Protein Summary

C1QTNF5
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesC1QTNF5, CTRP5, C1q and tumor necrosis factor related protein 5, C1q and TNF related 5, MFRP
External IDsOMIM: 608752 MGI: 2385958 HomoloGene: 9227 GeneCards: C1QTNF5
Orthologs
SpeciesHumanMouse
Entrez

114902

235312

Ensembl

ENSG00000223953

ENSMUSG00000079592

UniProt

Q9BXJ0

Q8K480
Q8K479

RefSeq (mRNA)

NM_015645
NM_001278431

NM_001040631
NM_001040632
NM_001190313
NM_001190319
NM_145613

RefSeq (protein)

NP_001265360
NP_056460

Location (UCSC)Chr 11: 119.34 – 119.34 MbChr 9: 44.02 – 44.02 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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( otherwise known as L-ORD).[5][6][7] The C1QTNF5 gene secreted and membrane-linked to a protein which is strongly expressed in retinal pigment epithelium cells.[8][9][10]

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.[11]

Clinical significance

A mutation in the C1QTNF5 gene causes late-onset retinal degeneration.[7] More specifically, a single missense mutation (S163R) in the encoded C1QTNF5 protein causes the Late-onset retinal degeneration disease(L-ORD).[6]

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.[5] C1QTNF5 gene associated with L-ORD leads to poor eye sight in dim to dark light which eventually evolves into night blindness known as nyctalopia.[12]

The mutation in the S163R is found in the globular c1q domain.[13] 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.[14] When there is a mutation in the C1q protein the gobular subunits within the C1q that contain binding cites for immune lignands become halted causing L-ORD which can lead to retinal pigment epithelium failure.[14] Retinal pigment epithelium (RPE) helps absorb light through binding to photoreceptors helping to regulate light exposure.[15]

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.[16] Those affected do not begin to see symptoms such as (trouble adjusting to dark or dim areas) 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.[5]

Structure

The structure of C1q and Tumor Necrosis Factor Related Protein 5 (C1QTNF5) which is also called CTRP5[17] 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.[9][18][19][8][20] The single mutation S163R is found in the gC1q domain which is the main reason for Late-onset retinal degeneration disease(L-ORD).[8][10][9][20] 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.[8]

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.[8]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000223953 - Ensembl, May 2017
  2. 1 2 3 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. 1 2 3 Lando L, Borooah S (2022-09-30). "Late-Onset Retinal Degeneration: Clinical Perspectives". Clinical Ophthalmology. 16: 3225–3246. doi:10.2147/OPTH.S362691. PMC 9531619. PMID 36204011.
  6. 1 2 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.
  7. 1 2 "Entrez Gene: C1QTNF5 C1q and tumor necrosis factor related protein 5".
  8. 1 2 3 4 5 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.
  9. 1 2 3 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.
  10. 1 2 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.
  11. ↑ 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.
  12. ↑ Mehra D, Le PH (2023), "Physiology, Night Vision", StatPearls, Treasure Island (FL): StatPearls Publishing, PMID 31424830, retrieved 2023-04-25
  13. ↑ 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 (2017-09-22). "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. ISSN 2045-2322. PMC 5610255. PMID 28939808.
  14. 1 2 Xiong X, Li C, Zheng Z, Du X (2021-01-13). "Novel globular C1q domain-containing protein (PmC1qDC-1) participates in shell formation and responses to pathogen-associated molecular patterns stimulation in Pinctada fucata martensii". Scientific Reports. 11 (1): 1105. doi:10.1038/s41598-020-80295-0. ISSN 2045-2322. PMC 7806589. PMID 33441832.
  15. ↑ Yang S, Zhou J, Li D (2021-07-28). "Functions and Diseases of the Retinal Pigment Epithelium". Frontiers in Pharmacology. 12: 727870. doi:10.3389/fphar.2021.727870. ISSN 1663-9812. PMC 8355697. PMID 34393803.
  16. ↑ Tu X, Palczewski K (April 2014). "The macular degeneration-linked C1QTNF5 (S163) mutation causes higher-order structural rearrangements". Journal of Structural Biology. 186 (1): 86–94. doi:10.1016/j.jsb.2014.02.001. PMC 3993933. PMID 24531000.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 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.
  20. 1 2 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

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