PKD2_MOUSE
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 03-AUG-2022, entry version 190.
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, 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: Homotetramer. Heterotetramer with PKD1, giving rise to a
CC complex formed by one PKD1 chain and three PKD2 chains (By similarity).
CC Interaction with PKD1 is required for ciliary localization
CC (PubMed:25405894). Isoform 1 interacts with PKD1 while isoform 3 does
CC not (PubMed:16192288). Interacts with PKD1L1 (PubMed:21307093,
CC PubMed:22983710). PKD1 requires the presence of PKD2 for stable
CC expression (PubMed:16192288). Interacts with CD2AP (PubMed:10913159).
CC Interacts with HAX1 (PubMed:10760273). Interacts with NEK8
CC (PubMed:18235101). Part of a complex containing AKAP5, ADCY5, ADCY6 and
CC PDE4C (PubMed:21670265). Interacts (via C-terminus) with TRPV4 (via C-
CC terminus) (PubMed:18695040). Interacts (via C-terminal acidic region)
CC with PACS1 and PACS2; these interactions retain the protein in the
CC endoplasmic reticulum and prevent trafficking to the cell membrane
CC (PubMed:15692563). Interacts with TMEM33 (PubMed:31048699).
CC {ECO:0000250|UniProtKB:Q13563, ECO:0000269|PubMed:10760273,
CC ECO:0000269|PubMed:10913159, ECO:0000269|PubMed:15692563,
CC ECO:0000269|PubMed:16192288, ECO:0000269|PubMed:18235101,
CC ECO:0000269|PubMed:18695040, ECO:0000269|PubMed:21307093,
CC ECO:0000269|PubMed:21670265, ECO:0000269|PubMed:25405894,
CC 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}. Note=PKD2 localization to the
CC plasma and ciliary membranes requires PKD1. PKD1:PKD2 interaction is
CC required to reach the Golgi apparatus form endoplasmic reticulum and
CC then 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). {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 ---------------------------------------------------------------------------
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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; 16.
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 GlyGen; O35245; 5 sites.
DR iPTMnet; O35245; -.
DR PhosphoSitePlus; O35245; -.
DR MaxQB; O35245; -.
DR PaxDb; O35245; -.
DR PeptideAtlas; O35245; -.
DR PRIDE; 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 Antibodypedia; 3871; 344 antibodies from 36 providers.
DR DNASU; 18764; -.
DR Ensembl; ENSMUST00000086831; ENSMUSP00000084041; ENSMUSG00000034462. [O35245-1]
DR GeneID; 18764; -.
DR KEGG; mmu:18764; -.
DR UCSC; uc012eab.1; mouse. [O35245-1]
DR UCSC; uc012eac.1; mouse. [O35245-3]
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; DGLYWDM; -.
DR OrthoDB; 426073at2759; -.
DR PhylomeDB; O35245; -.
DR TreeFam; TF316484; -.
DR Reactome; R-MMU-5620916; VxPx cargo-targeting to cilium.
DR BioGRID-ORCS; 18764; 4 hits in 73 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 272 other tissues.
DR Genevisible; O35245; MM.
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: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:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0071458; C:integral component of cytoplasmic side of endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0071556; C:integral component of lumenal side of endoplasmic reticulum membrane; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; ISO:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
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:0005261; F:cation channel 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: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: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 cation channel activity; ISO:MGI.
DR GO; GO:0005244; F:voltage-gated 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:0006874; P:cellular calcium ion homeostasis; IMP:MGI.
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:0042994; P:cytoplasmic sequestering of transcription factor; 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: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:0060315; P:negative regulation of ryanodine-sensitive calcium-release channel activity; IDA: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:0045737; P:positive regulation of cyclin-dependent protein serine/threonine kinase activity; ISO:MGI.
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:0031587; P:positive regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity; ISO:MGI.
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; 1.20.120.350; -; 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; IPR027359; Volt_channel_dom_sf.
DR Pfam; PF08016; PKD_channel; 1.
DR PRINTS; PR01433; POLYCYSTIN2.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS50222; EF_HAND_2; 1.
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; Transmembrane; Transmembrane helix; Transport;
KW 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
