Tbio RSPO1 R-spondin-1

Protein Summary

Description

Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors (PubMed:29769720). 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. Has a essential roles in ovary determination. Regulates Wnt signaling by antagonizing DKK1/KREM1-mediated internalization of LRP6 through an interaction with KREM1 (PubMed:17804805). This gene encodes a secreted activator protein with two cysteine-rich, furin-like domains and one thrombospondin type 1 domain. The encoded protein is a ligand for leucine-rich repeat-containing G-protein coupled receptors (LGR proteins) and positively regulates the Wnt signaling pathway. In mice, the protein induces the rapid onset of crypt cell proliferation and increases intestinal epithelial healing, providing a protective effect against chemotherapy-induced adverse effects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2014]

Uniprot Accession IDs

• Q2MKA7
• A2A420
• Q0H8S6
• Q14C72
• Q5T0F2
• Q8N7L5

Gene Name

• RSPO1

Ensembl ID

• ENST00000356545
• ENSP00000348944
• ENSG00000169218
• ENST00000401068
• ENSP00000383846
• ENST00000612451
• ENSP00000479832
• ENST00000615459
• ENSP00000481178

Symbol

• RSPO
• CRISTIN3

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
tissue	0.61
cell line	0.6
gene perturbation	0.6
cell type or tissue	0.57
PubMedID	0.57

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 284.41   (req: < 5)

Gene RIFs: 31   (req: <= 3)

Antibodies: 257   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 284.41   (req: >= 5)

Gene RIFs: 31   (req: > 3)

Antibodies: 257   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 9

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

tutorial

No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (0)

No active ligands found

Protein-Protein Interactions (117)

Explore Interacting Targets

1 – 10 of 117

• See Interactions on String-DB

LACRT

Tbio

Novelty:  0.03333799

p_int:  0.925771551

p_ni:  0.069407102

p_wrong:  0.004821347

Data Source:  BioPlex

CHTOP

Tbio

Novelty:  0.04170391

p_int:  0.897010672

p_ni:  0.102989328

Score:  0.254

Data Source:  BioPlex,STRINGDB

ZNF579

Tdark

Family:  TF

Novelty:  4.75515836

p_int:  0.877568616

p_ni:  0.122424754

p_wrong:  0.00000663

Score:  0.222

Data Source:  BioPlex,STRINGDB

HECTD3

Tdark

Family:  Enzyme

Novelty:  2.20874654

p_int:  0.797678589

p_ni:  0.202321411

Score:  0.167

Data Source:  BioPlex,STRINGDB

CEP76

Tdark

Novelty:  0.3880387

p_int:  0.765755989

p_ni:  0.233593253

p_wrong:  0.000650758

Score:  0.226

Data Source:  BioPlex,STRINGDB

C1QBP

Tbio

Novelty:  0.00532825

p_int:  0.765030273

p_ni:  0.234969727

Data Source:  BioPlex

ZZEF1

Tdark

Novelty:  0.33216648

p_int:  0.759688525

p_ni:  0.240311463

p_wrong:  1.2e-8

Score:  0.179

Data Source:  BioPlex,STRINGDB

RNF43

Tbio

Family:  Enzyme

Novelty:  0.01258908

Score:  0.998

Data Source:  Reactome,STRINGDB

LGR4

Tbio

Family:  GPCR

Novelty:  0.01180123

Score:  0.998

Data Source:  Reactome,STRINGDB

LGR5

Tbio

Family:  GPCR

Novelty:  0.00105035

Score:  0.997

Data Source:  Reactome,STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (7)

Reactome (4)

KEGG (1)

PathwayCommons (2)

Regulation of FZD by ubiquitination (R-HSA-4641263)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Regulation of FZD by ubiquitination	21 targets	R-HSA-4641263
Reactome	Signal Transduction	2704 targets	R-HSA-162582
Reactome	Signaling by WNT	299 targets	R-HSA-195721
Reactome	TCF dependent signaling in response to WNT	204 targets	R-HSA-201681

Name	Explore in Pharos	Explore in Source
Regulation of FZD by ubiquitination	21 targets	R-HSA-4641263
Signal Transduction	2704 targets	R-HSA-162582
Signaling by WNT	299 targets	R-HSA-195721
TCF dependent signaling in response to WNT	204 targets	R-HSA-201681

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (12)

Functions (4)

Components (3)

Processes (5)

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1 – 4 of 4

GO Term	Evidence	Assigned by
G protein-coupled receptor binding	Inferred from Physical Interaction (IPI)	UniProtKB
signaling receptor binding	Inferred from Physical Interaction (IPI)	UniProtKB
frizzled binding	Inferred from Biological aspect of Ancestor (IBA)	GO_Central
heparin binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Disease Associations (null)

No disease associations found

GWAS Traits (7)

• Explore on Target Illumination GWAS Analytics (TIGA)

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5

1 – 5 of 7

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
corneal topography	EFO_0004345	4	1	4		87.2
intraocular pressure measurement	EFO_0004695	4	4	5		71.3
Malignant epithelial tumor of ovary	Orphanet_398934	1	1	0	1.1	50.6
body mass index	EFO_0004340	1	1	1		40.7
ovarian carcinoma	EFO_0001075	1	1	0	1.1	35

• Explore on Target Illumination GWAS Analytics (TIGA)

Items per page:

5

1 – 5 of 7

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
corneal topography	EFO_0004345	4		87.2
intraocular pressure measurement	EFO_0004695	5		71.3
Malignant epithelial tumor of ovary	Orphanet_398934	0	1.1	50.6
body mass index	EFO_0004340	1		40.7
ovarian carcinoma	EFO_0001075	0	1.1	35

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Find similar targets by:

UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Alternative splicing
Complete proteome
Disulfide bond
Glycoprotein
Heparin-binding
Nucleus
Palmoplantar keratoderma
Reference proteome
Repeat

GWAS Trait Find Similar Targets

No Header	No Header
balding measurement
body mass index
corneal topography
endometrial carcinoma
intraocular pressure measurement
Malignant epithelial tumor of ovary
ovarian carcinoma

MGI Phenotype Find Similar Targets

No Header	No Header
adipose tissue phenotype
behavior/neurological phenotype
cellular phenotype
endocrine/exocrine gland phenotype
growth/size/body region phenotype
hearing/vestibular/ear phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
integument phenotype

IDG Resources

No IDG generated resources found

Orthologs (12)

1 – 5 of 12

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	R-spondin 1	VGNC:6988	469283
Macaque	R-spondin 1		713976
Mouse	R-spondin 1	MGI:2183426	192199
Rat	R-spondin 1	RGD:1565558	313589
Dog	R-spondin 1	VGNC:45782	608179

Species	Name	OMA	EggNOG	Inparanoid
Chimp	R-spondin 1
Macaque	R-spondin 1
Mouse	R-spondin 1
Rat	R-spondin 1
Dog	R-spondin 1

Publication Statistics

PubMed Score 284.41

PubMed score by year

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PubTator Score 111.82

PubTator score by year

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Related Publications

Text Mined References (59)

GeneRif Annotations (31)

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PMID	Year	Title