NPHP1_HUMAN
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 03-AUG-2022, entry version 201.
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 nephrocystin-
RT 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=10.1016/s0022-3476(00)01001-5;
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}.
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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; 97.
DR CORUM; O15259; -.
DR IntAct; O15259; 82.
DR MINT; O15259; -.
DR STRING; 9606.ENSP00000313169; -.
DR iPTMnet; O15259; -.
DR PhosphoSitePlus; O15259; -.
DR BioMuta; NPHP1; -.
DR EPD; O15259; -.
DR MassIVE; O15259; -.
DR PaxDb; O15259; -.
DR PeptideAtlas; O15259; -.
DR PRIDE; 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; 155 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 CTD; 4867; -.
DR DisGeNET; 4867; -.
DR GeneCards; NPHP1; -.
DR GeneReviews; NPHP1; -.
DR HGNC; HGNC:7905; NPHP1.
DR HPA; ENSG00000144061; Tissue enhanced (skeletal).
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; SHSHLAF; -.
DR OrthoDB; 676699at2759; -.
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; 15 hits in 1070 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 115 other tissues.
DR ExpressionAtlas; O15259; baseline and differential.
DR Genevisible; O15259; HS.
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 InterPro; IPR039687; NPHP1.
DR InterPro; IPR030642; NPHP1_SH3.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR15176:SF1; PTHR15176:SF1; 1.
DR Pfam; PF00018; SH3_1; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS50002; SH3; 1.
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; associated with 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
