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FLASH GENE

Symbol

RSPO1

contributors: mct/pgu - updated : 31-03-2018

HGNC name	R-spondin homolog (Xenopus laevis)
HGNC id	21679

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	23.54 kb     9 Exon(s)

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001038633 9 - 2995 NP_001033722 - 263 - 2007 17804805

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart         Endocrine adrenal gland           parathyroid         Reproductive female system breast mammary gland   highly   female system uterus       Urinary kidney tubule

cells

System Cell Pubmed Species Stage Rna symbol Digestive enterocyte not specific epithelial 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
	RSPO1 and RSPO3 and their receptor LGR4 form novel circuits in the brain to regulate energy homeostasis
	ZNRF3 binds RSPO1 and LGR5-RSPO1 with micromolar affinity via RSPO1 furin-like 1 (Fu1) domain
	LGR6 had a close interaction with RSPO1, RSPO2, RSPO3, and RSPO4

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

PPKSR

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed diabete type 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