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Protein

R-spondin-3

Gene

RSPO3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
  • 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.

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.

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.
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

  • frizzled binding Source: Ensembl
  • receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi124315. 3 interactors.
IntActiQ9BXY4. 2 interactors.
MINTiMINT-8297608.
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

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

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: November 22, 2017
This is version 131 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. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families