ID RSPO2_XENLA Reviewed; 243 AA.
AC Q5UE90;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 07-DEC-2004, sequence version 1.
DT 27-MAR-2024, entry version 79.
DE RecName: Full=R-spondin-2;
DE AltName: Full=Roof plate-specific spondin-2;
DE AltName: Full=XRspo2;
DE Flags: Precursor;
GN Name=rspo2;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL
RP STAGE, INDUCTION, AND DOMAIN.
RC TISSUE=Eye;
RX PubMed=15469841; DOI=10.1016/j.devcel.2004.07.019;
RA Kazanskaya O., Glinka A., del Barco Barrantes I., Stannek P., Niehrs C.,
RA Wu W.;
RT "R-Spondin2 is a secreted activator of Wnt/beta-catenin signaling and is
RT required for Xenopus myogenesis.";
RL Dev. Cell 7:525-534(2004).
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 (PubMed:15469841). 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 (By similarity).
CC {ECO:0000250|UniProtKB:Q5M7L6, ECO:0000250|UniProtKB:Q6UXX9,
CC ECO:0000269|PubMed:15469841}.
CC -!- SUBUNIT: Binds heparin. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:15469841}.
CC -!- DEVELOPMENTAL STAGE: Expressed from early gastrula stage and remains
CC constant throughout neurulation and organogenesis. Expressed throughout
CC the ectoderm of early gastrula. During gastrulation, it is detected in
CC the marginal zone in both deep and superficial layers but is excluded
CC from the Speemann organizer. At late gastrula, it persists in lateral
CC plate mesoderm and becomes detectable in the anterior neural plate. At
CC stage 15, it is expressed in 2 longitudinal stripes along the neural
CC plate, in the anterior neural plate, and in lateral and posterior
CC mesoderm. At tailbud stage, it is restricted in several regions of the
CC brain, including diencephalon and midbrain-hindbrain boundary,
CC pronephros and dorsal neural tube. Also detected in the dorsal- and
CC ventral-most portions of somites, the drosal fin and the proctodeum.
CC Expression in the brain of late tadpoles is mainly restricted to
CC diencephalon, including the zona limitans intrahalamica.
CC {ECO:0000269|PubMed:15469841}.
CC -!- INDUCTION: By Wnt proteins. {ECO:0000269|PubMed:15469841}.
CC -!- DOMAIN: The FU repeat is required for activation and stabilization of
CC beta-catenin. {ECO:0000269|PubMed:15469841}.
CC -!- SIMILARITY: Belongs to the R-spondin family. {ECO:0000305}.
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DR EMBL; AY753198; AAV31037.1; -; mRNA.
DR RefSeq; NP_001088999.1; NM_001095530.1.
DR RefSeq; XP_018122151.1; XM_018266662.1.
DR AlphaFoldDB; Q5UE90; -.
DR SMR; Q5UE90; -.
DR BioGRID; 106463; 2.
DR GlyCosmos; Q5UE90; 1 site, No reported glycans.
DR GeneID; 496383; -.
DR KEGG; xla:496383; -.
DR AGR; Xenbase:XB-GENE-946240; -.
DR CTD; 496383; -.
DR Xenbase; XB-GENE-946240; rspo2.L.
DR OMA; HGECLHA; -.
DR OrthoDB; 196918at2759; -.
DR Proteomes; UP000186698; Chromosome 6L.
DR Bgee; 496383; Expressed in lung and 9 other cell types or tissues.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
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:SF4; R-SPONDIN-2; 1.
DR Pfam; PF15913; Furin-like_2; 1.
DR Pfam; PF19028; TSP1_spondin; 1.
DR SMART; SM00261; FU; 2.
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 Developmental protein; Disulfide bond; Glycoprotein; Heparin-binding;
KW Reference proteome; Secreted; Sensory transduction; Signal;
KW Wnt signaling pathway.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..243
FT /note="R-spondin-2"
FT /id="PRO_0000234441"
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 204..243
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 204..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"
SQ SEQUENCE 243 AA; 27879 MW; 09CB4F20469A2880 CRC64;
MQFQLFSFAL IILNCVDYSH CQASRWRRSK RASYGTNPIC KGCLSCSKDN GCLRCQPKLF
FFLRREGMRQ YGECLQSCPP GYYGVRGPDM NRCSRCRIEN CDSCFSRDFC IKCKSGFYSL
KGQCFEECPE GFAPLDDTMV CVDGCEVGPW SEWGTCSRNN RTCGFKWGLE TRTRQIVKKP
AKDTIPCPTI AESRRCKMAI RHCPGGKRTT KKKDKRNKKK KKKLLERAQE QHSVVLATDR
SSQ
//
