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Protein

R-spondin-1

Gene

RSPO1

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. 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).9 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 suggesting possible therapeutic application in gastrointestinal diseases.

GO - Molecular functioni

  • G-protein coupled receptor binding Source: UniProtKB
  • 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
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

EuPathDBiHostDB:ENSG00000169218.13
HGNCiHGNC:21679 RSPO1
MIMi609595 gene
neXtProtiNX_Q2MKA7

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

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...) asparagineSequence 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
ProteomicsDBi61396
61397 [Q2MKA7-2]
61398 [Q2MKA7-3]

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 Expressed in 73 organ(s), highest expression level in ectocervix
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. Interacts (via FU repeats) with KREM1 (PubMed:17804805).By similarity9 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi129926, 13 interactors
DIPiDIP-59895N
IntActiQ2MKA7, 2 interactors
MINTiQ2MKA7
STRINGi9606.ENSP00000348944

Structurei

Secondary structure

1263
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiKOG3525 Eukaryota
COG1404 LUCA
GeneTreeiENSGT00390000011447
HOGENOMiHOG000290668
HOVERGENiHBG082751
InParanoidiQ2MKA7
KOiK19471
OMAiACFSHNF
OrthoDBiEOG091G0FYC
PhylomeDBiQ2MKA7
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 (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 No translation available.
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

Similar proteinsi

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 No translation available.
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, 2 interactors
MINTiQ2MKA7
STRINGi9606.ENSP00000348944

PTM databases

iPTMnetiQ2MKA7
PhosphoSitePlusiQ2MKA7

Polymorphism and mutation databases

BioMutaiRSPO1
DMDMi97189599

Proteomic databases

PaxDbiQ2MKA7
PeptideAtlasiQ2MKA7
PRIDEiQ2MKA7
ProteomicsDBi61396
61397 [Q2MKA7-2]
61398 [Q2MKA7-3]

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
EuPathDBiHostDB:ENSG00000169218.13
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
OMAiACFSHNF
OrthoDBiEOG091G0FYC
PhylomeDBiQ2MKA7
TreeFamiTF331799

Enzyme and pathway databases

ReactomeiR-HSA-4641263 Regulation of FZD by ubiquitination
SIGNORiQ2MKA7

Miscellaneous databases

ChiTaRSiRSPO1 human
GeneWikiiRSPO1
GenomeRNAii284654
PROiPR:Q2MKA7
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000169218 Expressed in 73 organ(s), highest expression level in ectocervix
CleanExiHS_RSPO1
GenevisibleiQ2MKA7 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 nameiRSPO1_HUMAN
AccessioniPrimary (citable) accession number: Q2MKA7
Secondary accession number(s): A2A420
, Q0H8S6, Q14C72, Q5T0F2, Q8N7L5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: February 7, 2006
Last modified: September 12, 2018
This is version 117 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

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health

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