뉴클레오폴린 62
Nucleoporin 62
핵포폴린 p62(p62)는 핵 봉투와 관련된 단백질 복합체다.p62 단백질은 핵공기 복합-라미나 분율과 연관되어 있다.p62는 61 kDa의[5] 수용성 세포질 전구체로 합성되며, 그 다음에 N-acetyllucosamine 잔여물을 첨가하는 수정, [6]그 다음에 다른 복잡한 단백질과의 연관성을 포함한다.
핵공극단지는 핵 외피를 가로질러 뻗어 있는 거대한 구조로, 핵과 세포질 사이의 고분자의 흐름을 조절하는 관문을 형성하고 있다.핵포폴린은 진핵세포에서 핵공기 복합체의 주요 성분이다.이 유전자에 의해 인코딩된 단백질은 핵포도핀을 함유한 FG-repeat의 일원으로 핵공기 중앙 플러그에 국부화되어 있다.이 단백질은 핵 국산화 신호가 포함된 단백질의 수입에 관여하는 수입 알파/베타 복합체와 관련된다.이 유전자의 다중 대본변형은 단일 단백질 등소형을 암호화한다.[7]
구조
P62는 아미노산 약 520개의 세린/트레오닌이 풍부한 단백질로 아미노 종단에는 테트라펩티드 반복이 있고 소수성 헵타드가 있는[8] 일련의 알파헬리컬 영역은 베타프로펠러 영역을 형성한다.P62는 p62 콤플렉스를 형성하는 p60, p54, p45 등 3개의 추가 단백질을 포함하는 콤플렉스로 조립된다. O-GlcNAcylation은 p62를 조립하고 상위 오더 콤플렉스로 분해하는 데 관여하는 것으로 보이며, Ser270에서 Thr294 사이의 세린/트레오닌 리치 링커 영역은 규제적인 것으로 보인다.[11]p62 콤플렉스는 모공 콤플렉스의 핵소체와 세포질 양쪽에 국부화되어 있으며, 핵 모공 콤플렉스에 대한 p62 콤플렉스의 상대적 직경은 모공 게이트에서 상호작용을 시사한다.[12]
함수
P62는 핵 밖으로 운반하는 동안 mRNA와 상호작용하는 것으로 보인다.[13]P62는 또한 세포질과 핵 사이에서 단백질을 밀거래하는 핵 운반 인자(NTF2) 단백질과 상호작용한다.[14]또 다른 단백질인 임페린(베타)은 p62의 헬리컬 로드 부분에 결합되며, NTF2는 또한 고차량의 탕구 복합체가 형성되었음을 시사한다.[15]리보프로테인 트랜스포터인 카리오페린 베타2(트랜스포틴)도 p62와 상호작용한다.[16]P62는 또한 Nup93과 상호작용하며,[17] Nup98이 고갈되었을 때 p62는 핵공기 복합체와 조립하지 못한다.[18]돌연변이 모공은 핵 국산화 신호나 M9 수입 신호로 단백질을 도킹/운반할 수 없었다.
병리학
p62 복합체 항체는 하나 이상의 자가면역 질환에 관여한다.P62 글리코실화는 당뇨병에서[19] 증가하며 다른 질병과의 연관성에 영향을 미칠 수 있다.p62는 또한 4기 1차 담도경화증에서도 더 자주 발생하며 중증 질환에 대한 예후도 있다.[20]
상호작용
뉴클레오폴린 62는 다음과 상호작용하는 것으로 나타났다.
참조
- ^ a b c GRCh38: 앙상블 릴리스 89: ENSG00000213024 - 앙상블, 2017년 5월
- ^ a b c GRCm38: 앙상블 릴리스 89: ENSMUSG00000109511 - 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.
- ^ Davis LI, Blobel G (1986). "Identification and characterization of a nuclear pore complex protein". Cell. 45 (5): 699–709. doi:10.1016/0092-8674(86)90784-1. PMID 3518946. S2CID 22170880.
- ^ Davis LI, Blobel G (1987). "Nuclear pore complex contains a family of glycoproteins that includes p62: glycosylation through a previously unidentified cellular pathway". Proc. Natl. Acad. Sci. U.S.A. 84 (21): 7552–6. Bibcode:1987PNAS...84.7552D. doi:10.1073/pnas.84.21.7552. PMC 299337. PMID 3313397.
- ^ "Entrez Gene: NUP62 nucleoporin 62kDa".
- ^ Starr CM, D'Onofrio M, Park MK, Hanover JA (1990). "Primary sequence and heterologous expression of nuclear pore glycoprotein p62". J. Cell Biol. 110 (6): 1861–71. doi:10.1083/jcb.110.6.1861. PMC 2116139. PMID 2190987.
- ^ Kita K, Omata S, Horigome T (1993). "Purification and characterization of a nuclear pore glycoprotein complex containing p62". J. Biochem. 113 (3): 377–82. doi:10.1093/oxfordjournals.jbchem.a124054. PMID 8486610.
- ^ Buss F, Stewart M (1995). "Macromolecular interactions in the nucleoporin p62 complex of rat nuclear pores: binding of nucleoporin p54 to the rod domain of p62". J. Cell Biol. 128 (3): 251–61. doi:10.1083/jcb.128.3.251. PMC 2120351. PMID 7531196.
- ^ Lubas WA, Smith M, Starr CM, Hanover JA (1995). "Analysis of nuclear pore protein p62 glycosylation". Biochemistry. 34 (5): 1686–94. doi:10.1021/bi00005a025. PMID 7849028.
- ^ Guan T, Müller S, Klier G, Panté N, Blevitt JM, Haner M, Paschal B, Aebi U, Gerace L (1995). "Structural analysis of the p62 complex, an assembly of O-linked glycoproteins that localizes near the central gated channel of the nuclear pore complex". Mol. Biol. Cell. 6 (11): 1591–603. doi:10.1091/mbc.6.11.1591. PMC 301313. PMID 8589458.
- ^ Dargemont C, Schmidt-Zachmann MS, Kühn LC (1995). "Direct interaction of nucleoporin p62 with mRNA during its export from the nucleus". J. Cell Sci. 108 (1): 257–63. doi:10.1242/jcs.108.1.257. PMID 7738103.
- ^ Bullock TL, Clarkson WD, Kent HM, Stewart M (1996). "The 1.6 angstroms resolution crystal structure of nuclear transport factor 2 (NTF2)". J. Mol. Biol. 260 (3): 422–31. doi:10.1006/jmbi.1996.0411. PMID 8757804.
- ^ a b Percipalle P, Clarkson WD, Kent HM, Rhodes D, Stewart M (1997). "Molecular interactions between the importin alpha/beta heterodimer and proteins involved in vertebrate nuclear protein import". J. Mol. Biol. 266 (4): 722–32. doi:10.1006/jmbi.1996.0801. PMID 9102465.
- ^ Yaseen NR, Blobel G (1997). "Cloning and characterization of human karyopherin β3". Proc. Natl. Acad. Sci. U.S.A. 94 (9): 4451–6. Bibcode:1997PNAS...94.4451Y. doi:10.1073/pnas.94.9.4451. PMC 20743. PMID 9114010.
- ^ a b Grandi P, Dang T, Pané N, Shevchenko A, Mann M, Forbes D, Hurt E (1997). "Nup93, a Vertebrate Homologue of Yeast Nic96p, Forms a Complex with a Novel 205-kDa Protein and Is Required for Correct Nuclear Pore Assembly". Mol. Biol. Cell. 8 (10): 2017–38. doi:10.1091/mbc.8.10.2017. PMC 25664. PMID 9348540.
- ^ Wu X, Kasper LH, Mantcheva RT, Mantchev GT, Springett MJ, van Deursen JM (2001). "Disruption of the FG nucleoporin NUP98 causes selective changes in nuclear pore complex stoichiometry and function". Proc. Natl. Acad. Sci. U.S.A. 98 (6): 3191–6. Bibcode:2001PNAS...98.3191W. doi:10.1073/pnas.051631598. PMC 30629. PMID 11248054.
- ^ Han I, Oh ES, Kudlow JE (2000). "Responsiveness of the state of O-linked N-acetylglucosamine modification of nuclear pore protein p62 to the extracellular glucose concentration". Biochem. J. 350 Pt 1 (Pt 1): 109–14. doi:10.1042/0264-6021:3500109. PMC 1221231. PMID 10926833.
- ^ Miyachi K, Hankins RW, Matsushima H, Kikuchi F, Inomata T, Horigome T, Shibata M, Onozuka Y, Ueno Y, Hashimoto E, Hayashi N, Shibuya A, Amaki S, Miyakawa H (2003). "Profile and clinical significance of anti-nuclear envelope antibodies found in patients with primary biliary cirrhosis: a multicenter study". J. Autoimmun. 20 (3): 247–54. doi:10.1016/S0896-8411(03)00033-7. PMID 12753810.
- ^ Yoshima T, Yura T, Yanagi H (Nov 1997). "The trimerization domain of human heat shock factor 2 is able to interact with nucleoporin p62". Biochem. Biophys. Res. Commun. 240 (1): 228–33. doi:10.1006/bbrc.1997.7662. PMID 9367915.
- ^ Ben-Efraim I, Gerace L (Jan 2001). "Gradient of increasing affinity of importin beta for nucleoporins along the pathway of nuclear import". J. Cell Biol. 152 (2): 411–7. doi:10.1083/jcb.152.2.411. PMC 2199621. PMID 11266456.
- ^ Hu T, Guan T, Gerace L (Aug 1996). "Molecular and functional characterization of the p62 complex, an assembly of nuclear pore complex glycoproteins". J. Cell Biol. 134 (3): 589–601. doi:10.1083/jcb.134.3.589. PMC 2120945. PMID 8707840.
- ^ Paschal BM, Gerace L (May 1995). "Identification of NTF2, a cytosolic factor for nuclear import that interacts with nuclear pore complex protein p62". J. Cell Biol. 129 (4): 925–37. doi:10.1083/jcb.129.4.925. PMC 2120498. PMID 7744965.
- ^ Gamper C, van Eyndhoven WG, Schweiger E, Mossbacher M, Koo B, Lederman S (2000). "TRAF-3 interacts with p62 nucleoporin, a component of the nuclear pore central plug that binds classical NLS-containing import complexes". Mol. Immunol. 37 (1–2): 73–84. doi:10.1016/S0161-5890(00)00015-8. PMID 10781837.
- ^ Kehlenbach RH, Dickmanns A, Kehlenbach A, Guan T, Gerace L (May 1999). "A role for RanBP1 in the release of CRM1 from the nuclear pore complex in a terminal step of nuclear export". J. Cell Biol. 145 (4): 645–57. doi:10.1083/jcb.145.4.645. PMC 2133185. PMID 10330396.
- ^ Lindsay ME, Holaska JM, Welch K, Paschal BM, Macara IG (Jun 2001). "Ran-binding protein 3 is a cofactor for Crm1-mediated nuclear protein export". J. Cell Biol. 153 (7): 1391–402. doi:10.1083/jcb.153.7.1391. PMC 2150735. PMID 11425870.
추가 읽기
- Stoffler D, Fahrenkrog B, Aebi U (1999). "The nuclear pore complex: from molecular architecture to functional dynamics". Curr. Opin. Cell Biol. 11 (3): 391–401. doi:10.1016/S0955-0674(99)80055-6. PMID 10395558.
- Geetha T, Wooten MW (2002). "Structure and functional properties of the ubiquitin binding protein p62". FEBS Lett. 512 (1–3): 19–24. doi:10.1016/S0014-5793(02)02286-X. PMID 11852044. S2CID 22029085.
- Carmo-Fonseca M, Kern H, Hurt EC (1991). "Human nucleoporin p62 and the essential yeast nuclear pore protein NSP1 show sequence homology and a similar domain organization". Eur. J. Cell Biol. 55 (1): 17–30. PMID 1915414.
- Paschal BM, Gerace L (1995). "Identification of NTF2, a cytosolic factor for nuclear import that interacts with nuclear pore complex protein p62". J. Cell Biol. 129 (4): 925–37. doi:10.1083/jcb.129.4.925. PMC 2120498. PMID 7744965.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Grote M, Kubitscheck U, Reichelt R, Peters R (1996). "Mapping of nucleoporins to the center of the nuclear pore complex by post-embedding immunogold electron microscopy". J. Cell Sci. 108 (9): 2963–72. doi:10.1242/jcs.108.9.2963. PMID 8537436.
- Guan T, Müller S, Klier G, Panté N, Blevitt JM, Haner M, Paschal B, Aebi U, Gerace L (1996). "Structural analysis of the p62 complex, an assembly of O-linked glycoproteins that localizes near the central gated channel of the nuclear pore complex". Mol. Biol. Cell. 6 (11): 1591–603. doi:10.1091/mbc.6.11.1591. PMC 301313. PMID 8589458.
- Park I, Chung J, Walsh CT, Yun Y, Strominger JL, Shin J (1996). "Phosphotyrosine-independent binding of a 62-kDa protein to the src homology 2 (SH2) domain of p56lck and its regulation by phosphorylation of Ser-59 in the lck unique N-terminal region". Proc. Natl. Acad. Sci. U.S.A. 92 (26): 12338–42. doi:10.1073/pnas.92.26.12338. PMC 40352. PMID 8618896.
- Joung I, Strominger JL, Shin J (1996). "Molecular cloning of a phosphotyrosine-independent ligand of the p56lck SH2 domain". Proc. Natl. Acad. Sci. U.S.A. 93 (12): 5991–5. Bibcode:1996PNAS...93.5991J. doi:10.1073/pnas.93.12.5991. PMC 39176. PMID 8650207.
- Vadlamudi RK, Joung I, Strominger JL, Shin J (1996). "p62, a phosphotyrosine-independent ligand of the SH2 domain of p56lck, belongs to a new class of ubiquitin-binding proteins". J. Biol. Chem. 271 (34): 20235–7. doi:10.1074/jbc.271.34.20235. PMID 8702753.
- Hu T, Guan T, Gerace L (1996). "Molecular and functional characterization of the p62 complex, an assembly of nuclear pore complex glycoproteins". J. Cell Biol. 134 (3): 589–601. doi:10.1083/jcb.134.3.589. PMC 2120945. PMID 8707840.
- Bullock TL, Clarkson WD, Kent HM, Stewart M (1996). "The 1.6 angstroms resolution crystal structure of nuclear transport factor 2 (NTF2)". J. Mol. Biol. 260 (3): 422–31. doi:10.1006/jmbi.1996.0411. PMID 8757804.
- Percipalle P, Clarkson WD, Kent HM, Rhodes D, Stewart M (1997). "Molecular interactions between the importin alpha/beta heterodimer and proteins involved in vertebrate nuclear protein import". J. Mol. Biol. 266 (4): 722–32. doi:10.1006/jmbi.1996.0801. PMID 9102465.
- Yaseen NR, Blobel G (1997). "Cloning and characterization of human karyopherin β3". Proc. Natl. Acad. Sci. U.S.A. 94 (9): 4451–6. Bibcode:1997PNAS...94.4451Y. doi:10.1073/pnas.94.9.4451. PMC 20743. PMID 9114010.
- Yoshima T, Yura T, Yanagi H (1997). "The trimerization domain of human heat shock factor 2 is able to interact with nucleoporin p62". Biochem. Biophys. Res. Commun. 240 (1): 228–33. doi:10.1006/bbrc.1997.7662. PMID 9367915.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Kehlenbach RH, Dickmanns A, Kehlenbach A, Guan T, Gerace L (1999). "A Role for RanBP1 in the Release of CRM1 from the Nuclear Pore Complex in a Terminal Step of Nuclear Export". J. Cell Biol. 145 (4): 645–57. doi:10.1083/jcb.145.4.645. PMC 2133185. PMID 10330396.
- Sanz L, Sanchez P, Lallena MJ, Diaz-Meco MT, Moscat J (1999). "The interaction of p62 with RIP links the atypical PKCs to NF-kappaB activation". EMBO J. 18 (11): 3044–53. doi:10.1093/emboj/18.11.3044. PMC 1171386. PMID 10356400.
- Rachubinski RA, Marcus SL, Capone JP (1999). "The p56(lck)-interacting protein p62 stimulates transcription via the SV40 enhancer". J. Biol. Chem. 274 (26): 18278–84. doi:10.1074/jbc.274.26.18278. PMID 10373430.
