NDP_MOUSE
ID NDP_MOUSE Reviewed; 131 AA.
AC P48744; Q5CZY6;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Norrin;
DE AltName: Full=Norrie disease protein homolog;
DE Flags: Precursor;
GN Name=Ndp; Synonyms=Ndph;
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].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=8789439; DOI=10.1093/hmg/5.1.51;
RA Berger W., van de Pol D., Baechner D., Oerlemans F., Winkens H.,
RA Hameister H., Wieringa B., Hendriks W., Ropers H.-H.;
RT "An animal model for Norrie disease (ND): gene targeting of the mouse ND
RT gene.";
RL Hum. Mol. Genet. 5:51-59(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=L129;
RX PubMed=8835523; DOI=10.1007/s003359900026;
RA Battinelli E.M., Boyd Y., Craig I.W., Breakefield X.O., Chen Z.Y.;
RT "Characterization and mapping of the mouse NDP (Norrie disease) locus
RT (Ndp).";
RL Mamm. Genome 7:93-97(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Wood J.;
RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; 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 [5]
RP TISSUE SPECIFICITY.
RX PubMed=10452356; DOI=10.1016/s0361-9230(99)00071-4;
RA Hartzer M.K., Cheng M., Liu X., Shastry B.S.;
RT "Localization of the Norrie disease gene mRNA by in situ hybridization.";
RL Brain Res. Bull. 49:355-358(1999).
RN [6]
RP FUNCTION, AND INTERACTION WITH TO FZD4.
RX PubMed=15035989; DOI=10.1016/s0092-8674(04)00216-8;
RA Xu Q., Wang Y., Dabdoub A., Smallwood P.M., Williams J., Woods C.,
RA Kelley M.W., Jiang L., Tasman W., Zhang K., Nathans J.;
RT "Vascular development in the retina and inner ear: control by Norrin and
RT Frizzled-4, a high-affinity ligand-receptor pair.";
RL Cell 116:883-895(2004).
RN [7]
RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH FZD4 AND TSPAN12.
RX PubMed=19837033; DOI=10.1016/j.cell.2009.07.048;
RA Junge H.J., Yang S., Burton J.B., Paes K., Shu X., French D.M., Costa M.,
RA Rice D.S., Ye W.;
RT "TSPAN12 regulates retinal vascular development by promoting Norrin-but not
RT Wnt-induced FZD4/beta-catenin signaling.";
RL Cell 139:299-311(2009).
CC -!- FUNCTION: Activates the canonical Wnt signaling pathway through FZD4
CC and LRP5 coreceptor. Plays a central role in retinal vascularization by
CC acting as a ligand for FZD4 that signals via stabilizing beta-catenin
CC (CTNNB1) and activating LEF/TCF-mediated transcriptional programs. Acts
CC in concert with TSPAN12 to activate FZD4 independently of the Wnt-
CC dependent activation of FZD4, suggesting the existence of a Wnt-
CC independent signaling that also promote accumulation the beta-catenin
CC (CTNNB1). May be involved in a pathway that regulates neural cell
CC differentiation and proliferation. Possible role in neuroectodermal
CC cell-cell interaction. {ECO:0000269|PubMed:15035989,
CC ECO:0000269|PubMed:19837033}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Component of a
CC complex, at least composed of TSPAN12, FZD4, LRP5/6 and norrin (NDP).
CC Binds FZD4 with high affinity. Interacts with LRP6 (via Beta-propellers
CC 1 and 2). {ECO:0000250|UniProtKB:Q00604, ECO:0000269|PubMed:15035989,
CC ECO:0000269|PubMed:19837033}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in the outer nuclear, inner nuclear and
CC ganglion cell layers of the retina. {ECO:0000269|PubMed:10452356}.
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DR EMBL; X92397; CAA63134.1; -; mRNA.
DR EMBL; X83794; CAA58725.1; -; Genomic_DNA.
DR EMBL; AL732321; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC090623; AAH90623.1; -; mRNA.
DR CCDS; CCDS30034.1; -.
DR PIR; S55380; S55380.
DR RefSeq; NP_035013.1; NM_010883.3.
DR AlphaFoldDB; P48744; -.
DR SMR; P48744; -.
DR BioGRID; 201713; 1.
DR STRING; 10090.ENSMUSP00000046692; -.
DR ChEMBL; CHEMBL2176820; -.
DR PhosphoSitePlus; P48744; -.
DR PaxDb; P48744; -.
DR PRIDE; P48744; -.
DR ProteomicsDB; 252866; -.
DR Antibodypedia; 514; 182 antibodies from 31 providers.
DR DNASU; 17986; -.
DR Ensembl; ENSMUST00000040134; ENSMUSP00000046692; ENSMUSG00000040138.
DR GeneID; 17986; -.
DR KEGG; mmu:17986; -.
DR UCSC; uc009ssc.1; mouse.
DR CTD; 4693; -.
DR MGI; MGI:102570; Ndp.
DR VEuPathDB; HostDB:ENSMUSG00000040138; -.
DR eggNOG; KOG1216; Eukaryota.
DR GeneTree; ENSGT00390000004304; -.
DR HOGENOM; CLU_153977_0_0_1; -.
DR InParanoid; P48744; -.
DR OMA; DPGRCMR; -.
DR OrthoDB; 1589857at2759; -.
DR PhylomeDB; P48744; -.
DR BioGRID-ORCS; 17986; 3 hits in 73 CRISPR screens.
DR PRO; PR:P48744; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; P48744; protein.
DR Bgee; ENSMUSG00000040138; Expressed in lumbar dorsal root ganglion and 72 other tissues.
DR Genevisible; P48744; MM.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:BHF-UCL.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005125; F:cytokine activity; IDA:BHF-UCL.
DR GO; GO:0005109; F:frizzled binding; IPI:BHF-UCL.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0046697; P:decidualization; IEA:Ensembl.
DR GO; GO:0035426; P:extracellular matrix-cell signaling; IDA:BHF-UCL.
DR GO; GO:0110135; P:Norrin signaling pathway; IDA:BHF-UCL.
DR GO; GO:0001890; P:placenta development; IMP:MGI.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL.
DR GO; GO:0061299; P:retina vasculature morphogenesis in camera-type eye; IGI:MGI.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR Gene3D; 2.10.90.10; -; 1.
DR InterPro; IPR006207; Cys_knot_C.
DR InterPro; IPR029034; Cystine-knot_cytokine.
DR InterPro; IPR006208; Glyco_hormone_CN.
DR InterPro; IPR003064; Norrie_dis.
DR PANTHER; PTHR28611; PTHR28611; 1.
DR Pfam; PF00007; Cys_knot; 1.
DR PRINTS; PR01304; NORRIEDSEASE.
DR SMART; SM00041; CT; 1.
DR PROSITE; PS01185; CTCK_1; 1.
DR PROSITE; PS01225; CTCK_2; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Reference proteome; Secreted; Signal;
KW Wnt signaling pathway.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..131
FT /note="Norrin"
FT /id="PRO_0000021796"
FT DOMAIN 37..130
FT /note="CTCK"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00039"
FT DISULFID 37..94
FT /evidence="ECO:0000250|UniProtKB:Q00604"
FT DISULFID 53..108
FT /evidence="ECO:0000250|UniProtKB:Q00604"
FT DISULFID 63..124
FT /evidence="ECO:0000250|UniProtKB:Q00604"
FT DISULFID 67..126
FT /evidence="ECO:0000250|UniProtKB:Q00604"
FT DISULFID 91
FT /note="Interchain (with C-93)"
FT /evidence="ECO:0000250|UniProtKB:Q00604"
FT DISULFID 93
FT /note="Interchain (with C-91)"
FT /evidence="ECO:0000250|UniProtKB:Q00604"
FT DISULFID 129
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:Q00604"
SQ SEQUENCE 131 AA; 14700 MW; A761D508AED1D1A3 CRC64;
MRNHVLAASI SMLSLLAIMG DTDSKTDSSF LMDSQRCMRH HYVDSISHPL YKCSSKMVLL
ARCEGHCSQA SRSEPLVSFS TVLKQPFRSS CHCCRPQTSK LKALRLRCSG GMRLTATYRY
ILSCHCEECS S
