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Protein

R-spondin-3

Gene

Rspo3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors, which acts as a key regulator of angiogenesis (PubMed:16543246, PubMed:21693646, PubMed:26766444). Upon binding to LGR4-6 (LGR4, LGR5 or LGR6), LGR4-6 associate with phosphorylated LRP6 and frizzled receptors that are activated by extracellular Wnt receptors, triggering the canonical Wnt signaling pathway to increase expression of target genes. Also regulates the canonical Wnt/beta-catenin-dependent pathway and non-canonical Wnt signaling by acting as an inhibitor of ZNRF3, an important regulator of the Wnt signaling pathway. Acts as a ligand for frizzled FZD8 and LRP6. May negatively regulate the TGF-beta pathway (PubMed:16543246, PubMed:21693646). Acts as a key regulator of angiogenesis by controlling vascular stability and pruning: acts by activating the non-canonical Wnt signaling pathway in endothelial cells (PubMed:26766444).3 Publications

GO - Molecular functioni

  • frizzled binding Source: MGI
  • heparin binding Source: MGI
  • signaling receptor binding Source: MGI

GO - Biological processi

Keywordsi

Molecular functionHeparin-binding
Biological processSensory transduction, Wnt signaling pathway

Enzyme and pathway databases

ReactomeiR-MMU-4641263 Regulation of FZD by ubiquitination

Names & Taxonomyi

Protein namesi
Recommended name:
R-spondin-3
Alternative name(s):
Cabriolet
Cysteine-rich and single thrombospondin domain-containing protein 11 Publication
Short name:
Cristin-11 Publication
Nucleopondin1 Publication
Roof plate-specific spondin-3
Gene namesi
Name:Rspo3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1920030 Rspo3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Disruption phenotypei

Embryonic lethality due to vascular remodeling defects (PubMed:26766444). Conditional knockout in endothelial cells results in impaired developmental and tumor vascular remodeling. Mice show endothelial cell apoptosis and vascular pruning, leading to reduced microvessel density (PubMed:26766444).1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000023444422 – 277R-spondin-3Add BLAST256

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi36N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi41 ↔ 48PROSITE-ProRule annotation
Disulfide bondi45 ↔ 54PROSITE-ProRule annotation
Disulfide bondi57 ↔ 76PROSITE-ProRule annotation
Disulfide bondi80 ↔ 95PROSITE-ProRule annotation
Disulfide bondi98 ↔ 105PROSITE-ProRule annotation
Disulfide bondi102 ↔ 111PROSITE-ProRule annotation
Disulfide bondi114 ↔ 125PROSITE-ProRule annotation
Disulfide bondi129 ↔ 142PROSITE-ProRule annotation
Disulfide bondi148 ↔ 190PROSITE-ProRule annotation
Disulfide bondi159 ↔ 166PROSITE-ProRule annotation
Disulfide bondi199 ↔ 206PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ2TJ95
PRIDEiQ2TJ95

PTM databases

iPTMnetiQ2TJ95
PhosphoSitePlusiQ2TJ95

Expressioni

Tissue specificityi

Highly expressed in endothelial cells (PubMed:26766444).1 Publication

Developmental stagei

Expressed from day 7.5 in the primitive streak. At day 9.5, it is expressed in various neural and mesodermal derivatives, mainly along dorsal neural tube, diencephalon, somites and tailbud mesoderm. Strongly expressed in limb buds, particularly in the morphogenetically active region such as the apical ectodermal ridge (AER).1 Publication

Gene expression databases

BgeeiENSMUSG00000019880 Expressed in 251 organ(s), highest expression level in vas deferens
CleanExiMM_RSPO3
ExpressionAtlasiQ2TJ95 baseline and differential
GenevisibleiQ2TJ95 MM

Interactioni

Subunit structurei

Interacts with the extracellular domain of FZD8 and LRP6 (PubMed:16543246). It however does not form a ternary complex with FZD8 and LRP6 (PubMed:16543246). Interacts with WNT1 (PubMed:16543246). Binds heparin. Interacts with LGR4, LGR5 and LGR6 (PubMed:21693646).2 Publications

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000090287

Structurei

3D structure databases

ProteinModelPortaliQ2TJ95
SMRiQ2TJ95
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati35 – 86FU 1Add BLAST52
Repeati92 – 135FU 2Add BLAST44
Domaini147 – 207TSP type-1PROSITE-ProRule annotationAdd BLAST61

Domaini

The FU repeats are required for activation and stabilization of beta-catenin.1 Publication

Sequence similaritiesi

Belongs to the R-spondin family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiKOG3525 Eukaryota
COG1404 LUCA
GeneTreeiENSGT00390000011447
HOGENOMiHOG000290668
HOVERGENiHBG082751
InParanoidiQ2TJ95
OMAiMECTSIV
OrthoDBiEOG091G0FYC
PhylomeDBiQ2TJ95
TreeFamiTF331799

Family and domain databases

CDDicd00064 FU, 1 hit
Gene3Di2.20.100.10, 1 hit
InterProiView protein in InterPro
IPR006212 Furin_repeat
IPR009030 Growth_fac_rcpt_cys_sf
IPR000884 TSP1_rpt
IPR036383 TSP1_rpt_sf
PfamiView protein in Pfam
PF15913 Furin-like_2, 1 hit
SMARTiView protein in SMART
SM00261 FU, 2 hits
SM00209 TSP1, 1 hit
SUPFAMiSSF57184 SSF57184, 1 hit
SSF82895 SSF82895, 1 hit
PROSITEiView protein in PROSITE
PS50092 TSP1, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

Q2TJ95-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MHLRLISCFF IILNFMEYIG SQNASRGRRQ RRMHPNVSQG CQGGCATCSD
60 70 80 90 100
YNGCLSCKPR LFFVLERIGM KQIGVCLSSC PSGYYGTRYP DINKCTKCKV
110 120 130 140 150
DCDTCFNKNF CTKCKSGFYL HLGKCLDSCP EGLEANNHTM ECVSIVHCEA
160 170 180 190 200
SEWSPWSPCM KKGKTCGFKR GTETRVRDIL QHPSAKGNLC PPTSETRTCI
210 220 230 240 250
VQRKKCSKGE RGKKGRERKR KKLNKEERKE TSSSSDSKGL ESSIETPDQQ
260 270
ENKERQQQQK RRARDKQQKS VSVSTVH
Length:277
Mass (Da):31,454
Last modified:May 16, 2006 - v2
Checksum:i9C5AD3A48AFF8C66
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A1L1SR88A0A1L1SR88_MOUSE
R-spondin-3
Rspo3
186Annotation score:

Sequence cautioni

The sequence BAC36296 differs from that shown. Reason: Frameshift at position 189.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti108K → Q in AAX57441 (PubMed:16543246).Curated1
Sequence conflicti108K → Q in BAC36296 (PubMed:15489334).Curated1
Sequence conflicti130P → A in BAC41353 (Ref. 2) Curated1
Sequence conflicti170R → G in BAB28811 (PubMed:15489334).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY864332 mRNA Translation: AAX57441.1
AB055811 mRNA Translation: BAC41353.1
AK013366 mRNA Translation: BAB28811.1
AK076308 mRNA Translation: BAC36296.1 Frameshift.
BC103794 mRNA Translation: AAI03795.1
BC145929 mRNA Translation: AAI45930.1
BC145931 mRNA Translation: AAI45932.1
CCDSiCCDS23761.1
RefSeqiNP_082627.3, NM_028351.3
UniGeneiMm.45191

Genome annotation databases

EnsembliENSMUST00000092623; ENSMUSP00000090287; ENSMUSG00000019880
GeneIDi72780
KEGGimmu:72780
UCSCiuc007etb.2 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY864332 mRNA Translation: AAX57441.1
AB055811 mRNA Translation: BAC41353.1
AK013366 mRNA Translation: BAB28811.1
AK076308 mRNA Translation: BAC36296.1 Frameshift.
BC103794 mRNA Translation: AAI03795.1
BC145929 mRNA Translation: AAI45930.1
BC145931 mRNA Translation: AAI45932.1
CCDSiCCDS23761.1
RefSeqiNP_082627.3, NM_028351.3
UniGeneiMm.45191

3D structure databases

ProteinModelPortaliQ2TJ95
SMRiQ2TJ95
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000090287

PTM databases

iPTMnetiQ2TJ95
PhosphoSitePlusiQ2TJ95

Proteomic databases

PaxDbiQ2TJ95
PRIDEiQ2TJ95

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000092623; ENSMUSP00000090287; ENSMUSG00000019880
GeneIDi72780
KEGGimmu:72780
UCSCiuc007etb.2 mouse

Organism-specific databases

CTDi84870
MGIiMGI:1920030 Rspo3

Phylogenomic databases

eggNOGiKOG3525 Eukaryota
COG1404 LUCA
GeneTreeiENSGT00390000011447
HOGENOMiHOG000290668
HOVERGENiHBG082751
InParanoidiQ2TJ95
OMAiMECTSIV
OrthoDBiEOG091G0FYC
PhylomeDBiQ2TJ95
TreeFamiTF331799

Enzyme and pathway databases

ReactomeiR-MMU-4641263 Regulation of FZD by ubiquitination

Miscellaneous databases

PROiPR:Q2TJ95
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000019880 Expressed in 251 organ(s), highest expression level in vas deferens
CleanExiMM_RSPO3
ExpressionAtlasiQ2TJ95 baseline and differential
GenevisibleiQ2TJ95 MM

Family and domain databases

CDDicd00064 FU, 1 hit
Gene3Di2.20.100.10, 1 hit
InterProiView protein in InterPro
IPR006212 Furin_repeat
IPR009030 Growth_fac_rcpt_cys_sf
IPR000884 TSP1_rpt
IPR036383 TSP1_rpt_sf
PfamiView protein in Pfam
PF15913 Furin-like_2, 1 hit
SMARTiView protein in SMART
SM00261 FU, 2 hits
SM00209 TSP1, 1 hit
SUPFAMiSSF57184 SSF57184, 1 hit
SSF82895 SSF82895, 1 hit
PROSITEiView protein in PROSITE
PS50092 TSP1, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiRSPO3_MOUSE
AccessioniPrimary (citable) accession number: Q2TJ95
Secondary accession number(s): A6H6M4
, Q3SYI9, Q5R2V4, Q8BVW2, Q9CSB2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: May 16, 2006
Last modified: September 12, 2018
This is version 102 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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