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Protein

R-spondin-2

Gene

RSPO2

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. Probably also acts as a ligand for frizzled and LRP receptors.3 Publications

GO - Molecular functioni

  • heparin binding Source: UniProtKB-KW
  • receptor binding Source: UniProtKB

GO - Biological processi

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.
SIGNORiQ6UXX9.

Names & Taxonomyi

Protein namesi
Recommended name:
R-spondin-2
Alternative name(s):
Roof plate-specific spondin-2
Short name:
hRspo2
Gene namesi
Name:RSPO2
ORF Names:UNQ9384/PRO34209
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:28583. RSPO2.

Subcellular locationi

GO - Cellular componenti

  • cell surface Source: Ensembl
  • extracellular region Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi340419.
OpenTargetsiENSG00000147655.
PharmGKBiPA142670968.

Polymorphism and mutation databases

BioMutaiRSPO2.
DMDMi147744588.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000023443922 – 243R-spondin-2Add BLAST222

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi40 ↔ 46PROSITE-ProRule annotation
Disulfide bondi43 ↔ 52PROSITE-ProRule annotation
Disulfide bondi55 ↔ 74PROSITE-ProRule annotation
Disulfide bondi78 ↔ 93PROSITE-ProRule annotation
Disulfide bondi96 ↔ 104PROSITE-ProRule annotation
Disulfide bondi101 ↔ 110PROSITE-ProRule annotation
Disulfide bondi113 ↔ 124PROSITE-ProRule annotation
Disulfide bondi128 ↔ 141PROSITE-ProRule annotation
Disulfide bondi145 ↔ 187PROSITE-ProRule annotation
Disulfide bondi156 ↔ 163PROSITE-ProRule annotation
Glycosylationi160N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi196 ↔ 203PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ6UXX9.
PeptideAtlasiQ6UXX9.
PRIDEiQ6UXX9.

PTM databases

PhosphoSitePlusiQ6UXX9.

Expressioni

Gene expression databases

BgeeiENSG00000147655.
CleanExiHS_RSPO2.
ExpressionAtlasiQ6UXX9. baseline and differential.
GenevisibleiQ6UXX9. HS.

Organism-specific databases

HPAiCAB025900.
HPA024764.
HPA053068.

Interactioni

Subunit structurei

Interacts with WNT1. Binds heparin (By similarity). Interacts with LGR4, LGR5 and LGR6.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
KRTAP10-4P603723EBI-8481036,EBI-10178153
KRTAP10-7P604093EBI-8481036,EBI-10172290
KRTAP10-9P604113EBI-8481036,EBI-10172052
PLEKHF2Q9H8W43EBI-8481036,EBI-742388

GO - Molecular functioni

  • receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi131049. 9 interactors.
IntActiQ6UXX9. 10 interactors.
MINTiMINT-8417715.
STRINGi9606.ENSP00000276659.

Structurei

3D structure databases

ProteinModelPortaliQ6UXX9.
SMRiQ6UXX9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati90 – 134FUAdd BLAST45
Domaini144 – 204TSP type-1PROSITE-ProRule annotationAdd BLAST61

Domaini

The FU repeat is required for activation and stabilization of beta-catenin.By similarity

Sequence similaritiesi

Belongs to the R-spondin family.Curated
Contains 1 FU (furin-like) repeat.Curated
Contains 1 TSP type-1 domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IMS2. Eukaryota.
ENOG410ZI6H. LUCA.
GeneTreeiENSGT00390000011447.
HOGENOMiHOG000290668.
HOVERGENiHBG082751.
InParanoidiQ6UXX9.
OMAiANRWRRS.
OrthoDBiEOG091G0FYC.
PhylomeDBiQ6UXX9.
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: Q6UXX9-1) [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
MQFRLFSFAL IILNCMDYSH CQGNRWRRSK RASYVSNPIC KGCLSCSKDN
60 70 80 90 100
GCSRCQQKLF FFLRREGMRQ YGECLHSCPS GYYGHRAPDM NRCARCRIEN
110 120 130 140 150
CDSCFSKDFC TKCKVGFYLH RGRCFDECPD GFAPLEETME CVEGCEVGHW
160 170 180 190 200
SEWGTCSRNN RTCGFKWGLE TRTRQIVKKP VKDTILCPTI AESRRCKMTM
210 220 230 240
RHCPGGKRTP KAKEKRNKKK KRKLIERAQE QHSVFLATDR ANQ
Length:243
Mass (Da):28,315
Last modified:May 15, 2007 - v2
Checksum:i96F44F105B21BB52
GO
Isoform 2 (identifier: Q6UXX9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-67: Missing.

Note: No experimental confirmation available.
Show »
Length:176
Mass (Da):20,426
Checksum:i0F9FD0E1AEE4CA85
GO
Isoform 3 (identifier: Q6UXX9-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     32-95: ASYVSNPICKGCLSCSKDNGCSRCQQKLFFFLRREGMRQYGECLHSCPSGYYGHRAPDMNRCAR → G
     143-143: Missing.

Note: No experimental confirmation available.
Show »
Length:179
Mass (Da):20,972
Checksum:i7C428C4A6C152798
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_026247186L → P.4 PublicationsCorresponds to variant rs601558dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0183211 – 67Missing in isoform 2. 1 PublicationAdd BLAST67
Alternative sequenceiVSP_01832232 – 95ASYVS…NRCAR → G in isoform 3. 1 PublicationAdd BLAST64
Alternative sequenceiVSP_018323143Missing in isoform 3. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY358166 mRNA. Translation: AAQ88533.1.
AK123023 mRNA. Translation: BAG53852.1.
AC025508 Genomic DNA. No translation available.
AP003479 Genomic DNA. No translation available.
CH471060 Genomic DNA. Translation: EAW91916.1.
BC027938 mRNA. Translation: AAH27938.1.
BC036554 mRNA. Translation: AAH36554.1.
CCDSiCCDS6307.1. [Q6UXX9-1]
CCDS64953.1. [Q6UXX9-3]
CCDS83314.1. [Q6UXX9-2]
RefSeqiNP_001269792.1. NM_001282863.1. [Q6UXX9-3]
NP_001304871.1. NM_001317942.1. [Q6UXX9-2]
NP_848660.3. NM_178565.4. [Q6UXX9-1]
UniGeneiHs.444834.

Genome annotation databases

EnsembliENST00000276659; ENSP00000276659; ENSG00000147655. [Q6UXX9-1]
ENST00000517781; ENSP00000427937; ENSG00000147655. [Q6UXX9-3]
ENST00000517939; ENSP00000428940; ENSG00000147655. [Q6UXX9-2]
GeneIDi340419.
KEGGihsa:340419.
UCSCiuc003ymq.4. human. [Q6UXX9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY358166 mRNA. Translation: AAQ88533.1.
AK123023 mRNA. Translation: BAG53852.1.
AC025508 Genomic DNA. No translation available.
AP003479 Genomic DNA. No translation available.
CH471060 Genomic DNA. Translation: EAW91916.1.
BC027938 mRNA. Translation: AAH27938.1.
BC036554 mRNA. Translation: AAH36554.1.
CCDSiCCDS6307.1. [Q6UXX9-1]
CCDS64953.1. [Q6UXX9-3]
CCDS83314.1. [Q6UXX9-2]
RefSeqiNP_001269792.1. NM_001282863.1. [Q6UXX9-3]
NP_001304871.1. NM_001317942.1. [Q6UXX9-2]
NP_848660.3. NM_178565.4. [Q6UXX9-1]
UniGeneiHs.444834.

3D structure databases

ProteinModelPortaliQ6UXX9.
SMRiQ6UXX9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi131049. 9 interactors.
IntActiQ6UXX9. 10 interactors.
MINTiMINT-8417715.
STRINGi9606.ENSP00000276659.

PTM databases

PhosphoSitePlusiQ6UXX9.

Polymorphism and mutation databases

BioMutaiRSPO2.
DMDMi147744588.

Proteomic databases

PaxDbiQ6UXX9.
PeptideAtlasiQ6UXX9.
PRIDEiQ6UXX9.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000276659; ENSP00000276659; ENSG00000147655. [Q6UXX9-1]
ENST00000517781; ENSP00000427937; ENSG00000147655. [Q6UXX9-3]
ENST00000517939; ENSP00000428940; ENSG00000147655. [Q6UXX9-2]
GeneIDi340419.
KEGGihsa:340419.
UCSCiuc003ymq.4. human. [Q6UXX9-1]

Organism-specific databases

CTDi340419.
DisGeNETi340419.
GeneCardsiRSPO2.
H-InvDBHIX0007721.
HGNCiHGNC:28583. RSPO2.
HPAiCAB025900.
HPA024764.
HPA053068.
MIMi610575. gene.
neXtProtiNX_Q6UXX9.
OpenTargetsiENSG00000147655.
PharmGKBiPA142670968.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IMS2. Eukaryota.
ENOG410ZI6H. LUCA.
GeneTreeiENSGT00390000011447.
HOGENOMiHOG000290668.
HOVERGENiHBG082751.
InParanoidiQ6UXX9.
OMAiANRWRRS.
OrthoDBiEOG091G0FYC.
PhylomeDBiQ6UXX9.
TreeFamiTF331799.

Enzyme and pathway databases

ReactomeiR-HSA-4641263. Regulation of FZD by ubiquitination.
SIGNORiQ6UXX9.

Miscellaneous databases

GeneWikiiRSPO2.
GenomeRNAii340419.
PROiQ6UXX9.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000147655.
CleanExiHS_RSPO2.
ExpressionAtlasiQ6UXX9. baseline and differential.
GenevisibleiQ6UXX9. 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 nameiRSPO2_HUMAN
AccessioniPrimary (citable) accession number: Q6UXX9
Secondary accession number(s): B3KVP0, Q4G0U4, Q8N6X6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: May 15, 2007
Last modified: November 30, 2016
This is version 108 of the entry and version 2 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 (PubMed:16357527).1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.