C1QTNF5



Protein Summary

C1q and tumor necrosis factor related protein 5, also known as C1QTNF5, is a protein which in humans is encoded by the C1QTNF5 gene, associated with late-onset retinal degeneration. The C1QTNF5 gene secreted and membrane-linked to a protein which is strongly expressed in retinal pigment epithelium cells.

Function

The CTRP5 protein is a member of the C1q / tumor necrosis factor superfamily, which shows diverse functions including cell adhesion and as components of the basement membrane.

Clinical significance

A mutation in the C1QTNF5 gene causes late-onset retinal degeneration.
More specifically, a single missense mutation in the encoded C1QTNF5 protein causes the Late-onset retinal degeneration disease.
Retinal degeneration is a genetic disorder that originates from the retina, a thin layer located towards the back part of the eye that senses for light. C1QTNF5 gene associated with L-ORD leads to poor eyesight in dim to dark light which eventually evolves into night blindness known as nyctalopia.
The mutation in the S163R is found in the globular c1q domain. C1q domain binds to ligands throughout the body that help boost immune responses. The C1q protein can distinguish the different types of potential bacteria and virus ligands that can bind to the C1q domain. When there is a mutation in the C1q protein the globular subunits within the C1q that contain binding cites for immune lignands become halted causing L-ORD which can lead to retinal pigment epithelium failure. Retinal pigment epithelium helps absorb light through binding to photoreceptors helping to regulate light exposure.

Origin

S163R mutation in the C1QTNF5 protein is an autosomal dominant disorder that is genetically inherited by one parent being a carrier for the mutation. Those affected do not begin to see symptoms such as until their 40's and early 50's, the reason for the delay in S163 mutation in the C1QTNF5 protein is still unknown, hence the name for the eye disorder Late -onset retinal degeneration beginning in a person's late stages of life.

Structure

The structure of C1q and Tumor Necrosis Factor Related Protein 5 which is also called CTRP5 has three essential domains. The first domain is a single peptide which is located in N-terminal, the second domain is a collage domain and the third domain is a globular complement 1q that exists in the C-terminal domain. The single mutation S163R is found in the gC1q domain which is the main reason for Late-onset retinal degeneration disease. C1QTNF5 is a part of the C1q family. However, there is a unique feature of the structure of C1QTNF5 that it does not own a Ca 2+ binding site as other members of the C1q family.

Crystal structure

Crystal structure of C1QTNF5 has been taken by Xiongying and Krzysztof and it has two characteristics. One is that the structure of C1QTNF5 seems not to have a Ca 2+ binding site in order to its stability. Also, it is necessary for the function of the members of the C1q family. Another feature is having an unusual sequence which is that generate a hydrophobic field. In this area, S163 and F182 build H bond, However, the mutation S163 will make a disruption to the H bond.