RSPO1_MOUSE
ID RSPO1_MOUSE Reviewed; 265 AA.
AC Q9Z132; Q3V1S3;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=R-spondin-1;
DE AltName: Full=Cysteine-rich and single thrombospondin domain-containing protein 3;
DE Short=Cristin-3;
DE Short=mCristin-3;
DE AltName: Full=Roof plate-specific spondin-1;
DE Flags: Precursor;
GN Name=Rspo1;
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 [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=14732490; DOI=10.1016/j.bbaexp.2003.10.009;
RA Kamata T., Katsube K., Michikawa M., Yamada M., Takada S., Mizusawa H.;
RT "R-spondin, a novel gene with thrombospondin type 1 domain, was expressed
RT in the dorsal neural tube and affected in Wnts mutants.";
RL Biochim. Biophys. Acta 1676:51-62(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Extraembryonic tissue, and Placenta;
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 [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, DEVELOPMENTAL STAGE, HEPARIN-BINDING, AND INTERACTION
RP WITH FZD8; LRP6 AND 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 DEVELOPMENTAL STAGE.
RX PubMed=17041600; DOI=10.1038/ng1907;
RA Parma P., Radi O., Vidal V., Chaboissier M.C., Dellambra E., Valentini S.,
RA Guerra L., Schedl A., Camerino G.;
RT "R-spondin1 is essential in sex determination, skin differentiation and
RT malignancy.";
RL Nat. Genet. 38:1304-1309(2006).
RN [6]
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 (PubMed:21693646). Also regulates the canonical Wnt/beta-catenin-
CC dependent pathway and non-canonical Wnt signaling by acting as an
CC inhibitor of ZNRF3, an important regulator of the Wnt signaling
CC pathway. Acts as a ligand for frizzled FZD8 and LRP6. May negatively
CC regulate the TGF-beta pathway. Has a essential roles in ovary
CC determination (By similarity). Regulates Wnt signaling by antagonizing
CC DKK1/KREM1-mediated internalization of LRP6 through an interaction with
CC KREM1 (By similarity). {ECO:0000250|UniProtKB:Q2MKA7,
CC ECO:0000269|PubMed:21693646}.
CC -!- SUBUNIT: Interacts with ZNRF3; promoting indirect interaction between
CC ZNRF3 and LGR4 and membrane clearance of ZNRF3. Identified in a complex
CC composed of RNF43, LGR5 and RSPO1 (By similarity). Interacts with the
CC extracellular domain of FZD8 and LRP6. It however does not form a
CC ternary complex with FZD8 and LRP6. Interacts with WNT1. Binds heparin.
CC Interacts with LGR4, LGR5 and LGR6 (PubMed:16543246, PubMed:21693646).
CC Interacts (via FU repeats) with KREM1 (By similarity).
CC {ECO:0000250|UniProtKB:Q2MKA7, ECO:0000269|PubMed:16543246,
CC ECO:0000269|PubMed:21693646}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:16543246}. Nucleus
CC {ECO:0000269|PubMed:14732490}. Note=Seems to mainly localize to
CC nucleoli. {ECO:0000269|PubMed:14732490}.
CC -!- TISSUE SPECIFICITY: Expressed in the dorsal part of the neural tube on
CC 10 and 12 dpc, especially in the boundary region between roof plate and
CC neuroepithelium. This expression is enhanced in the rostral part. Also
CC expressed in other tissues such as truncal region neighboring forelimbs
CC and mesenchymal tissues around the nasal cavity.
CC {ECO:0000269|PubMed:14732490}.
CC -!- DEVELOPMENTAL STAGE: Transiently expressed in the central nervous
CC system (CNS) during development. Predominantly expressed in the tailbud
CC of embryos. Also detected in the primitive streak, dorsal neural tube,
CC forebrain and migrating neural crests of embryos. Detected from day
CC 9.5, in various neural and mesodermal derivatives, mainly along dorsal
CC neural tube and diencephalon. Strongly expressed in limb buds,
CC particularly in the morphogenetically active region such as the apical
CC ectodermal ridge (AER). The developing skin showed expression in
CC patches of the developing dermis at 12.5 dpc and at lower levels at
CC 14.5 dpc. By 18.5 dpc expression is restricted to the dermal papilla of
CC the developing hair, which persisted into adulthood. In the developing
CC kidney, strong expression at 11.5 dpc in the uninduced metanephric
CC mesenchyme is observed. By 14.5 dpc this expression is restricted to
CC the condensing mesenchyme surrounding the ureter and the developing
CC nephrons. Specific expression in the urogenital ridge as early as 10.5
CC dpc in the coelomic epithelium. Sex-specific differences of expression
CC began to appear starting at 12.5 dpc, with an increase in the somatic
CC cells of the XX gonad. {ECO:0000269|PubMed:14732490,
CC ECO:0000269|PubMed:15469841, ECO:0000269|PubMed:16543246,
CC ECO:0000269|PubMed:17041600}.
CC -!- DOMAIN: The FU repeats are required for activation and stabilization of
CC beta-catenin. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the R-spondin family. {ECO:0000305}.
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DR EMBL; AB016768; BAA75640.1; -; mRNA.
DR EMBL; AK132277; BAE21077.1; -; mRNA.
DR CCDS; CCDS18633.1; -.
DR RefSeq; NP_619624.2; NM_138683.2.
DR AlphaFoldDB; Q9Z132; -.
DR SMR; Q9Z132; -.
DR STRING; 10090.ENSMUSP00000030687; -.
DR GlyGen; Q9Z132; 1 site.
DR PhosphoSitePlus; Q9Z132; -.
DR PaxDb; Q9Z132; -.
DR PRIDE; Q9Z132; -.
DR ProteomicsDB; 257045; -.
DR DNASU; 192199; -.
DR GeneID; 192199; -.
DR KEGG; mmu:192199; -.
DR CTD; 284654; -.
DR MGI; MGI:2183426; Rspo1.
DR eggNOG; KOG3525; Eukaryota.
DR InParanoid; Q9Z132; -.
DR OrthoDB; 1441603at2759; -.
DR PhylomeDB; Q9Z132; -.
DR Reactome; R-MMU-4641263; Regulation of FZD by ubiquitination.
DR BioGRID-ORCS; 192199; 2 hits in 73 CRISPR screens.
DR PRO; PR:Q9Z132; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q9Z132; protein.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0001664; F:G protein-coupled receptor binding; ISO:MGI.
DR GO; GO:0008201; F:heparin binding; IDA:MGI.
DR GO; GO:0005102; F:signaling receptor binding; IPI:MGI.
DR GO; GO:0007140; P:male meiotic nuclear division; IMP:MGI.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:2000052; P:positive regulation of non-canonical Wnt signaling pathway; IMP:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
DR GO; GO:2000254; P:regulation of male germ cell proliferation; IMP:MGI.
DR GO; GO:0002090; P:regulation of receptor internalization; ISO:MGI.
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; IPR042991; RSPO1.
DR InterPro; IPR043601; Rspo_Fu-CRD_dom.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR PANTHER; PTHR46987:SF5; PTHR46987:SF5; 1.
DR Pfam; PF15913; Furin-like_2; 1.
DR Pfam; PF00090; TSP_1; 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 Disulfide bond; Glycoprotein; Heparin-binding; Nucleus; Reference proteome;
KW Repeat; Secreted; Sensory transduction; Signal; Wnt signaling pathway.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..265
FT /note="R-spondin-1"
FT /id="PRO_0000234437"
FT REPEAT 34..85
FT /note="FU 1"
FT REPEAT 91..135
FT /note="FU 2"
FT DOMAIN 147..207
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT REGION 173..192
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 201..265
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 201..241
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 242..265
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 137
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 40..47
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 44..53
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 56..75
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 79..94
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 97..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"
FT CONFLICT 117
FT /note="A -> G (in Ref. 2; BAE21077)"
FT /evidence="ECO:0000305"
FT CONFLICT 236
FT /note="R -> G (in Ref. 2; BAE21077)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 265 AA; 29332 MW; FFEB8964743F5963 CRC64;
MRLGLCVVAL VLSWTHIAVG SRGIKGKRQR RISAEGSQAC AKGCELCSEV NGCLKCSPKL
FILLERNDIR QVGVCLPSCP PGYFDARNPD MNKCIKCKIE HCEACFSHNF CTKCQEALYL
HKGRCYPACP EGSTAANSTM ECGSPAQCEM SEWSPWGPCS KKRKLCGFRK GSEERTRRVL
HAPGGDHTTC SDTKETRKCT VRRTPCPEGQ KRRKGGQGRR ENANRHPARK NSKEPRSNSR
RHKGQQQPQP GTTGPLTSVG PTWAQ
