NPHP4_MOUSE
ID NPHP4_MOUSE Reviewed; 1425 AA.
AC P59240; B1AS30;
DT 27-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Nephrocystin-4;
DE AltName: Full=Nephroretinin;
GN Name=Nphp4;
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].
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 [2]
RP ERRATUM OF PUBMED:12244321.
RA Mollet G., Salomon R., Gribouval O., Silbermann F., Bacq D., Landthaler G.,
RA Milford D., Nayir A., Rizzoni G., Antignac C., Saunier S.;
RL Nat. Genet. 32:459-459(2002).
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 GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [7]
RP SUBCELLULAR LOCATION, SUBUNIT, AND INTERACTION WITH NPHP1; RPGRIP1L AND
RP IQCB1.
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 [8]
RP INTERACTION WITH SPATA7, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=29899041; DOI=10.1083/jcb.201712117;
RA Dharmat R., Eblimit A., Robichaux M.A., Zhang Z., Nguyen T.T., Jung S.Y.,
RA He F., Jain A., Li Y., Qin J., Overbeek P., Roepman R., Mardon G.,
RA Wensel T.G., Chen R.;
RT "SPATA7 maintains a novel photoreceptor-specific zone in the distal
RT connecting cilium.";
RL J. Cell Biol. 217:2851-2865(2018).
CC -!- FUNCTION: Involved in the organization of apical junctions; the
CC function is proposed to implicate a NPHP1-4-8 module. Does not seem to
CC be strictly required for ciliogenesis (By similarity). Required for
CC building functional cilia. Involved in the organization of the
CC subapical actin network in multiciliated epithelial cells. Seems to
CC recruit INT to basal bodies of motile cilia which subsequently
CC interacts with actin-modifying proteins such as DAAM1 (By similarity).
CC In cooperation with INVS may down-regulate the canonical Wnt pathway
CC and promote the Wnt-PCP pathway by regulating expression and
CC subcellular location of disheveled proteins. Stabilizes protein levels
CC of JADE1 and promotes its translocation to the nucleus leading to
CC cooperative inhibition of canonical Wnt signaling (By similarity). Acts
CC as negative regulator of the hippo pathway by association with LATS1
CC and modifying LATS1-dependent phosphorylation and localization of
CC WWTR1/TAZ (By similarity). {ECO:0000250|UniProtKB:B0DOB4,
CC ECO:0000250|UniProtKB:O75161}.
CC -!- SUBUNIT: Interacts with NPHP1 and RPGRIP1L/NPHP8; NPHP1, NPHP4 and
CC RPGRIP1L are proposed to form a functional NPHP1-4-8 module localized
CC to cell-cell contacts and the ciliary transition zone; NPHP4 mediates
CC the interaction between NPHP1 and RPGRIP1L. Interacts with IQCB1/NPHP5;
CC the interaction likely requires additional interactors
CC (PubMed:21565611). Interacts with RPGRIP1, CEP164, JADE1, PALS1, INADL,
CC PARD6A, INVS, DVL2. Interacts with INTU; INTU mediates the interaction
CC between NPHP4 and DAAM1. Interacts with JADE1 (By similarity).
CC Interacts with SPATA7 (PubMed:29899041). {ECO:0000250|UniProtKB:O75161,
CC ECO:0000269|PubMed:21565611, ECO:0000269|PubMed:29899041}.
CC -!- INTERACTION:
CC P59240; Q9QY53: Nphp1; NbExp=8; IntAct=EBI-4281265, EBI-77230;
CC P59240; Q8CG73: Rpgrip1l; NbExp=4; IntAct=EBI-4281265, EBI-4281130;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, cilium basal body
CC {ECO:0000269|PubMed:21565611, ECO:0000269|PubMed:29899041}. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000250|UniProtKB:O75161}. Cell junction, tight junction
CC {ECO:0000269|PubMed:21565611}. Note=In the retinal photoreceptor cell
CC layer, localizes at the connecting cilium (PubMed:29899041). In
CC cultured renal cells, it localizes diffusely in the cytoplasm but, as
CC cells approach confluence, it accumulates to basolateral tight
CC junctions (PubMed:21565611). Localizes to the ciliary transition zone
CC (PubMed:21565611). {ECO:0000269|PubMed:21565611,
CC ECO:0000269|PubMed:29899041}.
CC -!- TISSUE SPECIFICITY: Expressed in the retina (at protein level).
CC {ECO:0000269|PubMed:29899041}.
CC -!- SIMILARITY: Belongs to the NPHP4 family. {ECO:0000305}.
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DR EMBL; AY118229; AAM78559.1; -; mRNA.
DR EMBL; AL607109; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL611970; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466594; EDL14939.1; -; Genomic_DNA.
DR EMBL; CH466594; EDL14940.1; -; Genomic_DNA.
DR EMBL; BC138370; AAI38371.1; -; mRNA.
DR CCDS; CCDS38985.1; -.
DR RefSeq; NP_700473.2; NM_153424.2.
DR RefSeq; XP_006538935.1; XM_006538872.3.
DR RefSeq; XP_006538936.1; XM_006538873.3.
DR AlphaFoldDB; P59240; -.
DR BioGRID; 234431; 215.
DR CORUM; P59240; -.
DR IntAct; P59240; 70.
DR STRING; 10090.ENSMUSP00000080128; -.
DR iPTMnet; P59240; -.
DR PhosphoSitePlus; P59240; -.
DR MaxQB; P59240; -.
DR PaxDb; P59240; -.
DR PeptideAtlas; P59240; -.
DR PRIDE; P59240; -.
DR ProteomicsDB; 293954; -.
DR Antibodypedia; 27030; 124 antibodies from 24 providers.
DR DNASU; 260305; -.
DR Ensembl; ENSMUST00000056567; ENSMUSP00000049920; ENSMUSG00000039577.
DR Ensembl; ENSMUST00000081393; ENSMUSP00000080128; ENSMUSG00000039577.
DR GeneID; 260305; -.
DR KEGG; mmu:260305; -.
DR UCSC; uc008wap.1; mouse.
DR CTD; 261734; -.
DR MGI; MGI:2384210; Nphp4.
DR VEuPathDB; HostDB:ENSMUSG00000039577; -.
DR eggNOG; ENOG502QUNP; Eukaryota.
DR GeneTree; ENSGT00510000048827; -.
DR HOGENOM; CLU_004882_0_0_1; -.
DR InParanoid; P59240; -.
DR OMA; HVPFKFQ; -.
DR OrthoDB; 53958at2759; -.
DR PhylomeDB; P59240; -.
DR TreeFam; TF351573; -.
DR Reactome; R-MMU-2028269; Signaling by Hippo.
DR Reactome; R-MMU-5620912; Anchoring of the basal body to the plasma membrane.
DR BioGRID-ORCS; 260305; 0 hits in 71 CRISPR screens.
DR PRO; PR:P59240; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; P59240; protein.
DR Bgee; ENSMUSG00000039577; Expressed in lumbar subsegment of spinal cord and 110 other tissues.
DR Genevisible; P59240; MM.
DR GO; GO:0005923; C:bicellular tight junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005911; C:cell-cell junction; ISS:UniProtKB.
DR GO; GO:0005814; C:centriole; IDA:MGI.
DR GO; GO:0005813; C:centrosome; ISO:MGI.
DR GO; GO:0036064; C:ciliary basal body; ISO:MGI.
DR GO; GO:0097546; C:ciliary base; IDA:MGI.
DR GO; GO:0035869; C:ciliary transition zone; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:CACAO.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0097730; C:non-motile cilium; IBA:GO_Central.
DR GO; GO:0016604; C:nuclear body; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0032391; C:photoreceptor connecting cilium; IDA:MGI.
DR GO; GO:0120206; C:photoreceptor distal connecting cilium; IDA:MGI.
DR GO; GO:0097470; C:ribbon synapse; IDA:MGI.
DR GO; GO:0030317; P:flagellated sperm motility; IMP:MGI.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:MGI.
DR GO; GO:0045494; P:photoreceptor cell maintenance; IMP:MGI.
DR GO; GO:0035845; P:photoreceptor cell outer segment organization; IMP:MGI.
DR GO; GO:1903348; P:positive regulation of bicellular tight junction assembly; ISO:MGI.
DR GO; GO:1904491; P:protein localization to ciliary transition zone; IBA:GO_Central.
DR GO; GO:0060041; P:retina development in camera-type eye; IMP:MGI.
DR InterPro; IPR029775; NPHP4.
DR PANTHER; PTHR31043; PTHR31043; 1.
PE 1: Evidence at protein level;
KW Cell junction; Cell projection; Cilium; Cytoplasm; Cytoskeleton;
KW Phosphoprotein; Reference proteome; Tight junction.
FT CHAIN 1..1425
FT /note="Nephrocystin-4"
FT /id="PRO_0000159770"
FT REGION 448..554
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 822..1425
FT /note="Sufficient for basal bodies localization"
FT /evidence="ECO:0000250|UniProtKB:O75161"
FT COMPBIAS 495..541
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 145
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O75161"
SQ SEQUENCE 1425 AA; 157269 MW; DDB9739850AEA5C4 CRC64;
MGDWHRAFTQ NTLVPPHPQR ARQLGKESTA FQCILKWLDG PLIKQGILDM LSELECHLRV
TLFDVTYKHF FGRTWKTTVK PTNQPSKQPP RITFNEPLYF HTTLSHPSIV AVVEVVTEGR
KRDGTLQLLS CGFGILRIFG NKPESPTSAA QDKRLRLYHG TPRALLHPLL QDPIEQNKFM
RLMENCSLQY TLKPHPPLEP AFHLLPENLL VSGFQQIPGL LPPHGDTGDA LRKPRFQKPT
TWHLDDLFFT LYPSLEKFEE ELVQLLISDR EGVGLLDSGT LEVLERRLHV CVHNGLGFVQ
RPQVVVLVPE MDVALTRSAS FSRKISASSK NSSGNQALVL RSHLRLPEMV SHPAFAIVFQ
LEYVFNSPSG ADGGASSPTS ISSVACMHMV RWAVWNPDLE VGPGKVTLPL QGGVQQNPSR
CLVYKVPSAS MSSEEVKQVE SGTIQFQFSL SSDGPTEHAN GPRVGRRSSR KMPASPSGTP
APAARDLAAT QDSPVGPGLS LSQLTASPLS PALQSSSKPP LQPPDSSQSP EGPQLQAESV
LESRVSHLEA DLSQPASLQG TPAVEHLQEL PFTPLHAPIV VGAQTRSSRS QLSRAAMVLL
QSSGFPEILD ASQQPVEAVN PIDPVRFNPQ KEESDCLRGN EIVLQFLAFS RAAQDCPGTP
WPQTVYFTFQ FYRFPPETTP RLQLVKLDGT GKSGSGSLSH ILVPINKDGS FDAGSPGLQL
RYMVDPGFLK PGEQRWFAHY LAAQTLQVDV WDGDSLLLIG SAGVQMKHLL RQGRPAVQVS
HELEVVATEY EQEMMAVSGD VAGFGSVKPI GVHTVVKGRL HLTLANVGHA CEPRARGSNL
LPPSRSRVIS NDGASFFSGG SLLIPGGPKR KRVVQAQRLA DVDSELAAML LTHTRAGQGP
QAAGQEADAV HKRKLERMRL VRLQEAGGDS DSRRISLLAQ HSVRAQHSRD LQVIDAYRER
TKAESIAGVL SQAITTHHTL YATLGTAEFF EFALKNPHNT QHTVAIEIDS PELSIILDSQ
EWRYFKEATG LHTPLEEDMF HLRGSLAPQL YLRPRETAHI PLKFQSFSVG PLAPTQAPAE
VITEKDAESG PLWKCSAMPT KHAKVLFRVE TGQLIAVLCL TVEPQPHVVD QVFRFYHPEL
TFLKKAIRLP PWHTLPGAPV GMPGEDPPVH VRCSDPNVIC EAQNVGPGEP RDVFLKVASG
PSPEIKDFFV VIYADRWLAV PVQTWQVCLH SLQRVDVSCV AGQLTRLSLV LRGTQTVRKV
RAFTSHPQEL KTDPAGVFVL PPHGVQDLHV GVRPRRAGSR FVHLNLVDID YHQLVASWLV
CLSCRQPLIS KAFEITMAAG DEKGTNKRIT YTNPYPSRRT YRLHSDRPEL LRFKEDSFQV
AGGETYTIGL RFLPSGSAGQ EEILIYINDH EDKNEETFCV KVLYQ
