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   24-JAN-2024, entry version 147.
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   GlyCosmos; Q8BFU0; 1 site, No reported glycans.
DR   GlyGen; Q8BFU0; 1 site.
DR   iPTMnet; Q8BFU0; -.
DR   PhosphoSitePlus; Q8BFU0; -.
DR   PaxDb; 10090-ENSMUSP00000067325; -.
DR   PeptideAtlas; Q8BFU0; -.
DR   ProteomicsDB; 262715; -.
DR   Antibodypedia; 26506; 154 antibodies from 25 providers.
DR   DNASU; 239405; -.
DR   Ensembl; ENSMUST00000063492.8; ENSMUSP00000067325.7; ENSMUSG00000051920.8.
DR   Ensembl; ENSMUST00000226810.2; ENSMUSP00000154600.2; ENSMUSG00000051920.8.
DR   GeneID; 239405; -.
DR   KEGG; mmu:239405; -.
DR   UCSC; uc007vpg.1; mouse.
DR   AGR; MGI:1922667; -.
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; 196918at2759; -.
DR   PhylomeDB; Q8BFU0; -.
DR   TreeFam; TF331799; -.
DR   Reactome; R-MMU-4641263; Regulation of FZD by ubiquitination.
DR   BioGRID-ORCS; 239405; 2 hits in 76 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 158 other cell types or tissues.
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; 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.
DR   Genevisible; Q8BFU0; MM.
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
//