RSPO3_BOVIN
ID RSPO3_BOVIN Reviewed; 273 AA.
AC Q1RMU1;
DT 20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2006, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=R-spondin-3;
DE AltName: Full=Roof plate-specific spondin-3;
DE Flags: Precursor;
GN Name=RSPO3;
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=Uterus;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (APR-2006) 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. Also
CC regulates the canonical Wnt/beta-catenin-dependent pathway and non-
CC canonical Wnt signaling by acting as an inhibitor of ZNRF3, an
CC important regulator of the Wnt signaling pathway. Acts as a ligand for
CC frizzled FZD8 and LRP6. May negatively regulate the TGF-beta pathway.
CC Acts as a key regulator of angiogenesis by controlling vascular
CC stability and pruning: acts by activating the non-canonical Wnt
CC signaling pathway in endothelial cells (By similarity). Can also
CC amplify Wnt signaling pathway independently of LGR4-6 receptors,
CC possibly by acting as a direct antagonistic ligand to RNF43 and ZNRF3
CC (By similarity). {ECO:0000250|UniProtKB:Q2TJ95,
CC ECO:0000250|UniProtKB:Q9BXY4}.
CC -!- SUBUNIT: Interacts with the extracellular domain of FZD8 and LRP6. It
CC however does not form a ternary complex with FZD8 and LRP6. Interacts
CC with WNT1. Binds heparin. Interacts with LGR4, LGR5 and LGR6.
CC {ECO:0000250|UniProtKB:Q2TJ95}.
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; BC114713; AAI14714.1; -; mRNA.
DR RefSeq; NP_001069502.1; NM_001076034.1.
DR AlphaFoldDB; Q1RMU1; -.
DR SMR; Q1RMU1; -.
DR STRING; 9913.ENSBTAP00000010680; -.
DR PaxDb; Q1RMU1; -.
DR Ensembl; ENSBTAT00000010680; ENSBTAP00000010680; ENSBTAG00000008121.
DR GeneID; 534650; -.
DR KEGG; bta:534650; -.
DR CTD; 84870; -.
DR VEuPathDB; HostDB:ENSBTAG00000008121; -.
DR VGNC; VGNC:106906; RSPO3.
DR eggNOG; KOG3525; Eukaryota.
DR GeneTree; ENSGT00940000157815; -.
DR InParanoid; Q1RMU1; -.
DR OMA; WFFITLN; -.
DR OrthoDB; 1441603at2759; -.
DR Proteomes; UP000009136; Chromosome 9.
DR Bgee; ENSBTAG00000008121; Expressed in gluteus medius and 90 other tissues.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0005109; F:frizzled binding; IEA:Ensembl.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0001974; P:blood vessel remodeling; ISS:UniProtKB.
DR GO; GO:0060670; P:branching involved in labyrinthine layer morphogenesis; IEA:Ensembl.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:0060173; P:limb development; ISS:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IEA:Ensembl.
DR GO; GO:2000052; P:positive regulation of non-canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0002040; P:sprouting angiogenesis; ISS:UniProtKB.
DR CDD; cd00064; FU; 1.
DR Gene3D; 2.20.100.10; -; 1.
DR InterPro; IPR006212; Furin_repeat.
DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf.
DR InterPro; IPR042994; RSPO3.
DR InterPro; IPR043601; Rspo_Fu-CRD_dom.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR PANTHER; PTHR46987:SF1; PTHR46987:SF1; 2.
DR Pfam; PF15913; Furin-like_2; 1.
DR SMART; SM00261; FU; 2.
DR SMART; SM00209; TSP1; 1.
DR SUPFAM; SSF57184; SSF57184; 1.
DR SUPFAM; SSF82895; SSF82895; 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..21
FT /evidence="ECO:0000255"
FT CHAIN 22..273
FT /note="R-spondin-3"
FT /id="PRO_0000278645"
FT REPEAT 35..86
FT /note="FU 1"
FT REPEAT 92..135
FT /note="FU 2"
FT DOMAIN 147..207
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT REGION 201..273
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 221..263
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 36
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..142
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 148..190
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 159..166
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 199..206
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
SQ SEQUENCE 273 AA; 31057 MW; F17A07429663DE60 CRC64;
MHLRLISWFF IILNFMEYIG SQNASRGRRQ RRMHPNVSQG CQGGCATCSD YNGCLSCKPK
LFFVLERIGM KQIGVCLSSC PSGYYGTRYP DINKCTKCKA DCDTCFNKNF CTKCKSGFYL
HLGKCLDNCP EGLEANNHTM ECVSIVHCEA SEWSPWSPCT KKGKTCGFKR GTETRVREII
QHPSAKGNLC PPTSEARKCT VQRKKCPKGE RGRKGRERKR KKPNKEESKD AIPDNKGLEP
SRETPEQREN KQQQKKRKVQ DKQQKSVSVS TVH
