CDB25:0004189 RSPO1 — KREMEN1

Experimentally validated in Human; Orthology-inferred in Mouse, Rat, Frog, Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Sheep

Title

Journal:; Year Published:

Abstract

R-Spondin1 regulates Wnt signaling by inhibiting internalization of LRP6.

Proceedings of the National Academy of Sciences of the United States of America, 2007; PubMed, Homo sapiens RSPO1 — Homo sapiens KREMEN1

ABSTRACT: The R-Spondin (RSpo) family of secreted proteins act as potent activators of the Wnt/beta-catenin signaling pathway. We have previously shown that RSpo proteins can induce proliferative effects on the gastrointestinal epithelium in mice. Here we provide a mechanism whereby RSpo1 regulates cellular responsiveness to Wnt ligands by modulating the cell-surface levels of the coreceptor LRP6. We show that RSpo1 activity critically depends on the presence of canonical Wnt ligands and LRP6. Although RSpo1 does not directly activate LRP6, it interferes with DKK1/Kremen-mediated internalization of LRP6 through an interaction with Kremen, resulting in increased LRP6 levels on the cell surface. Our results support a model in which RSpo1 relieves the inhibition DKK1 imposes on the Wnt pathway.

Basic Information on RSPO1

Ligand Name: R-spondin 1

Other Symbols: FLJ40906, RSPONDIN

Ligand Location: secreted based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: RSPO1

GeneCards: RSPO1

HGNC Gene Group: Receptor ligands: R-spondin family

Functional Annotations for RSPO1

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Receptors for RSPO1

RSPO1 — FZD8 ・ RSPO1 — LGR4 ・ RSPO1 — LGR5 ・ RSPO1 — LGR6 ・ RSPO1 — LRP6 ・ RSPO1 — ZNRF3

Basic Information on KREMEN1

Receptor Name: kringle containing transmembrane protein 1

Other Symbols: KREMEN, KRM1

Receptor Location: cell membrane based on perplexity, uniprot

HGNC Gene Symbol Report: KREMEN1

GeneCards: KREMEN1

HGNC Gene Group: unknown

Functional Annotations for KREMEN1

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Ligands for KREMEN1

DKK1 — KREMEN1 ・ DKK2 — KREMEN1 ・ DKK4 — KREMEN1 ・ DKK3 — KREMEN1