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FLASH GENE
Symbol RSPO1 contributors: mct/pgu - updated : 31-03-2014
HGNC name R-spondin homolog (Xenopus laevis)
HGNC id 21679
Corresponding disease
PPKSR palmoplantar hyperkeratosis, with squamous cell carcinoma of skin and sex reversal
Location 1p34.3      Physical location : 38.076.950 - 38.100.491
Synonym name roof plate-specific spondin
Synonym symbol(s) FLJ40906, RSPONDIN, R-spondin, RP11-566C13.1, CRISTIN3, RSPO
DNA
TYPE functioning gene
STRUCTURE 23.54 kb     9 Exon(s)
MAPPING cloned Y linked N status provisional
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
9 - 2995 - 263 - 2007 17804805
EXPRESSION
Type restricted
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart    
Endocrineadrenal gland    
 parathyroid    
Reproductivefemale systembreastmammary gland highly
 female systemuterus   
Urinarykidneytubule   
cells
SystemCellPubmedSpeciesStageRna symbol
Digestiveenterocyte
not specificepithelial cell
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period embryo
Text in the dorsal part of the neural tube, especially in the boundary region between roof plate and neuroepithelium
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a leading signal peptide
  • two cystein-rich domain
  • two furin-like domain
  • one thrombospondin type 1 domain
  • a putative nuclear localization signal
  • HOMOLOGY
    interspecies homolog to murine Rspo1
    Homologene
    FAMILY
  • R-spondin family
  • CATEGORY transport
    SUBCELLULAR LOCALIZATION extracellular
        intracellular
    intracellular,nucleus
    basic FUNCTION
  • may be a crypt cell mitogen protein
  • inducing rapid onset of crypt cell proliferation in the small intestine and colon, involving beta-catenin stabilization
  • may have therapeutic application in gastrointestinal diseases
  • may contribute to the development of dorsal neural tube under the regulation of Wnts
  • playing an essential role in sex determination, skin differentiation and malignancy
  • regulates Wnt signaling by inhibiting internalization of LRP6
  • antagonizing DKK1 through an interaction with KREMEN1
  • could have a pivotal role in the suppression or antagonism of testicular determination and differentiation, rather than acting primaily as an ovarian determining gene
  • acting as a crucial regulator of canonical beta-catenin signaling required for female development
  • required to fully suppress the male differentiation program and to maintain germ cell survival during the development of XX gonads
  • may participate in suppressing the male pathway in the absence of Sry and maintaining oocyte survival through positively regulating WNT4 signaling
  • acted synergistically with Wnt3A to activate Wnt/beta-catenin signaling
  • potent and specific mitogen for the gastrointestinal epithelium
  • having essential roles in vertebrate development and its ligand-type activities overlap substantially with those of the canonical Wnt ligands in that both Rspo and canonical Wnt signaling result in the activation of beta-catenin
  • potentiate Wnt/beta-catenin signaling, an important pathway in embryonic development that is constitutively active in many cancers
  • modulate the Wnt pathway by a common mechanism and coexpression with specific Wnt ligands and DKK1 may determine their biological specificity
  • required for normal development of the mammary gland
  • RSPO1, RSPO2, RSPO3, RSPO4 can stimulate the proliferation of intestinal crypt stem cells, through enhancement of Wnt/CTNNB signaling
  • intestinal growth factor known to exert its effects through activation of the canonical Wnt (cWnt) signaling pathway and subsequent expression of cWnt target genes
  • upregulated in the ovary but not in the testis during critical early stages of gonad development in humans (between 6-9 weeks post conception), and may function as a tissue-specific amplifier of beta-catenin signaling to oppose testis determination
  • activates the WNT/CTNNB signaling pathway in germ cells
  • RSPO1/ CTNNB1 signaling is involved in meiosis in fetal germ cells and contributes to the cellular decision of germ cells to differentiate into oocyte or sperm
  • mimics ZNRF3 inhibition by increasing the membrane level of Wnt receptors
  • enhances Wnt signalling by inhibiting ZNRF3
  • RSPO1 and WNT4 are two new regulators of cell proliferation in the early gonad regardless of its sex, in addition to the specific role of these genes in ovarian differentiation
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS electron transport
    PATHWAY
    metabolism
    signaling
    a component
  • RSPO1-WNT-VEGFC-FLT4 signaling plays a crucial role as an endothelial-autonomous permissive cue for developmental angiogenesis
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with the extracelular domain of FZD8 and LRP6
  • binds heparin
  • regulating Wnt signaling by modulating levels of LRP6 on the cell surface, through inhibition of DKK1-dependent internalization of LRP6
  • soluble activator for Wnt/beta-catenin signaling
  • potentiate Wnt/CTNNB signaling by actually functioning as ligands of LGR4 and LGR5
  • each of the four R-spondins, secreted Wnt pathway agonists, can bind to LGR4, LGR5 and LGR6 (Pubmed 21727895)
  • interactions of WNT4, RSPO1, and other factors such as forkhead transcription factor 2 in ovarian development and function
  • LGR5 does not contact RNF43 but increases the affinity of RSPO1 to RNF43, supporting LGR5 as an engagement receptor and RNF43 as an effector receptor
  • WNT/RSPO1/CTNNB1 signals control axonal sorting and lineage progression in Schwann cell development
  • interacts with ZNRF3/RNF43 and LGR4 through distinct motifs
  • ZNRF3 binds RSPO1 and LGR5-RSPO1 with micromolar affinity via RSPO1 furin-like 1 (Fu1) domain
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) PPKSR
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --other  
    aberrantly methylated promoter associated CpG islands in acute lymphocytic leukemia
    tumoral     --other  
    potential targets to tackle the complex mammary development and its deregulation with potential links with breast cancers
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabetetype 2 
    RSPO1 and the cWnt signaling pathway may serve as a novel target to enhance beta-cell growth and function in patients with type 2 diabetes
    ANIMAL & CELL MODELS
  • in mouse xenograft model treated with chemotherapeutic agent 5-fluorouracil and with murine colon carcinoma cell line CT26 inoculated, Rspo1 treatment substantially reduced 5-FU-induced diarrhea and weight loss
  • zebrafish embryos lacking rspo1 or the proposed rspo1 receptor kremen form primary vessels by vasculogenesis, but are defective in subsequent angiogenesis
  • in XX Rspo1 (-/-) gonads, germ cell proliferation, expression of the early meiotic marker Stra8, and entry into meiosis are all impaired