Publication (1) C1QTNF5 Full Name
C1q and tumor necrosis factor related protein 5
C1QTNF5 Introduction
C1QTNF5, also known as CTRP5, is a protein that in humans is encoded by the C1QTNF5 gene. C1QTNF5 is a member of the C1q/TNF superfamily. It encodes a secreted glycoprotein with an N-terminal signal peptide, a collagen-like domain and a C-terminal C1q globular domain. C1QTNF5 is expressed in nearly all tissues, with marked enrichment in the retinal pigment epithelium (RPE) and ciliary body epithelium. The CTRP5 protein was reported to be mainly localized at the cell membrane and extracellular matrix in RPE cells. CTRP5 is co-localized with the membrane frizzled-related protein (MFRP) at cell membrane and it acts in synergy with MFRP to regulate intraocular microenvironment homeostasis. CTRP5 as a secreted factor could also be secreted into the vitreous cavity.
Figure 1. Working model for C1QTNF5 functions as an attachment factor to promote IAV entry. (Source: Yu L, et al.2024)
In retinal RPE cells, the core functions of CTRP5 involve cell–basement membrane adhesion, metabolic regulation, and extracellular matrix remodeling. On one hand, CTRP5 interacts with components of Bruch's membrane via its C1q domain, helping to maintain RPE polarity and barrier integrity. Knockdown experiments suggest that CTRP5 is an important contributor to RPE cell adhesion, suggesting CTRP5 as a molecular bridging agent. However, CTRP5 is also shown to play a role in the maintenance of RPE metabolic homeostasis: CTRP5 has recently been shown to activate AMPK signaling pathway to enhance fatty acid oxidation. In contrast, it has a tissue-specific effect on insulin sensitivity: Ctrp5 KO mice have improved insulin sensitivity and reduced hepatic steatosis in adipose tissue, and as a result, CTRP5 has been proposed as a negative regulator of metabolic syndrome. This so-called "functional paradox" could be explained by the variability in receptor expression between tissues and reprogramming of downstream signaling networks, however the molecular mechanisms are yet to be identified.
The majority of mutations in C1QTNF5 are pathogenic and result in a disorder known as Late-Onset Retinal Degeneration (L-ORD), which is inherited in an autosomal dominant manner. The most common pathogenic mutation is S163R, which is a missense mutation in the core of the C1q globular domain. The mutation results in protein misfolding, endoplasmic reticulum retention, and defective secretion, which ultimately results in toxic protein aggregation and UPR activation. Patients with L-ORD have been known to show abnormal dark adaptation and night blindness as early as adolescence. As the disease progresses, they experience progressive loss of central and peripheral vision, widespread deposit formation between the RPE and Bruch's membrane, and disorganization of the photoreceptor outer segments. These pathological features closely resemble those of age-related macular degeneration (AMD), though L-ORD manifests at a younger age. In addition to ocular pathology, some patients present with long anterior zonule (LAZ) and elevated intraocular pressure, underscoring the pleiotropic role of CTRP5 in ocular development.
Alternate Names for C1QTNF5
C1QTNF5
C1q and tumor necrosis factor related protein 5
CTRP5
complement C1q tumor necrosis factor-related protein 5
myonectin
C1q TNF-alpha-related protein 5
