Biology:C1QTNF5
 Generic protein structure example |
C1q and tumor necrosis factor related protein 5, also known as C1QTNF5, is a protein which in humans is encoded by the C1QTNF5 gene .[1][2] The C1QTNF5 gene secreted and membrane-linked to a protein which is strongly expressed in retinal pigment epithelium cells.[3][4][5]
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.[6]
Clinical significance
A mutation in the C1QTNF5 gene causes late-onset retinal degeneration.[2] More specifically, a single missense mutation (S163R) in the encoded C1QTNF5 protein causes the Late-onset retinal degeneration disease(L-ORD).[1]
Structure
The structure of C1q and Tumor Necrosis Factor Related Protein 5 (C1QTNF5) which is also called CTRP5[7] 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 (gC1q) that exists in the C-terminal domain.[4][8][9][3][10] The single mutation S163R is found in the gC1q domain which is the main reason for Late-onset retinal degeneration disease(L-ORD).[3][5][4][10] 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.[3]
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 (F181, F182, G183, G184, W185, P186) 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.[3]
References
- ↑ 1.0 1.1 "Novel pathogenic mutations in C1QTNF5 support a dominant negative disease mechanism in late-onset retinal degeneration". Scientific Reports 7 (1): 12147. September 2017. doi:10.1038/s41598-017-11898-3. PMID 28939808. Bibcode: 2017NatSR...712147S.
- ↑ 2.0 2.1 "Entrez Gene: C1QTNF5 C1q and tumor necrosis factor related protein 5". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=114902.
- ↑ 3.0 3.1 3.2 3.3 3.4 "Crystal structure of the globular domain of C1QTNF5: Implications for late-onset retinal macular degeneration". Journal of Structural Biology 180 (3): 439–46. December 2012. doi:10.1016/j.jsb.2012.07.011. PMID 22892318.
- ↑ 4.0 4.1 4.2 "Novel pathogenic mutations in C1QTNF5 support a dominant negative disease mechanism in late-onset retinal degeneration". Scientific Reports 7 (1): 12147. September 2017. doi:10.1038/s41598-017-11898-3. PMID 28939808. Bibcode: 2017NatSR...712147S.
- ↑ 5.0 5.1 "Mutation in a short-chain collagen gene, CTRP5, results in extracellular deposit formation in late-onset retinal degeneration: a genetic model for age-related macular degeneration". Human Molecular Genetics 12 (20): 2657–67. October 2003. doi:10.1093/hmg/ddg289. PMID 12944416.
- ↑ "The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor". Current Biology 8 (6): 335–8. March 1998. doi:10.1016/S0960-9822(98)70133-2. PMID 9512423.
- ↑ "Disease mechanisms in late-onset retinal macular degeneration associated with mutation in C1QTNF5". Human Molecular Genetics 15 (10): 1680–9. May 2006. doi:10.1093/hmg/ddl091. PMID 16600989.
- ↑ "CTRP5 is a membrane-associated and secretory protein in the RPE and ciliary body and the S163R mutation of CTRP5 impairs its secretion". Investigative Ophthalmology & Visual Science 47 (12): 5505–13. December 2006. doi:10.1167/iovs.06-0312. PMID 17122142.
- ↑ "A CTRP5 gene S163R mutation knock-in mouse model for late-onset retinal degeneration". Human Molecular Genetics 20 (10): 2000–14. May 2011. doi:10.1093/hmg/ddr080. PMID 21349921.
- ↑ 10.0 10.1 "Pathological Effects of Mutant C1QTNF5 (S163R) Expression in Murine Retinal Pigment Epithelium". Investigative Ophthalmology & Visual Science 56 (11): 6971–80. October 2015. doi:10.1167/iovs.15-17166. PMID 26513502.
Further reading
- "The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor". Current Biology 8 (6): 335–8. March 1998. doi:10.1016/S0960-9822(98)70133-2. PMID 9512423.
- "Mutation in a short-chain collagen gene, CTRP5, results in extracellular deposit formation in late-onset retinal degeneration: a genetic model for age-related macular degeneration". Human Molecular Genetics 12 (20): 2657–67. October 2003. doi:10.1093/hmg/ddg289. PMID 12944416.
- "Signal peptide prediction based on analysis of experimentally verified cleavage sites". Protein Science 13 (10): 2819–24. October 2004. doi:10.1110/ps.04682504. PMID 15340161.
- "Late-onset macular degeneration and long anterior lens zonules result from a CTRP5 gene mutation". Investigative Ophthalmology & Visual Science 46 (9): 3363–71. September 2005. doi:10.1167/iovs.05-0159. PMID 16123441.
- "Long anterior lens zonules in late-onset retinal degeneration (L-ORD)". American Journal of Ophthalmology 140 (6): 1127–9. December 2005. doi:10.1016/j.ajo.2005.06.023. PMID 16376663.
- "Insulin-dependent interactions of proteins with GLUT4 revealed through stable isotope labeling by amino acids in cell culture (SILAC)". Journal of Proteome Research 5 (1): 64–75. January 2006. doi:10.1021/pr0502626. PMID 16396496.
- "Disease mechanisms in late-onset retinal macular degeneration associated with mutation in C1QTNF5". Human Molecular Genetics 15 (10): 1680–9. May 2006. doi:10.1093/hmg/ddl091. PMID 16600989.
- Biochemical characterisation of the C1QTNF5 gene associated with late-onset retinal degeneration. A genetic model of age-related macular degeneration. 572. 2007. 41–8. doi:10.1007/0-387-32442-9_7. ISBN 978-0-387-28464-4. https://archive.org/details/isbn_9780387284644/page/41.
External links
- Human C1QTNF5 genome location and C1QTNF5 gene details page in the UCSC Genome Browser.
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