Q6UXX9 · RSPO2_HUMAN
- ProteinR-spondin-2
- GeneRSPO2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids243 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | cell surface | |
Cellular Component | extracellular region | |
Molecular Function | heparin binding | |
Molecular Function | signaling receptor binding | |
Biological Process | bone mineralization | |
Biological Process | canonical Wnt signaling pathway | |
Biological Process | dopaminergic neuron differentiation | |
Biological Process | embryonic forelimb morphogenesis | |
Biological Process | embryonic hindlimb morphogenesis | |
Biological Process | epithelial tube branching involved in lung morphogenesis | |
Biological Process | limb development | |
Biological Process | lung growth | |
Biological Process | negative regulation of odontogenesis of dentin-containing tooth | |
Biological Process | osteoblast differentiation | |
Biological Process | positive regulation of canonical Wnt signaling pathway | |
Biological Process | positive regulation of Wnt signaling pathway | |
Biological Process | trachea cartilage morphogenesis |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Is a key regulator of the Wnt signaling pathway and plays a pivotal role in various development processes, stem cell regulation, and morphogenesis.
Names & Taxonomy
Protein names
- Recommended nameR-spondin-2
- Alternative names
Gene names
- Community suggested namesRSPO2
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ6UXX9
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Tetraamelia syndrome 2 (TETAMS2)
- Note
- 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 alsoMIM:618021
Natural variants in TETAMS2
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_081037 | 70-243 | missing | in TETAMS2; loss of LGR5-, RNF43- and ZNRF3-binding; complete loss of amplification of WNT3A signaling | |
VAR_081038 | 137-243 | missing | in TETAMS2 |
Humerofemoral hypoplasia with radiotibial ray deficiency (HHRRD)
- Note
- 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 alsoMIM:618022
Natural variants in HHRRD
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_081036 | 69 | R>C | in HHRRD; loss of LGR5-, RNF43- and ZNRF3-binding; decreased ability to amplify WNT3A signaling; dbSNP:rs758888137 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_081036 | 69 | in HHRRD; loss of LGR5-, RNF43- and ZNRF3-binding; decreased ability to amplify WNT3A signaling; dbSNP:rs758888137 | |||
Sequence: R → C | ||||||
Natural variant | VAR_081037 | 70-243 | in TETAMS2; loss of LGR5-, RNF43- and ZNRF3-binding; complete loss of amplification of WNT3A signaling | |||
Sequence: Missing | ||||||
Mutagenesis | 105 | Loss of LGR5-binding, no effect on interaction with RNF43 and ZNRF3, no effect on WNT3A signaling; when associated with A-109. | ||||
Sequence: F → A | ||||||
Mutagenesis | 109 | Loss of LGR5-binding, no effect on interaction with RNF43 and ZNRF3, no effect on WNT3A signaling; when associated with A-105. | ||||
Sequence: F → A | ||||||
Natural variant | VAR_081038 | 137-243 | in TETAMS2 | |||
Sequence: Missing | ||||||
Natural variant | VAR_026247 | 186 | in dbSNP:rs601558 | |||
Sequence: L → P |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 317 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-21 | |||||
Sequence: MQFRLFSFALIILNCMDYSHC | ||||||
Chain | PRO_0000234439 | 22-243 | R-spondin-2 | |||
Sequence: QGNRWRRSKRASYVSNPICKGCLSCSKDNGCSRCQQKLFFFLRREGMRQYGECLHSCPSGYYGHRAPDMNRCARCRIENCDSCFSKDFCTKCKVGFYLHRGRCFDECPDGFAPLEETMECVEGCEVGHWSEWGTCSRNNRTCGFKWGLETRTRQIVKKPVKDTILCPTIAESRRCKMTMRHCPGGKRTPKAKEKRNKKKKRKLIERAQEQHSVFLATDRANQ | ||||||
Disulfide bond | 40↔46 | |||||
Sequence: CKGCLSC | ||||||
Disulfide bond | 43↔52 | |||||
Sequence: CLSCSKDNGC | ||||||
Disulfide bond | 55↔74 | |||||
Sequence: CQQKLFFFLRREGMRQYGEC | ||||||
Disulfide bond | 78↔93 | |||||
Sequence: CPSGYYGHRAPDMNRC | ||||||
Disulfide bond | 96↔104 | |||||
Sequence: CRIENCDSC | ||||||
Disulfide bond | 101↔110 | |||||
Sequence: CDSCFSKDFC | ||||||
Disulfide bond | 113↔124 | |||||
Sequence: CKVGFYLHRGRC | ||||||
Disulfide bond | 128↔141 | |||||
Sequence: CPDGFAPLEETMEC | ||||||
Disulfide bond | 145↔187 | |||||
Sequence: CEVGHWSEWGTCSRNNRTCGFKWGLETRTRQIVKKPVKDTILC | ||||||
Disulfide bond | 156↔163 | |||||
Sequence: CSRNNRTC | ||||||
Glycosylation | 160 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 196↔203 | |||||
Sequence: CKMTMRHC |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Binds heparin (By similarity).
Interacts with LGR4, LGR5 and LGR6 (PubMed:21727895, PubMed:21909076, PubMed:22615920, PubMed:29769720).
Interacts with E3 ubiquitin ligases RNF43 and ZNRF3 (PubMed:29769720).
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for repeat, domain, compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Repeat | 90-134 | FU | ||||
Sequence: MNRCARCRIENCDSCFSKDFCTKCKVGFYLHRGRCFDECPDGFAP | ||||||
Domain | 144-204 | TSP type-1 | ||||
Sequence: GCEVGHWSEWGTCSRNNRTCGFKWGLETRTRQIVKKPVKDTILCPTIAESRRCKMTMRHCP | ||||||
Compositional bias | 204-223 | Basic residues | ||||
Sequence: PGGKRTPKAKEKRNKKKKRK | ||||||
Region | 204-243 | Disordered | ||||
Sequence: PGGKRTPKAKEKRNKKKKRKLIERAQEQHSVFLATDRANQ |
Domain
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 3 isoforms produced by Alternative splicing.
Q6UXX9-1
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.
- Name1
- Length243
- Mass (Da)28,315
- Last updated2007-05-15 v2
- Checksum96F44F105B21BB52
Q6UXX9-2
- Name2
- Differences from canonical
- 1-67: Missing
Q6UXX9-3
- Name3
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A590UJ52 | A0A590UJ52_HUMAN | RSPO2 | 38 | ||
E5RH25 | E5RH25_HUMAN | RSPO2 | 121 | ||
E5RGU9 | E5RGU9_HUMAN | RSPO2 | 76 |
Features
Showing features for alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_018321 | 1-67 | in isoform 2 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_018322 | 32-95 | in isoform 3 | |||
Sequence: ASYVSNPICKGCLSCSKDNGCSRCQQKLFFFLRREGMRQYGECLHSCPSGYYGHRAPDMNRCAR → G | ||||||
Alternative sequence | VSP_018323 | 143 | in isoform 3 | |||
Sequence: Missing | ||||||
Compositional bias | 204-223 | Basic residues | ||||
Sequence: PGGKRTPKAKEKRNKKKKRK |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AY358166 EMBL· GenBank· DDBJ | AAQ88533.1 EMBL· GenBank· DDBJ | mRNA | ||
AK123023 EMBL· GenBank· DDBJ | BAG53852.1 EMBL· GenBank· DDBJ | mRNA | ||
AC025508 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AP003479 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471060 EMBL· GenBank· DDBJ | EAW91916.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC027938 EMBL· GenBank· DDBJ | AAH27938.1 EMBL· GenBank· DDBJ | mRNA | ||
BC036554 EMBL· GenBank· DDBJ | AAH36554.1 EMBL· GenBank· DDBJ | mRNA |