FKBP4
FKBP4| FKBP4 | |||||||||||||||||||||||||
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| 식별자 | |||||||||||||||||||||||||
| 에일리어스 | FKBP4, FKBP51, FKBP52, FKBP59, HBI, Hsp56, PPIase, p52, FK506 결합단백질4, FKBP 프롤릴 이성질화효소4 | ||||||||||||||||||||||||
| 외부 ID | OMIM: 600611 MGI: 95543 HomoloGene: 36085 GeneCard: FKBP4 | ||||||||||||||||||||||||
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| 맞춤법 | |||||||||||||||||||||||||
| 종. | 인간 | 마우스 | |||||||||||||||||||||||
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| 앙상블 | |||||||||||||||||||||||||
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| RefSeq(mRNA) | |||||||||||||||||||||||||
| RefSeq(단백질) | |||||||||||||||||||||||||
| 장소(UCSC) | Chr 12: 2.79 ~2.81 Mb | Chr 6: 128.41 ~128.42 Mb | |||||||||||||||||||||||
| PubMed 검색 | [3] | [4] | |||||||||||||||||||||||
| 위키데이터 | |||||||||||||||||||||||||
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FK506 결합단백질 4는 FKBP4 [5][6]유전자에 의해 인체 내에서 암호화되는 단백질이다.
기능.
이 유전자에 의해 코드된 단백질은 면역 조절과 단백질 접힘과 밀매를 수반하는 기본적인 세포 과정에 역할을 하는 면역필린 단백질 패밀리의 구성원이다.이 암호화된 단백질은 면역억제제 FK506 및 라파마이신에 결합하는 시스-트랜스 프롤릴 이성질체이다.FK506 결합단백질 1A(FKBP1A)와 구조적, 기능적으로 유사성이 높으나 FKBP1A와 달리 FK506과 복합될 경우 면역억제 활성이 없다.그것은 간섭자 조절인자-4와 상호작용하며, B와 T 림프구에서 면역 조절 유전자 발현에 중요한 역할을 한다.이 암호화된 단백질은 피타노일-CoA 알파-히드록실화효소와 관련이 있는 것으로 알려져 있다.그것은 또한 두 개의 열충격 단백질(hsp90 및 hsp70)과 연관될 수 있으며, 따라서 스테로이드 호르몬 수용체의 헤테로올리고머 형태의 세포 내 밀매에 역할을 할 수 있다.이 단백질은 아데노 관련 바이러스 타입 2 벡터(AAV)와 강하게 상관하여 인간 세포주에서 AAV 매개 트랜스젠 발현을 현저하게 증가시킨다.따라서 이 암호화된 단백질은 인간 유전자 [6]치료에서 AAV 벡터의 최적 사용에 중요한 의미를 갖는 것으로 생각된다.
구조.
이 단백질은 TPR 반복을 포함하고 PPlase 도메인을 가지고 있습니다.
임상적 의의
최근 연구에 따르면 FKBP4는 타우 단백질이 병원성으로 변하는 것을 막는 역할을 할 수 있다.이것은 새로운 알츠하이머 약의 개발과 임상 [7]증상의 시작 전에 병을 발견하는 데 중요한 것으로 입증될 수 있다.
상호 작용
FKBP4는 GLMN과 [8][9]대화하는 것으로 나타났습니다.
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- 글루코콜티코이드수용체
- 면역필린
- FKBP5
- FKBP3 - DNA 결합 FKBP.[10]
레퍼런스
- ^ a b c GRCh38: 앙상블 릴리즈 89: ENSG00000004478 - 앙상블, 2017년 5월
- ^ a b c GRCm38: 앙상블 릴리즈 89: ENSMUSG000030357 - 앙상블, 2017년 5월
- ^ "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.
- ^ Peattie DA, Harding MW, Fleming MA, DeCenzo MT, Lippke JA, Livingston DJ, Benasutti M (November 1992). "Expression and characterization of human FKBP52, an immunophilin that associates with the 90-kDa heat shock protein and is a component of steroid receptor complexes". Proceedings of the National Academy of Sciences of the United States of America. 89 (22): 10974–8. Bibcode:1992PNAS...8910974P. doi:10.1073/pnas.89.22.10974. PMC 50465. PMID 1279700.
- ^ a b "Entrez Gene: FKBP4 FK506 binding protein 4, 59kDa".
- ^ Blair LJ, Baker JD, Sabbagh JJ, Dickey CA (April 2015). "The emerging role of peptidyl-prolyl isomerase chaperones in tau oligomerization, amyloid processing, and Alzheimer's disease". Journal of Neurochemistry. 133 (1): 1–13. doi:10.1111/jnc.13033. PMC 4361273. PMID 25628064.
- ^ Chambraud B, Radanyi C, Camonis JH, Shazand K, Rajkowski K, Baulieu EE (December 1996). "FAP48, a new protein that forms specific complexes with both immunophilins FKBP59 and FKBP12. Prevention by the immunosuppressant drugs FK506 and rapamycin". The Journal of Biological Chemistry. 271 (51): 32923–9. doi:10.1074/jbc.271.51.32923. PMID 8955134.
- ^ Neye H (March 2001). "Mutation of FKBP associated protein 48 (FAP48) at proline 219 disrupts the interaction with FKBP12 and FKBP52". Regulatory Peptides. 97 (2–3): 147–52. doi:10.1016/S0167-0115(00)00206-8. PMID 11164950. S2CID 20617551.
- ^ Prakash, Ajit; Shin, Joon; Rajan, Sreekanth; Yoon, Ho Sup (2016-04-07). "Structural basis of nucleic acid recognition by FK506-binding protein 25 (FKBP25), a nuclear immunophilin". Nucleic Acids Research. 44 (6): 2909–2925. doi:10.1093/nar/gkw001. ISSN 0305-1048. PMC 4824100. PMID 26762975.
추가 정보
- Schiene-Fischer C, Yu C (April 2001). "Receptor accessory folding helper enzymes: the functional role of peptidyl prolyl cis/trans isomerases". FEBS Letters. 495 (1–2): 1–6. doi:10.1016/S0014-5793(01)02326-2. PMID 11322937. S2CID 42263861.
- Yem AW, Tomasselli AG, Heinrikson RL, Zurcher-Neely H, Ruff VA, Johnson RA, Deibel MR (February 1992). "The Hsp56 component of steroid receptor complexes binds to immobilized FK506 and shows homology to FKBP-12 and FKBP-13". The Journal of Biological Chemistry. 267 (5): 2868–71. doi:10.1016/S0021-9258(19)50664-0. PMID 1371107.
- Tai PK, Albers MW, Chang H, Faber LE, Schreiber SL (May 1992). "Association of a 59-kilodalton immunophilin with the glucocorticoid receptor complex". Science. 256 (5061): 1315–8. Bibcode:1992Sci...256.1315T. doi:10.1126/science.1376003. PMID 1376003.
- Wiederrecht G, Hung S, Chan HK, Marcy A, Martin M, Calaycay J, Boulton D, Sigal N, Kincaid RL, Siekierka JJ (October 1992). "Characterization of high molecular weight FK-506 binding activities reveals a novel FK-506-binding protein as well as a protein complex". The Journal of Biological Chemistry. 267 (30): 21753–60. doi:10.1016/S0021-9258(19)36676-1. PMID 1383226.
- Sanchez ER, Faber LE, Henzel WJ, Pratt WB (May 1990). "The 56-59-kilodalton protein identified in untransformed steroid receptor complexes is a unique protein that exists in cytosol in a complex with both the 70- and 90-kilodalton heat shock proteins". Biochemistry. 29 (21): 5145–52. doi:10.1021/bi00473a021. PMID 2378870.
- Alnemri ES, Fernandes-Alnemri T, Nelki DS, Dudley K, DuBois GC, Litwack G (July 1993). "Overexpression, characterization, and purification of a recombinant mouse immunophilin FKBP-52 and identification of an associated phosphoprotein". Proceedings of the National Academy of Sciences of the United States of America. 90 (14): 6839–43. Bibcode:1993PNAS...90.6839A. doi:10.1073/pnas.90.14.6839. PMC 47028. PMID 8341706.
- Chambraud B, Radanyi C, Camonis JH, Shazand K, Rajkowski K, Baulieu EE (December 1996). "FAP48, a new protein that forms specific complexes with both immunophilins FKBP59 and FKBP12. Prevention by the immunosuppressant drugs FK506 and rapamycin". The Journal of Biological Chemistry. 271 (51): 32923–9. doi:10.1074/jbc.271.51.32923. PMID 8955134.
- Bruner KL, Derfoul A, Robertson NM, Guerriero G, Fernandes-Alnemri T, Alnemri ES, Litwack G (1998). "The unliganded mineralocorticoid receptor is associated with heat shock proteins 70 and 90 and the immunophilin FKBP-52". Receptors & Signal Transduction. 7 (2): 85–98. PMID 9392437.
- Miyata Y, Chambraud B, Radanyi C, Leclerc J, Lebeau MC, Renoir JM, Shirai R, Catelli MG, Yahara I, Baulieu EE (December 1997). "Phosphorylation of the immunosuppressant FK506-binding protein FKBP52 by casein kinase II: regulation of HSP90-binding activity of FKBP52". Proceedings of the National Academy of Sciences of the United States of America. 94 (26): 14500–5. Bibcode:1997PNAS...9414500M. doi:10.1073/pnas.94.26.14500. PMC 25035. PMID 9405642.
- Bermingham NA, Rauf S, Katsanis N, Martin JE, Hunter AJ, Fisher EM (March 1998). "The immunophilin FKBP4 (FKBP52/FKBP59) maps to the distal short arm of human chromosome 12". Mammalian Genome. 9 (3): 268. doi:10.1007/s003359900746. PMID 9501323. S2CID 8388657.
- Chambraud B, Radanyi C, Camonis JH, Rajkowski K, Schumacher M, Baulieu EE (March 1999). "Immunophilins, Refsum disease, and lupus nephritis: the peroxisomal enzyme phytanoyl-COA alpha-hydroxylase is a new FKBP-associated protein". Proceedings of the National Academy of Sciences of the United States of America. 96 (5): 2104–9. Bibcode:1999PNAS...96.2104C. doi:10.1073/pnas.96.5.2104. PMC 26744. PMID 10051602.
- Mamane Y, Sharma S, Petropoulos L, Lin R, Hiscott J (February 2000). "Posttranslational regulation of IRF-4 activity by the immunophilin FKBP52". Immunity. 12 (2): 129–40. doi:10.1016/S1074-7613(00)80166-1. PMID 10714679.
- Neye H (March 2001). "Mutation of FKBP associated protein 48 (FAP48) at proline 219 disrupts the interaction with FKBP12 and FKBP52". Regulatory Peptides. 97 (2–3): 147–52. doi:10.1016/S0167-0115(00)00206-8. PMID 11164950. S2CID 20617551.
- Galigniana MD, Radanyi C, Renoir JM, Housley PR, Pratt WB (May 2001). "Evidence that the peptidylprolyl isomerase domain of the hsp90-binding immunophilin FKBP52 is involved in both dynein interaction and glucocorticoid receptor movement to the nucleus". The Journal of Biological Chemistry. 276 (18): 14884–9. doi:10.1074/jbc.M010809200. PMID 11278753.
- Qing K, Hansen J, Weigel-Kelley KA, Tan M, Zhou S, Srivastava A (October 2001). "Adeno-associated virus type 2-mediated gene transfer: role of cellular FKBP52 protein in transgene expression". Journal of Virology. 75 (19): 8968–76. doi:10.1128/JVI.75.19.8968-8976.2001. PMC 114465. PMID 11533160.
- Guo Y, Guettouche T, Fenna M, Boellmann F, Pratt WB, Toft DO, Smith DF, Voellmy R (December 2001). "Evidence for a mechanism of repression of heat shock factor 1 transcriptional activity by a multichaperone complex". The Journal of Biological Chemistry. 276 (49): 45791–9. doi:10.1074/jbc.M105931200. PMID 11583998.
- Davies TH, Ning YM, Sánchez ER (February 2002). "A new first step in activation of steroid receptors: hormone-induced switching of FKBP51 and FKBP52 immunophilins". The Journal of Biological Chemistry. 277 (7): 4597–600. doi:10.1074/jbc.C100531200. PMID 11751894.
외부 링크
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