CDB20:0002709 DKK2 — KREMEN1

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

Title

Journal:; Year Published:

Abstract

EpCAM is an endoderm-specific Wnt derepressor that licenses hepatic development.

Developmental cell, 2013; PubMed, Danio rerio dkk2 — Danio rerio kremen1

ABSTRACT: Mechanisms underlying cell-type-specific response to morphogens or signaling molecules during embryonic development are poorly understood. To learn how response to the liver-inductive Wnt2bb signal is achieved, we identify an endoderm-enriched, single transmembrane protein, epithelial-cell-adhesion-molecule (EpCAM), as an endoderm-specific Wnt derepressor in zebrafish. hi2151/epcam mutants exhibit defective liver development similar to prt/wnt2bb mutants. EpCAM directly binds to Kremen1 and disrupts the Kremen1-Dickkopf2 (Dkk2) interaction, which prevents Kremen1-Dkk2-mediated removal of Lipoprotein-receptor-related protein 6 (Lrp6) from the cell surface. These data lead to a model in which EpCAM derepresses Lrp6 and cooperates with Wnt ligand to activate Wnt signaling through stabilizing membrane Lrp6 and allowing Lrp6 clustering into active signalosomes. Thus, EpCAM cell autonomously licenses and cooperatively activates Wnt2bb signaling in endodermal cells. Our results identify EpCAM as the key molecule and its functional mechanism to confer endodermal cells the competence to respond to the liver-inductive Wnt2bb signal.

Basic Information on DKK2

Ligand Name: dickkopf Wnt signaling pathway inhibitor 2

Other Symbols: N/A

Ligand Location: secreted based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: DKK2

GeneCards: DKK2

HGNC Gene Group: unknown

Functional Annotations for DKK2

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 DKK2

DKK2 — KREMEN2 ・ DKK2 — LRP6

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 ・ DKK4 — KREMEN1 ・ DKK3 — KREMEN1 ・ RSPO1 — KREMEN1