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Protein

R-spondin-1

Gene

RSPO1

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. 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.8 Publications

GO - Molecular functioni

  • G-protein coupled receptor binding Source: UniProtKB
  • heparin binding Source: UniProtKB-KW
  • receptor binding Source: UniProtKB

GO - Biological processi

  • positive regulation of canonical Wnt signaling pathway Source: UniProtKB
  • positive regulation of protein phosphorylation Source: UniProtKB
  • positive regulation of Wnt signaling pathway Source: UniProtKB
  • regulation of receptor internalization Source: BHF-UCL
  • Wnt signaling pathway Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Sensory transduction, Wnt signaling pathway

Keywords - Ligandi

Heparin-binding

Enzyme and pathway databases

ReactomeiR-HSA-4641263. Regulation of FZD by ubiquitination.
SIGNORiQ2MKA7.

Names & Taxonomyi

Protein namesi
Recommended name:
R-spondin-1
Alternative name(s):
Roof plate-specific spondin-1
Short name:
hRspo1
Gene namesi
Name:RSPO1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:21679. RSPO1.

Subcellular locationi

  • Secreted By similarity
  • Nucleus By similarity

  • Note: Seems to mainly localize to nucleoli.By similarity

GO - Cellular componenti

  • extracellular region Source: ParkinsonsUK-UCL
  • nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Nucleus, Secreted

Pathology & Biotechi

Involvement in diseasei

Keratoderma, palmoplantar, with squamous cell carcinoma of skin and sex reversal (PKKSCC)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA recessive syndrome characterized by XX (female to male) SRY-independent sex reversal, palmoplantar hyperkeratosis and predisposition to squamous cell carcinoma of the skin.
See also OMIM:610644

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi66R → A: Strongly reduces activation of Wnt signaling. 1 Publication1
Mutagenesisi66R → W: Reduces activation of Wnt signaling. 1 Publication1
Mutagenesisi70R → C or E: Strongly reduces activation of Wnt signaling. 1 Publication1
Mutagenesisi71Q → E: No effect on activation of Wnt signaling. 1 Publication1
Mutagenesisi71Q → R: Strongly reduces activation of Wnt signaling. 1 Publication1
Mutagenesisi73G → E or R: Strongly reduces activation of Wnt signaling. 1 Publication1
Mutagenesisi87R → A: Nearly abolishes activation of Wnt signaling. 2 Publications1
Mutagenesisi106F → A: Abolishes activation of Wnt signaling. Abolishes LGR4 binding. 2 Publications1
Mutagenesisi106F → E: Abolishes activation of Wnt signaling. 2 Publications1
Mutagenesisi110F → A: Nearly abolishes activation of Wnt signaling. 2 Publications1
Mutagenesisi110F → E: Abolishes activation of Wnt signaling. 2 Publications1
Mutagenesisi122K → A: Strongly reduces affinity for LGR4. 1 Publication1
Mutagenesisi124R → A: Strongly reduces affinity for LGR4. 1 Publication1

Keywords - Diseasei

Palmoplantar keratoderma

Organism-specific databases

DisGeNETi284654.
MalaCardsiRSPO1.
MIMi610644. phenotype.
OpenTargetsiENSG00000169218.
Orphaneti85112. Palmoplantar keratoderma - XX sex reversal - predisposition to squamous cell carcinoma.
PharmGKBiPA142670967.

Polymorphism and mutation databases

BioMutaiRSPO1.
DMDMi97189599.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
ChainiPRO_000023443621 – 263R-spondin-1Add BLAST243

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi40 ↔ 47Combined sources1 Publication
Disulfide bondi44 ↔ 53Combined sources1 Publication
Disulfide bondi56 ↔ 75Combined sources1 Publication
Disulfide bondi79 ↔ 94Combined sources1 Publication
Disulfide bondi97 ↔ 105Combined sources1 Publication
Disulfide bondi102 ↔ 111Combined sources1 Publication
Disulfide bondi114 ↔ 125Combined sources1 Publication
Disulfide bondi129 ↔ 142Combined sources1 Publication
Glycosylationi137N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi148 ↔ 190PROSITE-ProRule annotation
Disulfide bondi159 ↔ 166PROSITE-ProRule annotation
Disulfide bondi199 ↔ 206PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ2MKA7.
PeptideAtlasiQ2MKA7.
PRIDEiQ2MKA7.

PTM databases

iPTMnetiQ2MKA7.
PhosphoSitePlusiQ2MKA7.

Expressioni

Tissue specificityi

Abundantly expressed in adrenal glands, ovary, testis, thyroid and trachea but not in bone marrow, spinal cord, stomach, leukocytes colon, small intestine, prostate, thymus and spleen.1 Publication

Gene expression databases

BgeeiENSG00000169218.
CleanExiHS_RSPO1.
GenevisibleiQ2MKA7. HS.

Organism-specific databases

HPAiHPA046154.

Interactioni

Subunit structurei

Interacts with the extracellular domain of FZD8 and LRP6. It however does not form a ternary complex with FZD8 and LRP6. Interacts with WNT1. Binds heparin (By similarity). Interacts with ZNRF3; promoting indirect interaction between ZNRF3 and LGR4 and membrane clearance of ZNRF3. Interacts with LGR4, LGR5 and LGR6. Identified in a complex composed of RNF43, LGR5 and RSPO1.By similarity8 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
ZNRF3Q9ULT63EBI-10045219,EBI-949772

GO - Molecular functioni

  • G-protein coupled receptor binding Source: UniProtKB
  • receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi129926. 13 interactors.
DIPiDIP-59895N.
IntActiQ2MKA7. 1 interactor.
STRINGi9606.ENSP00000348944.

Structurei

Secondary structure

1263
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi44 – 48Combined sources5
Turni49 – 51Combined sources3
Beta strandi52 – 56Combined sources5
Beta strandi60 – 67Combined sources8
Beta strandi70 – 78Combined sources9
Beta strandi83 – 87Combined sources5
Beta strandi92 – 96Combined sources5
Beta strandi102 – 107Combined sources6
Beta strandi110 – 114Combined sources5
Beta strandi119 – 121Combined sources3
Beta strandi124 – 126Combined sources3
Turni131 – 134Combined sources4
Beta strandi136 – 141Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4BSOX-ray2.20A31-146[»]
4BSPX-ray2.00A31-146[»]
4BSRX-ray3.20C/D31-146[»]
4BSSX-ray3.20C/D/G/H31-146[»]
4BSTX-ray4.30C/D31-146[»]
4BSUX-ray3.20C/D/G/H31-146[»]
4CDKX-ray2.80E/F/G/H31-145[»]
4KNGX-ray2.50M/P35-144[»]
4KT1X-ray2.50E39-128[»]
4LI2X-ray3.19B33-144[»]
4QXFX-ray2.25C/E34-135[»]
ProteinModelPortaliQ2MKA7.
SMRiQ2MKA7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati34 – 85FU 1Add BLAST52
Repeati91 – 135FU 2Add BLAST45
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
Contains 2 FU (furin-like) repeats.Curated
Contains 1 TSP type-1 domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiKOG3525. Eukaryota.
COG1404. LUCA.
GeneTreeiENSGT00390000011447.
HOGENOMiHOG000290668.
HOVERGENiHBG082751.
InParanoidiQ2MKA7.
KOiK19471.
OMAiLVLSWMH.
OrthoDBiEOG091G0FYC.
PhylomeDBiQ2MKA7.
TreeFamiTF331799.

Family and domain databases

InterProiIPR006212. Furin_repeat.
IPR009030. Growth_fac_rcpt_.
IPR000884. TSP1_rpt.
[Graphical view]
PfamiPF15913. Furin-like_2. 1 hit.
[Graphical view]
SMARTiSM00261. FU. 2 hits.
SM00209. TSP1. 1 hit.
[Graphical view]
SUPFAMiSSF57184. SSF57184. 1 hit.
SSF82895. SSF82895. 1 hit.
PROSITEiPS50092. TSP1. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q2MKA7-1) [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
MRLGLCVVAL VLSWTHLTIS SRGIKGKRQR RISAEGSQAC AKGCELCSEV
60 70 80 90 100
NGCLKCSPKL FILLERNDIR QVGVCLPSCP PGYFDARNPD MNKCIKCKIE
110 120 130 140 150
HCEACFSHNF CTKCKEGLYL HKGRCYPACP EGSSAANGTM ECSSPAQCEM
160 170 180 190 200
SEWSPWGPCS KKQQLCGFRR GSEERTRRVL HAPVGDHAAC SDTKETRRCT
210 220 230 240 250
VRRVPCPEGQ KRRKGGQGRR ENANRNLARK ESKEAGAGSR RRKGQQQQQQ
260
QGTVGPLTSA GPA
Length:263
Mass (Da):28,959
Last modified:February 7, 2006 - v1
Checksum:i43794A881B1C0278
GO
Isoform 2 (identifier: Q2MKA7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-32: MRLGLCVVALVLSWTHLTISSRGIKGKRQRRI → MIFRV

Note: No experimental confirmation available.
Show »
Length:236
Mass (Da):25,975
Checksum:i8D08802127EC5668
GO
Isoform 3 (identifier: Q2MKA7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     146-208: Missing.

Show »
Length:200
Mass (Da):21,775
Checksum:iD55BBB18F4F86924
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti150M → V in BAC05263 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0183201 – 32MRLGL…RQRRI → MIFRV in isoform 2. 1 PublicationAdd BLAST32
Alternative sequenceiVSP_043265146 – 208Missing in isoform 3. 1 PublicationAdd BLAST63

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ318235 mRNA. Translation: ABC54570.1.
DQ165084 mRNA. Translation: ABA54597.1.
DQ165085 mRNA. Translation: ABA54598.1.
AK098225 mRNA. Translation: BAC05263.1.
AL513220 Genomic DNA. Translation: CAM12882.1.
AL513220 Genomic DNA. Translation: CAM12883.1.
AL513220 Genomic DNA. Translation: CAI15785.1.
BC114966 mRNA. Translation: AAI14967.1.
CCDSiCCDS41304.1. [Q2MKA7-1]
CCDS55590.1. [Q2MKA7-3]
CCDS55591.1. [Q2MKA7-2]
RefSeqiNP_001033722.1. NM_001038633.3. [Q2MKA7-1]
NP_001229837.1. NM_001242908.1. [Q2MKA7-1]
NP_001229838.1. NM_001242909.1. [Q2MKA7-2]
NP_001229839.1. NM_001242910.1. [Q2MKA7-3]
XP_006710646.1. XM_006710583.3. [Q2MKA7-1]
UniGeneiHs.135015.

Genome annotation databases

EnsembliENST00000356545; ENSP00000348944; ENSG00000169218. [Q2MKA7-1]
ENST00000401068; ENSP00000383846; ENSG00000169218. [Q2MKA7-1]
ENST00000612451; ENSP00000479832; ENSG00000169218. [Q2MKA7-3]
ENST00000615459; ENSP00000481178; ENSG00000169218. [Q2MKA7-2]
GeneIDi284654.
KEGGihsa:284654.
UCSCiuc031txm.2. human. [Q2MKA7-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ318235 mRNA. Translation: ABC54570.1.
DQ165084 mRNA. Translation: ABA54597.1.
DQ165085 mRNA. Translation: ABA54598.1.
AK098225 mRNA. Translation: BAC05263.1.
AL513220 Genomic DNA. Translation: CAM12882.1.
AL513220 Genomic DNA. Translation: CAM12883.1.
AL513220 Genomic DNA. Translation: CAI15785.1.
BC114966 mRNA. Translation: AAI14967.1.
CCDSiCCDS41304.1. [Q2MKA7-1]
CCDS55590.1. [Q2MKA7-3]
CCDS55591.1. [Q2MKA7-2]
RefSeqiNP_001033722.1. NM_001038633.3. [Q2MKA7-1]
NP_001229837.1. NM_001242908.1. [Q2MKA7-1]
NP_001229838.1. NM_001242909.1. [Q2MKA7-2]
NP_001229839.1. NM_001242910.1. [Q2MKA7-3]
XP_006710646.1. XM_006710583.3. [Q2MKA7-1]
UniGeneiHs.135015.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4BSOX-ray2.20A31-146[»]
4BSPX-ray2.00A31-146[»]
4BSRX-ray3.20C/D31-146[»]
4BSSX-ray3.20C/D/G/H31-146[»]
4BSTX-ray4.30C/D31-146[»]
4BSUX-ray3.20C/D/G/H31-146[»]
4CDKX-ray2.80E/F/G/H31-145[»]
4KNGX-ray2.50M/P35-144[»]
4KT1X-ray2.50E39-128[»]
4LI2X-ray3.19B33-144[»]
4QXFX-ray2.25C/E34-135[»]
ProteinModelPortaliQ2MKA7.
SMRiQ2MKA7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi129926. 13 interactors.
DIPiDIP-59895N.
IntActiQ2MKA7. 1 interactor.
STRINGi9606.ENSP00000348944.

PTM databases

iPTMnetiQ2MKA7.
PhosphoSitePlusiQ2MKA7.

Polymorphism and mutation databases

BioMutaiRSPO1.
DMDMi97189599.

Proteomic databases

PaxDbiQ2MKA7.
PeptideAtlasiQ2MKA7.
PRIDEiQ2MKA7.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000356545; ENSP00000348944; ENSG00000169218. [Q2MKA7-1]
ENST00000401068; ENSP00000383846; ENSG00000169218. [Q2MKA7-1]
ENST00000612451; ENSP00000479832; ENSG00000169218. [Q2MKA7-3]
ENST00000615459; ENSP00000481178; ENSG00000169218. [Q2MKA7-2]
GeneIDi284654.
KEGGihsa:284654.
UCSCiuc031txm.2. human. [Q2MKA7-1]

Organism-specific databases

CTDi284654.
DisGeNETi284654.
GeneCardsiRSPO1.
HGNCiHGNC:21679. RSPO1.
HPAiHPA046154.
MalaCardsiRSPO1.
MIMi609595. gene.
610644. phenotype.
neXtProtiNX_Q2MKA7.
OpenTargetsiENSG00000169218.
Orphaneti85112. Palmoplantar keratoderma - XX sex reversal - predisposition to squamous cell carcinoma.
PharmGKBiPA142670967.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3525. Eukaryota.
COG1404. LUCA.
GeneTreeiENSGT00390000011447.
HOGENOMiHOG000290668.
HOVERGENiHBG082751.
InParanoidiQ2MKA7.
KOiK19471.
OMAiLVLSWMH.
OrthoDBiEOG091G0FYC.
PhylomeDBiQ2MKA7.
TreeFamiTF331799.

Enzyme and pathway databases

ReactomeiR-HSA-4641263. Regulation of FZD by ubiquitination.
SIGNORiQ2MKA7.

Miscellaneous databases

ChiTaRSiRSPO1. human.
GeneWikiiRSPO1.
GenomeRNAii284654.
PROiQ2MKA7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000169218.
CleanExiHS_RSPO1.
GenevisibleiQ2MKA7. HS.

Family and domain databases

InterProiIPR006212. Furin_repeat.
IPR009030. Growth_fac_rcpt_.
IPR000884. TSP1_rpt.
[Graphical view]
PfamiPF15913. Furin-like_2. 1 hit.
[Graphical view]
SMARTiSM00261. FU. 2 hits.
SM00209. TSP1. 1 hit.
[Graphical view]
SUPFAMiSSF57184. SSF57184. 1 hit.
SSF82895. SSF82895. 1 hit.
PROSITEiPS50092. TSP1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRSPO1_HUMAN
AccessioniPrimary (citable) accession number: Q2MKA7
Secondary accession number(s): A2A420
, Q0H8S6, Q14C72, Q5T0F2, Q8N7L5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: February 7, 2006
Last modified: November 2, 2016
This is version 105 of the entry and version 1 of the sequence. [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

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 suggesting possible therapeutic application in gastrointestinal diseases.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.