NDP_MACFA
ID NDP_MACFA Reviewed; 133 AA.
AC Q60HE4; Q4R4Y3;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 61.
DE RecName: Full=Norrin;
DE AltName: Full=Norrie disease protein homolog;
DE Flags: Precursor;
GN Name=NDP; ORFNames=QflA-19459, QtrA-10693;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Frontal cortex;
RA Kusuda J., Osada N., Tanuma R., Hirata M., Sugano S., Hashimoto K.;
RT "Isolation and characterization of cDNA for macaque neurological disease
RT genes.";
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Temporal cortex;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) 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; AB125183; BAD51971.1; -; mRNA.
DR EMBL; AB169761; BAE01842.1; -; mRNA.
DR RefSeq; NP_001272185.1; NM_001285256.1.
DR AlphaFoldDB; Q60HE4; -.
DR SMR; Q60HE4; -.
DR STRING; 9541.XP_005593404.1; -.
DR Ensembl; ENSMFAT00000019832; ENSMFAP00000045528; ENSMFAG00000000487.
DR GeneID; 102117357; -.
DR VEuPathDB; HostDB:ENSMFAG00000000487; -.
DR eggNOG; KOG1216; Eukaryota.
DR GeneTree; ENSGT00390000004304; -.
DR OMA; DPGRCMR; -.
DR OrthoDB; 1589857at2759; -.
DR Proteomes; UP000233100; Chromosome X.
DR Bgee; ENSMFAG00000000487; Expressed in cerebellum and 2 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:0005615; C:extracellular space; IEA:Ensembl.
DR GO; GO:0005125; F:cytokine activity; IEA:Ensembl.
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_0000021795"
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; 15044 MW; D219E8B7F957286A CRC64;
MRKHVLAASF SMLSLLVIMG DTDSKTDSSF IMDSDPRRCM RHHYVDSISH PLYKCSSKMV
LLARCEGHCS QASRSEPLVS FSTVLKQPFR SSCHCCRPQT SKLKALRLRC SGGMRLTATY
RYILSCHCEE CNS
