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UniProtKB - Q6UXX9 (RSPO2_HUMAN)

Protein

R-spondin-2

Gene

RSPO2

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 (PubMed:21909076, PubMed:21727895, PubMed:22615920). During embryonic development, plays a crucial role in limb specification, amplifying the Wnt signaling pathway independently of LGR4-6 receptors, possibly by acting as a direct antagonistic ligand to RNF43 and ZNRF3, hence governing the number of limbs an embryo should form (PubMed:29769720).4 Publications

GO - Molecular functioni

  • frizzled binding Source: GO_Central
  • heparin binding Source: UniProtKB-KW
  • signaling receptor binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionDevelopmental protein, Heparin-binding
Biological processSensory transduction, Wnt signaling pathway

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000147655.10
HGNCiHGNC:28583 RSPO2
MIMi610575 gene
neXtProtiNX_Q6UXX9

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

Involvement in diseasei

Tetraamelia syndrome 2 (TETAMS2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of tetraamelia, a rare disease characterized by rudimentary appendages or complete absence of all four limbs, and other anomalies such as craniofacial, nervous system, pulmonary, skeletal and urogenital defects. TETAMS2 patients manifest limb deformities, bilateral agenesis of the lungs, abnormalities of the pulmonary vasculature, labioscrotal fold aplasia, and dysmorphic features including bilateral cleft lip/palate, ankyloglossia, mandibular hypoplasia, and microretrognathia. TETAMS2 transmission pattern is consistent with autosomal recessive inheritance.
See also OMIM:618021
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_08103770 – 243Missing in TETAMS2; loss of LGR5-, RNF43- and ZNRF3-binding; complete loss of amplification of WNT3A signaling. 1 PublicationAdd BLAST174
Natural variantiVAR_081038137 – 243Missing in TETAMS2. 1 PublicationAdd BLAST107
Humerofemoral hypoplasia with radiotibial ray deficiency (HHRRD)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA severe disease characterized by reduction of all four limbs as well as hypoplasia of the upper limb girdle and pelvis. Rudimentary finger- or toe-like appendages may be present. HHRRD transmission pattern is consistent with autosomal recessive inheritance.
See also OMIM:618022
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_08103669R → C in HHRRD; loss of LGR5-, RNF43- and ZNRF3-binding; decreased ability to amplify WNT3A signaling. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi105F → A: Loss of LGR5-binding, no effect on interaction with RNF43 and ZNRF3, no effect on WNT3A signaling; when associated with A-109. 1 Publication1
Mutagenesisi109F → A: Loss of LGR5-binding, no effect on interaction with RNF43 and ZNRF3, no effect on WNT3A signaling; when associated with A-105. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi340419
MIMi618021 phenotype
618022 phenotype
OpenTargetsiENSG00000147655
Orphaneti3301 Tetraamelia-multiple malformations syndrome
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...) asparagineSequence analysis1
Disulfide bondi196 ↔ 203PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ6UXX9
PeptideAtlasiQ6UXX9
PRIDEiQ6UXX9
ProteomicsDBi67672
67673 [Q6UXX9-2]
67674 [Q6UXX9-3]

PTM databases

PhosphoSitePlusiQ6UXX9

Expressioni

Gene expression databases

BgeeiENSG00000147655 Expressed in 100 organ(s), highest expression level in lung
CleanExiHS_RSPO2
ExpressionAtlasiQ6UXX9 baseline and differential
GenevisibleiQ6UXX9 HS

Organism-specific databases

HPAiCAB025900
HPA024764
HPA053068

Interactioni

Subunit structurei

Interacts with WNT1 (By similarity). Binds heparin (By similarity). Interacts with LGR4, LGR5 and LGR6 (PubMed:21909076, PubMed:21727895, PubMed:22615920, PubMed:29769720). Interacts with E3 ubiquitin ligases RNF43 and ZNRF3 (PubMed:29769720).By similarity4 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi131049, 10 interactors
IntActiQ6UXX9, 12 interactors
MINTiQ6UXX9
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

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IMS2 Eukaryota
ENOG410ZI6H LUCA
GeneTreeiENSGT00390000011447
HOGENOMiHOG000290668
HOVERGENiHBG082751
InParanoidiQ6UXX9
OMAiDNGCIRC
OrthoDBiEOG091G0FYC
PhylomeDBiQ6UXX9
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

This entry has 3 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 5 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E5RH25E5RH25_HUMAN
R-spondin-2
RSPO2
121Annotation score:
E5RGU9E5RGU9_HUMAN
R-spondin-2
RSPO2
76Annotation score:
E5RHC3E5RHC3_HUMAN
R-spondin-2
RSPO2
168Annotation score:
E5RJU7E5RJU7_HUMAN
R-spondin-2
RSPO2
89Annotation score:
E5RJA2E5RJA2_HUMAN
R-spondin-2
RSPO2
89Annotation score:

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_08103669R → C in HHRRD; loss of LGR5-, RNF43- and ZNRF3-binding; decreased ability to amplify WNT3A signaling. 1 Publication1
Natural variantiVAR_08103770 – 243Missing in TETAMS2; loss of LGR5-, RNF43- and ZNRF3-binding; complete loss of amplification of WNT3A signaling. 1 PublicationAdd BLAST174
Natural variantiVAR_081038137 – 243Missing in TETAMS2. 1 PublicationAdd BLAST107
Natural variantiVAR_026247186L → P4 PublicationsCorresponds to variant dbSNP:rs601558Ensembl.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

Similar proteinsi

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, 10 interactors
IntActiQ6UXX9, 12 interactors
MINTiQ6UXX9
STRINGi9606.ENSP00000276659

PTM databases

PhosphoSitePlusiQ6UXX9

Polymorphism and mutation databases

BioMutaiRSPO2
DMDMi147744588

Proteomic databases

PaxDbiQ6UXX9
PeptideAtlasiQ6UXX9
PRIDEiQ6UXX9
ProteomicsDBi67672
67673 [Q6UXX9-2]
67674 [Q6UXX9-3]

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
EuPathDBiHostDB:ENSG00000147655.10
GeneCardsiRSPO2
H-InvDBiHIX0007721
HGNCiHGNC:28583 RSPO2
HPAiCAB025900
HPA024764
HPA053068
MIMi610575 gene
618021 phenotype
618022 phenotype
neXtProtiNX_Q6UXX9
OpenTargetsiENSG00000147655
Orphaneti3301 Tetraamelia-multiple malformations syndrome
PharmGKBiPA142670968
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IMS2 Eukaryota
ENOG410ZI6H LUCA
GeneTreeiENSGT00390000011447
HOGENOMiHOG000290668
HOVERGENiHBG082751
InParanoidiQ6UXX9
OMAiDNGCIRC
OrthoDBiEOG091G0FYC
PhylomeDBiQ6UXX9
TreeFamiTF331799

Enzyme and pathway databases

ReactomeiR-HSA-4641263 Regulation of FZD by ubiquitination
SIGNORiQ6UXX9

Miscellaneous databases

GeneWikiiRSPO2
GenomeRNAii340419
PROiPR:Q6UXX9
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000147655 Expressed in 100 organ(s), highest expression level in lung
CleanExiHS_RSPO2
ExpressionAtlasiQ6UXX9 baseline and differential
GenevisibleiQ6UXX9 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 nameiRSPO2_HUMAN
AccessioniPrimary (citable) accession number: Q6UXX9
Secondary accession number(s): B3KVP0, Q4G0U4, Q8N6X6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 16, 2006
Last sequence update: May 15, 2007
Last modified: November 7, 2018
This is version 123 of the entry and version 2 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
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