ID   NDP_BOVIN               Reviewed;         133 AA.
AC   Q2KI78;
DT   25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT   07-MAR-2006, sequence version 1.
DT   03-AUG-2022, entry version 86.
DE   RecName: Full=Norrin;
DE   AltName: Full=Norrie disease protein homolog;
DE   Flags: Precursor;
GN   Name=NDP;
OS   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Hypothalamus;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases.
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 (By similarity). {ECO:0000250}.
CC   -!- SUBUNIT: Homodimer; disulfide-linked. Component of a complex, at least
CC       composed of TSPAN12, FZD4, LRP5/6 and norrin (NDP). Binds FZD4 with
CC       high affinity. Interacts with LRP6 (via Beta-propellers 1 and 2).
CC       {ECO:0000250|UniProtKB:Q00604}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
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DR   EMBL; BC112738; AAI12739.1; -; mRNA.
DR   RefSeq; NP_001039555.1; NM_001046090.2.
DR   RefSeq; XP_005228345.1; XM_005228288.3.
DR   RefSeq; XP_005228346.1; XM_005228289.3.
DR   RefSeq; XP_005228347.1; XM_005228290.3.
DR   RefSeq; XP_010820371.1; XM_010822069.2.
DR   AlphaFoldDB; Q2KI78; -.
DR   SMR; Q2KI78; -.
DR   STRING; 9913.ENSBTAP00000016757; -.
DR   PaxDb; Q2KI78; -.
DR   Ensembl; ENSBTAT00000016757; ENSBTAP00000016757; ENSBTAG00000012623.
DR   Ensembl; ENSBTAT00000072339; ENSBTAP00000066041; ENSBTAG00000012623.
DR   GeneID; 511596; -.
DR   KEGG; bta:511596; -.
DR   CTD; 4693; -.
DR   VEuPathDB; HostDB:ENSBTAG00000012623; -.
DR   VGNC; VGNC:31939; NDP.
DR   eggNOG; KOG1216; Eukaryota.
DR   GeneTree; ENSGT00390000004304; -.
DR   HOGENOM; CLU_153977_0_0_1; -.
DR   InParanoid; Q2KI78; -.
DR   OMA; DPGRCMR; -.
DR   OrthoDB; 1589857at2759; -.
DR   Proteomes; UP000009136; Chromosome X.
DR   Bgee; ENSBTAG00000012623; Expressed in uterine cervix and 66 other tissues.
DR   GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR   GO; GO:0062023; C:collagen-containing extracellular matrix; IEA:Ensembl.
DR   GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR   GO; GO:0005615; C:extracellular space; IEA:Ensembl.
DR   GO; GO:0005125; F:cytokine activity; IBA:GO_Central.
DR   GO; GO:0005109; F:frizzled binding; IEA:Ensembl.
DR   GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR   GO; GO:0035426; P:extracellular matrix-cell signaling; IEA:Ensembl.
DR   GO; GO:0110135; P:Norrin signaling pathway; IEA:Ensembl.
DR   GO; GO:0001890; P:placenta development; IEA:Ensembl.
DR   GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IEA:Ensembl.
DR   GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IEA:Ensembl.
DR   GO; GO:0061299; P:retina vasculature morphogenesis in camera-type eye; IEA:Ensembl.
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   2: Evidence at transcript level;
KW   Disulfide bond; Reference proteome; Secreted; Signal;
KW   Wnt signaling pathway.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000255"
FT   CHAIN           25..133
FT                   /note="Norrin"
FT                   /id="PRO_0000247542"
FT   DOMAIN          39..132
FT                   /note="CTCK"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00039"
FT   DISULFID        39..96
FT                   /evidence="ECO:0000250|UniProtKB:Q00604"
FT   DISULFID        55..110
FT                   /evidence="ECO:0000250|UniProtKB:Q00604"
FT   DISULFID        65..126
FT                   /evidence="ECO:0000250|UniProtKB:Q00604"
FT   DISULFID        69..128
FT                   /evidence="ECO:0000250|UniProtKB:Q00604"
FT   DISULFID        93
FT                   /note="Interchain (with C-95)"
FT                   /evidence="ECO:0000250|UniProtKB:Q00604"
FT   DISULFID        95
FT                   /note="Interchain (with C-93)"
FT                   /evidence="ECO:0000250|UniProtKB:Q00604"
FT   DISULFID        131
FT                   /note="Interchain"
FT                   /evidence="ECO:0000250|UniProtKB:Q00604"
SQ   SEQUENCE   133 AA;  14978 MW;  42FABB6950BF72DF CRC64;
     MRNHVLAASF SMLSLLALMG DTDSKTESSF MMDSDPQRCM RHHYVDSISH PLYKCSSKMV
     LLARCEGHCS QASRSEPLVS FSTVLKQPFR SSCHCCRPQT SKLKALRLRC SGGMRLTATY
     RYILSCHCEE CSS