pkd2. DR VEuPathDB; HostDB:ENSMUSG00000034462; -. DR eggNOG; KOG3599; Eukaryota. DR GeneTree; ENSGT00940000159025; -. DR HOGENOM; CLU_012097_0_0_1; -. DR InParanoid; O35245; -. DR OMA; RHEHRSC; -. DR OrthoDB; 56358at2759; -. DR PhylomeDB; O35245; -. DR TreeFam; TF316484; -. DR Reactome; R-MMU-5620916; VxPx cargo-targeting to cilium. DR BioGRID-ORCS; 18764; 4 hits in 78 CRISPR screens. DR ChiTaRS; Pkd2; mouse. DR PRO; PR:O35245; -. DR Proteomes; UP000000589; Chromosome 5. DR RNAct; O35245; Protein. DR Bgee; ENSMUSG00000034462; Expressed in ciliary body and 274 other cell types or tissues. DR GO; GO:0045180; C:basal cortex; IDA:BHF-UCL. DR GO; GO:0009925; C:basal plasma membrane; ISO:MGI. DR GO; GO:0016323; C:basolateral plasma membrane; IEA:UniProtKB-SubCell. DR GO; GO:0034703; C:cation channel complex; ISS:UniProtKB. DR GO; GO:0036064; C:ciliary basal body; IDA:MGI. DR GO; GO:0060170; C:ciliary membrane; IMP:UniProtKB. DR GO; GO:0005929; C:cilium; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0098554; C:cytoplasmic side of endoplasmic reticulum membrane; ISO:MGI. DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005829; C:cytosol; ISO:MGI. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:MGI. DR GO; GO:0070062; C:extracellular exosome; ISS:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0030027; C:lamellipodium; ISO:MGI. DR GO; GO:0098553; C:lumenal side of endoplasmic reticulum membrane; ISO:MGI. DR GO; GO:0016020; C:membrane; ISO:MGI. DR GO; GO:0140494; C:migrasome; ISS:UniProtKB. DR GO; GO:0072686; C:mitotic spindle; IDA:BHF-UCL. DR GO; GO:0031514; C:motile cilium; IDA:MGI. DR GO; GO:0097730; C:non-motile cilium; IDA:MGI. DR GO; GO:0005886; C:plasma membrane; IDA:MGI. DR GO; GO:0002133; C:polycystin complex; IDA:UniProtKB. DR GO; GO:0042805; F:actinin binding; ISO:MGI. DR GO; GO:0051393; F:alpha-actinin binding; ISO:MGI. DR GO; GO:0051117; F:ATPase binding; IPI:MGI. DR GO; GO:0005262; F:calcium channel activity; IDA:MGI. DR GO; GO:0005509; F:calcium ion binding; IDA:BHF-UCL. DR GO; GO:0048763; F:calcium-induced calcium release activity; ISO:MGI. DR GO; GO:0015267; F:channel activity; IMP:MGI. DR GO; GO:0008092; F:cytoskeletal protein binding; ISO:MGI. DR GO; GO:0043398; F:HLH domain binding; ISO:MGI. DR GO; GO:0042802; F:identical protein binding; IPI:BHF-UCL. DR GO; GO:0005261; F:monoatomic cation channel activity; ISO:MGI. DR GO; GO:0051371; F:muscle alpha-actinin binding; ISO:MGI. DR GO; GO:0015271; F:outward rectifier potassium channel activity; IMP:UniProtKB. DR GO; GO:0051219; F:phosphoprotein binding; ISO:MGI. DR GO; GO:0005267; F:potassium channel activity; IDA:MGI. DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI. DR GO; GO:0005102; F:signaling receptor binding; IPI:MGI. DR GO; GO:0140416; F:transcription regulator inhibitor activity; ISO:MGI. DR GO; GO:0044325; F:transmembrane transporter binding; ISO:MGI. DR GO; GO:0005245; F:voltage-gated calcium channel activity; ISO:MGI. DR GO; GO:0022843; F:voltage-gated monoatomic cation channel activity; ISO:MGI. DR GO; GO:0005244; F:voltage-gated monoatomic ion channel activity; ISO:MGI. DR GO; GO:0005249; F:voltage-gated potassium channel activity; ISO:MGI. DR GO; GO:0005248; F:voltage-gated sodium channel activity; ISO:MGI. DR GO; GO:0035904; P:aorta development; IEA:Ensembl. DR GO; GO:0001658; P:branching involved in ureteric bud morphogenesis; IEA:Ensembl. DR GO; GO:0070588; P:calcium ion transmembrane transport; IMP:UniProtKB. DR GO; GO:0006816; P:calcium ion transport; IDA:ComplexPortal. DR GO; GO:0198738; P:cell-cell signaling by wnt; ISS:UniProtKB. DR GO; GO:0071277; P:cellular response to calcium ion; IMP:UniProtKB. DR GO; GO:0071320; P:cellular response to cAMP; ISO:MGI. DR GO; GO:0071498; P:cellular response to fluid shear stress; IMP:BHF-UCL. DR GO; GO:0071464; P:cellular response to hydrostatic pressure; ISO:MGI. DR GO; GO:0071470; P:cellular response to osmotic stress; ISO:MGI. DR GO; GO:0044782; P:cilium organization; ISO:MGI. DR GO; GO:0050982; P:detection of mechanical stimulus; IMP:MGI. DR GO; GO:0003127; P:detection of nodal flow; IMP:BHF-UCL. DR GO; GO:0007368; P:determination of left/right symmetry; IMP:MGI. DR GO; GO:0071910; P:determination of liver left/right asymmetry; ISO:MGI. DR GO; GO:0001892; P:embryonic placenta development; IMP:BHF-UCL. DR GO; GO:0051649; P:establishment of localization in cell; IMP:MGI. DR GO; GO:0007507; P:heart development; IMP:MGI. DR GO; GO:0001947; P:heart looping; ISO:MGI. DR GO; GO:0098662; P:inorganic cation transmembrane transport; ISO:MGI. DR GO; GO:0006874; P:intracellular calcium ion homeostasis; IMP:MGI. DR GO; GO:0001822; P:kidney development; IMP:MGI. DR GO; GO:0001889; P:liver development; IGI:MGI. DR GO; GO:0072177; P:mesonephric duct development; IEA:Ensembl. DR GO; GO:0072218; P:metanephric ascending thin limb development; IEA:Ensembl. DR GO; GO:0072214; P:metanephric cortex development; IEA:Ensembl. DR GO; GO:0072219; P:metanephric cortical collecting duct development; IEA:Ensembl. DR GO; GO:0072235; P:metanephric distal tubule development; IEA:Ensembl. DR GO; GO:0072075; P:metanephric mesenchyme development; IEA:Ensembl. DR GO; GO:0035502; P:metanephric part of ureteric bud development; IEA:Ensembl. DR GO; GO:0072284; P:metanephric S-shaped body morphogenesis; IEA:Ensembl. DR GO; GO:0072208; P:metanephric smooth muscle tissue development; IEA:Ensembl. DR GO; GO:2000134; P:negative regulation of G1/S transition of mitotic cell cycle; ISO:MGI. DR GO; GO:0021915; P:neural tube development; IEA:Ensembl. DR GO; GO:0060674; P:placenta blood vessel development; IMP:BHF-UCL. DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:MGI. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB. 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; ISO:MGI. DR GO; GO:0071805; P:potassium ion transmembrane transport; IMP:UniProtKB. DR GO; GO:0051290; P:protein heterotetramerization; ISS:UniProtKB. DR GO; GO:0051289; P:protein homotetramerization; ISO:MGI. DR GO; GO:0051262; P:protein tetramerization; ISS:UniProtKB. DR GO; GO:0007259; P:receptor signaling pathway via JAK-STAT; IDA:MGI. DR GO; GO:0090279; P:regulation of calcium ion import; ISO:MGI. DR GO; GO:0051726; P:regulation of cell cycle; IDA:MGI. DR GO; GO:0042127; P:regulation of cell population proliferation; ISO:MGI. DR GO; GO:0051209; P:release of sequestered calcium ion into cytosol; IMP:BHF-UCL. DR GO; GO:0061441; P:renal artery morphogenesis; IEA:Ensembl. DR GO; GO:0061333; P:renal tubule morphogenesis; IMP:UniProtKB. DR GO; GO:0035725; P:sodium ion transmembrane transport; ISO:MGI. DR GO; GO:0021510; P:spinal cord development; IEA:Ensembl. DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW. 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; O35245; MM. PE 1: Evidence at protein level; KW Alternative splicing; Calcium; Calcium channel; Calcium transport; KW Cell membrane; Cell projection; Cilium; Coiled coil; Cytoplasmic vesicle; KW Disulfide bond; Endoplasmic reticulum; Glycoprotein; Golgi apparatus; KW Ion channel; Ion transport; Membrane; Metal-binding; Methylation; KW Phosphoprotein; Potassium; Potassium channel; Potassium transport; KW Reference proteome; Secreted; Transmembrane; Transmembrane helix; KW Transport; Voltage-gated channel; Wnt signaling pathway. FT CHAIN 1..966 FT /note="Polycystin-2" FT /id="PRO_0000164357" FT TOPO_DOM 1..217 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT TRANSMEM 218..239 FT /note="Helical; Name=S1" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT TOPO_DOM 240..466 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT TRANSMEM 467..487 FT /note="Helical; Name=S2" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT TOPO_DOM 488..503 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT TRANSMEM 504..524 FT /note="Helical; Name=S3" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT TOPO_DOM 525..550 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT TRANSMEM 551..571 FT /note="Helical; Name=S4" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT TOPO_DOM 572..595 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT TRANSMEM 596..617 FT /note="Helical; Name=5" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT TOPO_DOM 618..629 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT INTRAMEM 630..644 FT /note="Pore-forming" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT TOPO_DOM 645..652 FT /note="Extracellular" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT TRANSMEM 653..673 FT /note="Helical; Name=S6" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT TOPO_DOM 674..966 FT /note="Cytoplasmic" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT DOMAIN 748..783 FT /note="EF-hand" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT REGION 1..106 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 147..179 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 764..828 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 801..820 FT /note="Linker" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT REGION 808..819 FT /note="Important for interaction with PACS1 and PACS2" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT REGION 914..966 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 831..870 FT /evidence="ECO:0000250|UniProtKB:Q13563" FT MOTIF 639..641 FT /note="Selectivity filter" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT COMPBIAS 90..106 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 764..792 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 761 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT BINDING 763 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT BINDING 765 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT BINDING 767 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT BINDING 772 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT MOD_RES 72 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT MOD_RES 76 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT MOD_RES 135 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0007744|PubMed:24129315" FT MOD_RES 799 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q13563" FT MOD_RES 806 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 810 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT MOD_RES 827 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21183079" FT CARBOHYD 297 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 303 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 326 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 360 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 373 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 329..342 FT /evidence="ECO:0000250|UniProtKB:Q13563" FT VAR_SEQ 474..481 FT /note="CEIIFCFF -> FICSSYGD (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_042485" FT VAR_SEQ 482..966 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_042486" FT VAR_SEQ 515..570 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:16192288" FT /id="VSP_042487" FT VAR_SEQ 631..644 FT /note="IFTQFRIILGDINF -> IICSWRSSMIRTLK (in isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_042488" FT VAR_SEQ 645..966 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000305" FT /id="VSP_042489" FT VAR_SEQ 746..839 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000305" FT /id="VSP_042490" FT MUTAGEN 6 FT /note="R->G: No effect on location at nodal cilia and can FT rescue the laterality defect of null mutants. Abolishes FT location at nodal cilia and cannot complement the FT laterality defect of null mutants; when associated with DEL FT 819-966." FT /evidence="ECO:0000269|PubMed:22983710" FT MUTAGEN 442 FT /note="E->G: In lrm4; mice exhibit gross left-right FT abnormalities. Embryos do not show defects in kidney FT development. The nodes appear normal. Abolishes location at FT nodal cilia, but does not affect interaction with Pkd1l1." FT /evidence="ECO:0000269|PubMed:21307093, FT ECO:0000269|PubMed:22983710" FT MUTAGEN 509 FT /note="D->V: Abolishes location at nodal cilia and cannot FT complement the laterality defect of null mutants." FT /evidence="ECO:0000269|PubMed:22983710" FT MUTAGEN 819..966 FT /note="Missing: Abolishes location at nodal cilia and FT cannot complement the laterality defect of null mutants; FT when associated with G-6." FT /evidence="ECO:0000269|PubMed:22983710" FT CONFLICT 365 FT /note="M -> I (in Ref. 1; AAC53388)" FT /evidence="ECO:0000305" FT CONFLICT 370 FT /note="K -> R (in Ref. 1; AAC53388)" FT /evidence="ECO:0000305" FT CONFLICT 560 FT /note="S -> A (in Ref. 1; AAC53388)" FT /evidence="ECO:0000305" FT CONFLICT 688..689 FT /note="DL -> SV (in Ref. 2; CAA74551)" FT /evidence="ECO:0000305" FT CONFLICT 746 FT /note="K -> E (in Ref. 2; CAA73727/CAA74551 and 3; FT ACN11624)" FT /evidence="ECO:0000305" FT CONFLICT 800 FT /note="S -> N (in Ref. 4; BAC35407)" FT /evidence="ECO:0000305" FT CONFLICT 942 FT /note="P -> S (in Ref. 1; AAC53388)" FT /evidence="ECO:0000305" FT CONFLICT 957 FT /note="G -> S (in Ref. 1; AAC53388)" FT /evidence="ECO:0000305" SQ SEQUENCE 966 AA; 108982 MW; 59B96AB3AE5226D3 CRC64; MVNSRRVQPQ PPGDAGRSPA PRASGPGRLV AGGAGLAVPG GLGEQRGLEI EMERIRQAAA RDPPAGASAS PSPPLSSCSR QAWSRDNPGF EAEEDDDDDE VEGEEGGMVV EMDVEWRPGS RRSASSSAVS SVGARGRGLG SYRGAAHLSG RRRRLEDQGA QCPSPAGGGD PLHRHLPLEG QPPRVAWAER LVRGLRGLWG TRLMEESNAN REKYLKSVLR ELVTYLFFLV VLCILTYGMM SSNVYYYTRT LSQLFIDTPV SKTEKTNFKT LSSMEDFWKF TEGSFLDGLY WKAQTSNHTQ ADNRSFIFYE NLLLGVPRLR QLRVRNGSCS IPQDLRDEIK ECYDVYSVSS EDRAPFGPRN GTAWMYTSEK ELNGSSHWGI IASYSGAGYY LDLSRTREET AAQLAGLRRN FWLDRGTRAA FIDFSVYNAN INLFCVVRLL AEFPATGGVV PSWQFQPVKL IRYVTAFDFF LAACEIIFCF FIIYYVVEEI LEIRIHRLSY FRSFWNCLDV VIVVLSVVAM VINIYRMSNA EGLLQFLEDQ NSFPNFEHVA YWQIQFNNIS AVMVFLVWIK LFKFINFNRT MSQLSTTMSR CAKDLFGFTI MFSIIFLAYA QLAYLVFGTQ VDDFSTFQEC IFTQFRIILG DINFAEIEEA NRVLGPLYFT TFVFFMFFIL LNMFLAIIND SYSEVKSDLA QQKAEMELSD LIRKGCQKAL VKLKLKRNTV DAISESLRQG GGKLNFDELR QDLKGKGHTD AEIEAIFTKY DQDGDQELTE REHQQMRDDL EKEREDLDLE HSSLPRPMSS RSFPRSLDDS EEEDDEDSGH SSRRRGSISS GVSYEEFQVL VRRVDRMEHS IGSIVSKIDA VIVKLEIMER AKLKRREVLG RLLDGVAEDA RLGRDSEIHR EQMERLVREE LERWESDDAA SQTGHGVSTQ VGLGGQPHPR NPRPPSSQSA EGLEGGGGNG SANVHA //