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Protein

R-spondin-3

Gene

RSPO3

Organism
Homo sapiens (Human)
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. 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:21727895, PubMed:21909076, PubMed:22615920). 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 (By similarity).By similarity3 Publications

Miscellaneous

Upon injection into mice, it induces rapid onset of crypt cell proliferation involving beta-catenin stabilization. It also displays efficacy in a model of chemotherapy-induced intestinal mucositis (PubMed:16357527).1 Publication

GO - Molecular functioni

  • frizzled binding Source: Ensembl
  • heparin binding Source: UniProtKB-KW
  • signaling receptor binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionHeparin-binding
Biological processSensory transduction, Wnt signaling pathway

Enzyme and pathway databases

ReactomeiR-HSA-4641263 Regulation of FZD by ubiquitination
R-HSA-8939256 RUNX1 regulates transcription of genes involved in WNT signaling
SIGNORiQ9BXY4

Names & Taxonomyi

Protein namesi
Recommended name:
R-spondin-3
Alternative name(s):
Protein with TSP type-1 repeat
Short name:
hPWTSR
Roof plate-specific spondin-3
Short name:
hRspo3
Thrombospondin type-1 domain-containing protein 2
Gene namesi
Name:RSPO3
Synonyms:PWTSR, THSD2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000146374.13
HGNCiHGNC:20866 RSPO3
MIMi610574 gene
neXtProtiNX_Q9BXY4

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

Organism-specific databases

DisGeNETi84870
OpenTargetsiENSG00000146374
PharmGKBiPA134885289

Polymorphism and mutation databases

DMDMi74752442

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000023444322 – 272R-spondin-3Add BLAST251

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

PaxDbiQ9BXY4
PeptideAtlasiQ9BXY4
PRIDEiQ9BXY4
ProteomicsDBi79540
79541 [Q9BXY4-2]

PTM databases

iPTMnetiQ9BXY4
PhosphoSitePlusiQ9BXY4

Expressioni

Tissue specificityi

Ubiquitously expressed. Expressed at higher level in placenta, small intestine, fetal thymus and lymph node (PubMed:12463421). Highly expressed in endothelial cells (PubMed:26766444).2 Publications

Gene expression databases

BgeeiENSG00000146374 Expressed in 173 organ(s), highest expression level in myometrium
CleanExiHS_RSPO3
GenevisibleiQ9BXY4 HS

Organism-specific databases

HPAiHPA029957

Interactioni

Subunit structurei

Interacts with the extracellular domain of FZD8 and LRP6 (By similarity). It however does not form a ternary complex with FZD8 and LRP6 (By similarity). Interacts with WNT1 (By similarity). Binds heparin. Interacts with LGR4, LGR5 and LGR6 (PubMed:21727895, PubMed:21909076, PubMed:22615920).By similarity3 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi124315, 3 interactors
IntActiQ9BXY4, 2 interactors
MINTiQ9BXY4
STRINGi9606.ENSP00000349131

Structurei

3D structure databases

ProteinModelPortaliQ9BXY4
SMRiQ9BXY4
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.By similarity

Sequence similaritiesi

Belongs to the R-spondin family.Curated

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiKOG3525 Eukaryota
COG1404 LUCA
GeneTreeiENSGT00390000011447
HOGENOMiHOG000290668
HOVERGENiHBG082751
InParanoidiQ9BXY4
OMAiMECTSIV
OrthoDBiEOG091G0FYC
PhylomeDBiQ9BXY4
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

Sequences (2)i

Sequence statusi: Complete.

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

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q9BXY4-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MHLRLISWLF IILNFMEYIG SQNASRGRRQ RRMHPNVSQG CQGGCATCSD
60 70 80 90 100
YNGCLSCKPR LFFALERIGM KQIGVCLSSC PSGYYGTRYP DINKCTKCKA
110 120 130 140 150
DCDTCFNKNF CTKCKSGFYL HLGKCLDNCP EGLEANNHTM ECVSIVHCEV
160 170 180 190 200
SEWNPWSPCT KKGKTCGFKR GTETRVREII QHPSAKGNLC PPTNETRKCT
210 220 230 240 250
VQRKKCQKGE RGKKGRERKR KKPNKGESKE AIPDSKSLES SKEIPEQREN
260 270
KQQQKKRKVQ DKQKSVSVST VH
Length:272
Mass (Da):30,929
Last modified:June 1, 2001 - v1
Checksum:iCACAEC6B7E781189
GO
Isoform 2 (identifier: Q9BXY4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     266-272: VSVSTVH → GIEVTLAEGLTSVSQRTQPTPCRRRYL

Note: No experimental confirmation available.
Show »
Length:292
Mass (Da):33,233
Checksum:iE0B2781ECDD4A6F3
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti41C → R in BAB55051 (PubMed:14702039).Curated1
Sequence conflicti170R → I in BAB55051 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_018324266 – 272VSVSTVH → GIEVTLAEGLTSVSQRTQPT PCRRRYL in isoform 2. 1 Publication7

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF251057 mRNA Translation: AAK34947.1
AK027346 mRNA Translation: BAB55051.1
AK314912 mRNA Translation: BAG37424.1
AL590733 Genomic DNA No translation available.
AL031776 Genomic DNA No translation available.
CH471051 Genomic DNA Translation: EAW48115.1
BC022367 mRNA Translation: AAH22367.1
CCDSiCCDS5135.1 [Q9BXY4-1]
RefSeqiNP_116173.2, NM_032784.4 [Q9BXY4-1]
UniGeneiHs.135254

Genome annotation databases

EnsembliENST00000356698; ENSP00000349131; ENSG00000146374 [Q9BXY4-1]
ENST00000368317; ENSP00000357300; ENSG00000146374 [Q9BXY4-2]
GeneIDi84870
KEGGihsa:84870
UCSCiuc003qar.5 human [Q9BXY4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF251057 mRNA Translation: AAK34947.1
AK027346 mRNA Translation: BAB55051.1
AK314912 mRNA Translation: BAG37424.1
AL590733 Genomic DNA No translation available.
AL031776 Genomic DNA No translation available.
CH471051 Genomic DNA Translation: EAW48115.1
BC022367 mRNA Translation: AAH22367.1
CCDSiCCDS5135.1 [Q9BXY4-1]
RefSeqiNP_116173.2, NM_032784.4 [Q9BXY4-1]
UniGeneiHs.135254

3D structure databases

ProteinModelPortaliQ9BXY4
SMRiQ9BXY4
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124315, 3 interactors
IntActiQ9BXY4, 2 interactors
MINTiQ9BXY4
STRINGi9606.ENSP00000349131

PTM databases

iPTMnetiQ9BXY4
PhosphoSitePlusiQ9BXY4

Polymorphism and mutation databases

DMDMi74752442

Proteomic databases

PaxDbiQ9BXY4
PeptideAtlasiQ9BXY4
PRIDEiQ9BXY4
ProteomicsDBi79540
79541 [Q9BXY4-2]

Protocols and materials databases

DNASUi84870
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000356698; ENSP00000349131; ENSG00000146374 [Q9BXY4-1]
ENST00000368317; ENSP00000357300; ENSG00000146374 [Q9BXY4-2]
GeneIDi84870
KEGGihsa:84870
UCSCiuc003qar.5 human [Q9BXY4-1]

Organism-specific databases

CTDi84870
DisGeNETi84870
EuPathDBiHostDB:ENSG00000146374.13
GeneCardsiRSPO3
HGNCiHGNC:20866 RSPO3
HPAiHPA029957
MIMi610574 gene
neXtProtiNX_Q9BXY4
OpenTargetsiENSG00000146374
PharmGKBiPA134885289
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3525 Eukaryota
COG1404 LUCA
GeneTreeiENSGT00390000011447
HOGENOMiHOG000290668
HOVERGENiHBG082751
InParanoidiQ9BXY4
OMAiMECTSIV
OrthoDBiEOG091G0FYC
PhylomeDBiQ9BXY4
TreeFamiTF331799

Enzyme and pathway databases

ReactomeiR-HSA-4641263 Regulation of FZD by ubiquitination
R-HSA-8939256 RUNX1 regulates transcription of genes involved in WNT signaling
SIGNORiQ9BXY4

Miscellaneous databases

ChiTaRSiRSPO3 human
GeneWikiiRSPO3
GenomeRNAii84870
PROiPR:Q9BXY4
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000146374 Expressed in 173 organ(s), highest expression level in myometrium
CleanExiHS_RSPO3
GenevisibleiQ9BXY4 HS

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_HUMAN
AccessioniPrimary (citable) accession number: Q9BXY4
Secondary accession number(s): B2RC27, Q5VTV4, Q96K87
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: June 1, 2001
Last modified: September 12, 2018
This is version 135 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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