RSPO2_XENTR
ID RSPO2_XENTR Reviewed; 243 AA.
AC Q5M7L6;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=R-spondin-2;
DE AltName: Full=Roof plate-specific spondin-2;
DE Flags: Precursor;
GN Name=rspo2;
OS Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Embryo;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=29769720; DOI=10.1038/s41586-018-0118-y;
RA Szenker-Ravi E., Altunoglu U., Leushacke M., Bosso-Lefevre C., Khatoo M.,
RA Thi Tran H., Naert T., Noelanders R., Hajamohideen A., Beneteau C.,
RA de Sousa S.B., Karaman B., Latypova X., Basaran S., Yuecel E.B., Tan T.T.,
RA Vlaminck L., Nayak S.S., Shukla A., Girisha K.M., Le Caignec C.,
RA Soshnikova N., Uyguner Z.O., Vleminckx K., Barker N., Kayserili H.,
RA Reversade B.;
RT "RSPO2 inhibition of RNF43 and ZNRF3 governs limb development independently
RT of LGR4/5/6.";
RL Nature 557:564-569(2018).
CC -!- FUNCTION: Activator of the canonical Wnt signaling pathway by acting as
CC a ligand for lgr4-6 receptors. Upon binding to lgr4-6 (lgr4, lgr5 or
CC lgr6), lgr4-6 associate with phosphorylated lrp6 and frizzled receptors
CC that are activated by extracellular Wnt receptors, triggering the
CC canonical Wnt signaling pathway to increase expression of target genes.
CC Acts both in the canonical. Wnt/beta-catenin-dependent pathway and in
CC non-canonical Wnt signaling pathway (By similarity). Activates neural
CC markers and promotes muscle formation. Overexpression blocks activin,
CC nodal and BMP4 signaling, suggesting that it may negatively regulate
CC the TGF-beta pathway (By similarity). During embryonic development,
CC plays a crucial role in limb specification, amplifying the Wnt
CC signaling pathway independently of LGR4-6 receptors, possibly by acting
CC as a direct antagonistic ligand to RNF43 and ZNRF3, hence governing the
CC number of limbs an embryo should form (PubMed:29769720).
CC {ECO:0000250|UniProtKB:Q5UE90, ECO:0000250|UniProtKB:Q6UXX9,
CC ECO:0000269|PubMed:29769720}.
CC -!- SUBUNIT: Binds heparin. {ECO:0000250|UniProtKB:Q8BFU0}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q5UE90}.
CC -!- DOMAIN: The FU repeat is required for activation and stabilization of
CC beta-catenin. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mutant animals exhibit marked forelimb and
CC hindlimb amelia. {ECO:0000269|PubMed:29769720}.
CC -!- SIMILARITY: Belongs to the R-spondin family. {ECO:0000305}.
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DR EMBL; BC088569; AAH88569.1; -; mRNA.
DR RefSeq; NP_001011386.1; NM_001011386.1.
DR RefSeq; XP_012820077.1; XM_012964623.2.
DR PDB; 4C8V; X-ray; 2.20 A; A/B/C/D/E/F/G/H=35-144.
DR PDB; 4C8W; X-ray; 3.10 A; I/J=35-144.
DR PDB; 4C9A; X-ray; 2.40 A; B/D=35-144.
DR PDB; 4C9E; X-ray; 3.00 A; B/D/F/H=35-144.
DR PDB; 4C9R; X-ray; 2.10 A; B/D=35-144.
DR PDB; 4C9U; X-ray; 3.00 A; B/D=35-144.
DR PDB; 4C9V; X-ray; 2.70 A; B=35-144.
DR PDBsum; 4C8V; -.
DR PDBsum; 4C8W; -.
DR PDBsum; 4C9A; -.
DR PDBsum; 4C9E; -.
DR PDBsum; 4C9R; -.
DR PDBsum; 4C9U; -.
DR PDBsum; 4C9V; -.
DR AlphaFoldDB; Q5M7L6; -.
DR SMR; Q5M7L6; -.
DR STRING; 8364.ENSXETP00000063896; -.
DR PaxDb; Q5M7L6; -.
DR DNASU; 496854; -.
DR Ensembl; ENSXETT00000065307; ENSXETP00000063896; ENSXETG00000003600.
DR GeneID; 496854; -.
DR KEGG; xtr:496854; -.
DR CTD; 340419; -.
DR Xenbase; XB-GENE-946235; rspo2.
DR eggNOG; KOG3525; Eukaryota.
DR HOGENOM; CLU_064219_1_0_1; -.
DR InParanoid; Q5M7L6; -.
DR OMA; HGECLHA; -.
DR OrthoDB; 1441603at2759; -.
DR PhylomeDB; Q5M7L6; -.
DR TreeFam; TF331799; -.
DR Reactome; R-XTR-4641263; Regulation of FZD by ubiquitination.
DR Proteomes; UP000008143; Chromosome 6.
DR Proteomes; UP000790000; Unplaced.
DR Bgee; ENSXETG00000003600; Expressed in gastrula and 7 other tissues.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0033335; P:anal fin development; IEA:Ensembl.
DR GO; GO:0033336; P:caudal fin development; IEA:Ensembl.
DR GO; GO:0033337; P:dorsal fin development; IEA:Ensembl.
DR GO; GO:0033339; P:pectoral fin development; IEA:Ensembl.
DR GO; GO:0033340; P:pelvic fin development; IEA:Ensembl.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IEA:InterPro.
DR GO; GO:0001501; P:skeletal system development; IEA:Ensembl.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
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; IPR042993; RSPO2/4.
DR InterPro; IPR043601; Rspo_Fu-CRD_dom.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR PANTHER; PTHR46987:SF4; PTHR46987:SF4; 1.
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 1: Evidence at protein level;
KW 3D-structure; Developmental protein; Disulfide bond; Glycoprotein;
KW Heparin-binding; Reference proteome; Secreted; Sensory transduction;
KW Signal; Wnt signaling pathway.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..243
FT /note="R-spondin-2"
FT /id="PRO_0000234442"
FT REPEAT 90..134
FT /note="FU"
FT DOMAIN 144..204
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT REGION 202..243
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 206..223
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 160
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 40..46
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 43..52
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 55..74
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 78..93
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 96..104
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 101..110
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 113..124
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 128..141
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 145..187
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 156..163
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 196..203
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT STRAND 43..47
FT /evidence="ECO:0007829|PDB:4C9R"
FT TURN 48..50
FT /evidence="ECO:0007829|PDB:4C9R"
FT STRAND 51..55
FT /evidence="ECO:0007829|PDB:4C9R"
FT STRAND 59..66
FT /evidence="ECO:0007829|PDB:4C9R"
FT STRAND 69..77
FT /evidence="ECO:0007829|PDB:4C9R"
FT STRAND 82..86
FT /evidence="ECO:0007829|PDB:4C9R"
FT STRAND 91..95
FT /evidence="ECO:0007829|PDB:4C9R"
FT STRAND 101..106
FT /evidence="ECO:0007829|PDB:4C9R"
FT STRAND 109..113
FT /evidence="ECO:0007829|PDB:4C9R"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:4C9R"
FT STRAND 123..127
FT /evidence="ECO:0007829|PDB:4C9R"
FT STRAND 132..135
FT /evidence="ECO:0007829|PDB:4C8V"
FT STRAND 138..142
FT /evidence="ECO:0007829|PDB:4C9R"
SQ SEQUENCE 243 AA; 27937 MW; 554CE54725F83E97 CRC64;
MQFQLFSFVL IILNCVDYSH CQANRWRRSK RASYGTNPIC KGCLSCSKDN GCLRCQPKLF
FYLRREGMRQ YGECLQSCPP GYYGVRGPDM NRCSRCRIEN CDSCFSRDFC IKCKSGFYSH
KGQCFEECPE GFAPLDDTMV CVDGCEVGPW SEWGTCSRNN RTCGFKWGLE TRTRQIVKKP
AKDTIPCPTI AESRRCKMAM RHCPGGTRTT KKKDKKNKKK KKKLLERAQE QHSVVLATDR
SSQ
