ID NPHP3_HUMAN Reviewed; 1330 AA. AC Q7Z494; Q5JPE3; Q5JPE6; Q68D99; Q6NVH3; Q7Z492; Q7Z493; Q8N9R2; Q8NCM5; AC Q96N70; Q96NK2; DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2003, sequence version 1. DT 27-MAR-2024, entry version 174. DE RecName: Full=Nephrocystin-3; GN Name=NPHP3; Synonyms=KIAA2000; 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), NUCLEOTIDE SEQUENCE [MRNA] OF RP 117-1330, NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5), NUCLEOTIDE SEQUENCE RP [MRNA] OF 584-1330 (ISOFORM 3), INTERACTION WITH NPHP1, TISSUE SPECIFICITY, RP AND VARIANTS NPHP3 THR-360; SER-386; HIS-397; PRO-1141; VAL-1221; ARG-1252 RP AND THR-1314. RX PubMed=12872122; DOI=10.1038/ng1216; RA Olbrich H., Fliegauf M., Hoefele J., Kispert A., Otto E., Volz A., RA Wolf M.T., Sasmaz G., Trauer U., Reinhardt R., Sudbrak R., Antignac C., RA Gretz N., Walz G., Schermer B., Benzing T., Hildebrandt F., Omran H.; RT "Mutations in a novel gene, NPHP3, cause adolescent nephronophthisis, RT tapeto-retinal degeneration and hepatic fibrosis."; RL Nat. Genet. 34:455-459(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Brain; RX PubMed=12056414; DOI=10.1093/dnares/9.2.47; RA Ohara O., Nagase T., Mitsui G., Kohga H., Kikuno R., Hiraoka S., RA Takahashi Y., Kitajima S., Saga Y., Koseki H.; RT "Characterization of size-fractionated cDNA libraries generated by the in RT vitro recombination-assisted method."; RL DNA Res. 9:47-57(2002). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 319-1330. RC TISSUE=Brain, Mammary gland, and Uterus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), AND NUCLEOTIDE SEQUENCE RP [LARGE SCALE MRNA] OF 555-1330 (ISOFORM 6). RC TISSUE=Fetal kidney, and Lymph node; RX PubMed=17974005; DOI=10.1186/1471-2164-8-399; RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., RA Wiemann S., Schupp I.; RT "The full-ORF clone resource of the German cDNA consortium."; RL BMC Genomics 8:399-399(2007). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7). RC TISSUE=Salivary gland; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP SUBCELLULAR LOCATION. RX PubMed=20462968; DOI=10.1152/ajprenal.00043.2010; RA Zhou W., Dai J., Attanasio M., Hildebrandt F.; RT "Nephrocystin-3 is required for ciliary function in zebrafish embryos."; RL Am. J. Physiol. 299:F55-F62(2010). RN [7] RP MYRISTOYLATION AT GLY-2, INTERACTION WITH UNC119 AND UNC119B, AND RP SUBCELLULAR LOCATION. RX PubMed=22085962; DOI=10.1101/gad.173443.111; RA Wright K.J., Baye L.M., Olivier-Mason A., Mukhopadhyay S., Sang L., RA Kwong M., Wang W., Pretorius P.R., Sheffield V.C., Sengupta P., RA Slusarski D.C., Jackson P.K.; RT "An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary RT cilium."; RL Genes Dev. 25:2347-2360(2011). RN [8] RP INTERACTION WITH CEP164. RX PubMed=22863007; DOI=10.1016/j.cell.2012.06.028; RA Chaki M., Airik R., Ghosh A.K., Giles R.H., Chen R., Slaats G.G., Wang H., RA Hurd T.W., Zhou W., Cluckey A., Gee H.Y., Ramaswami G., Hong C.J., RA Hamilton B.A., Cervenka I., Ganji R.S., Bryja V., Arts H.H., RA van Reeuwijk J., Oud M.M., Letteboer S.J., Roepman R., Husson H., RA Ibraghimov-Beskrovnaya O., Yasunaga T., Walz G., Eley L., Sayer J.A., RA Schermer B., Liebau M.C., Benzing T., Le Corre S., Drummond I., Janssen S., RA Allen S.J., Natarajan S., O'Toole J.F., Attanasio M., Saunier S., RA Antignac C., Koenekoop R.K., Ren H., Lopez I., Nayir A., Stoetzel C., RA Dollfus H., Massoudi R., Gleeson J.G., Andreoli S.P., Doherty D.G., RA Lindstrad A., Golzio C., Katsanis N., Pape L., Abboud E.B., Al-Rajhi A.A., RA Lewis R.A., Omran H., Lee E.Y., Wang S., Sekiguchi J.M., Saunders R., RA Johnson C.A., Garner E., Vanselow K., Andersen J.S., Shlomai J., RA Nurnberg G., Nurnberg P., Levy S., Smogorzewska A., Otto E.A., RA Hildebrandt F.; RT "Exome capture reveals ZNF423 and CEP164 mutations, linking renal RT ciliopathies to DNA damage response signaling."; RL Cell 150:533-548(2012). RN [9] RP INTERACTION WITH NEK8. RX PubMed=23418306; DOI=10.1093/hmg/ddt070; RA Frank V., Habbig S., Bartram M.P., Eisenberger T., Veenstra-Knol H.E., RA Decker C., Boorsma R.A., Goebel H., Nuernberg G., Griessmann A., Franke M., RA Borgal L., Kohli P., Voelker L.A., Doetsch J., Nuernberg P., Benzing T., RA Bolz H.J., Johnson C., Gerkes E.H., Schermer B., Bergmann C.; RT "Mutations in NEK8 link multiple organ dysplasia with altered Hippo RT signalling and increased c-MYC expression."; RL Hum. Mol. Genet. 22:2177-2185(2013). RN [10] RP INTERACTION WITH ANKS6; INVS AND NEK8. RX PubMed=23793029; DOI=10.1038/ng.2681; RA Hoff S., Halbritter J., Epting D., Frank V., Nguyen T.M., van Reeuwijk J., RA Boehlke C., Schell C., Yasunaga T., Helmstadter M., Mergen M., Filhol E., RA Boldt K., Horn N., Ueffing M., Otto E.A., Eisenberger T., Elting M.W., RA van Wijk J.A., Bockenhauer D., Sebire N.J., Rittig S., Vyberg M., Ring T., RA Pohl M., Pape L., Neuhaus T.J., Elshakhs N.A., Koon S.J., Harris P.C., RA Grahammer F., Huber T.B., Kuehn E.W., Kramer-Zucker A., Bolz H.J., RA Roepman R., Saunier S., Walz G., Hildebrandt F., Bergmann C., RA Lienkamp S.S.; RT "ANKS6 is a central component of a nephronophthisis module linking NEK8 to RT INVS and NPHP3."; RL Nat. Genet. 45:951-956(2013). RN [11] RP VARIANT RHPD1 GLN-973, INVOLVEMENT IN MKS7, FUNCTION, AND INTERACTION WITH RP INVS. RX PubMed=18371931; DOI=10.1016/j.ajhg.2008.02.017; RA Bergmann C., Fliegauf M., Bruechle N.O., Frank V., Olbrich H., RA Kirschner J., Schermer B., Schmedding I., Kispert A., Kraenzlin B., RA Nuernberg G., Becker C., Grimm T., Girschick G., Lynch S.A., Kelehan P., RA Senderek J., Neuhaus T.J., Stallmach T., Zentgraf H., Nuernberg P., RA Gretz N., Lo C., Lienkamp S., Schaefer T., Walz G., Benzing T., Zerres K., RA Omran H.; RT "Loss of nephrocystin-3 function can cause embryonic lethality, Meckel- RT Gruber-like syndrome, situs inversus, and renal-hepatic-pancreatic RT dysplasia."; RL Am. J. Hum. Genet. 82:959-970(2008). CC -!- FUNCTION: Required for normal ciliary development and function. CC Inhibits disheveled-1-induced canonical Wnt-signaling activity and may CC also play a role in the control of non-canonical Wnt signaling which CC regulates planar cell polarity. Probably acts as a molecular switch CC between different Wnt signaling pathways. Required for proper CC convergent extension cell movements. {ECO:0000269|PubMed:18371931}. CC -!- SUBUNIT: Interacts with NPHP1 and INVS/NPHP2. Interacts (when CC myristoylated) with UNC119 and UNC119B; interaction is required for CC localization to cilium. Interacts with CEP164. Component of a complex CC containing at least ANKS6, INVS, NEK8 and NPHP3. ANKS6 may organize CC complex assembly by linking INVS and NPHP3 to NEK8 and INVS may target CC the complex to the proximal ciliary axoneme. CC {ECO:0000269|PubMed:12872122, ECO:0000269|PubMed:18371931, CC ECO:0000269|PubMed:22085962, ECO:0000269|PubMed:22863007, CC ECO:0000269|PubMed:23418306, ECO:0000269|PubMed:23793029}. CC -!- INTERACTION: CC Q7Z494; Q9UPV0: CEP164; NbExp=2; IntAct=EBI-2804263, EBI-3937015; CC Q7Z494; Q9Y265: RUVBL1; NbExp=2; IntAct=EBI-2804263, EBI-353675; CC Q7Z494; Q13432: UNC119; NbExp=3; IntAct=EBI-2804263, EBI-711260; CC -!- SUBCELLULAR LOCATION: Cell projection, cilium CC {ECO:0000269|PubMed:20462968, ECO:0000269|PubMed:22085962}. CC Note=Localization to cilium is mediated via interaction with UNC119 and CC UNC119B, which bind to the myristoyl moiety of the N-terminus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=7; CC Comment=Additional isoforms seem to exist.; CC Name=1; CC IsoId=Q7Z494-1; Sequence=Displayed; CC Name=2; CC IsoId=Q7Z494-2; Sequence=VSP_014480, VSP_014481; CC Name=3; CC IsoId=Q7Z494-3; Sequence=VSP_014488, VSP_014489; CC Name=4; CC IsoId=Q7Z494-4; Sequence=VSP_014482, VSP_014483; CC Name=5; CC IsoId=Q7Z494-5; Sequence=VSP_014486, VSP_014487; CC Name=6; CC IsoId=Q7Z494-6; Sequence=VSP_014490, VSP_014491; CC Name=7; CC IsoId=Q7Z494-7; Sequence=VSP_014484, VSP_014485; CC -!- TISSUE SPECIFICITY: Widely expressed at low level. Expressed in heart, CC placenta, liver, skeletal muscle, kidney and pancreas. Expressed at CC very low level in brain and lung. {ECO:0000269|PubMed:12872122}. CC -!- DISEASE: Nephronophthisis 3 (NPHP3) [MIM:604387]: An autosomal CC recessive disorder resulting in end-stage renal disease. It is CC characterized by polyuria, polydipsia, anemia. Onset of terminal renal CC failure occurr significantly later (median age, 19 years) than in CC juvenile nephronophthisis. Renal pathology is characterized by CC alterations of tubular basement membranes, tubular atrophy and CC dilation, sclerosing tubulointerstitial nephropathy, and renal cyst CC development predominantly at the corticomedullary junction. CC {ECO:0000269|PubMed:12872122}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Renal-hepatic-pancreatic dysplasia 1 (RHPD1) [MIM:208540]: A CC disease characterized by cystic malformations of the kidneys, liver, CC and pancreas. The pathological findings consist of multicystic CC dysplastic kidneys, dilated and dysgenetic bile ducts, a dysplastic CC pancreas with dilated ducts, cysts, fibrosis and inflammatory CC infiltrates. {ECO:0000269|PubMed:18371931}. Note=The disease is caused CC by variants affecting the gene represented in this entry. CC -!- DISEASE: Meckel syndrome 7 (MKS7) [MIM:267010]: A disorder CC characterized by a combination of renal cysts and variably associated CC features including developmental anomalies of the central nervous CC system (typically encephalocele), hepatic ductal dysplasia and cysts, CC and polydactyly. {ECO:0000269|PubMed:18371931}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- SEQUENCE CAUTION: CC Sequence=BAB70891.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAC02709.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC Sequence=BAC04268.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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; AY257864; AAP83423.1; -; mRNA. DR EMBL; AY257865; AAP83424.1; -; mRNA. DR EMBL; AY257866; AAP83425.1; -; mRNA. DR EMBL; AB082531; BAC02709.1; ALT_INIT; mRNA. DR EMBL; AK055253; BAB70891.1; ALT_INIT; mRNA. DR EMBL; AK055893; BAB71038.1; -; mRNA. DR EMBL; AK094015; BAC04268.1; ALT_INIT; mRNA. DR EMBL; AL832863; CAI46200.2; -; mRNA. DR EMBL; AL832877; CAI46202.1; -; Transcribed_RNA. DR EMBL; CR749498; CAH18321.1; -; mRNA. DR EMBL; BC068082; AAH68082.1; -; mRNA. DR CCDS; CCDS3078.1; -. [Q7Z494-1] DR RefSeq; NP_694972.3; NM_153240.4. [Q7Z494-1] DR PDB; 5L7K; X-ray; 2.10 A; B=2-7. DR PDBsum; 5L7K; -. DR AlphaFoldDB; Q7Z494; -. DR SMR; Q7Z494; -. DR BioGRID; 117962; 37. DR CORUM; Q7Z494; -. DR IntAct; Q7Z494; 26. DR MINT; Q7Z494; -. DR STRING; 9606.ENSP00000338766; -. DR CarbonylDB; Q7Z494; -. DR iPTMnet; Q7Z494; -. DR PhosphoSitePlus; Q7Z494; -. DR BioMuta; NPHP3; -. DR DMDM; 68565783; -. DR EPD; Q7Z494; -. DR jPOST; Q7Z494; -. DR MassIVE; Q7Z494; -. DR MaxQB; Q7Z494; -. DR PaxDb; 9606-ENSP00000338766; -. DR PeptideAtlas; Q7Z494; -. DR ProteomicsDB; 69163; -. [Q7Z494-1] DR ProteomicsDB; 69164; -. [Q7Z494-2] DR ProteomicsDB; 69165; -. [Q7Z494-3] DR ProteomicsDB; 69166; -. [Q7Z494-4] DR ProteomicsDB; 69167; -. [Q7Z494-5] DR ProteomicsDB; 69168; -. [Q7Z494-6] DR ProteomicsDB; 69169; -. [Q7Z494-7] DR Pumba; Q7Z494; -. DR Antibodypedia; 2070; 130 antibodies from 23 providers. DR DNASU; 27031; -. DR Ensembl; ENST00000337331.10; ENSP00000338766.5; ENSG00000113971.21. [Q7Z494-1] DR Ensembl; ENST00000383282.3; ENSP00000372769.2; ENSG00000113971.21. [Q7Z494-7] DR Ensembl; ENST00000683570.1; ENSP00000508409.1; ENSG00000113971.21. [Q7Z494-4] DR GeneID; 27031; -. DR KEGG; hsa:27031; -. DR MANE-Select; ENST00000337331.10; ENSP00000338766.5; NM_153240.5; NP_694972.3. DR UCSC; uc003epe.3; human. [Q7Z494-1] DR AGR; HGNC:7907; -. DR CTD; 27031; -. DR DisGeNET; 27031; -. DR GeneCards; NPHP3; -. DR GeneReviews; NPHP3; -. DR HGNC; HGNC:7907; NPHP3. DR HPA; ENSG00000113971; Low tissue specificity. DR MalaCards; NPHP3; -. DR MIM; 208540; phenotype. DR MIM; 267010; phenotype. DR MIM; 604387; phenotype. DR MIM; 608002; gene. DR neXtProt; NX_Q7Z494; -. DR OpenTargets; ENSG00000113971; -. DR OpenTargets; ENSG00000274810; -. DR Orphanet; 93591; Infantile nephronophthisis. DR Orphanet; 93589; Late-onset nephronophthisis. DR Orphanet; 3032; NPHP3-related Meckel-like syndrome. DR Orphanet; 294415; Renal-hepatic-pancreatic dysplasia. DR Orphanet; 3156; Senior-Loken syndrome. DR PharmGKB; PA31708; -. DR VEuPathDB; HostDB:ENSG00000113971; -. DR eggNOG; KOG1840; Eukaryota. DR GeneTree; ENSGT00940000156398; -. DR HOGENOM; CLU_1744706_0_0_1; -. DR InParanoid; Q7Z494; -. DR OMA; TWHEENP; -. DR OrthoDB; 38814at2759; -. DR PhylomeDB; Q7Z494; -. DR TreeFam; TF314010; -. DR PathwayCommons; Q7Z494; -. DR Reactome; R-HSA-5624138; Trafficking of myristoylated proteins to the cilium. DR SignaLink; Q7Z494; -. DR BioGRID-ORCS; 27031; 36 hits in 1151 CRISPR screens. DR GeneWiki; NPHP3; -. DR GenomeRNAi; 27031; -. DR Pharos; Q7Z494; Tbio. DR PRO; PR:Q7Z494; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q7Z494; Protein. DR Bgee; ENSG00000113971; Expressed in superficial temporal artery and 190 other cell types or tissues. DR ExpressionAtlas; Q7Z494; baseline and differential. DR GO; GO:0097546; C:ciliary base; IBA:GO_Central. DR GO; GO:0097543; C:ciliary inversin compartment; IBA:GO_Central. DR GO; GO:0005929; C:cilium; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005576; C:extracellular region; IEA:GOC. DR GO; GO:0003283; P:atrial septum development; IMP:BHF-UCL. DR GO; GO:0060271; P:cilium assembly; ISS:UniProtKB. DR GO; GO:0060026; P:convergent extension; IBA:GO_Central. DR GO; GO:0060027; P:convergent extension involved in gastrulation; IGI:BHF-UCL. DR GO; GO:0071908; P:determination of intestine left/right asymmetry; IMP:BHF-UCL. DR GO; GO:0007368; P:determination of left/right symmetry; IMP:BHF-UCL. DR GO; GO:0071910; P:determination of liver left/right asymmetry; IMP:BHF-UCL. DR GO; GO:0035469; P:determination of pancreatic left/right asymmetry; IMP:BHF-UCL. DR GO; GO:0071909; P:determination of stomach left/right asymmetry; IMP:BHF-UCL. DR GO; GO:0060287; P:epithelial cilium movement involved in determination of left/right asymmetry; IC:BHF-UCL. DR GO; GO:0007163; P:establishment or maintenance of cell polarity; IEA:Ensembl. DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl. DR GO; GO:0001947; P:heart looping; IMP:BHF-UCL. DR GO; GO:0001822; P:kidney development; IMP:BHF-UCL. DR GO; GO:0060993; P:kidney morphogenesis; IMP:BHF-UCL. DR GO; GO:0006629; P:lipid metabolic process; IEA:Ensembl. DR GO; GO:0030324; P:lung development; IMP:BHF-UCL. DR GO; GO:0048496; P:maintenance of animal organ identity; IMP:HGNC-UCL. DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:UniProtKB. DR GO; GO:1905515; P:non-motile cilium assembly; IEA:Ensembl. DR GO; GO:0045494; P:photoreceptor cell maintenance; IMP:HGNC-UCL. DR GO; GO:2000095; P:regulation of Wnt signaling pathway, planar cell polarity pathway; IDA:BHF-UCL. DR GO; GO:0072189; P:ureter development; IMP:BHF-UCL. DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW. DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1. DR Gene3D; 1.25.40.10; Tetratricopeptide repeat domain; 3. DR InterPro; IPR027417; P-loop_NTPase. DR InterPro; IPR011990; TPR-like_helical_dom_sf. DR InterPro; IPR019734; TPR_repeat. DR PANTHER; PTHR45641:SF1; NEPHROCYSTIN-3; 1. DR PANTHER; PTHR45641; TETRATRICOPEPTIDE REPEAT PROTEIN (AFU_ORTHOLOGUE AFUA_6G03870); 1. DR Pfam; PF13424; TPR_12; 3. DR Pfam; PF13176; TPR_7; 1. DR SMART; SM00028; TPR; 8. DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1. DR SUPFAM; SSF48452; TPR-like; 2. DR PROSITE; PS50005; TPR; 8. DR PROSITE; PS50293; TPR_REGION; 1. DR Genevisible; Q7Z494; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell projection; Ciliopathy; Cilium; KW Coiled coil; Disease variant; Lipoprotein; Meckel syndrome; Myristate; KW Nephronophthisis; Reference proteome; Repeat; TPR repeat; KW Wnt signaling pathway. FT INIT_MET 1 FT /note="Removed" FT CHAIN 2..1330 FT /note="Nephrocystin-3" FT /id="PRO_0000106301" FT REPEAT 471..504 FT /note="TPR 1" FT REPEAT 885..918 FT /note="TPR 2" FT REPEAT 920..942 FT /note="TPR 3" FT REPEAT 943..976 FT /note="TPR 4" FT REPEAT 985..1018 FT /note="TPR 5" FT REPEAT 1027..1060 FT /note="TPR 6" FT REPEAT 1093..1126 FT /note="TPR 7" FT REPEAT 1135..1168 FT /note="TPR 8" FT REPEAT 1177..1210 FT /note="TPR 9" FT REPEAT 1219..1252 FT /note="TPR 10" FT REPEAT 1261..1294 FT /note="TPR 11" FT REGION 1296..1330 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 83..207 FT /evidence="ECO:0000255" FT COMPBIAS 1301..1330 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT LIPID 2 FT /note="N-myristoyl glycine" FT /evidence="ECO:0000269|PubMed:22085962" FT VAR_SEQ 1..720 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12056414" FT /id="VSP_014480" FT VAR_SEQ 132..181 FT /note="ALQKTYQKILREKESALEAKYQAMERAATFEHDRDKVKRQFKIFRETKEN FT -> VTPGWAATPGDPWEARPSCSLSKPSGFESSAETAHFNLRGHILFESEMIP (in FT isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_014482" FT VAR_SEQ 132..150 FT /note="ALQKTYQKILREKESALEA -> GLAAVARSRLTATWNSWAQ (in FT isoform 7)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_014484" FT VAR_SEQ 151..1330 FT /note="Missing (in isoform 7)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_014485" FT VAR_SEQ 182..1330 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_014483" FT VAR_SEQ 224..239 FT /note="AAGTQCEYWTGGALGS -> VSLESDQHPGIFIANF (in isoform 5)" FT /evidence="ECO:0000303|PubMed:12872122" FT /id="VSP_014486" FT VAR_SEQ 240..1330 FT /note="Missing (in isoform 5)" FT /evidence="ECO:0000303|PubMed:12872122" FT /id="VSP_014487" FT VAR_SEQ 630..636 FT /note="QVEKHMK -> VVAYTSS (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12872122, FT ECO:0000303|PubMed:17974005" FT /id="VSP_014488" FT VAR_SEQ 637..1330 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:12872122, FT ECO:0000303|PubMed:17974005" FT /id="VSP_014489" FT VAR_SEQ 697..704 FT /note="EKKLERHC -> CWESRQFR (in isoform 6)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_014490" FT VAR_SEQ 705..1330 FT /note="Missing (in isoform 6)" FT /evidence="ECO:0000303|PubMed:17974005" FT /id="VSP_014491" FT VAR_SEQ 1330 FT /note="R -> RKVQSNLLSPEGLSNICAQEKTTRFTSS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:12056414" FT /id="VSP_014481" FT VARIANT 360 FT /note="S -> T (in NPHP3; dbSNP:rs119456960)" FT /evidence="ECO:0000269|PubMed:12872122" FT /id="VAR_022815" FT VARIANT 386 FT /note="N -> S (in NPHP3; dbSNP:rs142021049)" FT /evidence="ECO:0000269|PubMed:12872122" FT /id="VAR_022816" FT VARIANT 397 FT /note="R -> H (in NPHP3; dbSNP:rs755094682)" FT /evidence="ECO:0000269|PubMed:12872122" FT /id="VAR_022817" FT VARIANT 973 FT /note="R -> Q (in RHPD1; dbSNP:rs119456963)" FT /evidence="ECO:0000269|PubMed:18371931" FT /id="VAR_044121" FT VARIANT 1141 FT /note="L -> P (in NPHP3; dbSNP:rs1057521090)" FT /evidence="ECO:0000269|PubMed:12872122" FT /id="VAR_022818" FT VARIANT 1221 FT /note="A -> V (in NPHP3; dbSNP:rs202048210)" FT /evidence="ECO:0000269|PubMed:12872122" FT /id="VAR_022819" FT VARIANT 1252 FT /note="S -> R (in NPHP3; dbSNP:rs143451766)" FT /evidence="ECO:0000269|PubMed:12872122" FT /id="VAR_022820" FT VARIANT 1305 FT /note="R -> C (in dbSNP:rs35485382)" FT /id="VAR_044122" FT VARIANT 1314 FT /note="S -> T (in NPHP3; likely benign; dbSNP:rs75316802)" FT /evidence="ECO:0000269|PubMed:12872122" FT /id="VAR_022821" FT CONFLICT 223 FT /note="T -> TT (in Ref. 4; CAI46202)" FT /evidence="ECO:0000305" FT HELIX 3..6 FT /evidence="ECO:0007829|PDB:5L7K" SQ SEQUENCE 1330 AA; 150864 MW; 99C1F17C9A5117F8 CRC64; MGTASSLVSP AGGEVIEDTY GAGGGEACEI PVEVKPKARL LRNSFRRGAG AAAGAGPGSL PRGVGAGGLL GASFKSTGSS VPELEYAAAE YERLRKEYEI FRVSKNQELL SMGRREAKLD TENKRLRAEL QALQKTYQKI LREKESALEA KYQAMERAAT FEHDRDKVKR QFKIFRETKE NEIQDLLRAK RELESKLQRL QAQGIQVFDP GESDSDDNCT DVTAAGTQCE YWTGGALGSE PSIGSMIQLQ QSFRGPEFAH SSIDVEGPFA NVNRDDWDIA VASLLQVTPL FSHSLWSNTV RCYLIYTDET QPEMDLFLKD YSPKLKRMCE TMGYFFHAVY FPIDVENQYL TVRKWEIEKS SLVILFIHLT LPSLLLEDCE EAFLKNPEGK PRLIFHRLED GKVSSDSVQQ LIDQVSNLNK TSKAKIIDHS GDPAEGVYKT YICVEKIIKQ DILGFENTDL ETKDLGSEDS IPEEDDFGDV LWDIHDEQEQ METFQQASNS AHELGFEKYY QRLNDLVAAP APIPPLLVSG GPGSGKSLLL SKWIQLQQKN SPNTLILSHF VGRPMSTSSE SSLIIKRLTL KLMQHSWSVS ALTLDPAKLL EEFPRWLEKL SARHQGSIII VIDSIDQVQQ VEKHMKWLID PLPVNVRVIV SVNVETCPPA WRLWPTLHLD PLSPKDAKSI IIAECHSVDI KLSKEQEKKL ERHCRSATTC NALYVTLFGK MIARAGRAGN LDKILHQCFQ CQDTLSLYRL VLHSIRESMA NDVDKELMKQ ILCLVNVSHN GVSESELMEL YPEMSWTFLT SLIHSLYKMC LLTYGCGLLR FQHLQAWETV RLEYLEGPTV TSSYRQKLIN YFTLQLSQDR VTWRSADELP WLFQQQGSKQ KLHDCLLNLF VSQNLYKRGH FAELLSYWQF VGKDKSAMAT EYFDSLKQYE KNCEGEDNMS CLADLYETLG RFLKDLGLLS QAIVPLQRSL EIRETALDPD HPRVAQSLHQ LASVYVQWKK FGNAEQLYKQ ALEISENAYG ADHPYTAREL EALATLYQKQ NKYEQAEHFR KKSFKIHQKA IKKKGNLYGF ALLRRRALQL EELTLGKDTP DNARTLNELG VLYYLQNNLE TADQFLKRSL EMRERVLGPD HPDCAQSLNN LAALCNEKKQ YDKAEELYER ALDIRRRALA PDHPSLAYTV KHLAILYKKM GKLDKAVPLY ELAVEIRQKS FGPKHPSVAT ALVNLAVLYS QMKKHVEALP LYERALKIYE DSLGRMHPRV GETLKNLAVL SYEGGDFEKA AELYKRAMEI KEAETSLLGG KAPSRHSSSG DTFSLKTAHS PNVFLQQGQR //