미오토

미오토
사용 가능한 구조
PDB	Ortholog 검색: PDBe RCSB
PDB ID 코드 목록
	2KDG, 2KKQ
식별자
에일리어스	MYOT, LGMD1, LGMD1A, MFM3, TTID, TTOD, myotilin
외부 ID	OMIM : 604103 MGI : 1889800 HomoloGene : 4942 GenCard : MYOT
유전자 위치(인간)
크르.	5번 염색체(인간)
끝.	137,887,851 bp
유전자 위치(마우스)
크르.	18번 염색체(쥐)
끝.	44,488,791 bp
RNA발현패턴
	상단 표시 위치:
	위근; ; 외측 광대근; ; 설체; ; 아킬레스건; ; 삼각근; ; 정강이뼈전근; ; 경골 신경; ; 좌심실; ; 창호; ; 위점막;
	추가 참조 표현식 데이터
	추가 참조 표현식 데이터
유전자 존재론
분자 함수	액틴 결합; 근육의 구조 성분; GO:0001948 단백질 결합; α-액티닌; 축삭유도수용체활성;
셀룰러 컴포넌트	세포질; 사콜레마; 혈장막; Z디스크; 세포골격; 막; 액틴 세포골격; 축삭; 신경세포체;
생물학적 과정	근육 수축; 혈장막 접착 분자에 의한 호모세포 접착; 축삭 유도; 시냅스 조직;
	출처:아미고 / QuickGO
맞춤법
	9499
	58916
	ENSG00000120729
	ENSMUSG000024471
	Q9UBF9
	Q9JIF9
	NM_006790; NM_001135940; NM_001300911
	NM_001033621
	NP_001129412; NP_001287840; NP_006781
	NP_001028793
	위키데이터
인간 보기/편집	마우스 표시/편집

미오틸린은 인간에서 미오트 ^[5]^[6]^[7]유전자에 의해 암호화되는 단백질이다.미오틸린(근섬유 티틴 유사 단백질)은 TTID(TiTin Immunoglobulin Domain)로도 알려진 근육 단백질로 육종 Z-디스크 내에서 발견된다.

구조.

마이오틸린은 496개의 ^[8]아미노산으로 구성된 55.3 kDa 단백질이다.미오틸린은 원래 Z-디스크에 ^[9]국재화된 두 개의 Ig 유사 도메인을 가진 새로운 알파-액티닌 결합 파트너로 확인되었다.I형 Ig 유사 도메인은 C 말단 절반에 존재하며, 팔라딘의 Ig 도메인 2-3과 미오팔라딘의 Ig 도메인 4-5에 가장 상동적이며, 티틴의 Z-디스크 Ig 도메인 7 및 8에 보다 멀리 관련된다.C 말단 영역은 Z 밴드 단백질의 결합 부위를 호스트하며, 2 Ig 도메인은 myotilin의 ^[10]호모다이머라이제이션 부위이다.반면, 미오틸린의 N-말단 부분은 특이하며, 알려진 단백질에 대한 호몰로지가 없는 세린이 풍부한 영역으로 구성된다.몇몇 질병 관련 돌연변이는 세린이 풍부한 ^[11]영역 내에서 세린 잔기를 포함한다.인체 조직에서의 미오틸린 발현은 주로 줄무늬가 있는 근육과 신경으로 제한된다.근육에서 미오틸린은 주로 Z-디스크 안에서 발견된다.마이오틸린은 호모디머를 형성하고 알파-액티닌, 액틴,^[12] 필라민 C,^[13] FATZ-1,^[14] FATZ-2^[14] 및 ^[15]ZASP와 결합한다.

기능.

마이오틸린은 티틴 및 알파-액티닌과 함께 줄무늬 근육의 Z-디스크에 있는 육식동물에게 구조적 무결성을 부여하는 구조 단백질이다.마이오틸린은 시험관내 및 비근육세포에서 액틴다발의 형성을 유도한다.3원복합체 마이오틸린/액틴/알파액티닌을 체외에서 관찰할 수 있으며, 이러한 조건에서 형성된 액틴다발은 알파액티닌에 의해서만 유도되는 것보다 더 촘촘하게 포장된 것처럼 보인다.myotilin은 분해 속도를 늦춤으로써 F-actin을 안정화시키는 것으로 입증되었다.잘린 미오틸린의 이소성 과발현은 초기 근섬유소의 교란과 비정질 세포질 침전물에서의 미오틸린과 티틴의 공동 축적을 일으킨다.성숙한 육식동물에서 야생형 미오틸린은 알파-액티닌 및 Z-디스크 티틴에 의해 열원소화되어 육식단백질의 전형적인 줄무늬 패턴을 나타낸다.생쥐에서 미오틸린 유전자의 표적 교란은 근육 ^[16]기능에 큰 변화를 일으키지 않는다.한편, 돌연변이된 미오틸린을 가진 트랜스제닉 마우스는 근육위축증이 ^[17]발병한다.

임상적 의의

미오틸린은 다양한 형태의 근디스트로피로 변이된다: 림-거들 근디스트로피 타입 1A(LGM1A), 근섬유 근디스트로피(MFM), 구상체 근디로피 및 원위근 마이오패스.^[11]병리학의 기초가 되는 메커니즘은 아직 연구 중이다.병원성 돌연변이(Ser55Phe , Thr57Ile , Ser60Cys , Ser95Ile )를 수용하는 미오틸린의 액틴 결합 특성은 열화 ^[19]속도는 느리지만 ^[18]정상인 것으로 나타났다.놀랍게도 YFP-융접 구조는 myotilin 돌연변이로 구성되어 있다(Ser55Phe , Ser55).Ile, Thr57Ile, Ser60Cys, Ser60Phe, Ser95Ile, Arg405Lys )는 Z-디스크에 정상적으로 국소화되어 근육세포에서 정상적인 ^[20]동역학을 보였다.

레퍼런스

^ ^a ^b ^c GRCh38: 앙상블 릴리즈 89: ENSG00000120729 - 앙상블, 2017년 5월
^ ^a ^b ^c GRCm38: 앙상블 릴리즈 89: ENSMUSG000024471 - 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.
^ Godley LA, Lai F, Liu J, Zhao N, Le Beau MM (Nov 1999). "TTID: A novel gene at 5q31 encoding a protein with titin-like features". Genomics. 60 (2): 226–33. doi:10.1006/geno.1999.5912. PMID 10486214.
^ Salmikangas P, Mykkanen OM, Gronholm M, Heiska L, Kere J, Carpen O (Aug 1999). "Myotilin, a novel sarcomeric protein with two Ig-like domains, is encoded by a candidate gene for limb-girdle muscular dystrophy". Hum Mol Genet. 8 (7): 1329–36. doi:10.1093/hmg/8.7.1329. PMID 10369880. S2CID 16176213.
^ "Entrez Gene: MYOT myotilin".
^ "Myotilin protein information". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
^ Salmikangas P, Mykkänen OM, Grönholm M, Heiska L, Kere J, Carpén O (Jul 1999). "Myotilin, a novel sarcomeric protein with two Ig-like domains, is encoded by a candidate gene for limb-girdle muscular dystrophy". Human Molecular Genetics. 8 (7): 1329–36. doi:10.1093/hmg/8.7.1329. PMID 10369880. S2CID 16176213.
^ Shalaby S, Mitsuhashi H, Matsuda C, Minami N, Noguchi S, Nonaka I, Nishino I, Hayashi YK (Jun 2009). "Defective myotilin homodimerization caused by a novel mutation in MYOT exon 9 in the first Japanese limb girdle muscular dystrophy 1A patient". Journal of Neuropathology and Experimental Neurology. 68 (6): 701–7. doi:10.1097/NEN.0b013e3181a7f703. PMID 19458539.
^ ^a ^b Selcen D (Mar 2011). "Myofibrillar myopathies". Neuromuscular Disorders. 21 (3): 161–71. doi:10.1016/j.nmd.2010.12.007. PMC 3052736. PMID 21256014.
^ Salmikangas P, van der Ven PF, Lalowski M, Taivainen A, Zhao F, Suila H, Schröder R, Lappalainen P, Fürst DO, Carpén O (Jan 2003). "Myotilin, the limb-girdle muscular dystrophy 1A (LGMD1A) protein, cross-links actin filaments and controls sarcomere assembly". Human Molecular Genetics. 12 (2): 189–203. doi:10.1093/hmg/ddg020. PMID 12499399.
^ van der Ven PF, Wiesner S, Salmikangas P, Auerbach D, Himmel M, Kempa S, Hayess K, Pacholsky D, Taivainen A, Schröder R, Carpén O, Fürst DO (Oct 2000). "Indications for a novel muscular dystrophy pathway. gamma-filamin, the muscle-specific filamin isoform, interacts with myotilin". The Journal of Cell Biology. 151 (2): 235–248. doi:10.1083/jcb.151.2.235. PMC 2192634. PMID 11038172.
^ ^a ^b Gontier Y, Taivainen A, Fontao L, Sonnenberg A, van der Flier A, Carpen O, Faulkner G, Borradori L (Aug 2005). "The Z-disc proteins myotilin and FATZ-1 interact with each other and are connected to the sarcolemma via muscle-specific filamins". Journal of Cell Science. 118 (Pt 16): 3739–49. doi:10.1242/jcs.02484. PMID 16076904.
^ von Nandelstadh P, Ismail M, Gardin C, Suila H, Zara I, Belgrano A, Valle G, Carpen O, Faulkner G (Feb 2009). "A class III PDZ binding motif in the myotilin and FATZ families binds enigma family proteins: a common link for Z-disc myopathies". Molecular and Cellular Biology. 29 (3): 822–34. doi:10.1128/MCB.01454-08. PMC 2630697. PMID 19047374.
^ Moza M, et al. (2007). "Targeted deletion of the muscular dystrophy gene myotilin does not perturb muscle structure or function in mice". Mol Cell Biol. 27 (1): 244–252. doi:10.1128/mcb.00561-06. PMC 1800670. PMID 17074808.
^ Garvey SM, et al. (2006). "Transgenic mice expressing the myotilin T57I mutation unite the pathology associated with LGMD1A and MFM". Hum Mol Genet. 15 (15): 2348–62. doi:10.1093/hmg/ddl160. PMID 16801328.
^ von Nandelstadh P, Grönholm M, Moza M, Lamberg A, Savilahti H, Carpén O (Oct 2005). "Actin-organising properties of the muscular dystrophy protein myotilin". Experimental Cell Research. 310 (1): 131–9. doi:10.1016/j.yexcr.2005.06.027. PMID 16122733.
^ von Nandelstadh P, Soliymani R, Baumann M, Carpen O (May 2011). "Analysis of myotilin turnover provides mechanistic insight into the role of myotilinopathy-causing mutations". The Biochemical Journal. 436 (1): 113–21. doi:10.1042/BJ20101672. PMID 21361873.
^ Wang J, Dube DK, Mittal B, Sanger JM, Sanger JW (Dec 2011). "Myotilin dynamics in cardiac and skeletal muscle cells". Cytoskeleton. 68 (12): 661–70. doi:10.1002/cm.20542. PMC 3240742. PMID 22021208.

추가 정보

Speer MC, Yamaoka LH, Gilchrist JH, Gaskell CP, Stajich JM, Vance JM, Kazantsev A, Lastra AA, Haynes CS, Beckmann JS (Jun 1992). "Confirmation of genetic heterogeneity in limb-girdle muscular dystrophy: linkage of an autosomal dominant form to chromosome 5q". American Journal of Human Genetics. 50 (6): 1211–7. PMC 1682558. PMID 1598902.
Dixon MJ, Read AP, Donnai D, Colley A, Dixon J, Williamson R (Jul 1991). "The gene for Treacher Collins syndrome maps to the long arm of chromosome 5". American Journal of Human Genetics. 49 (1): 17–22. PMC 1683211. PMID 1676560.
Bartoloni L, Horrigan SK, Viles KD, Gilchrist JM, Stajich JM, Vance JM, Yamaoka LH, Pericak-Vance MA, Westbrook CA, Speer MC (Dec 1998). "Use of a CEPH meiotic breakpoint panel to refine the locus of limb-girdle muscular dystrophy type 1A (LGMD1A) to a 2-Mb interval on 5q31". Genomics. 54 (2): 250–5. doi:10.1006/geno.1998.5579. PMID 9828127.
Hauser MA, Horrigan SK, Salmikangas P, Torian UM, Viles KD, Dancel R, Tim RW, Taivainen A, Bartoloni L, Gilchrist JM, Stajich JM, Gaskell PC, Gilbert JR, Vance JM, Pericak-Vance MA, Carpen O, Westbrook CA, Speer MC (Sep 2000). "Myotilin is mutated in limb girdle muscular dystrophy 1A". Human Molecular Genetics. 9 (14): 2141–7. doi:10.1093/hmg/9.14.2141. PMID 10958653.
van der Ven PF, Wiesner S, Salmikangas P, Auerbach D, Himmel M, Kempa S, Hayess K, Pacholsky D, Taivainen A, Schröder R, Carpén O, Fürst DO (Oct 2000). "Indications for a novel muscular dystrophy pathway. gamma-filamin, the muscle-specific filamin isoform, interacts with myotilin". The Journal of Cell Biology. 151 (2): 235–48. doi:10.1083/jcb.151.2.235. PMC 2192634. PMID 11038172.
Hauser MA, Conde CB, Kowaljow V, Zeppa G, Taratuto AL, Torian UM, Vance J, Pericak-Vance MA, Speer MC, Rosa AL (Dec 2002). "myotilin Mutation found in second pedigree with LGMD1A". American Journal of Human Genetics. 71 (6): 1428–32. doi:10.1086/344532. PMC 378586. PMID 12428213.
Salmikangas P, van der Ven PF, Lalowski M, Taivainen A, Zhao F, Suila H, Schröder R, Lappalainen P, Fürst DO, Carpén O (Jan 2003). "Myotilin, the limb-girdle muscular dystrophy 1A (LGMD1A) protein, cross-links actin filaments and controls sarcomere assembly". Human Molecular Genetics. 12 (2): 189–203. doi:10.1093/hmg/ddg020. PMID 12499399.
Battle MA, Maher VM, McCormick JJ (Jun 2003). "ST7 is a novel low-density lipoprotein receptor-related protein (LRP) with a cytoplasmic tail that interacts with proteins related to signal transduction pathways". Biochemistry. 42 (24): 7270–82. doi:10.1021/bi034081y. PMID 12809483.
Selcen D, Engel AG (Apr 2004). "Mutations in myotilin cause myofibrillar myopathy". Neurology. 62 (8): 1363–71. doi:10.1212/01.wnl.0000123576.74801.75. PMID 15111675. S2CID 23068161.
Witt SH, Granzier H, Witt CC, Labeit S (Jul 2005). "MURF-1 and MURF-2 target a specific subset of myofibrillar proteins redundantly: towards understanding MURF-dependent muscle ubiquitination". Journal of Molecular Biology. 350 (4): 713–22. doi:10.1016/j.jmb.2005.05.021. PMID 15967462.
Gontier Y, Taivainen A, Fontao L, Sonnenberg A, van der Flier A, Carpen O, Faulkner G, Borradori L (Aug 2005). "The Z-disc proteins myotilin and FATZ-1 interact with each other and are connected to the sarcolemma via muscle-specific filamins". Journal of Cell Science. 118 (Pt 16): 3739–49. doi:10.1242/jcs.02484. PMID 16076904.
von Nandelstadh P, Grönholm M, Moza M, Lamberg A, Savilahti H, Carpén O (Oct 2005). "Actin-organising properties of the muscular dystrophy protein myotilin". Experimental Cell Research. 310 (1): 131–9. doi:10.1016/j.yexcr.2005.06.027. PMID 16122733.
Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
Foroud T, Pankratz N, Batchman AP, Pauciulo MW, Vidal R, Miravalle L, Goebel HH, Cushman LJ, Azzarelli B, Horak H, Farlow M, Nichols WC (Dec 2005). "A mutation in myotilin causes spheroid body myopathy". Neurology. 65 (12): 1936–40. doi:10.1212/01.wnl.0000188872.28149.9a. PMID 16380616. S2CID 9593230.
Garvey SM, Senderek J, Beckmann JS, Seboun E, Jackson CE, Hauser MA (May 2006). "Myotilin is not the causative gene for vocal cord and pharyngeal weakness with distal myopathy (VCPDM)". Annals of Human Genetics. 70 (Pt 3): 414–6. doi:10.1111/j.1529-8817.2005.00252.x. PMID 16674563. S2CID 26853063.
Pénisson-Besnier I, Talvinen K, Dumez C, Vihola A, Dubas F, Fardeau M, Hackman P, Carpen O, Udd B (Jul 2006). "Myotilinopathy in a family with late onset myopathy". Neuromuscular Disorders. 16 (7): 427–31. doi:10.1016/j.nmd.2006.04.009. PMID 16793270. S2CID 21589529.

외부 링크

Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (Oct 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circ Res. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
근섬유근병증에 대한 GeneReviews/NIH/NCBI/UW 엔트리
PDB for UniProt: Q9UBF9(Myotilin)에서 PDBe-KB에 있는 모든 구조 정보의 개요.

[refGRCh38Ensembl-1] GRCh38: 앙상블 릴리즈 89: ENSG00000120729 - 앙상블, 2017년 5월

[refGRCm38Ensembl-2] GRCm38: 앙상블 릴리즈 89: ENSMUSG000024471 - 앙상블, 2017년 5월

[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.

[pmid10486214-5] Godley LA, Lai F, Liu J, Zhao N, Le Beau MM (Nov 1999). "TTID: A novel gene at 5q31 encoding a protein with titin-like features". Genomics. 60 (2): 226–33. doi:10.1006/geno.1999.5912. PMID 10486214.

[pmid10369880-6] Salmikangas P, Mykkanen OM, Gronholm M, Heiska L, Kere J, Carpen O (Aug 1999). "Myotilin, a novel sarcomeric protein with two Ig-like domains, is encoded by a candidate gene for limb-girdle muscular dystrophy". Hum Mol Genet. 8 (7): 1329–36. doi:10.1093/hmg/8.7.1329. PMID 10369880. S2CID 16176213.

[entrez-7] "Entrez Gene: MYOT myotilin".

[url_COPaKB-8] "Myotilin protein information". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).

[9] Salmikangas P, Mykkänen OM, Grönholm M, Heiska L, Kere J, Carpén O (Jul 1999). "Myotilin, a novel sarcomeric protein with two Ig-like domains, is encoded by a candidate gene for limb-girdle muscular dystrophy". Human Molecular Genetics. 8 (7): 1329–36. doi:10.1093/hmg/8.7.1329. PMID 10369880. S2CID 16176213.

[pmid19458539-10] Shalaby S, Mitsuhashi H, Matsuda C, Minami N, Noguchi S, Nonaka I, Nishino I, Hayashi YK (Jun 2009). "Defective myotilin homodimerization caused by a novel mutation in MYOT exon 9 in the first Japanese limb girdle muscular dystrophy 1A patient". Journal of Neuropathology and Experimental Neurology. 68 (6): 701–7. doi:10.1097/NEN.0b013e3181a7f703. PMID 19458539.

[pmid21256014-11] Selcen D (Mar 2011). "Myofibrillar myopathies". Neuromuscular Disorders. 21 (3): 161–71. doi:10.1016/j.nmd.2010.12.007. PMC 3052736. PMID 21256014.

[12] Salmikangas P, van der Ven PF, Lalowski M, Taivainen A, Zhao F, Suila H, Schröder R, Lappalainen P, Fürst DO, Carpén O (Jan 2003). "Myotilin, the limb-girdle muscular dystrophy 1A (LGMD1A) protein, cross-links actin filaments and controls sarcomere assembly". Human Molecular Genetics. 12 (2): 189–203. doi:10.1093/hmg/ddg020. PMID 12499399.

[13] van der Ven PF, Wiesner S, Salmikangas P, Auerbach D, Himmel M, Kempa S, Hayess K, Pacholsky D, Taivainen A, Schröder R, Carpén O, Fürst DO (Oct 2000). "Indications for a novel muscular dystrophy pathway. gamma-filamin, the muscle-specific filamin isoform, interacts with myotilin". The Journal of Cell Biology. 151 (2): 235–248. doi:10.1083/jcb.151.2.235. PMC 2192634. PMID 11038172.

[pmid16076904-14] Gontier Y, Taivainen A, Fontao L, Sonnenberg A, van der Flier A, Carpen O, Faulkner G, Borradori L (Aug 2005). "The Z-disc proteins myotilin and FATZ-1 interact with each other and are connected to the sarcolemma via muscle-specific filamins". Journal of Cell Science. 118 (Pt 16): 3739–49. doi:10.1242/jcs.02484. PMID 16076904.

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[pmid22021208-20] Wang J, Dube DK, Mittal B, Sanger JM, Sanger JW (Dec 2011). "Myotilin dynamics in cardiac and skeletal muscle cells". Cytoskeleton. 68 (12): 661–70. doi:10.1002/cm.20542. PMC 3240742. PMID 22021208.

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