RSPO4_MOUSE
ID RSPO4_MOUSE Reviewed; 228 AA.
AC Q8BJ73;
DT 16-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 16-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=R-spondin-4;
DE AltName: Full=Cysteine-rich and single thrombospondin domain-containing protein 4;
DE Short=Cristin-4;
DE Short=mCristin-4;
DE AltName: Full=Roof plate-specific spondin-4;
DE Flags: Precursor;
GN Name=Rspo4;
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] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Retina;
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] (ISOFORM 1).
RC TISSUE=Limb;
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 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.
CC {ECO:0000269|PubMed:21693646}.
CC -!- SUBUNIT: Binds heparin (By similarity). Interacts with LGR4, LGR5 and
CC LGR6. {ECO:0000250, ECO:0000269|PubMed:21693646}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8BJ73-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8BJ73-2; Sequence=VSP_018326, VSP_018327;
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=BAC25643.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK020904; BAC25643.1; ALT_FRAME; mRNA.
DR EMBL; BC048707; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS38272.1; -. [Q8BJ73-1]
DR RefSeq; NP_001035779.1; NM_001040689.1. [Q8BJ73-1]
DR AlphaFoldDB; Q8BJ73; -.
DR SMR; Q8BJ73; -.
DR STRING; 10090.ENSMUSP00000041578; -.
DR GlyGen; Q8BJ73; 1 site.
DR PhosphoSitePlus; Q8BJ73; -.
DR PaxDb; Q8BJ73; -.
DR PRIDE; Q8BJ73; -.
DR Antibodypedia; 54131; 79 antibodies from 19 providers.
DR DNASU; 228770; -.
DR Ensembl; ENSMUST00000042217; ENSMUSP00000041578; ENSMUSG00000032852. [Q8BJ73-1]
DR GeneID; 228770; -.
DR KEGG; mmu:228770; -.
DR UCSC; uc008nep.1; mouse. [Q8BJ73-1]
DR CTD; 343637; -.
DR MGI; MGI:1924467; Rspo4.
DR VEuPathDB; HostDB:ENSMUSG00000032852; -.
DR eggNOG; KOG3525; Eukaryota.
DR GeneTree; ENSGT00940000160937; -.
DR HOGENOM; CLU_064219_1_1_1; -.
DR InParanoid; Q8BJ73; -.
DR OMA; NTRECQG; -.
DR PhylomeDB; Q8BJ73; -.
DR TreeFam; TF331799; -.
DR Reactome; R-MMU-4641263; Regulation of FZD by ubiquitination.
DR BioGRID-ORCS; 228770; 2 hits in 71 CRISPR screens.
DR ChiTaRS; Rspo4; mouse.
DR PRO; PR:Q8BJ73; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q8BJ73; protein.
DR Bgee; ENSMUSG00000032852; Expressed in urethra mesenchymal layer and 63 other tissues.
DR ExpressionAtlas; Q8BJ73; baseline and differential.
DR Genevisible; Q8BJ73; MM.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR GO; GO:0035878; P:nail development; ISO:MGI.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; ISO:MGI.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR CDD; cd00064; FU; 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 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 PROSITE; PS50092; TSP1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Disulfide bond; Glycoprotein; Heparin-binding;
KW Reference proteome; Secreted; Sensory transduction; Signal;
KW Wnt signaling pathway.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..228
FT /note="R-spondin-4"
FT /id="PRO_0000234447"
FT REPEAT 85..128
FT /note="FU"
FT DOMAIN 138..197
FT /note="TSP type-1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT REGION 193..228
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 206..220
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 34
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 35..41
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 38..47
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 50..69
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 73..88
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 91..98
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 95..104
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 107..118
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 122..135
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 139..181
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 150..157
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DISULFID 190..196
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT VAR_SEQ 146
FT /note="S -> R (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_018326"
FT VAR_SEQ 147..228
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_018327"
SQ SEQUENCE 228 AA; 25866 MW; AD7C6BA55284F5A1 CRC64;
MRAPLCLLLL LAHAVDMLAL YRRKKQAGTG LGGNCTGCVI CSEENGCSTC QQRLFLFIRR
EGIRQYGKCV HDCPLGFFGI RGQEANRCKK CGATCESCFS QDFCIRCKRR FHLYKGKCLP
SCPPGTLTHQ STRECQEECE PSPWGSWSPC IHNGKTCGSG WGLETRVREA GPAKQEETAS
CRVLSESRKC PIKRLCPGER NPRQKNRKDR RQRKDRKLER RPHQRGSQ
