ID RSPO3_DANRE Reviewed; 317 AA.
AC Q5R328; A4QNT6;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 2.
DT 27-MAR-2024, entry version 103.
DE RecName: Full=R-spondin-3;
DE AltName: Full=Cabriolet;
DE AltName: Full=Roof plate-specific spondin-3;
DE Flags: Precursor;
GN Name=rspo3; ORFNames=sb:cb387, zgc:162040;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Embryo;
RA Mieda M., Hirate Y., Aoki M., Sasaki K., Okamoto H.;
RT "Nucleopondin, a novel nuclear protein with a thrombospondin type I repeat,
RT is expressed in dynamic spatial and temporal patterns in zebrafish and
RT mouse development.";
RL Submitted (DEC-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=WIK;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (APR-2007) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Activator of the canonical Wnt signaling pathway by acting as
CC a ligand for lgr4-6 receptors, which acts as a key regulator of
CC angiogenesis. Upon binding to lgr4-6 (lgr4, lgr5 or lgr6), lgr4-6
CC associate with phosphorylated lrp6 and frizzled receptors that are
CC activated by extracellular Wnt receptors, triggering the canonical Wnt
CC signaling pathway to increase expression of target genes. Acts both in
CC the canonical. Wnt/beta-catenin-dependent pathway and in non-canonical
CC Wnt signaling pathway. Acts as a key regulator of angiogenesis by
CC controlling vascular stability and pruning: acts by activating the non-
CC canonical Wnt signaling pathway in endothelial cells (By similarity).
CC Can also amplify Wnt signaling pathway independently of LGR4-6
CC receptors, possibly by acting as a direct antagonistic ligand to RNF43
CC and ZNRF3 (By similarity). {ECO:0000250|UniProtKB:Q2TJ95,
CC ECO:0000250|UniProtKB:Q9BXY4}.
CC -!- SUBUNIT: Binds heparin. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q2TJ95}.
CC -!- DOMAIN: The FU repeats are required for activation and stabilization of
CC beta-catenin. {ECO:0000250|UniProtKB:Q2TJ95}.
CC -!- SIMILARITY: Belongs to the R-spondin family. {ECO:0000305}.
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DR EMBL; AB035930; BAD74061.1; -; mRNA.
DR EMBL; BC139514; AAI39515.1; -; mRNA.
DR RefSeq; NP_001017358.1; NM_001017358.1.
DR AlphaFoldDB; Q5R328; -.
DR SMR; Q5R328; -.
DR STRING; 7955.ENSDARP00000058577; -.
DR GlyCosmos; Q5R328; 2 sites, No reported glycans.
DR PaxDb; 7955-ENSDARP00000058577; -.
DR GeneID; 100007702; -.
DR KEGG; dre:100007702; -.
DR AGR; ZFIN:ZDB-GENE-030131-9814; -.
DR CTD; 84870; -.
DR ZFIN; ZDB-GENE-030131-9814; rspo3.
DR eggNOG; KOG3525; Eukaryota.
DR InParanoid; Q5R328; -.
DR OrthoDB; 196918at2759; -.
DR PhylomeDB; Q5R328; -.
DR Reactome; R-DRE-4641263; Regulation of FZD by ubiquitination.
DR PRO; PR:Q5R328; -.
DR Proteomes; UP000000437; Chromosome 16.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0060612; P:adipose tissue development; IMP:ZFIN.
DR GO; GO:0001974; P:blood vessel remodeling; ISS:UniProtKB.
DR GO; GO:1904888; P:cranial skeletal system development; IMP:ZFIN.
DR GO; GO:0060829; P:negative regulation of canonical Wnt signaling pathway involved in neural plate anterior/posterior pattern formation; IMP:ZFIN.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IMP:ZFIN.
DR GO; GO:2000052; P:positive regulation of non-canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0048919; P:posterior lateral line neuromast development; IMP:ZFIN.
DR GO; GO:0042481; P:regulation of odontogenesis; IMP:ZFIN.
DR GO; GO:0002040; P:sprouting angiogenesis; ISS:UniProtKB.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR CDD; cd00064; FU; 1.
DR Gene3D; 2.20.100.10; Thrombospondin type-1 (TSP1) repeat; 1.
DR InterPro; IPR006212; Furin_repeat.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR043601; Rspo_Fu-CRD_dom.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR InterPro; IPR044004; TSP1_spondin_dom.
DR PANTHER; PTHR46987; NEUROHYPOPHYSIAL HORMONES, N-TERMINAL DOMAIN CONTAINING PROTEIN; 1.
DR PANTHER; PTHR46987:SF1; R-SPONDIN-3; 1.
DR Pfam; PF15913; Furin-like_2; 1.
DR Pfam; PF19028; TSP1_spondin; 1.
DR SMART; SM00261; FU; 3.
DR SMART; SM00209; TSP1; 1.
DR SUPFAM; SSF57184; Growth factor receptor domain; 1.
DR SUPFAM; SSF82895; TSP-1 type 1 repeat; 1.
DR PROSITE; PS50092; TSP1; 1.
PE 2: Evidence at transcript level;
KW Disulfide bond; Glycoprotein; Heparin-binding; Reference proteome; Repeat;
KW Secreted; Sensory transduction; Signal; Wnt signaling pathway.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..317
FT /note="R-spondin-3"
FT /id="PRO_0000234445"
FT REPEAT 34..86
FT /note="FU 1"
FT REPEAT 92..135
FT /note="FU 2"
FT REPEAT 139..183
FT /note="FU 3"
FT DOMAIN 194..254
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT REGION 251..317
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 265..317
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 184
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 300
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 41..48
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 45..54
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 57..76
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 80..95
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 98..105
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 102..111
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 114..125
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 129..189
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 195..237
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 206..213
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 246..253
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT CONFLICT 298
FT /note="N -> S (in Ref. 1; BAD74061)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 317 AA; 35943 MW; 72A788840768CACE CRC64;
MQLQLISIVL ILHFMEYTNC QHHGSRHRGN KQVSGVSSQG CQGGCQTCSV YNGCLTCKPK
LFIHLERDGM RQIGVCLASC PNGFYGTRSP DRNDCIKCGS ECDSCFNRNF CLRCRAGSYL
HKGKCMESCP DGLVPSDTKK ECVAACPALC DLCQNSDTCT RCVPGHFLHA GQCHHVCPDE
FEPNDSMECI PTVHCEVSEW SEWGTCSRSG KTCGFKWGEE TRTRKVLQNP SPMGSPCPPT
SEKRECFVKK KRCKPPKGQR RGEKKKRFNL QEKVTAEARR ERKREREKET IDREESENRN
KTEQRRRRDQ SRDAGTV
//
