CDB25:0003114 ANGPTL4 — SDC4

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

Title

Journal:; Year Published:

Abstract

Angiopoietin-like 4 Is a Wnt Signaling Antagonist that Promotes LRP6 Turnover.

Developmental cell, 2017; PubMed, Homo sapiens ANGPTL4 — Homo sapiens SDC4

ABSTRACT: Angiopoietin-like 4 (ANGPTL4) is a secreted signaling protein that is implicated in cardiovascular disease, metabolic disorder, and cancer. Outside of its role in lipid metabolism, ANGPTL4 signaling remains poorly understood. Here, we identify ANGPTL4 as a Wnt signaling antagonist that binds to syndecans and forms a ternary complex with the Wnt co-receptor Lipoprotein receptor-related protein 6 (LRP6). This protein complex is internalized via clathrin-mediated endocytosis and degraded in lysosomes, leading to attenuation of Wnt/β-catenin signaling. Angptl4 is expressed in the Spemann organizer of Xenopus embryos and acts as a Wnt antagonist to promote notochord formation and prevent muscle differentiation. This unexpected function of ANGPTL4 invites re-interpretation of its diverse physiological effects in light of Wnt signaling and may open therapeutic avenues for human disease.

Basic Information on ANGPTL4

Ligand Name: angiopoietin like 4

Other Symbols: pp1158, PGAR, ARP4, HFARP, FIAF, NL2

Ligand Location: secreted based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: ANGPTL4

GeneCards: ANGPTL4

HGNC Gene Group: Fibrinogen C domain containing, Angiopoietin like family

Functional Annotations for ANGPTL4

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 ANGPTL4

ANGPTL4 — CDH11 ・ ANGPTL4 — CDH5 ・ ANGPTL4 — CLDN5 ・ ANGPTL4 — ITGA5 ・ ANGPTL4 — ITGB1 ・ ANGPTL4 — ITGB5 ・ ANGPTL4 — LEPR ・ ANGPTL4 — NRP2 ・ ANGPTL4 — SDC1 ・ ANGPTL4 — SDC2 ・ ANGPTL4 — SDC3

Basic Information on SDC4

Receptor Name: syndecan 4

Other Symbols: SYND4, amphiglycan, ryudocan

Receptor Location: cell membrane based on hpa, perplexity

HGNC Gene Symbol Report: SDC4

GeneCards: SDC4

HGNC Gene Group: Proteoglycans

Functional Annotations for SDC4

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 SDC4

ADAM12 — SDC4 ・ CCL5 — SDC4 ・ CXCL10 — SDC4 ・ FGF2 — SDC4 ・ MDK — SDC4 ・ RSPO3 — SDC4 ・ TFPI — SDC4 ・ TGM2 — SDC4 ・ THBS1 — SDC4 ・ CCN1 — SDC4 ・ FN1 — SDC4 ・ LAMA3 — SDC4 ・ PTN — SDC4 ・ THY1 — SDC4