Datasheet

Biological Description

Specificity	UNC5B Antibody [H5N21] detects endogenous levels of total UNC5B protein.
Background	UNC5B, a dependence receptor of the UNC5 family involved in netrin-1-mediated repulsion during axon guidance and vascular development, is characterized by two extracellular Ig-like domains (Ig1–2) and two thrombospondin type 1 repeats (TSP1) that mediate netrin-1 binding, a process further enhanced by heparan sulfates. It possesses a single transmembrane helix and a cytoplasmic region containing ZU5, UPA, and death domains (DD), where caspase-3 cleaves at DLVD↓N (Asp931) to release the pro-apoptotic intracellular domain (ICD), with residues such as Phe601 in UPA stabilizing the autoinhibited, closed conformation. In the absence of netrin-1, UNC5B homodimers adopt an open cytosolic state in which the DD recruits DAPK1 following its dephosphorylation at Ser308, activating the kinase and stimulating p53/Bax/caspase-9-dependent apoptosis; simultaneously, UNC5B-DCC heterodimers expose DCC’s P1 domain, leading to repulsive signaling via Rac1/Cdc42 inhibition and PAK/LIMK/cofilin-mediated collapse of F-actin protrusions, thereby pruning excessive axons or vascular tip cell filopodia. Upon netrin-1 binding, closed ZU5-UPA interactions are stabilized, blocking DAPK1 access and shifting signaling to pro-angiogenic PI3K/Akt survival pathways alongside continued repulsive cytoskeletal modulation. Predominantly expressed in endothelial and neuronal tissues, UNC5B-mediated pruning is essential for central and peripheral nervous system circuit refinement and vascular patterning, while the splice isoform UNC5B-Δ8 (generated by NOVA2-mediated exon 8 skipping) promotes constitutive, netrin-1-insensitive apoptosis to ensure tip cell competition. Epigenetic silencing or oncogenic mutations of UNC5B, frequent in colorectal cancer, disrupt the balance between repulsion and survival, fueling tumor angiogenesis, metastasis, and poor prognosis.

Specificity

UNC5B Antibody [H5N21] detects endogenous levels of total UNC5B protein.

Background

UNC5B, a dependence receptor of the UNC5 family involved in netrin-1-mediated repulsion during axon guidance and vascular development, is characterized by two extracellular Ig-like domains (Ig1–2) and two thrombospondin type 1 repeats (TSP1) that mediate netrin-1 binding, a process further enhanced by heparan sulfates. It possesses a single transmembrane helix and a cytoplasmic region containing ZU5, UPA, and death domains (DD), where caspase-3 cleaves at DLVD↓N (Asp931) to release the pro-apoptotic intracellular domain (ICD), with residues such as Phe601 in UPA stabilizing the autoinhibited, closed conformation. In the absence of netrin-1, UNC5B homodimers adopt an open cytosolic state in which the DD recruits DAPK1 following its dephosphorylation at Ser308, activating the kinase and stimulating p53/Bax/caspase-9-dependent apoptosis; simultaneously, UNC5B-DCC heterodimers expose DCC’s P1 domain, leading to repulsive signaling via Rac1/Cdc42 inhibition and PAK/LIMK/cofilin-mediated collapse of F-actin protrusions, thereby pruning excessive axons or vascular tip cell filopodia. Upon netrin-1 binding, closed ZU5-UPA interactions are stabilized, blocking DAPK1 access and shifting signaling to pro-angiogenic PI3K/Akt survival pathways alongside continued repulsive cytoskeletal modulation. Predominantly expressed in endothelial and neuronal tissues, UNC5B-mediated pruning is essential for central and peripheral nervous system circuit refinement and vascular patterning, while the splice isoform UNC5B-Δ8 (generated by NOVA2-mediated exon 8 skipping) promotes constitutive, netrin-1-insensitive apoptosis to ensure tip cell competition. Epigenetic silencing or oncogenic mutations of UNC5B, frequent in colorectal cancer, disrupt the balance between repulsion and survival, fueling tumor angiogenesis, metastasis, and poor prognosis.

Usage Information

Application

IF

Dilution

IF

1:200

Reactivity

Human

Source

Mouse Monoclonal Antibody

MW

Storage Buffer

PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage
(from the date of receipt)

-20°C (avoid freeze-thaw cycles), 2 years

References

https://pubmed.ncbi.nlm.nih.gov/34381052/
https://pubmed.ncbi.nlm.nih.gov/30084000/

UNC5B Antibody [H5N21]

Biological Description

Usage Information

References

Application Data