C1QTNF5 – Wikipedia

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Protein-coding gene in the species Homo sapiens

C1q and tumor necrosis factor related protein 5, also known as C1QTNF5, is a protein which in humans is encoded by the C1QTNF5 gene .[5][6] The C1QTNF5 gene secreted and membrane-linked to a protein which is strongly expressed in retinal pigment epithelium cells.[7][8][9]

Function[edit]

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.[10]

Clinical significance[edit]

A mutation in the C1QTNF5 gene causes late-onset retinal degeneration.[6]
More specifically, a single missense mutation (S163R) in the encoded C1QTNF5 protein causes the Late-onset retinal degeneration disease(L-ORD).[5]

Structure[edit]

The structure of C1q and Tumor Necrosis Factor Related Protein 5 (C1QTNF5) which is also called CTRP5[11] 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.[8][12][13][7][14] The single mutation S163R is found in the gC1q domain which is the main reason for Late-onset retinal degeneration disease(L-ORD).[7][9][8][14] 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.[7]

Crystal structure[edit]

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.[7]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000223953 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000079592 – Ensembl, May 2017
  3. ^ “Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ “Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b Stanton CM, Borooah S, Drake C, Marsh JA, Campbell S, Lennon A, Soares DC, Vallabh NA, Sahni J, Cideciyan AV, Dhillon B, Vitart V, Jacobson SG, Wright AF, Hayward C (September 2017). “Novel pathogenic mutations in C1QTNF5 support a dominant negative disease mechanism in late-onset retinal degeneration”. Scientific Reports. 7 (1): 12147. Bibcode:2017NatSR…712147S. doi:10.1038/s41598-017-11898-3. PMC 5610255. PMID 28939808.
  6. ^ a b “Entrez Gene: C1QTNF5 C1q and tumor necrosis factor related protein 5”.
  7. ^ a b c d e Tu X, Palczewski K (December 2012). “Crystal structure of the globular domain of C1QTNF5: Implications for late-onset retinal macular degeneration”. Journal of Structural Biology. 180 (3): 439–46. doi:10.1016/j.jsb.2012.07.011. PMC 3496058. PMID 22892318.
  8. ^ a b c Stanton CM, Borooah S, Drake C, Marsh JA, Campbell S, Lennon A, Soares DC, Vallabh NA, Sahni J, Cideciyan AV, Dhillon B, Vitart V, Jacobson SG, Wright AF, Hayward C (September 2017). “Novel pathogenic mutations in C1QTNF5 support a dominant negative disease mechanism in late-onset retinal degeneration”. Scientific Reports. 7 (1): 12147. Bibcode:2017NatSR…712147S. doi:10.1038/s41598-017-11898-3. PMC 5610255. PMID 28939808.
  9. ^ a b Hayward C, Shu X, Cideciyan AV, Lennon A, Barran P, Zareparsi S, Sawyer L, Hendry G, Dhillon B, Milam AH, Luthert PJ, Swaroop A, Hastie ND, Jacobson SG, Wright AF (October 2003). “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. doi:10.1093/hmg/ddg289. PMID 12944416.
  10. ^ Shapiro L, Scherer PE (March 1998). “The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor”. Current Biology. 8 (6): 335–8. doi:10.1016/S0960-9822(98)70133-2. PMID 9512423. S2CID 14287212.
  11. ^ Shu X, Tulloch B, Lennon A, Vlachantoni D, Zhou X, Hayward C, Wright AF (May 2006). “Disease mechanisms in late-onset retinal macular degeneration associated with mutation in C1QTNF5”. Human Molecular Genetics. 15 (10): 1680–9. doi:10.1093/hmg/ddl091. PMID 16600989.
  12. ^ Mandal MN, Vasireddy V, Reddy GB, Wang X, Moroi SE, Pattnaik BR, Hughes BA, Heckenlively JR, Hitchcock PF, Jablonski MM, Ayyagari R (December 2006). “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. doi:10.1167/iovs.06-0312. PMID 17122142.
  13. ^ Chavali VR, Khan NW, Cukras CA, Bartsch DU, Jablonski MM, Ayyagari R (May 2011). “A CTRP5 gene S163R mutation knock-in mouse model for late-onset retinal degeneration”. Human Molecular Genetics. 20 (10): 2000–14. doi:10.1093/hmg/ddr080. PMC 3080610. PMID 21349921.
  14. ^ a b Dinculescu A, Min SH, Dyka FM, Deng WT, Stupay RM, Chiodo V, Smith WC, Hauswirth WW (October 2015). “Pathological Effects of Mutant C1QTNF5 (S163R) Expression in Murine Retinal Pigment Epithelium”. Investigative Ophthalmology & Visual Science. 56 (11): 6971–80. doi:10.1167/iovs.15-17166. PMC 4627469. PMID 26513502.

Further reading[edit]

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