Ku70

Ku70
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

1JEQ, 1JEY, 1JJR, 3RZX

Identifikatori
AliasiXRCC6
Vanjski ID-jeviOMIM: 152690 MGI: 95606 HomoloGene: 37483 GeneCards: XRCC6
EC broj5.6.2.4 4.2.99.18, 5.6.2.4
Lokacija gena (čovjek)
Hromosom 22 (čovjek)
Hrom.Hromosom 22 (čovjek)[1]
Hromosom 22 (čovjek)
Genomska lokacija za Ku70
Genomska lokacija za Ku70
Bend22q13.2Početak41,621,163 bp[1]
Kraj41,664,048 bp[1]
Lokacija gena (miš)
Hromosom 15 (miš)
Hrom.Hromosom 15 (miš)[2]
Hromosom 15 (miš)
Genomska lokacija za Ku70
Genomska lokacija za Ku70
Bend15 E1|15 38.33 cMPočetak81,872,036 bp[2]
Kraj81,924,286 bp[2]
Ontologija gena
Molekularna funkcija nucleotide binding
double-stranded telomeric DNA binding
telomeric DNA binding
GO:0008026 helicase activity
5'-deoxyribose-5-phosphate lyase activity
GO:0004003 DNA helicase activity
protein C-terminus binding
catalytic activity
GO:0001948, GO:0016582 vezivanje za proteine
lyase activity
hydrolase activity
ATP binding
vezivanje sa DNK
double-stranded DNA binding
oštećeno vezivanje sa DNK
vezivanje sa RNK
cyclin binding
GO:0032403 protein-containing complex binding
Ćelijska komponenta citosol
nuclear telomere cap complex
membrana
transcription regulator complex
hromosom
nukleoplazma
nonhomologous end joining complex
jedro
Ku70:Ku80 complex
citoplazma
extracellular region
secretory granule lumen
ficolin-1-rich granule lumen
protein-DNA complex
Jedarce
GO:0009327 makromolekulani kompleks
Biološki proces double-strand break repair via classical nonhomologous end joining
protein heterotetramerization
GO:0009373 regulation of transcription, DNA-templated
regulation of smooth muscle cell proliferation
transcription, DNA-templated
cellular response to DNA damage stimulus
GO:0060469, GO:0009371 positive regulation of transcription, DNA-templated
DNA ligation
establishment of integrated proviral latency
metabolizam
GO:0045996 negative regulation of transcription, DNA-templated
double-strand break repair via nonhomologous end joining
telomere maintenance
positive regulation of type I interferon production
GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II
DNA duplex unwinding
GO:0100026 Popravka DNK
cellular hyperosmotic salinity response
brain development
DNA recombination
neutrophil degranulation
cellular response to gamma radiation
cellular response to X-ray
positive regulation of protein kinase activity
activation of innate immune response
immune system process
Urođeni imunski sistem
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_001469
NM_001288976
NM_001288977
NM_001288978

NM_010247

RefSeq (bjelančevina)
NP_001275905
NP_001275906
NP_001275907
NP_001460
NP_001275905.1

NP_001460.1

NP_034377

Lokacija (UCSC)Chr 22: 41.62 – 41.66 MbChr 15: 81.87 – 81.92 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Ku70 jest protein koji je kod ljudi kodiran genom XRCC6sa hromosoma 22.[5][6]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 609 aminokiselina, a molekulska težina 69.843 Da.[5]

1020304050
MSGWESYYKTEGDEEAEEEQEENLEASGDYKYSGRDSLIFLVDASKAMFE
SQSEDELTPFDMSIQCIQSVYISKIISSDRDLLAVVFYGTEKDKNSVNFK
NIYVLQELDNPGAKRILELDQFKGQQGQKRFQDMMGHGSDYSLSEVLWVC
ANLFSDVQFKMSHKRIMLFTNEDNPHGNDSAKASRARTKAGDLRDTGIFL
DLMHLKKPGGFDISLFYRDIISIAEDEDLRVHFEESSKLEDLLRKVRAKE
TRKRALSRLKLKLNKDIVISVGIYNLVQKALKPPPIKLYRETNEPVKTKT
RTFNTSTGGLLLPSDTKRSQIYGSRQIILEKEETEELKRFDDPGLMLMGF
KPLVLLKKHHYLRPSLFVYPEESLVIGSSTLFSALLIKCLEKEVAALCRY
TPRRNIPPYFVALVPQEEELDDQKIQVTPPGFQLVFLPFADDKRKMPFTE
KIMATPEQVGKMKAIVEKLRFTYRSDSFENPVLQQHFRNLEALALDLMEP
EQAVDLTLPKVEAMNKRLGSLVDEFKELVYPPDYNPEGKVTKRKHDNEGS
GSKRPKVEYSEEELKTHISKGTLGKFTVPMLKEACRAYGLKSGLKKQELL
EALTKHFQD

Funkcija

Ku70 i Ku80 zajeno čine Ku heterodimer, koji se vezuje za krajeve dvolančanog prekida DNK i potreban je za put popravka DNK nehomolognim spajanjem krajevaa (NHEJ). Također potreban je za V(D)J rekombinaciju, koja koristi NHEJ put za promoviranje raznolikosti antigena u imunskom sistemu sisara.

Osim svoje uloge u NHEJ, Ku je također potreban za održavanje dužine telomere i utišavanje subtelomernih gena.[7]

Ku je prvobitno identificiran kada je otkriveno da pacijenti sa sistemskim eritemskim lupusom imaju visok nivo autoantitijela na protein.[5]

Starenje

Mišje embrionske matične ćelije sa homozigotnim Ku70 mutacijama, odnosno Ku70–/– ćelije , imaju značajno povećanu osetljivost na ionizirajuće zračenje u poređenju sa heterozigotnim Ku70+/– ili divljim tipom Ku70 +/+ embrionskih matičnih ćelija.[8] Mutantni miševi s nedostatkom Ku70 imaju rano starenje.[9] Koristeći nekoliko specifičnih kriterija starenja, otkriveno je da mutantni miševi pokazuju iste znakove starenja kao kontrolni miševi, ali u znatno ranijoj hronološkoj dobi. Ovi rezultati sugeriraju da smanjena sposobnost popravljanja dvostrukih lanaca DNK uzrokuje rano starenje i da divlji tip gena Ku70 ima važnu ulogu u osiguranju dugovječnosti.[10]

Klinički značaj

Mutacija ovog gena je opisana u skupu od 24 porodice sa autizmom.[11] Iako ovo sugeriše da ovaj gen može imati ulogu u razvoju autizma, potrebno je dalje istraživanje.

Nomenklatura

Ku70 se pominje sa nekoliko imena uključujući:

  • Lupus Ku autoantigeni protein p70
  • Podjedinica 1 ATP-ovisne DNK-helikaze 2
  • Rendgenski popravak koji dopunjuje defektnu popravku u ćelijama kineskog hrčka 6
  • Rendgenski popravak unakrsnog komplementarnog 6 (XRCC6)

Interakcije

Pokazalo se da Ku70 reaguje sa:

Reference

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000196419 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000022471 - Ensembl, maj 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 c "Entrez Gene: XRCC6 X-ray repair complementing defective repair in Chinese hamster cells 6 (Ku autoantigen, 70kDa)".
  6. ^ Pace P, Mosedale G, Hodskinson MR, Rosado IV, Sivasubramaniam M, Patel KJ (Jul 2010). "Ku70 corrupts DNA repair in the absence of the Fanconi anemia pathway". Science. 329 (5988): 219–23. Bibcode:2010Sci...329..219P. doi:10.1126/science.1192277. PMID 20538911. S2CID 206527645.
  7. ^ Boulton SJ, Jackson SP (Mar 1998). "Components of the Ku-dependent non-homologous end-joining pathway are involved in telomeric length maintenance and telomeric silencing". The EMBO Journal. 17 (6): 1819–28. doi:10.1093/emboj/17.6.1819. PMC 1170529. PMID 9501103.
  8. ^ Gu Y, Jin S, Gao Y, Weaver DT, Alt FW (Jul 1997). "Ku70-deficient embryonic stem cells have increased ionizing radiosensitivity, defective DNA end-binding activity, and inability to support V(D)J recombination". Proceedings of the National Academy of Sciences of the United States of America. 94 (15): 8076–81. Bibcode:1997PNAS...94.8076G. doi:10.1073/pnas.94.15.8076. PMC 21559. PMID 9223317.
  9. ^ Li H, Vogel H, Holcomb VB, Gu Y, Hasty P (Dec 2007). "Deletion of Ku70, Ku80, or both causes early aging without substantially increased cancer". Molecular and Cellular Biology. 27 (23): 8205–14. doi:10.1128/MCB.00785-07. PMC 2169178. PMID 17875923.
  10. ^ Bernstein H, Payne CM, Bernstein C, Garewal H, Dvorak K (2008). Cancer and aging as consequences of un-repaired DNA damage. In: New Research on DNA Damages (Editors: Honoka Kimura and Aoi Suzuki) Nova Science Publishers, Inc., New York, Chapter 1, pp. 1-47. open access, but read only https://www.novapublishers.com/catalog/product_info.php?products_id=43247 Arhivirano 25. 10. 2014. na Wayback Machine ISBN 978-1604565812
  11. ^ Sjaarda CP, Wood S, McNaughton AJ, Taylor S, Hudson ML, Liu X, Guerin A, Ayub M (decembar 2019). "Exome sequencing identifies de novo splicing variant in XRCC6 in sporadic case of autism". Journal of Human Genetics. 65 (3): 287–296. doi:10.1038/s10038-019-0707-0. PMID 31827253. S2CID 209312195.
  12. ^ Song K, Jung Y, Jung D, Lee I (Mar 2001). "Human Ku70 interacts with heterochromatin protein 1alpha". The Journal of Biological Chemistry. 276 (11): 8321–7. doi:10.1074/jbc.M008779200. PMID 11112778.
  13. ^ Goudelock DM, Jiang K, Pereira E, Russell B, Sanchez Y (Aug 2003). "Regulatory interactions between the checkpoint kinase Chk1 and the proteins of the DNA-dependent protein kinase complex". The Journal of Biological Chemistry. 278 (32): 29940–7. doi:10.1074/jbc.M301765200. PMID 12756247.
  14. ^ a b c Barlev NA, Poltoratsky V, Owen-Hughes T, Ying C, Liu L, Workman JL, Berger SL (Mar 1998). "Repression of GCN5 histone acetyltransferase activity via bromodomain-mediated binding and phosphorylation by the Ku-DNA-dependent protein kinase complex". Molecular and Cellular Biology. 18 (3): 1349–58. doi:10.1128/mcb.18.3.1349. PMC 108848. PMID 9488450.
  15. ^ Schild-Poulter C, Pope L, Giffin W, Kochan JC, Ngsee JK, Traykova-Andonova M, Haché RJ (maj 2001). "The binding of Ku antigen to homeodomain proteins promotes their phosphorylation by DNA-dependent protein kinase". The Journal of Biological Chemistry. 276 (20): 16848–56. doi:10.1074/jbc.M100768200. PMID 11279128.
  16. ^ Gell D, Jackson SP (Sep 1999). "Mapping of protein-protein interactions within the DNA-dependent protein kinase complex". Nucleic Acids Research. 27 (17): 3494–502. doi:10.1093/nar/27.17.3494. PMC 148593. PMID 10446239.
  17. ^ Yang CR, Yeh S, Leskov K, Odegaard E, Hsu HL, Chang C, Kinsella TJ, Chen DJ, Boothman DA (maj 1999). "Isolation of Ku70-binding proteins (KUBs)". Nucleic Acids Research. 27 (10): 2165–74. doi:10.1093/nar/27.10.2165. PMC 148436. PMID 10219089.
  18. ^ Singleton BK, Torres-Arzayus MI, Rottinghaus ST, Taccioli GE, Jeggo PA (maj 1999). "The C terminus of Ku80 activates the DNA-dependent protein kinase catalytic subunit" (PDF). Molecular and Cellular Biology. 19 (5): 3267–77. doi:10.1128/mcb.19.5.3267. PMC 84121. PMID 10207052.
  19. ^ a b Song K, Jung D, Jung Y, Lee SG, Lee I (Sep 2000). "Interaction of human Ku70 with TRF2". FEBS Letters. 481 (1): 81–5. doi:10.1016/S0014-5793(00)01958-X. PMID 10984620.
  20. ^ Goedecke W, Eijpe M, Offenberg HH, van Aalderen M, Heyting C (Oct 1999). "Mre11 and Ku70 interact in somatic cells, but are differentially expressed in early meiosis". Nature Genetics. 23 (2): 194–8. doi:10.1038/13821. PMID 10508516. S2CID 13443404.
  21. ^ Ko L, Cardona GR, Chin WW (maj 2000). "Thyroid hormone receptor-binding protein, an LXXLL motif-containing protein, functions as a general coactivator". Proceedings of the National Academy of Sciences of the United States of America. 97 (11): 6212–7. Bibcode:2000PNAS...97.6212K. doi:10.1073/pnas.97.11.6212. PMC 18584. PMID 10823961.
  22. ^ Ko L, Chin WW (Mar 2003). "Nuclear receptor coactivator thyroid hormone receptor-binding protein (TRBP) interacts with and stimulates its associated DNA-dependent protein kinase". The Journal of Biological Chemistry. 278 (13): 11471–9. doi:10.1074/jbc.M209723200. PMID 12519782.
  23. ^ Grandvaux N, Grizot S, Vignais PV, Dagher MC (Feb 1999). "The Ku70 autoantigen interacts with p40phox in B lymphocytes". Journal of Cell Science. 112 (4): 503–13. doi:10.1242/jcs.112.4.503. PMID 9914162.
  24. ^ Ohta S, Shiomi Y, Sugimoto K, Obuse C, Tsurimoto T (Oct 2002). "A proteomics approach to identify proliferating cell nuclear antigen (PCNA)-binding proteins in human cell lysates. Identification of the human CHL12/RFCs2-5 complex as a novel PCNA-binding protein". The Journal of Biological Chemistry. 277 (43): 40362–7. doi:10.1074/jbc.M206194200. PMID 12171929.
  25. ^ Balajee AS, Geard CR (Mar 2001). "Chromatin-bound PCNA complex formation triggered by DNA damage occurs independent of the ATM gene product in human cells". Nucleic Acids Research. 29 (6): 1341–51. doi:10.1093/nar/29.6.1341. PMC 29758. PMID 11239001.
  26. ^ Romero F, Multon MC, Ramos-Morales F, Domínguez A, Bernal JA, Pintor-Toro JA, Tortolero M (Mar 2001). "Human securin, hPTTG, is associated with Ku heterodimer, the regulatory subunit of the DNA-dependent protein kinase". Nucleic Acids Research. 29 (6): 1300–7. doi:10.1093/nar/29.6.1300. PMC 29753. PMID 11238996.
  27. ^ Shao RG, Cao CX, Zhang H, Kohn KW, Wold MS, Pommier Y (Mar 1999). "Replication-mediated DNA damage by camptothecin induces phosphorylation of RPA by DNA-dependent protein kinase and dissociates RPA:DNA-PK complexes". The EMBO Journal. 18 (5): 1397–406. doi:10.1093/emboj/18.5.1397. PMC 1171229. PMID 10064605.
  28. ^ Chai W, Ford LP, Lenertz L, Wright WE, Shay JW (Dec 2002). "Human Ku70/80 associates physically with telomerase through interaction with hTERT". The Journal of Biological Chemistry. 277 (49): 47242–7. doi:10.1074/jbc.M208542200. PMID 12377759.
  29. ^ Romero F, Dargemont C, Pozo F, Reeves WH, Camonis J, Gisselbrecht S, Fischer S (Jan 1996). "p95vav associates with the nuclear protein Ku-70". Molecular and Cellular Biology. 16 (1): 37–44. doi:10.1128/mcb.16.1.37. PMC 230976. PMID 8524317.
  30. ^ Karmakar P, Snowden CM, Ramsden DA, Bohr VA (Aug 2002). "Ku heterodimer binds to both ends of the Werner protein and functional interaction occurs at the Werner N-terminus". Nucleic Acids Research. 30 (16): 3583–91. doi:10.1093/nar/gkf482. PMC 134248. PMID 12177300.
  31. ^ Li B, Comai L (Sep 2000). "Functional interaction between Ku and the werner syndrome protein in DNA end processing". The Journal of Biological Chemistry. 275 (37): 28349–52. doi:10.1074/jbc.C000289200. PMID 10880505.

Dopunska literatura

Vanjski linkovi

  • PDBe-KB provides an overview of all the structure information available in the PDB for Human X-ray repair cross-complementing protein 6

Content Disclaimer

Informasi ini disarikan dari Wikipedia dan disajikan kembali untuk tujuan edukasi. Konten tersedia di bawah lisensi CC BY-SA 3.0. Kami tidak bertanggung jawab atas ketidakakuratan data yang bersumber dari kontribusi publik tersebut.

  1. The information displayed on this website is sourced in part or in whole from Wikipedia and has been adapted for the purpose of restating it. We strive to provide accurate and relevant information, however:
  2. There is no guarantee of absolute accuracy. Wikipedia is an open, collaborative project that can be edited by anyone, so information is subject to change.
  3. It is not intended to constitute professional advice. The content displayed is for informational and educational purposes only. For important decisions (e.g., medical, legal, or financial), please consult a professional.
  4. Content copyright. Wikipedia is licensed under the Creative Commons Attribution-ShareAlike License (CC BY-SA). This means that content may be reused with appropriate attribution and shared under a similar license.
  5. Responsible use. Any risk arising from the use of information from this website is entirely the responsibility of the user.