UniProtKB - Q6UXX9 (RSPO2_HUMAN)
Protein
R-spondin-2
Gene
RSPO2
Organism
Homo sapiens (Human)
Status
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
- heparin binding Source: UniProtKB-KW
- signaling receptor binding Source: UniProtKB
GO - Biological processi
- bone mineralization Source: Ensembl
- dopaminergic neuron differentiation Source: Ensembl
- embryonic forelimb morphogenesis Source: Ensembl
- embryonic hindlimb morphogenesis Source: Ensembl
- epithelial tube branching involved in lung morphogenesis Source: Ensembl
- limb development Source: UniProtKB
- lung growth Source: Ensembl
- negative regulation of odontogenesis of dentin-containing tooth Source: Ensembl
- osteoblast differentiation Source: Ensembl
- positive regulation of canonical Wnt signaling pathway Source: Ensembl
- positive regulation of Wnt signaling pathway Source: UniProtKB
- trachea cartilage morphogenesis Source: Ensembl
- Wnt signaling pathway Source: UniProtKB-KW
Keywordsi
Molecular function | Developmental protein, Heparin-binding |
Biological process | Sensory transduction, Wnt signaling pathway |
Enzyme and pathway databases
PathwayCommonsi | Q6UXX9 |
Reactomei | R-HSA-4641263, Regulation of FZD by ubiquitination |
SIGNORi | Q6UXX9 |
Names & Taxonomyi
Protein namesi | Recommended name: R-spondin-2Alternative name(s): Roof plate-specific spondin-2 Short name: hRspo2 |
Gene namesi | Name:RSPO2 ORF Names:UNQ9384/PRO34209 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000147655.10 |
HGNCi | HGNC:28583, RSPO2 |
MIMi | 610575, gene |
neXtProti | NX_Q6UXX9 |
Subcellular locationi
Extracellular region or secreted
- Secreted By similarity
Extracellular region or secreted
- extracellular region Source: Reactome
Other locations
- cell surface Source: Ensembl
Keywords - Cellular componenti
SecretedPathology & 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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_081037 | 70 – 243 | Missing in TETAMS2; loss of LGR5-, RNF43- and ZNRF3-binding; complete loss of amplification of WNT3A signaling. 1 PublicationAdd BLAST | 174 | |
Natural variantiVAR_081038 | 137 – 243 | Missing in TETAMS2. 1 PublicationAdd BLAST | 107 |
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.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_081036 | 69 | R → C in HHRRD; loss of LGR5-, RNF43- and ZNRF3-binding; decreased ability to amplify WNT3A signaling. 1 PublicationCorresponds to variant dbSNP:rs758888137EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 105 | F → A: Loss of LGR5-binding, no effect on interaction with RNF43 and ZNRF3, no effect on WNT3A signaling; when associated with A-109. 1 Publication | 1 | |
Mutagenesisi | 109 | F → A: Loss of LGR5-binding, no effect on interaction with RNF43 and ZNRF3, no effect on WNT3A signaling; when associated with A-105. 1 Publication | 1 |
Keywords - Diseasei
Disease mutationOrganism-specific databases
DisGeNETi | 340419 |
MalaCardsi | RSPO2 |
MIMi | 618021, phenotype 618022, phenotype |
OpenTargetsi | ENSG00000147655 |
Orphaneti | 3301, Tetraamelia-multiple malformations syndrome |
PharmGKBi | PA142670968 |
Miscellaneous databases
Pharosi | Q6UXX9, Tbio |
Polymorphism and mutation databases
BioMutai | RSPO2 |
DMDMi | 147744588 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 21 | Sequence analysisAdd BLAST | 21 | |
ChainiPRO_0000234439 | 22 – 243 | R-spondin-2Add BLAST | 222 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 40 ↔ 46 | PROSITE-ProRule annotation | ||
Disulfide bondi | 43 ↔ 52 | PROSITE-ProRule annotation | ||
Disulfide bondi | 55 ↔ 74 | PROSITE-ProRule annotation | ||
Disulfide bondi | 78 ↔ 93 | PROSITE-ProRule annotation | ||
Disulfide bondi | 96 ↔ 104 | PROSITE-ProRule annotation | ||
Disulfide bondi | 101 ↔ 110 | PROSITE-ProRule annotation | ||
Disulfide bondi | 113 ↔ 124 | PROSITE-ProRule annotation | ||
Disulfide bondi | 128 ↔ 141 | PROSITE-ProRule annotation | ||
Disulfide bondi | 145 ↔ 187 | PROSITE-ProRule annotation | ||
Disulfide bondi | 156 ↔ 163 | PROSITE-ProRule annotation | ||
Glycosylationi | 160 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 196 ↔ 203 | PROSITE-ProRule annotation |
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
PaxDbi | Q6UXX9 |
PeptideAtlasi | Q6UXX9 |
PRIDEi | Q6UXX9 |
ProteomicsDBi | 67672 [Q6UXX9-1] 67673 [Q6UXX9-2] 67674 [Q6UXX9-3] |
PTM databases
GlyGeni | Q6UXX9, 1 site |
PhosphoSitePlusi | Q6UXX9 |
Expressioni
Gene expression databases
Bgeei | ENSG00000147655, Expressed in lung and 124 other tissues |
ExpressionAtlasi | Q6UXX9, baseline and differential |
Genevisiblei | Q6UXX9, HS |
Organism-specific databases
HPAi | ENSG00000147655, Tissue enhanced (brain, placenta) |
Interactioni
Subunit structurei
Binary interactionsi
Hide detailsQ6UXX9
With | #Exp. | IntAct |
---|---|---|
KRTAP10-4 [P60372] | 3 | EBI-8481036,EBI-10178153 |
KRTAP10-7 [P60409] | 3 | EBI-8481036,EBI-10172290 |
KRTAP10-9 [P60411] | 3 | EBI-8481036,EBI-10172052 |
PLEKHF2 [Q9H8W4] | 3 | EBI-8481036,EBI-742388 |
Isoform 2 [Q6UXX9-2]
GO - Molecular functioni
- signaling receptor binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 131049, 20 interactors |
IntActi | Q6UXX9, 15 interactors |
MINTi | Q6UXX9 |
STRINGi | 9606.ENSP00000276659 |
Miscellaneous databases
RNActi | Q6UXX9, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 90 – 134 | FUAdd BLAST | 45 | |
Domaini | 144 – 204 | TSP type-1PROSITE-ProRule annotationAdd BLAST | 61 |
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
SignalPhylogenomic databases
eggNOGi | KOG3525, Eukaryota |
GeneTreei | ENSGT00940000159194 |
HOGENOMi | CLU_064219_1_0_1 |
InParanoidi | Q6UXX9 |
OMAi | KQHSIFL |
OrthoDBi | 1441603at2759 |
PhylomeDBi | Q6UXX9 |
TreeFami | TF331799 |
Family and domain databases
CDDi | cd00064, FU, 1 hit |
Gene3Di | 2.20.100.10, 1 hit |
InterProi | View protein in InterPro IPR006212, Furin_repeat IPR009030, Growth_fac_rcpt_cys_sf IPR042993, RSPO2 IPR043601, Rspo_Fu-CRD_dom IPR000884, TSP1_rpt IPR036383, TSP1_rpt_sf |
PANTHERi | PTHR23275:SF79, PTHR23275:SF79, 1 hit |
Pfami | View protein in Pfam PF15913, Furin-like_2, 1 hit |
SMARTi | View protein in SMART SM00261, FU, 2 hits SM00209, TSP1, 1 hit |
SUPFAMi | SSF57184, SSF57184, 1 hit SSF82895, SSF82895, 1 hit |
PROSITEi | View protein in PROSITE PS50092, TSP1, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 3 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 sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketE5RH25 | E5RH25_HUMAN | R-spondin-2 | RSPO2 | 121 | Annotation score: | ||
E5RGU9 | E5RGU9_HUMAN | R-spondin-2 | RSPO2 | 76 | Annotation score: | ||
A0A590UJ52 | A0A590UJ52_HUMAN | R-spondin-2 | RSPO2 | 38 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_081036 | 69 | R → C in HHRRD; loss of LGR5-, RNF43- and ZNRF3-binding; decreased ability to amplify WNT3A signaling. 1 PublicationCorresponds to variant dbSNP:rs758888137EnsemblClinVar. | 1 | |
Natural variantiVAR_081037 | 70 – 243 | Missing in TETAMS2; loss of LGR5-, RNF43- and ZNRF3-binding; complete loss of amplification of WNT3A signaling. 1 PublicationAdd BLAST | 174 | |
Natural variantiVAR_081038 | 137 – 243 | Missing in TETAMS2. 1 PublicationAdd BLAST | 107 | |
Natural variantiVAR_026247 | 186 | L → P4 PublicationsCorresponds to variant dbSNP:rs601558Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_018321 | 1 – 67 | Missing in isoform 2. 1 PublicationAdd BLAST | 67 | |
Alternative sequenceiVSP_018322 | 32 – 95 | ASYVS…NRCAR → G in isoform 3. 1 PublicationAdd BLAST | 64 | |
Alternative sequenceiVSP_018323 | 143 | Missing in isoform 3. 1 Publication | 1 |
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 |
CCDSi | CCDS6307.1 [Q6UXX9-1] CCDS64953.1 [Q6UXX9-3] CCDS83314.1 [Q6UXX9-2] |
RefSeqi | NP_001269792.1, NM_001282863.1 [Q6UXX9-3] NP_001304871.1, NM_001317942.1 [Q6UXX9-2] NP_848660.3, NM_178565.4 [Q6UXX9-1] |
Genome annotation databases
Ensembli | ENST00000276659; ENSP00000276659; ENSG00000147655 [Q6UXX9-1] ENST00000517781; ENSP00000427937; ENSG00000147655 [Q6UXX9-3] ENST00000517939; ENSP00000428940; ENSG00000147655 [Q6UXX9-2] |
GeneIDi | 340419 |
KEGGi | hsa:340419 |
UCSCi | uc003ymq.4, human [Q6UXX9-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar 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 |
CCDSi | CCDS6307.1 [Q6UXX9-1] CCDS64953.1 [Q6UXX9-3] CCDS83314.1 [Q6UXX9-2] |
RefSeqi | NP_001269792.1, NM_001282863.1 [Q6UXX9-3] NP_001304871.1, NM_001317942.1 [Q6UXX9-2] NP_848660.3, NM_178565.4 [Q6UXX9-1] |
3D structure databases
SMRi | Q6UXX9 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 131049, 20 interactors |
IntActi | Q6UXX9, 15 interactors |
MINTi | Q6UXX9 |
STRINGi | 9606.ENSP00000276659 |
PTM databases
GlyGeni | Q6UXX9, 1 site |
PhosphoSitePlusi | Q6UXX9 |
Polymorphism and mutation databases
BioMutai | RSPO2 |
DMDMi | 147744588 |
Proteomic databases
PaxDbi | Q6UXX9 |
PeptideAtlasi | Q6UXX9 |
PRIDEi | Q6UXX9 |
ProteomicsDBi | 67672 [Q6UXX9-1] 67673 [Q6UXX9-2] 67674 [Q6UXX9-3] |
Protocols and materials databases
Antibodypediai | 26506, 131 antibodies |
Genome annotation databases
Ensembli | ENST00000276659; ENSP00000276659; ENSG00000147655 [Q6UXX9-1] ENST00000517781; ENSP00000427937; ENSG00000147655 [Q6UXX9-3] ENST00000517939; ENSP00000428940; ENSG00000147655 [Q6UXX9-2] |
GeneIDi | 340419 |
KEGGi | hsa:340419 |
UCSCi | uc003ymq.4, human [Q6UXX9-1] |
Organism-specific databases
CTDi | 340419 |
DisGeNETi | 340419 |
EuPathDBi | HostDB:ENSG00000147655.10 |
GeneCardsi | RSPO2 |
HGNCi | HGNC:28583, RSPO2 |
HPAi | ENSG00000147655, Tissue enhanced (brain, placenta) |
MalaCardsi | RSPO2 |
MIMi | 610575, gene 618021, phenotype 618022, phenotype |
neXtProti | NX_Q6UXX9 |
OpenTargetsi | ENSG00000147655 |
Orphaneti | 3301, Tetraamelia-multiple malformations syndrome |
PharmGKBi | PA142670968 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3525, Eukaryota |
GeneTreei | ENSGT00940000159194 |
HOGENOMi | CLU_064219_1_0_1 |
InParanoidi | Q6UXX9 |
OMAi | KQHSIFL |
OrthoDBi | 1441603at2759 |
PhylomeDBi | Q6UXX9 |
TreeFami | TF331799 |
Enzyme and pathway databases
PathwayCommonsi | Q6UXX9 |
Reactomei | R-HSA-4641263, Regulation of FZD by ubiquitination |
SIGNORi | Q6UXX9 |
Miscellaneous databases
BioGRID-ORCSi | 340419, 2 hits in 843 CRISPR screens |
ChiTaRSi | RSPO2, human |
GeneWikii | RSPO2 |
GenomeRNAii | 340419 |
Pharosi | Q6UXX9, Tbio |
PROi | PR:Q6UXX9 |
RNActi | Q6UXX9, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000147655, Expressed in lung and 124 other tissues |
ExpressionAtlasi | Q6UXX9, baseline and differential |
Genevisiblei | Q6UXX9, HS |
Family and domain databases
CDDi | cd00064, FU, 1 hit |
Gene3Di | 2.20.100.10, 1 hit |
InterProi | View protein in InterPro IPR006212, Furin_repeat IPR009030, Growth_fac_rcpt_cys_sf IPR042993, RSPO2 IPR043601, Rspo_Fu-CRD_dom IPR000884, TSP1_rpt IPR036383, TSP1_rpt_sf |
PANTHERi | PTHR23275:SF79, PTHR23275:SF79, 1 hit |
Pfami | View protein in Pfam PF15913, Furin-like_2, 1 hit |
SMARTi | View protein in SMART SM00261, FU, 2 hits SM00209, TSP1, 1 hit |
SUPFAMi | SSF57184, SSF57184, 1 hit SSF82895, SSF82895, 1 hit |
PROSITEi | View protein in PROSITE PS50092, TSP1, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | RSPO2_HUMAN | |
Accessioni | Q6UXX9Primary (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: | December 2, 2020 | |
This is version 138 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human chromosome 8
Human chromosome 8: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations