ID NPHP1_HUMAN Reviewed; 732 AA. AC O15259; O14837; DT 16-NOV-2001, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 27-MAR-2024, entry version 210. DE RecName: Full=Nephrocystin-1; DE AltName: Full=Juvenile nephronophthisis 1 protein; GN Name=NPHP1; Synonyms=NPH1; 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] (ISOFORMS 1 AND 2). RC TISSUE=Fetal kidney; RX PubMed=9361039; DOI=10.1093/hmg/6.13.2317; RA Saunier S., Calado J., Heilig R., Silbermann F., Benessy F., Morin G., RA Konrad M., Broyer M., Gubler M.-C., Weissenbach J., Antignac C.; RT "A novel gene that encodes a protein with a putative src homology 3 domain RT is a candidate gene for familial juvenile nephronophthisis."; RL Hum. Mol. Genet. 6:2317-2323(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-732 (ISOFORM 4), AND ALTERNATIVE SPLICING. RX PubMed=9326933; DOI=10.1038/ng1097-149; RA Hildebrandt F., Otto E., Rensing C., Nothwang H.G., Vollmer M., Adolphs J., RA Hanusch H., Brandis M.; RT "A novel gene encoding an SH3 domain protein is mutated in nephronophthisis RT type 1."; RL Nat. Genet. 17:149-153(1997). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). 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 [5] RP INVOLVEMENT IN SLSN1. RX PubMed=9856524; DOI=10.1016/s0272-6386(98)70083-6; RA Caridi G., Murer L., Bellantuono R., Sorino P., Caringella D.A., RA Gusmano R., Ghiggeri G.M.; RT "Renal-retinal syndromes: association of retinal anomalies and recessive RT nephronophthisis in patients with homozygous deletion of the NPH1 locus."; RL Am. J. Kidney Dis. 32:1059-1062(1998). RN [6] RP INTERACTION WITH NPHP4. RX PubMed=12244321; DOI=10.1038/ng996; RA Mollet G., Salomon R., Gribouval O., Silbermann F., Bacq D., Landthaler G., RA Milford D., Nayir A., Rizzoni G., Antignac C., Saunier S.; RT "The gene mutated in juvenile nephronophthisis type 4 encodes a novel RT protein that interacts with nephrocystin."; RL Nat. Genet. 32:300-305(2002). RN [7] RP INTERACTION WITH INVS. RX PubMed=12872123; DOI=10.1038/ng1217; RA Otto E.A., Schermer B., Obara T., O'Toole J.F., Hiller K.S., Mueller A.M., RA Ruf R.G., Hoefele J., Beekmann F., Landau D., Foreman J.W., Goodship J.A., RA Strachan T., Kispert A., Wolf M.T., Gagnadoux M.F., Nivet H., Antignac C., RA Walz G., Drummond I.A., Benzing T., Hildebrandt F.; RT "Mutations in INVS encoding inversin cause nephronophthisis type 2, linking RT renal cystic disease to the function of primary cilia and left-right axis RT determination."; RL Nat. Genet. 34:413-420(2003). RN [8] RP INTERACTION WITH NPHP3. 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 [9] RP PHOSPHORYLATION AT SER-121; SER-123 AND SER-126, INTERACTION WITH PACS1, RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF SER-121; RP SER-123 AND SER-126. RX PubMed=16308564; DOI=10.1038/sj.emboj.7600885; RA Schermer B., Hoepker K., Omran H., Ghenoiu C., Fliegauf M., Fekete A., RA Horvath J., Koettgen M., Hackl M., Zschiedrich S., Huber T.B., RA Kramer-Zucker A., Zentgraf H., Blaukat A., Walz G., Benzing T.; RT "Phosphorylation by casein kinase 2 induces PACS-1 binding of nephrocystin RT and targeting to cilia."; RL EMBO J. 24:4415-4424(2005). RN [10] RP INVOLVEMENT IN JBTS4. RX PubMed=15138899; DOI=10.1086/421846; RA Parisi M.A., Bennett C.L., Eckert M.L., Dobyns W.B., Gleeson J.G., RA Shaw D.W.W., McDonald R., Eddy A., Chance P.F., Glass I.A.; RT "The NPHP1 gene deletion associated with juvenile nephronophthisis is RT present in a subset of individuals with Joubert syndrome."; RL Am. J. Hum. Genet. 75:82-91(2004). RN [11] RP SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE. RX PubMed=16885411; DOI=10.1681/asn.2005121351; RA Fliegauf M., Horvath J., von Schnakenburg C., Olbrich H., Mueller D., RA Thumfart J., Schermer B., Pazour G.J., Neumann H.P., Zentgraf H., RA Benzing T., Omran H.; RT "Nephrocystin specifically localizes to the transition zone of renal and RT respiratory cilia and photoreceptor connecting cilia."; RL J. Am. Soc. Nephrol. 17:2424-2433(2006). RN [12] RP INTERACTION WITH TNK2, AND TISSUE SPECIFICITY. RX PubMed=18477472; DOI=10.1016/j.bbrc.2008.05.016; RA Eley L., Moochhala S.H., Simms R., Hildebrandt F., Sayer J.A.; RT "Nephrocystin-1 interacts directly with Ack1 and is expressed in human RT collecting duct."; RL Biochem. Biophys. Res. Commun. 371:877-882(2008). RN [13] RP INTERACTION WITH AHI1. RX PubMed=18633336; DOI=10.1038/ki.2008.377; RA Eley L., Gabrielides C., Adams M., Johnson C.A., Hildebrandt F., RA Sayer J.A.; RT "Jouberin localizes to collecting ducts and interacts with RT nephrocystin-1."; RL Kidney Int. 74:1139-1149(2008). RN [14] RP INTERACTION WITH PKD1, AND MUTAGENESIS OF PRO-203. RX PubMed=20856870; DOI=10.1371/journal.pone.0012719; RA Wodarczyk C., Distefano G., Rowe I., Gaetani M., Bricoli B., Muorah M., RA Spitaleri A., Mannella V., Ricchiuto P., Pema M., Castelli M., RA Casanova A.E., Mollica L., Banzi M., Boca M., Antignac C., Saunier S., RA Musco G., Boletta A.; RT "Nephrocystin-1 forms a complex with polycystin-1 via a polyproline RT motif/SH3 domain interaction and regulates the apoptotic response in RT mammals."; RL PLoS ONE 5:E12719-E12719(2010). RN [15] RP INTERACTION WITH IQCB1; INVS AND NPHP4, AND SUBCELLULAR LOCATION. RX PubMed=21565611; DOI=10.1016/j.cell.2011.04.019; RA Sang L., Miller J.J., Corbit K.C., Giles R.H., Brauer M.J., Otto E.A., RA Baye L.M., Wen X., Scales S.J., Kwong M., Huntzicker E.G., Sfakianos M.K., RA Sandoval W., Bazan J.F., Kulkarni P., Garcia-Gonzalo F.R., Seol A.D., RA O'Toole J.F., Held S., Reutter H.M., Lane W.S., Rafiq M.A., Noor A., RA Ansar M., Devi A.R., Sheffield V.C., Slusarski D.C., Vincent J.B., RA Doherty D.A., Hildebrandt F., Reiter J.F., Jackson P.K.; RT "Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes RT and pathways."; RL Cell 145:513-528(2011). RN [16] RP INTERACTION WITH PTK2B/PYK2, AND PHOSPHORYLATION AT TYR-46; TYR-349 AND RP TYR-721. RX PubMed=21357692; DOI=10.1074/jbc.m110.165464; RA Liebau M.C., Hopker K., Muller R.U., Schmedding I., Zank S., Schairer B., RA Fabretti F., Hohne M., Bartram M.P., Dafinger C., Hackl M., Burst V., RA Habbig S., Zentgraf H., Blaukat A., Walz G., Benzing T., Schermer B.; RT "Nephrocystin-4 regulates Pyk2-induced tyrosine phosphorylation of RT nephrocystin-1 to control targeting to monocilia."; RL J. Biol. Chem. 286:14237-14245(2011). RN [17] RP INTERACTION WITH KIF7. RX PubMed=21633164; DOI=10.1172/jci43639; RA Dafinger C., Liebau M.C., Elsayed S.M., Hellenbroich Y., Boltshauser E., RA Korenke G.C., Fabretti F., Janecke A.R., Ebermann I., Nurnberg G., RA Nurnberg P., Zentgraf H., Koerber F., Addicks K., Elsobky E., Benzing T., RA Schermer B., Bolz H.J.; RT "Mutations in KIF7 link Joubert syndrome with Sonic Hedgehog signaling and RT microtubule dynamics."; RL J. Clin. Invest. 121:2662-2667(2011). RN [18] RP INVOLVEMENT IN JBTS4. RX PubMed=26477546; DOI=10.1016/j.ajhg.2015.09.009; RG Care4Rare Canada Consortium; RA Srour M., Hamdan F.F., McKnight D., Davis E., Mandel H., RA Schwartzentruber J., Martin B., Patry L., Nassif C., Dionne-Laporte A., RA Ospina L.H., Lemyre E., Massicotte C., Laframboise R., Maranda B., RA Labuda D., Decarie J.C., Rypens F., Goldsher D., Fallet-Bianco C., RA Soucy J.F., Laberge A.M., Maftei C., Boycott K., Brais B., Boucher R.M., RA Rouleau G.A., Katsanis N., Majewski J., Elpeleg O., Kukolich M.K., RA Shalev S., Michaud J.L.; RT "Joubert Syndrome in French Canadians and Identification of Mutations in RT CEP104."; RL Am. J. Hum. Genet. 97:744-753(2015). RN [19] RP STRUCTURE BY NMR OF 147-212, AND MUTAGENESIS OF LEU-180. RX PubMed=15723349; DOI=10.1002/prot.20344; RA le Maire A., Weber T., Saunier S., Broutin I., Antignac C., Ducruix A., RA Dardel F.; RT "Solution NMR structure of the SH3 domain of human nephrocystin and RT analysis of a mutation-causing juvenile nephronophthisis."; RL Proteins 59:347-355(2005). RN [20] RP VARIANT NPHP1 ARG-342. RX PubMed=10839884; DOI=10.1067/mpd.2000.106225; RA Betz R., Rensing C., Otto E., Mincheva A., Zehnder D., Lichter P., RA Hildebrandt F.; RT "Children with ocular motor apraxia type Cogan carry deletions in the gene RT (NPHP1) for juvenile nephronophthisis."; RL J. Pediatr. 136:828-831(2000). RN [21] RP VARIANT LEU-5, AND CHARACTERIZATION OF VARIANT LEU-5. RX PubMed=24746959; DOI=10.1016/j.ajhg.2014.03.017; RA Lindstrand A., Davis E.E., Carvalho C.M., Pehlivan D., Willer J.R., RA Tsai I.C., Ramanathan S., Zuppan C., Sabo A., Muzny D., Gibbs R., Liu P., RA Lewis R.A., Banin E., Lupski J.R., Clark R., Katsanis N.; RT "Recurrent CNVs and SNVs at the NPHP1 locus contribute pathogenic alleles RT to Bardet-Biedl syndrome."; RL Am. J. Hum. Genet. 94:745-754(2014). CC -!- FUNCTION: Together with BCAR1 it may play a role in the control of CC epithelial cell polarity (By similarity). Involved in the organization CC of apical junctions in kidney cells together with NPHP4 and CC RPGRIP1L/NPHP8 (By similarity). Does not seem to be strictly required CC for ciliogenesis (By similarity). Seems to help to recruit PTK2B/PYK2 CC to cell matrix adhesions, thereby initiating phosphorylation of CC PTK2B/PYK2 and PTK2B/PYK2-dependent signaling (By similarity). May play CC a role in the regulation of intraflagellar transport (IFT) during cilia CC assembly. Required for normal retina development (By similarity). In CC connecting photoreceptor cilia influences the movement of some IFT CC proteins such as IFT88 and WDR19. Involved in spermatogenesis (By CC similarity). {ECO:0000250|UniProtKB:Q9QY53}. CC -!- SUBUNIT: Interacts with BCAR1, PTK2B/PYK2 and tensin. Interacts with CC INVS and NPHP3. Interacts with PACS1; the interaction is dependent on CC NPHP1 phosphorylation by CK2. Interacts with KIF7. Interacts with AHI1 CC and TNK2. Interacts with NPHP4 in a complex containing NPHP1, NPHP4 and CC RPGRIP1L. Interacts with IQCB1; the interaction likely requires CC additional interactors. Interacts with ANKS3 (By similarity).Interacts CC with SPATA7 (By similarity). Interacts with FLNA (By similarity). CC {ECO:0000250|UniProtKB:Q9QY53, ECO:0000269|PubMed:12244321, CC ECO:0000269|PubMed:12872122, ECO:0000269|PubMed:12872123, CC ECO:0000269|PubMed:16308564, ECO:0000269|PubMed:18477472, CC ECO:0000269|PubMed:18633336, ECO:0000269|PubMed:20856870, CC ECO:0000269|PubMed:21357692, ECO:0000269|PubMed:21565611, CC ECO:0000269|PubMed:21633164}. CC -!- INTERACTION: CC O15259; Q13444: ADAM15; NbExp=4; IntAct=EBI-953828, EBI-77818; CC O15259; Q8N157: AHI1; NbExp=4; IntAct=EBI-953828, EBI-1049056; CC O15259; O75161: NPHP4; NbExp=18; IntAct=EBI-953828, EBI-4281852; CC O15259; P98161: PKD1; NbExp=2; IntAct=EBI-953828, EBI-1752013; CC O15259; Q14289: PTK2B; NbExp=2; IntAct=EBI-953828, EBI-298640; CC O15259; Q9Y265: RUVBL1; NbExp=2; IntAct=EBI-953828, EBI-353675; CC -!- SUBCELLULAR LOCATION: Cell junction {ECO:0000250|UniProtKB:Q9QY53}. CC Cell junction, adherens junction {ECO:0000250|UniProtKB:Q9QY53}. Cell CC projection, cilium {ECO:0000269|PubMed:16885411}. Cytoplasm, CC cytoskeleton, cilium axoneme {ECO:0000269|PubMed:16308564, CC ECO:0000269|PubMed:16885411}. Cell junction, tight junction. Note=In CC the retinal photoreceptor cell layer, localizes at the connecting CC cilium (By similarity). Colocalizes with E-cadherin and BCAR1 at or CC near the cell-cell adherens junctions (By similarity). Localized to CC respiratory cilia axoneme (PubMed:16308564, PubMed:16885411). Localized CC to the transition zone of respiratory cilia (PubMed:16885411). CC Localized to the transition zone of photoreceptor-connecting cilia and CC renal monocilia (By similarity). In cultured renal cells, it localizes CC diffusely in the cytoplasm but, as cells approach confluence, it CC accumulates at basolateral tight junctions (By similarity). CC {ECO:0000250|UniProtKB:Q9QY53, ECO:0000269|PubMed:16308564, CC ECO:0000269|PubMed:16885411}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=NPHP1; CC IsoId=O15259-1; Sequence=Displayed; CC Name=2; Synonyms=NPHP1-8A; CC IsoId=O15259-2; Sequence=VSP_003424; CC Name=3; CC IsoId=O15259-3; Sequence=VSP_010073, VSP_010074; CC Name=4; CC IsoId=O15259-4; Sequence=VSP_024381; CC -!- TISSUE SPECIFICITY: Widespread expression, with highest levels in CC pituitary gland, spinal cord, thyroid gland, testis, skeletal muscle, CC lymph node and trachea. Weakly expressed in heart, kidney and pancreas. CC Expressed in nasal epithelial cells (at protein level) CC (PubMed:16308564). Expressed in the renal collecting duct (at protein CC level) (PubMed:18477472). {ECO:0000269|PubMed:16308564, CC ECO:0000269|PubMed:18477472}. CC -!- DEVELOPMENTAL STAGE: During in vitro ciliogenesis translocalizes from CC the cytoplasm to the ciliary transition zone during epithelial cell CC polarization. {ECO:0000269|PubMed:16885411}. CC -!- DOMAIN: The SH3 domain mediates the stable interaction with Cas. CC {ECO:0000250}. CC -!- PTM: Phosphorylation by CK2 is required for the interaction with PACS1 CC and the targeting to the base region of cilia. CC {ECO:0000269|PubMed:16308564, ECO:0000269|PubMed:21357692}. CC -!- DISEASE: Nephronophthisis 1 (NPHP1) [MIM:256100]: An autosomal CC recessive inherited disease characterized by anemia, polyuria, CC polydipsia, isosthenuria and death in uremia. Symmetrical destruction CC of the kidneys involving both tubules and glomeruli occurs. The CC underlying pathology is a chronic tubulo-interstitial nephropathy with CC characteristic tubular basement membrane thickening and medullary cyst CC formation. Associations with extrarenal symptoms, especially ocular CC lesions, are frequent. The age at death ranges from about 4 to 15 CC years. {ECO:0000269|PubMed:10839884}. Note=The disease is caused by CC variants affecting the gene represented in this entry. CC -!- DISEASE: Senior-Loken syndrome 1 (SLSN1) [MIM:266900]: A renal-retinal CC disorder characterized by progressive wasting of the filtering unit of CC the kidney (nephronophthisis), with or without medullary cystic renal CC disease, and progressive eye disease. Typically this disorder becomes CC apparent during the first year of life. {ECO:0000269|PubMed:9856524}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- DISEASE: Joubert syndrome 4 (JBTS4) [MIM:609583]: A disorder presenting CC with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal CC breathing abnormalities and psychomotor delay. Neuroradiologically, it CC is characterized by cerebellar vermian hypoplasia/aplasia, thickened CC and reoriented superior cerebellar peduncles, and an abnormally large CC interpeduncular fossa, giving the appearance of a molar tooth on CC transaxial slices (molar tooth sign). Additional variable features CC include retinal dystrophy and renal disease. Joubert syndrome type 4 is CC a phenotypically mild form. {ECO:0000269|PubMed:15138899, CC ECO:0000269|PubMed:26477546}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: Nephronophthisis type 1 patients deficient for NPHP1 CC show normal overall integrity of respiratory cilia. CC -!- SIMILARITY: Belongs to the nephrocystin-1 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; AJ001815; CAA05030.1; -; mRNA. DR EMBL; AF023674; AAC51771.1; -; mRNA. DR EMBL; AC013268; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC140479; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC009789; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; BC062574; AAH62574.1; -; mRNA. DR CCDS; CCDS2086.1; -. [O15259-4] DR CCDS; CCDS46384.1; -. [O15259-3] DR CCDS; CCDS46385.1; -. [O15259-1] DR CCDS; CCDS46386.1; -. [O15259-2] DR RefSeq; NP_000263.2; NM_000272.3. [O15259-4] DR RefSeq; NP_001121650.1; NM_001128178.1. [O15259-2] DR RefSeq; NP_001121651.1; NM_001128179.1. [O15259-3] DR RefSeq; NP_997064.2; NM_207181.2. [O15259-1] DR PDB; 1S1N; NMR; -; A=147-212. DR PDB; 6O1Q; NMR; -; A=1-115. DR PDBsum; 1S1N; -. DR PDBsum; 6O1Q; -. DR AlphaFoldDB; O15259; -. DR SMR; O15259; -. DR BioGRID; 110927; 98. DR ComplexPortal; CPX-2806; NPHP transition zone complex. DR CORUM; O15259; -. DR IntAct; O15259; 82. DR MINT; O15259; -. DR STRING; 9606.ENSP00000313169; -. DR GlyGen; O15259; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O15259; -. DR PhosphoSitePlus; O15259; -. DR BioMuta; NPHP1; -. DR EPD; O15259; -. DR MassIVE; O15259; -. DR PaxDb; 9606-ENSP00000313169; -. DR PeptideAtlas; O15259; -. DR ProteomicsDB; 48545; -. [O15259-1] DR ProteomicsDB; 48546; -. [O15259-2] DR ProteomicsDB; 48547; -. [O15259-3] DR ProteomicsDB; 48548; -. [O15259-4] DR ABCD; O15259; 1 sequenced antibody. DR Antibodypedia; 18009; 172 antibodies from 27 providers. DR DNASU; 4867; -. DR Ensembl; ENST00000316534.8; ENSP00000313169.4; ENSG00000144061.14. [O15259-4] DR Ensembl; ENST00000355301.8; ENSP00000347452.4; ENSG00000144061.14. [O15259-3] DR Ensembl; ENST00000393272.7; ENSP00000376953.3; ENSG00000144061.14. [O15259-1] DR Ensembl; ENST00000445609.7; ENSP00000389879.3; ENSG00000144061.14. [O15259-2] DR Ensembl; ENST00000676053.1; ENSP00000502475.1; ENSG00000144061.14. [O15259-3] DR GeneID; 4867; -. DR KEGG; hsa:4867; -. DR MANE-Select; ENST00000445609.7; ENSP00000389879.3; NM_001128178.3; NP_001121650.1. [O15259-2] DR UCSC; uc002tfl.6; human. [O15259-1] DR AGR; HGNC:7905; -. DR CTD; 4867; -. DR DisGeNET; 4867; -. DR GeneCards; NPHP1; -. DR GeneReviews; NPHP1; -. DR HGNC; HGNC:7905; NPHP1. DR HPA; ENSG00000144061; Tissue enhanced (choroid plexus, skeletal muscle). DR MalaCards; NPHP1; -. DR MIM; 256100; phenotype. DR MIM; 266900; phenotype. DR MIM; 607100; gene. DR MIM; 609583; phenotype. DR neXtProt; NX_O15259; -. DR OpenTargets; ENSG00000144061; -. DR Orphanet; 110; Bardet-Biedl syndrome. DR Orphanet; 220497; Joubert syndrome with renal defect. DR Orphanet; 93592; Juvenile nephronophthisis. DR Orphanet; 3156; Senior-Loken syndrome. DR PharmGKB; PA31706; -. DR VEuPathDB; HostDB:ENSG00000144061; -. DR eggNOG; ENOG502QU7K; Eukaryota. DR GeneTree; ENSGT00390000007701; -. DR HOGENOM; CLU_024987_1_0_1; -. DR InParanoid; O15259; -. DR OMA; CYLIALM; -. DR OrthoDB; 2900795at2759; -. DR PhylomeDB; O15259; -. DR TreeFam; TF320679; -. DR PathwayCommons; O15259; -. DR Reactome; R-HSA-5620912; Anchoring of the basal body to the plasma membrane. DR SignaLink; O15259; -. DR SIGNOR; O15259; -. DR BioGRID-ORCS; 4867; 17 hits in 1148 CRISPR screens. DR ChiTaRS; NPHP1; human. DR EvolutionaryTrace; O15259; -. DR GeneWiki; NPHP1; -. DR GenomeRNAi; 4867; -. DR Pharos; O15259; Tbio. DR PRO; PR:O15259; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; O15259; Protein. DR Bgee; ENSG00000144061; Expressed in right uterine tube and 117 other cell types or tissues. DR ExpressionAtlas; O15259; baseline and differential. DR GO; GO:0005912; C:adherens junction; IEA:UniProtKB-SubCell. DR GO; GO:0005923; C:bicellular tight junction; IEA:UniProtKB-SubCell. DR GO; GO:0005911; C:cell-cell junction; IDA:UniProtKB. DR GO; GO:0005929; C:cilium; IBA:GO_Central. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-KW. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0016020; C:membrane; NAS:UniProtKB. DR GO; GO:0031514; C:motile cilium; IDA:UniProtKB. DR GO; GO:0032391; C:photoreceptor connecting cilium; ISS:UniProtKB. DR GO; GO:0005198; F:structural molecule activity; NAS:UniProtKB. DR GO; GO:0030036; P:actin cytoskeleton organization; NAS:UniProtKB. DR GO; GO:0030030; P:cell projection organization; ISS:UniProtKB. DR GO; GO:0098609; P:cell-cell adhesion; NAS:UniProtKB. DR GO; GO:1903348; P:positive regulation of bicellular tight junction assembly; IMP:UniProtKB. DR GO; GO:0090251; P:protein localization involved in establishment of planar polarity; IBA:GO_Central. DR GO; GO:0060041; P:retina development in camera-type eye; ISS:UniProtKB. DR GO; GO:0007165; P:signal transduction; NAS:UniProtKB. DR GO; GO:0048515; P:spermatid differentiation; ISS:UniProtKB. DR GO; GO:0007632; P:visual behavior; NAS:UniProtKB. DR CDD; cd11770; SH3_Nephrocystin; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR InterPro; IPR039687; NPHP1. DR InterPro; IPR030642; NPHP1_SH3. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR PANTHER; PTHR15176; NEPHROCYSTIN; 1. DR PANTHER; PTHR15176:SF1; NEPHROCYSTIN-1; 1. DR Pfam; PF00018; SH3_1; 1. DR SMART; SM00326; SH3; 1. DR SUPFAM; SSF50044; SH3-domain; 1. DR PROSITE; PS50002; SH3; 1. DR Genevisible; O15259; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell junction; Cell projection; KW Ciliopathy; Cilium; Cilium biogenesis/degradation; Coiled coil; Cytoplasm; KW Cytoskeleton; Differentiation; Disease variant; Joubert syndrome; KW Leber congenital amaurosis; Nephronophthisis; Phosphoprotein; KW Reference proteome; Senior-Loken syndrome; SH3 domain; Spermatogenesis; KW Tight junction. FT CHAIN 1..732 FT /note="Nephrocystin-1" FT /id="PRO_0000159585" FT DOMAIN 152..212 FT /note="SH3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT REGION 103..153 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 205..244 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 3..105 FT /evidence="ECO:0000255" FT COILED 127..150 FT /evidence="ECO:0000255" FT COMPBIAS 113..144 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 212..233 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 46 FT /note="Phosphotyrosine; by FAK2" FT /evidence="ECO:0000269|PubMed:21357692" FT MOD_RES 121 FT /note="Phosphoserine; by CK2" FT /evidence="ECO:0000305|PubMed:16308564" FT MOD_RES 123 FT /note="Phosphoserine; by CK2" FT /evidence="ECO:0000305|PubMed:16308564" FT MOD_RES 126 FT /note="Phosphoserine; by CK2" FT /evidence="ECO:0000305|PubMed:16308564" FT MOD_RES 349 FT /note="Phosphotyrosine; by FAK2" FT /evidence="ECO:0000269|PubMed:21357692" FT MOD_RES 721 FT /note="Phosphotyrosine; by SRC" FT /evidence="ECO:0000269|PubMed:21357692" FT VAR_SEQ 49..110 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_010073" FT VAR_SEQ 258..313 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_010074" FT VAR_SEQ 258..312 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:9361039" FT /id="VSP_003424" FT VAR_SEQ 313 FT /note="Q -> QQ (in isoform 4)" FT /evidence="ECO:0000303|PubMed:9326933" FT /id="VSP_024381" FT VARIANT 5 FT /note="R -> L (changed function; unable to rescue the FT corresponding loss of function zebrafish mutant which FT displays a cilium function alteration phenotype; FT dbSNP:rs190983114)" FT /evidence="ECO:0000269|PubMed:24746959" FT /id="VAR_077633" FT VARIANT 342 FT /note="G -> R (in NPHP1; patients show Cogan-type FT congenital ocular motor apraxia; dbSNP:rs121907899)" FT /evidence="ECO:0000269|PubMed:10839884" FT /id="VAR_012160" FT MUTAGEN 121 FT /note="S->A: Impairs interaction with PACS1; when FT associated with A-123 and A-126." FT /evidence="ECO:0000269|PubMed:16308564" FT MUTAGEN 123 FT /note="S->A: Impairs interaction with PACS1; when FT associated with A-121 and A-126." FT /evidence="ECO:0000269|PubMed:16308564" FT MUTAGEN 126 FT /note="S->A: Impairs interaction with PACS1; when FT associated with A-121 and A-123." FT /evidence="ECO:0000269|PubMed:16308564" FT MUTAGEN 180 FT /note="L->P: Loss of SH3 domain fold." FT /evidence="ECO:0000269|PubMed:15723349" FT MUTAGEN 203 FT /note="P->L: Does not affect fold stability, as assessed by FT circular dichroism thermal denaturation melting curves and FT by NMR spectroscopy. Affects interaction with PKD1." FT /evidence="ECO:0000269|PubMed:20856870" FT HELIX 9..31 FT /evidence="ECO:0007829|PDB:6O1Q" FT HELIX 35..37 FT /evidence="ECO:0007829|PDB:6O1Q" FT HELIX 39..65 FT /evidence="ECO:0007829|PDB:6O1Q" FT TURN 69..72 FT /evidence="ECO:0007829|PDB:6O1Q" FT HELIX 77..104 FT /evidence="ECO:0007829|PDB:6O1Q" FT STRAND 155..159 FT /evidence="ECO:0007829|PDB:1S1N" FT STRAND 166..169 FT /evidence="ECO:0007829|PDB:1S1N" FT STRAND 175..181 FT /evidence="ECO:0007829|PDB:1S1N" FT STRAND 186..193 FT /evidence="ECO:0007829|PDB:1S1N" FT STRAND 195..197 FT /evidence="ECO:0007829|PDB:1S1N" FT STRAND 199..204 FT /evidence="ECO:0007829|PDB:1S1N" FT STRAND 207..209 FT /evidence="ECO:0007829|PDB:1S1N" SQ SEQUENCE 732 AA; 83299 MW; 270125F56F2C50F7 CRC64; MLARRQRDPL QALRRRNQEL KQQVDSLLSE SQLKEALEPN KRQHIYQRCI QLKQAIDENK NALQKLSKAD ESAPVANYNQ RKEEEHTLLD KLTQQLQGLA VTISRENITE VGAPTEEEEE SESEDSEDSG GEEEDAEEEE EEKEENESHK WSTGEEYIAV GDFTAQQVGD LTFKKGEILL VIEKKPDGWW IAKDAKGNEG LVPRTYLEPY SEEEEGQESS EEGSEEDVEA VDETADGAEV KQRTDPHWSA VQKAISEAGI FCLVNHVSFC YLIVLMRNRM ETVEDTNGSE TGFRAWNVQS RGRIFLVSKP VLQINTVDVL TTMGAIPAGF RPSTLSQLLE EGNQFRANYF LQPELMPSQL AFRDLMWDAT EGTIRSRPSR ISLILTLWSC KMIPLPGMSI QVLSRHVRLC LFDGNKVLSN IHTVRATWQP KKPKTWTFSP QVTRILPCLL DGDCFIRSNS ASPDLGILFE LGISYIRNST GERGELSCGW VFLKLFDASG VPIPAKTYEL FLNGGTPYEK GIEVDPSISR RAHGSVFYQI MTMRRQPQLL VKLRSLNRRS RNVLSLLPET LIGNMCSIHL LIFYRQILGD VLLKDRMSLQ STDLISHPML ATFPMLLEQP DVMDALRSSW AGKESTLKRS EKRDKEFLKS TFLLVYHDCV LPLLHSTRLP PFRWAEEETE TARWKVITDF LKQNQENQGA LQALLSPDGV HEPFDLSEQT YDFLGEMRKN AV //