NPHP3_MOUSE
ID NPHP3_MOUSE Reviewed; 1325 AA.
AC Q7TNH6; D6RHB4; E9Q5X1; E9QN29; Q69Z39; Q8C798; Q8C7Z3; Q9D6D1;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 22-FEB-2012, sequence version 2.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=Nephrocystin-3;
GN Name=Nphp3; Synonyms=Kiaa2000;
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), DEVELOPMENTAL STAGE, AND VARIANT
RP PCY SER-614.
RC STRAIN=BALB/cJ;
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 [MRNA] (ISOFORM 2), AND NUCLEOTIDE SEQUENCE [LARGE
RP SCALE MRNA] OF 735-1324.
RC STRAIN=C57BL/6J; TISSUE=Brain, Cerebellum, and Heart;
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 63-1325 (ISOFORM 1).
RC TISSUE=Pancreatic islet;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
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 that
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 (By similarity). Interacts with CEP164 (By
CC similarity). Component of a complex containing at least ANKS6, INVS,
CC NEK8 and NPHP3. ANKS6 may organize complex assembly by linking INVS and
CC NPHP3 to NEK8 and INVS may target the complex to the proximal ciliary
CC axoneme (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell projection, cilium {ECO:0000250}.
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 {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=Q7TNH6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7TNH6-2; Sequence=VSP_014492, VSP_014493;
CC -!- DEVELOPMENTAL STAGE: In gastrulation-stage embryos, it is confined to
CC the node between 7.5 and 8.25 dpc In sections of 14.5 and 16.5 dpc.
CC embryos, it is strongly expressed in neural tissue (brain and
CC ganglions). Also weakly expressed included in kidney tubules, retina,
CC respiratory epithelium, biliary tract and liver. In the adult kidney,
CC it is weakly but specifically expressed in distal tubules located at
CC the cortico-medullary border, which corresponds to the site of cyst
CC formation in mice lacking Nphp3. Expressed in retina and liver.
CC {ECO:0000269|PubMed:12872122}.
CC -!- DISEASE: Note=Defects in Nphp3 may be the cause of polycystic kidney
CC disease (pcy). Pcy is a recessive disorder causing chronic renal
CC failure. The Pcy phenotype can be slowed by diet modification such as
CC protein restriction, administration of soy-based proteins,
CC administration of methylprednisolone or treatment with V2R antagonist.
CC In contrast administration of bicarbonate/citrate has no effect.
CC -!- DISRUPTION PHENOTYPE: Mice show situs inversus, congenital heart
CC defects, and embryonic lethality. {ECO:0000269|PubMed:18371931}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB29319.1; Type=Erroneous termination; Note=Extended C-terminus.; Evidence={ECO:0000305};
CC Sequence=BAC33481.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAC34915.1; Type=Erroneous initiation; Note=Extended 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; AY259499; AAP84621.1; -; mRNA.
DR EMBL; AK014393; BAB29319.1; ALT_SEQ; mRNA.
DR EMBL; AK048877; BAC33481.1; ALT_FRAME; mRNA.
DR EMBL; AC138739; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AK052281; BAC34915.1; ALT_INIT; mRNA.
DR EMBL; AK173327; BAD32605.1; -; mRNA.
DR CCDS; CCDS40749.1; -. [Q7TNH6-1]
DR RefSeq; NP_082997.3; NM_028721.3. [Q7TNH6-1]
DR RefSeq; NP_766048.1; NM_172460.1. [Q7TNH6-2]
DR AlphaFoldDB; Q7TNH6; -.
DR SMR; Q7TNH6; -.
DR BioGRID; 216433; 15.
DR IntAct; Q7TNH6; 7.
DR STRING; 10090.ENSMUSP00000035167; -.
DR iPTMnet; Q7TNH6; -.
DR PhosphoSitePlus; Q7TNH6; -.
DR EPD; Q7TNH6; -.
DR MaxQB; Q7TNH6; -.
DR PaxDb; Q7TNH6; -.
DR PRIDE; Q7TNH6; -.
DR ProteomicsDB; 293952; -. [Q7TNH6-1]
DR ProteomicsDB; 293953; -. [Q7TNH6-2]
DR DNASU; 74025; -.
DR Ensembl; ENSMUST00000035167; ENSMUSP00000035167; ENSMUSG00000032558. [Q7TNH6-1]
DR GeneID; 74025; -.
DR KEGG; mmu:74025; -.
DR UCSC; uc009rhb.2; mouse. [Q7TNH6-2]
DR UCSC; uc009rhc.2; mouse. [Q7TNH6-1]
DR CTD; 27031; -.
DR MGI; MGI:1921275; Nphp3.
DR VEuPathDB; HostDB:ENSMUSG00000032558; -.
DR eggNOG; KOG1840; Eukaryota.
DR GeneTree; ENSGT00940000156398; -.
DR HOGENOM; CLU_007418_0_0_1; -.
DR InParanoid; Q7TNH6; -.
DR OMA; RCYLMYT; -.
DR OrthoDB; 377554at2759; -.
DR PhylomeDB; Q7TNH6; -.
DR TreeFam; TF314010; -.
DR Reactome; R-MMU-5624138; Trafficking of myristoylated proteins to the cilium.
DR BioGRID-ORCS; 74025; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Nphp3; mouse.
DR PRO; PR:Q7TNH6; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q7TNH6; protein.
DR Bgee; ENSMUSG00000032558; Expressed in ventricular zone and 62 other tissues.
DR ExpressionAtlas; Q7TNH6; baseline and differential.
DR Genevisible; Q7TNH6; MM.
DR GO; GO:0097546; C:ciliary base; IDA:MGI.
DR GO; GO:0097543; C:ciliary inversin compartment; IDA:MGI.
DR GO; GO:0005929; C:cilium; ISS:UniProtKB.
DR GO; GO:0003283; P:atrial septum development; ISO:MGI.
DR GO; GO:0060271; P:cilium assembly; IMP:BHF-UCL.
DR GO; GO:0060026; P:convergent extension; IBA:GO_Central.
DR GO; GO:0060027; P:convergent extension involved in gastrulation; ISO:MGI.
DR GO; GO:0071908; P:determination of intestine left/right asymmetry; ISO:MGI.
DR GO; GO:0007368; P:determination of left/right symmetry; IMP:BHF-UCL.
DR GO; GO:0071910; P:determination of liver left/right asymmetry; ISO:MGI.
DR GO; GO:0035469; P:determination of pancreatic left/right asymmetry; ISO:MGI.
DR GO; GO:0071909; P:determination of stomach left/right asymmetry; ISO:MGI.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; IMP:MGI.
DR GO; GO:0030198; P:extracellular matrix organization; IMP:MGI.
DR GO; GO:0001947; P:heart looping; ISO:MGI.
DR GO; GO:0001822; P:kidney development; IMP:MGI.
DR GO; GO:0060993; P:kidney morphogenesis; IMP:BHF-UCL.
DR GO; GO:0006629; P:lipid metabolic process; IMP:MGI.
DR GO; GO:0030324; P:lung development; ISO:MGI.
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; ISS:UniProtKB.
DR GO; GO:1905515; P:non-motile cilium assembly; IMP:MGI.
DR GO; GO:0045494; P:photoreceptor cell maintenance; ISO:MGI.
DR GO; GO:0032092; P:positive regulation of protein binding; IMP:MGI.
DR GO; GO:2000095; P:regulation of Wnt signaling pathway, planar cell polarity pathway; ISS:UniProtKB.
DR GO; GO:0072189; P:ureter development; ISO:MGI.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 1.25.40.10; -; 3.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR019734; TPR_repeat.
DR Pfam; PF13176; TPR_7; 1.
DR SMART; SM00028; TPR; 8.
DR SUPFAM; SSF48452; SSF48452; 2.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS50005; TPR; 8.
DR PROSITE; PS50293; TPR_REGION; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; Cilium; Coiled coil;
KW Disease variant; Lipoprotein; Myristate; Reference proteome; Repeat;
KW TPR repeat; Wnt signaling pathway.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..1325
FT /note="Nephrocystin-3"
FT /id="PRO_0000106302"
FT REPEAT 467..500
FT /note="TPR 1"
FT REPEAT 881..914
FT /note="TPR 2"
FT REPEAT 916..937
FT /note="TPR 3"
FT REPEAT 938..971
FT /note="TPR 4"
FT REPEAT 980..1013
FT /note="TPR 5"
FT REPEAT 1022..1055
FT /note="TPR 6"
FT REPEAT 1088..1121
FT /note="TPR 7"
FT REPEAT 1130..1163
FT /note="TPR 8"
FT REPEAT 1172..1205
FT /note="TPR 9"
FT REPEAT 1214..1247
FT /note="TPR 10"
FT REPEAT 1256..1289
FT /note="TPR 11"
FT REGION 1..20
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1293..1325
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 107..203
FT /evidence="ECO:0000255"
FT COMPBIAS 1295..1325
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 447..462
FT /note="DILGLENTDVEEKDGG -> VNMRFSVKFSSKIASW (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_014492"
FT VAR_SEQ 463..1325
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_014493"
FT VARIANT 614
FT /note="I -> S (in pcy)"
FT /evidence="ECO:0000269|PubMed:12872122"
FT CONFLICT 308
FT /note="P -> H (in Ref. 1; AAP84621)"
FT /evidence="ECO:0000305"
FT CONFLICT 493
FT /note="T -> A (in Ref. 1; AAP84621)"
FT /evidence="ECO:0000305"
FT CONFLICT 674
FT /note="I -> L (in Ref. 1; AAP84621)"
FT /evidence="ECO:0000305"
FT CONFLICT 678
FT /note="T -> I (in Ref. 1; AAP84621)"
FT /evidence="ECO:0000305"
FT CONFLICT 684
FT /note="M -> V (in Ref. 1; AAP84621)"
FT /evidence="ECO:0000305"
FT CONFLICT 706
FT /note="Missing (in Ref. 1; AAP84621)"
FT /evidence="ECO:0000305"
FT CONFLICT 732
FT /note="H -> R (in Ref. 1; AAP84621)"
FT /evidence="ECO:0000305"
FT CONFLICT 799
FT /note="V -> I (in Ref. 1; AAP84621)"
FT /evidence="ECO:0000305"
FT CONFLICT 849
FT /note="A -> T (in Ref. 1; AAP84621)"
FT /evidence="ECO:0000305"
FT CONFLICT 1092
FT /note="N -> D (in Ref. 2; BAB29319)"
FT /evidence="ECO:0000305"
FT CONFLICT 1293
FT /note="L -> S (in Ref. 2; BAB29319)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1325 AA; 150289 MW; 6265F1CC7D9809CC CRC64;
MGTASSLVSP TGGEVIEDTY GAGGGEACEI PVEVKPKARL LRSSFRRGAG AGPGSLPRAA
GGGGLLGASF KSTGSSVPEL EYAAAEFERL KKEYEIFRVS KNQELLSMGR REAKLDTENK
RLRAELQALQ KTYQKILREK EGALEAKYQA MERAVTFEHD RDRVKRQFKI FRETKENEIQ
DLLRAKRELE SKLQRLQAQG IQVFDPGESD SDDNCTDVTA AGTQCEYWAS RALGSEHSIG
SMIQLPQPFR GPEFAHSSID VEGPFANINR DDWDAAVAGL LQATPLFSHS LWSHPVRCYL
IYTDETQPEM ELFLKDHSPK LKRMCETMGY FFLAVYFPLD VENQYLTVRK WEIEKSSLVI
LFLHSTLPSF LLEDCEEAFL QNPEGKPGLI YHRLEDGKVT CDSVQQFLDQ VSNLGKTTKA
KIIEHSGDPA EGVCKIYVGV EKIIKQDILG LENTDVEEKD GGREDSTPEE DDFGDVLWDI
HDEQEQMEAF QQTSSSAHEL GFEKYYQRLD DLVVAPAPIP PLLVSGGPGS GKSLLLSKWI
QLQQKHFPNT LILSHFVGRP MSTSSESSLI IKRLTLKLMQ HFWAVSALTL DPAKLLEEFP
HWLEKLSARH QGSIIIIIDS IDQVQQVEKH MKWLIDPLPV NVRVIVSVNV ETCPTAWRLW
PTLHLDPLSP KDAISIITAE CYSMDVRLSR EQEKMLEQHC RPATTRHALY VTLFSKMMAC
AGRGGNVAET LHQCLQCQDT VSLYKLVLHH VRESMPSDRD KEWMTQILCL INVSHNGVSE
SELMELYPEM SWLSLTSIVH SLHKMHLLTY SCGLLRFQHL QAWETVRLQY LEDPALVSSY
REKLISYFAS QLSQDRVTWR SADELPWLFQ QQGSKQKLHS CLLNLLVAQN LYKRGHFAEL
LSYWQFVGKD KGAMATEYFE SLKQYENSEG EENMLCLADL YETLGRFLKD LGLLSQAVVP
LQRSLEIRET ALDPDHPRVA QSLHQLAGVY VQWKKFGDAE QLYKQALEIS ENAYGADHPH
AARELEALAT LYHKQNKYEQ AEHFRKKSVI IRQQATRRKG SLYGFALLRR RALQLEELTL
GKDKPENART LNELGVLYFL QNNLETAEQF LKRSLEMRER VLGPDHPDCA QSLNNLAALC
NEKKQYEKAE ELYERALDIR RRALAPDHPS LAYTVKHLAI LYKKTGKVDK AVPLYELAVE
IRQKSFGPKH PSVATALVNL AVLHSQMKKH SEALPLYERA LKIYEDSLGR MHPRVGETLK
NLAVLSYEEG NFEKAAELYK RAMEIKEAET SLLGGKAPSR QSSSGDTFLF KTTHSPNVFL
PQGQS
