RSPO2_MOUSE
ID RSPO2_MOUSE Reviewed; 243 AA.
AC Q8BFU0; Q7TPX3;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=R-spondin-2;
DE AltName: Full=Cysteine-rich and single thrombospondin domain-containing protein 2;
DE Short=Cristin-2;
DE Short=mCristin-2;
DE AltName: Full=Roof plate-specific spondin-2;
DE Flags: Precursor;
GN Name=Rspo2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Eye, and Hippocampus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Egg;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP DEVELOPMENTAL STAGE.
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).
RN [4]
RP SUBCELLULAR LOCATION, HEPARIN-BINDING, AND INTERACTION WITH WNT1.
RX PubMed=16543246; DOI=10.1074/jbc.m508324200;
RA Nam J.-S., Turcotte T.J., Smith P.F., Choi S., Yoon J.K.;
RT "Mouse cristin/R-spondin family proteins are novel ligands for the Frizzled
RT 8 and LRP6 receptors and activate beta-catenin-dependent gene expression.";
RL J. Biol. Chem. 281:13247-13257(2006).
RN [5]
RP FUNCTION, AND INTERACTION WITH LGR4 AND LGR5.
RX PubMed=21693646; DOI=10.1073/pnas.1106083108;
RA Carmon K.S., Gong X., Lin Q., Thomas A., Liu Q.;
RT "R-spondins function as ligands of the orphan receptors LGR4 and LGR5 to
RT regulate Wnt/beta-catenin signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:11452-11457(2011).
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 Also regulates the canonical Wnt/beta-catenin-dependent pathway and
CC non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an
CC important regulator of the Wnt signaling pathway. Probably also acts as
CC a ligand for frizzled and LRP receptors (PubMed:21693646). During
CC embryonic development, plays a crucial role in limb specification,
CC amplifying the Wnt signaling pathway independently of LGR4-6 receptors,
CC possibly by acting as a direct antagonistic ligand to RNF43 and ZNRF3,
CC hence governing the number of limbs an embryo should form (By
CC similarity). {ECO:0000250|UniProtKB:Q6UXX9,
CC ECO:0000269|PubMed:21693646}.
CC -!- SUBUNIT: Interacts with WNT1 (PubMed:16543246). Binds heparin
CC (PubMed:16543246). Interacts with LGR4, LGR5 and LGR6
CC (PubMed:21693646). {ECO:0000269|PubMed:16543246,
CC ECO:0000269|PubMed:21693646}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16543246}.
CC -!- DEVELOPMENTAL STAGE: Detected from day 9.5 in various neural and
CC mesodermal derivatives, mainly along diencephalon. Strongly expressed
CC in limb buds, particularly in the morphogenetically active region such
CC as the apical ectodermal ridge (AER). {ECO:0000269|PubMed:15469841}.
CC -!- DOMAIN: The FU repeat is required for activation and stabilization of
CC beta-catenin. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the R-spondin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BC052844; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK049891; BAC33974.1; -; mRNA.
DR EMBL; AK087485; BAC39893.1; -; mRNA.
DR EMBL; BC052844; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS27451.1; -.
DR RefSeq; NP_766403.1; NM_172815.3.
DR RefSeq; XP_006520968.1; XM_006520905.1.
DR PDB; 4C99; X-ray; 2.80 A; B/D=37-144.
DR PDB; 4UFR; X-ray; 2.20 A; B/D=39-144.
DR PDB; 4UFS; X-ray; 4.80 A; B=39-144.
DR PDBsum; 4C99; -.
DR PDBsum; 4UFR; -.
DR PDBsum; 4UFS; -.
DR AlphaFoldDB; Q8BFU0; -.
DR SMR; Q8BFU0; -.
DR BioGRID; 232079; 4.
DR CORUM; Q8BFU0; -.
DR STRING; 10090.ENSMUSP00000067325; -.
DR GlyGen; Q8BFU0; 1 site.
DR iPTMnet; Q8BFU0; -.
DR PhosphoSitePlus; Q8BFU0; -.
DR PaxDb; Q8BFU0; -.
DR PeptideAtlas; Q8BFU0; -.
DR PRIDE; Q8BFU0; -.
DR ProteomicsDB; 262715; -.
DR Antibodypedia; 26506; 101 antibodies from 25 providers.
DR DNASU; 239405; -.
DR Ensembl; ENSMUST00000063492; ENSMUSP00000067325; ENSMUSG00000051920.
DR Ensembl; ENSMUST00000226810; ENSMUSP00000154600; ENSMUSG00000051920.
DR GeneID; 239405; -.
DR KEGG; mmu:239405; -.
DR UCSC; uc007vpg.1; mouse.
DR CTD; 340419; -.
DR MGI; MGI:1922667; Rspo2.
DR VEuPathDB; HostDB:ENSMUSG00000051920; -.
DR eggNOG; KOG3525; Eukaryota.
DR GeneTree; ENSGT00940000159194; -.
DR HOGENOM; CLU_064219_1_0_1; -.
DR InParanoid; Q8BFU0; -.
DR OMA; HGECLHA; -.
DR OrthoDB; 1441603at2759; -.
DR PhylomeDB; Q8BFU0; -.
DR TreeFam; TF331799; -.
DR Reactome; R-MMU-4641263; Regulation of FZD by ubiquitination.
DR BioGRID-ORCS; 239405; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Rspo2; mouse.
DR PRO; PR:Q8BFU0; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q8BFU0; protein.
DR Bgee; ENSMUSG00000051920; Expressed in primary oocyte and 157 other tissues.
DR Genevisible; Q8BFU0; MM.
DR GO; GO:0009986; C:cell surface; IDA:MGI.
DR GO; GO:0005576; C:extracellular region; IDA:MGI.
DR GO; GO:0008201; F:heparin binding; IDA:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0030282; P:bone mineralization; IGI:MGI.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:MGI.
DR GO; GO:0071542; P:dopaminergic neuron differentiation; IMP:MGI.
DR GO; GO:0035115; P:embryonic forelimb morphogenesis; IMP:MGI.
DR GO; GO:0035116; P:embryonic hindlimb morphogenesis; IMP:MGI.
DR GO; GO:0060441; P:epithelial tube branching involved in lung morphogenesis; IMP:MGI.
DR GO; GO:0060173; P:limb development; ISO:MGI.
DR GO; GO:0060437; P:lung growth; IMP:MGI.
DR GO; GO:0042489; P:negative regulation of odontogenesis of dentin-containing tooth; IMP:MGI.
DR GO; GO:0001649; P:osteoblast differentiation; IGI:MGI.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:MGI.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; ISO:MGI.
DR GO; GO:0060535; P:trachea cartilage morphogenesis; IGI:MGI.
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..23
FT /evidence="ECO:0000255"
FT CHAIN 24..243
FT /note="R-spondin-2"
FT /id="PRO_0000234440"
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"
FT STRAND 43..45
FT /evidence="ECO:0007829|PDB:4C99"
FT STRAND 48..55
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 59..65
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 67..77
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 82..87
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 90..95
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 101..106
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 109..113
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 118..120
FT /evidence="ECO:0007829|PDB:4UFR"
FT STRAND 123..127
FT /evidence="ECO:0007829|PDB:4UFR"
FT TURN 136..139
FT /evidence="ECO:0007829|PDB:4UFR"
SQ SEQUENCE 243 AA; 28276 MW; ED76A08D61012ED7 CRC64;
MRFCLFSFAL IILNCMDYSQ CQGNRWRRNK RASYVSNPIC KGCLSCSKDN GCSRCQQKLF
FFLRREGMRQ YGECLHSCPS GYYGHRAPDM NRCARCRIEN CDSCFSKDFC TKCKVGFYLH
RGRCFDECPD GFAPLDETME CVEGCEVGHW SEWGTCSRNN RTCGFKWGLE TRTRQIVKKP
AKDTIPCPTI AESRRCKMAM RHCPGGKRTP KAKEKRNKKK RRKLIERAQE QHSVFLATDR
VNQ
