C1QTNF5
Protein 5 srodan C1q i tumorskom faktoru nekroze, znan i kao C1QTNF5, je protein koji je kod ljudi kodiran genom C1QTNF5.[5][6] The C1QTNF5 gene secreted and membrane-linked to a protein which is strongly expressed in retinal pigment epithelium cells.[7][8][9]
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 243 aminokiseline, a molekulska težina 25.298 Da.[10]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MRPLLVLLLL | GLAAGSPPLD | DNKIPSLCPG | HPGLPGTPGH | HGSQGLPGRD | ||||
| GRDGRDGAPG | APGEKGEGGR | PGLPGPRGDP | GPRGEAGPAG | PTGPAGECSV | ||||
| PPRSAFSAKR | SESRVPPPSD | APLPFDRVLV | NEQGHYDAVT | GKFTCQVPGV | ||||
| YYFAVHATVY | RASLQFDLVK | NGESIASFFQ | FFGGWPKPAS | LSGGAMVRLE | ||||
| PEDQVWVQVG | VGDYIGIYAS | IKTDSTFSGF | LVYSDWHSSP | VFA |
Struktura
urediStruktura proteina 5 povezanog sa C1q faktorom nekroze tumora i C1QTNF5 koji se naziva i CTRP5[11] ima tri bitna domena. Prvi je jedan peptid koji se nalazi u N-terminalu, drugi je kolažni domenn, a treći domen je globularni komplement 1q (gC1q), u C-terminalnom domenu.[7][8][12][13][14] Pojedinačna mutacija S163R nalazi se u gC1q domenu što je glavni razlog za kasnopojavnu bolest degeneracije mrežnjače (L-ORD).[7][8][9][14] C1QTNF5 je dio porodice C1q. Međutim, postoji jedinstvena karakteristika strukture C1QTNF5 da ne posjeduje Ca2+ mjesto vezanja kao drugi članovi porodice C1q.[7]
Kristalna struktura
urediKristalnu strukturu C1QTNF5 odredili su Xiongying i Krzysztof i ona ima dvije karakteristike. Jedna je da struktura C1QTNF5 izgleda nema mjesto vezanja Ca2+ radi njegove stabilnosti. Također, potrebna je za funkciju članova porodice C1q. Druga značajka je da ima neobičnu sekvencu (F181, F182, G183, G184, W185, P186) koja generira hidrofobno polje. U ovom području, S163 i F182 grade H vezu, međutim, mutacija S163 će poremetiti H vezu.[7]
Funkcija
urediProtein CTRP5 je član nadporodice C1q /faktora tumorske nekroze, koja pokazuje različite funkcije uključujući ćelijsku adheziju i kao komponente bazne membrane.[15]
Klinički značaj
urediMutacija u genu C1QTNF5 uzrokuje kasni početak degeneracije mrežnjače.[6] Preciznije, jedna misens mutacija (S163R) u kodiranom proteinu C1QTNF5 uzrokuje kasnu pojavu retinalne degeneracije (L-ORD).[5]
Reference
uredi- ^ a b c GRCh38: Ensembl release 89: ENSG00000223953 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000079592 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ 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 (septembar 2017). "Novel pathogenic mutations in C1QTNF5 support a dominant negative disease mechanism in late-onset retinal degeneration". Scientific Reports. 7 (1): 12147. doi:10.1038/s41598-017-11898-3. PMC 5610255. PMID 28939808.
- ^ a b "Entrez Gene: C1QTNF5 C1q and tumor necrosis factor related protein 5".
- ^ a b c d e Tu X, Palczewski K (decembar 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.
- ^ 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 (septembar 2017). "Novel pathogenic mutations in C1QTNF5 support a dominant negative disease mechanism in late-onset retinal degeneration". Scientific Reports. 7 (1): 12147. doi:10.1038/s41598-017-11898-3. PMC 5610255. PMID 28939808.
- ^ 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 (oktobar 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.
- ^ "UniProt, Q9BXJ0". Pristupljeno 19. 8. 2021.
- ^ Shu X, Tulloch B, Lennon A, Vlachantoni D, Zhou X, Hayward C, Wright AF (maj 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.
- ^ Mandal MN, Vasireddy V, Reddy GB, Wang X, Moroi SE, Pattnaik BR, Hughes BA, Heckenlively JR, Hitchcock PF, Jablonski MM, Ayyagari R (decembar 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.
- ^ Chavali VR, Khan NW, Cukras CA, Bartsch DU, Jablonski MM, Ayyagari R (maj 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.
- ^ a b Dinculescu A, Min SH, Dyka FM, Deng WT, Stupay RM, Chiodo V, Smith WC, Hauswirth WW (oktobar 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.
- ^ Shapiro L, Scherer PE (mart 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.
Dopunska literatura
uredi- Shapiro L, Scherer PE (mart 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.
- 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 (oktobar 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.
- Zhang Z, Henzel WJ (oktobar 2004). "Signal peptide prediction based on analysis of experimentally verified cleavage sites". Protein Science. 13 (10): 2819–24. doi:10.1110/ps.04682504. PMC 2286551. PMID 15340161.
- Ayyagari R, Mandal MN, Karoukis AJ, Chen L, McLaren NC, Lichter M, Wong DT, Hitchcock PF, Caruso RC, Moroi SE, Maumenee IH, Sieving PA (septembar 2005). "Late-onset macular degeneration and long anterior lens zonules result from a CTRP5 gene mutation". Investigative Ophthalmology & Visual Science. 46 (9): 3363–71. doi:10.1167/iovs.05-0159. PMID 16123441.
- Subrayan V, Morris B, Armbrecht AM, Wright AF, Dhillon B (decembar 2005). "Long anterior lens zonules in late-onset retinal degeneration (L-ORD)". American Journal of Ophthalmology. 140 (6): 1127–9. doi:10.1016/j.ajo.2005.06.023. PMID 16376663.
- Foster LJ, Rudich A, Talior I, Patel N, Huang X, Furtado LM, Bilan PJ, Mann M, Klip A (januar 2006). "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. doi:10.1021/pr0502626. PMID 16396496.
- Shu X, Tulloch B, Lennon A, Vlachantoni D, Zhou X, Hayward C, Wright AF (maj 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.
- Shu X, Tulloch B, Lennon A, Hayward C, O'Connell M, Cideciyan AV, Jacobson SG, Wright AF (2007). Biochemical characterisation of the C1QTNF5 gene associated with late-onset retinal degeneration. A genetic model of age-related macular degeneration. Advances in Experimental Medicine and Biology. 572. str. 41–8. doi:10.1007/0-387-32442-9_7. ISBN 978-0-387-28464-4. PMID 17249553.
Vanjski linkovi
uredi- Lokacija ljudskog genoma C1QTNF5 i stranica sa detaljima o genu C1QTNF5 u UCSC Genome Browseru.