Q2I0M5 · RSPO4_HUMAN
- ProteinR-spondin-4
- GeneRSPO4
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids234 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Activator of the canonical Wnt signaling pathway by acting as a ligand for LGR4-6 receptors (PubMed:29769720).
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:21727895, PubMed:21909076).
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:21727895, PubMed:21909076).
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 | extracellular region | |
Molecular Function | heparin binding | |
Biological Process | nail development | |
Biological Process | positive regulation of Wnt signaling pathway | |
Biological Process | Wnt signaling pathway |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameR-spondin-4
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ2I0M5
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Nail disorder, non-syndromic congenital, 4 (NDNC4)
- Note
- DescriptionA nail disorder characterized by congenital anonychia or its milder phenotypic variant hyponychia. Anonychia/hyponychia is the absence or severe hypoplasia of all fingernails and toenails without significant bone anomalies.
- See alsoMIM:206800
Natural variants in NDNC4
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_030399 | 65 | Q>R | in NDNC4; dbSNP:rs74315420 | |
VAR_030400 | 95 | C>F | in NDNC4; dbSNP:rs780506366 | |
VAR_030401 | 107 | C>R | in NDNC4; dbSNP:rs74315421 | |
VAR_030402 | 118 | C>Y | in NDNC4; dbSNP:rs74315422 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_030399 | 65 | in NDNC4; dbSNP:rs74315420 | |||
Sequence: Q → R | ||||||
Natural variant | VAR_030400 | 95 | in NDNC4; dbSNP:rs780506366 | |||
Sequence: C → F | ||||||
Natural variant | VAR_052665 | 106 | in dbSNP:rs6140807 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_030401 | 107 | in NDNC4; dbSNP:rs74315421 | |||
Sequence: C → R | ||||||
Natural variant | VAR_030402 | 118 | in NDNC4; dbSNP:rs74315422 | |||
Sequence: C → Y |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 357 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, glycosylation, disulfide bond.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-19 | |||||
Sequence: MRAPLCLLLLVAHAVDMLA | ||||||
Chain | PRO_0000234446 | 20-234 | R-spondin-4 | |||
Sequence: LNRRKKQVGTGLGGNCTGCIICSEENGCSTCQQRLFLFIRREGIRQYGKCLHDCPPGYFGIRGQEVNRCKKCGATCESCFSQDFCIRCKRQFYLYKGKCLPTCPPGTLAHQNTRECQGECELGPWGGWSPCTHNGKTCGSAWGLESRVREAGRAGHEEAATCQVLSESRKCPIQRPCPGERSPGQKKGRKDRRPRKDRKLDRRLDVRPRQPGLQP | ||||||
Glycosylation | 34 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 35↔41 | |||||
Sequence: CTGCIIC | ||||||
Disulfide bond | 38↔47 | |||||
Sequence: CIICSEENGC | ||||||
Disulfide bond | 50↔69 | |||||
Sequence: CQQRLFLFIRREGIRQYGKC | ||||||
Disulfide bond | 73↔88 | |||||
Sequence: CPPGYFGIRGQEVNRC | ||||||
Disulfide bond | 91↔98 | |||||
Sequence: CGATCESC | ||||||
Disulfide bond | 95↔104 | |||||
Sequence: CESCFSQDFC | ||||||
Disulfide bond | 107↔118 | |||||
Sequence: CKRQFYLYKGKC | ||||||
Disulfide bond | 122↔135 | |||||
Sequence: CPPGTLAHQNTREC | ||||||
Disulfide bond | 139↔181 | |||||
Sequence: CELGPWGGWSPCTHNGKTCGSAWGLESRVREAGRAGHEEAATC | ||||||
Disulfide bond | 150↔157 | |||||
Sequence: CTHNGKTC | ||||||
Disulfide bond | 190↔196 | |||||
Sequence: CPIQRPC |
Post-translational modification
Tyr-112 may be phosphorylated; however as this position is probably extracellular, the vivo relevance is not proven.
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Binds heparin (By similarity).
Interacts with LGR4, LGR5 and LGR6
Interacts with LGR4, LGR5 and LGR6
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q2I0M5 | ANKRD11 X5D778 | 3 | EBI-12821217, EBI-17183751 | |
BINARY | Q2I0M5 | DHX57 Q6P158 | 3 | EBI-12821217, EBI-1051531 | |
BINARY | Q2I0M5 | GNG13 Q9P2W3 | 3 | EBI-12821217, EBI-11427343 | |
BINARY | Q2I0M5 | GPSM3 Q9Y4H4 | 3 | EBI-12821217, EBI-347538 | |
BINARY | Q2I0M5 | GUCD1 Q96NT3-2 | 3 | EBI-12821217, EBI-11978177 | |
BINARY | Q2I0M5 | HGS O14964 | 3 | EBI-12821217, EBI-740220 | |
BINARY | Q2I0M5 | KLHL38 Q2WGJ6 | 3 | EBI-12821217, EBI-6426443 | |
BINARY | Q2I0M5 | MAPK9 P45984 | 3 | EBI-12821217, EBI-713568 | |
BINARY | Q2I0M5 | MKRN3 Q13064 | 3 | EBI-12821217, EBI-2340269 | |
BINARY | Q2I0M5 | PIH1D2 Q8WWB5 | 3 | EBI-12821217, EBI-10232538 | |
BINARY | Q2I0M5 | STK16 O75716 | 3 | EBI-12821217, EBI-749295 | |
BINARY | Q2I0M5 | USP20 Q9Y2K6 | 3 | EBI-12821217, EBI-2511991 | |
BINARY | Q2I0M5 | ZNF330 Q9Y3S2 | 3 | EBI-12821217, EBI-373456 | |
BINARY | Q2I0M5 | ZNF77 Q15935 | 3 | EBI-12821217, EBI-12840750 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for repeat, domain, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Repeat | 85-128 | FU | ||||
Sequence: VNRCKKCGATCESCFSQDFCIRCKRQFYLYKGKCLPTCPPGTLA | ||||||
Domain | 138-197 | TSP type-1 | ||||
Sequence: ECELGPWGGWSPCTHNGKTCGSAWGLESRVREAGRAGHEEAATCQVLSESRKCPIQRPCP | ||||||
Region | 190-234 | Disordered | ||||
Sequence: CPIQRPCPGERSPGQKKGRKDRRPRKDRKLDRRLDVRPRQPGLQP |
Domain
The FU repeat is required for activation and stabilization of beta-catenin.
Sequence similarities
Belongs to the R-spondin family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 2 isoforms produced by Alternative splicing.
Q2I0M5-1
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
- Length234
- Mass (Da)26,171
- Last updated2006-05-16 v2
- Checksum853E4494533B73F7
Q2I0M5-2
- Name2
- Differences from canonical
- 137-198: Missing
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_018325 | 137-198 | in isoform 2 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
DQ355152 EMBL· GenBank· DDBJ | ABC75877.1 EMBL· GenBank· DDBJ | mRNA | ||
AK122609 EMBL· GenBank· DDBJ | - | mRNA | No translation available. | |
AL050325 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |