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{{Infobox_gene}}
'''Titin''' {{IPAc-en|ˈ|t|aɪ|t|ɪ|n}}, juga dikenal sebagai '''connectin''', adalah suatu [[protein]] yang pada [[manusia]], dikodekan oleh [[gen]] ''TTN''.<ref name= "Entrez_ 7273">{{cite web | title = Entrez Gene: TTN titin| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7273| accessdate = }}</ref><ref name="pmid2129545">{{cite journal | vauthors = Labeit S, Barlow DP, Gautel M, Gibson T, Holt J, Hsieh CL, Francke U, Leonard K, Wardale J, Whiting A | title = A regular pattern of two types of 100-residue motif in the sequence of titin | journal = Nature | volume = 345 | issue = 6272 | pages = 273–6 | date = May 1990 | pmid = 2129545 | doi = 10.1038/345273a0 }}</ref> Titin adalah sebuah protein raksasa, panjangnya lebih dari 1 [[Mikrometer|µm]],<ref>{{cite web | url=http://www.ks.uiuc.edu/Research/z1z2/ | title=The Chain-like Elasticity of Titin | publisher=Theoretical and Computational Biophysics Group, University of Illinois | accessdate=25 September 2014 | author=Eric H. Lee}}</ref> fungsinya yaitu sebagai mata air molekuler yang bertanggung jawab atas elastisitas pasif [[otot]]. Protein ini terdiri dari 244 domain [[protein]] terlipat secara individual yang dihubungkan dengan urutan [[peptida]] yang tidak terstruktur.<ref name="pmid7569978">{{cite journal | vauthors = Labeit S, Kolmerer B | title = Titins: giant proteins in charge of muscle ultrastructure and elasticity | journal = Science | volume = 270 | issue = 5234 | pages = 293–6 | date = October 1995 | pmid = 7569978 | doi = 10.1126/science.270.5234.293 }}</ref> Domain ini [[denaturasi (biokimia)|terbuka]] saat protein diregangkan dan [[lipatan protein|terlipat kembali]] saat ketegangan dihilangkan.<ref name="pmid11222304">{{cite journal | vauthors = Minajeva A, Kulke M, Fernandez JM, Linke WA | author-link2 = Matthew Kulke | title = Unfolding of titin domains explains the viscoelastic behavior of skeletal myofibrils | journal = Biophysical Journal | volume = 80 | issue = 3 | pages = 1442–51 | date = March 2001 | pmid = 11222304 | pmc = 1301335 | doi = 10.1016/S0006-3495(01)76116-4 }}</ref>
Titin berperan penting dalam kontraksi [[jaringan otot lurik]]. Protein ini menghubungkan [[Myofibril#Penampakan|garis Z]] ke [[Myofibril#Penampakan|garis M]] di dalam [[sarkomer]]. Protein ini berperan memaksa transmisi pada garis Z dan ketegangan istirahat di area [[Myofibril#Penampakan|Pita I]].<ref name="pmid11846417">{{cite journal | vauthors = Itoh-Satoh M, Hayashi T, Nishi H, Koga Y, Arimura T, Koyanagi T, Takahashi M, Hohda S, Ueda K, Nouchi T, Hiroe M, Marumo F, Imaizumi T, Yasunami M, Kimura A | title = Titin mutations as the molecular basis for dilated cardiomyopathy | journal = Biochemical and Biophysical Research Communications | volume = 291 | issue = 2 | pages = 385–93 | date = February 2002 | pmid = 11846417 | doi = 10.1006/bbrc.2002.6448 }}</ref> Protein ini membatasi jangkauan gerak sarkomer ketika dalam kondisi tegang, sehingga berkontribusi terhadap kekakuan pasif otot. Variasi dalam urutan titin antara berbagai jenis otot (mis., Jantung atau kerangka) telah berkorelasi dengan perbedaan sifat mekanik otot-otot ini.<ref name= "Entrez_ 7273"/><ref>{{OMIM|188840}}</ref>
Titin adalah protein paling banyak ketiga yang ada dalam otot (setelah [[myosin]] dan [[actin]]), tubuh manusia dewasa paling tidak mengandung sekitar 0,5 kg titin.<ref name="pmid9012751">{{cite journal | vauthors = Labeit S, Kolmerer B, Linke WA | title = The giant protein titin. Emerging roles in physiology and pathophysiology | journal = Circulation Research | volume = 80 | issue = 2 | pages = 290–4 | date = February 1997 | pmid = 9012751 | doi = 10.1161/01.RES.80.2.290 }}</ref> Dengan panjang ~27.000 sampai ~33.000 [[asam amino]] (tergantung pada [[sambungan alternatif|sambatan isoform]]), titin adalah [[protein]] terbesar yang diketahui.<ref name="pmid14563922">{{cite journal | vauthors = Opitz CA, Kulke M, Leake MC, Neagoe C, Hinssen H, Hajjar RJ, Linke WA | title = Damped elastic recoil of the titin spring in myofibrils of human myocardium | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 100 | issue = 22 | pages = 12688–93 | date = October 2003 | pmid = 14563922 | pmc = 240679 | doi = 10.1073/pnas.2133733100 }}</ref> Lebih jauh lagi, gen titin mengandung jumlah terbesar [[exon]] (363) yang ditemukan pada gen tunggal manapun,<ref name="pmid11717165">{{cite journal | vauthors = Bang ML, Centner T, Fornoff F, Geach AJ, Gotthardt M, McNabb M, Witt CC, Labeit D, Gregorio CC, Granzier H, Labeit S | title = The complete gene sequence of titin, expression of an unusual approximately 700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system | journal = Circulation Research | volume = 89 | issue = 11 | pages = 1065–72 | date = November 2001 | pmid = 11717165 | doi = 10.1161/hh2301.100981 }}</ref> serta ekson tunggal terpanjang (17.106 bp).
== Penemuan ==
[[Reiji Natori]] pada tahun 1954 adalah orang pertama yang mengusulkan struktur elastis pada serat otot sebagai penyebab kembalinya otot ke keadaan istirahat saat otot-otot diregangkan dan kemudian dilepaskan.<ref name = "Natori_1954">{{cite journal | vauthors = Natori R | title = Skinned Fibres of Skeletal Muscle and the Mechanism of Muscle Contraction－A Chronological Account of the Author's Investigations into Muscle Physiology | journal = Jikeikai Medical Journal | year = 1954 | volume = 54 | issue = 1 | pages = | url = http://ir.jikei.ac.jp/bitstream/10328/3410/1/54-1-51.pdf }}</ref> Pada tahun 1977, [[Koscak Maruyama]] dan rekan kerja mengisolasi protein elastis dari serat otot, yang mereka sebut connectin.<ref name="pmid914784">{{cite journal | vauthors = Maruyama K, Matsubara S, Natori R, Nonomura Y, Kimura S | title = Connectin, an elastic protein of muscle. Characterization and Function | journal = Journal of Biochemistry | volume = 82 | issue = 2 | pages = 317–37 | date = August 1977 | pmid = 914784 | doi = | url = http://jb.oxfordjournals.org/content/82/2/317.long }}</ref> Dua tahun kemudian, [[Kuan Wang]] dan rekan kerjanya mengidentifikasi pita ''dobel'' pada [[gel elektroforesis]] yang sesuai dengan protein elastis dengan berat molekul tinggi, yang mereka beri nama titin.<ref name="pmid291034">{{cite journal | vauthors = Wang K, McClure J, Tu A | title = Titin: major myofibrillar components of striated muscle | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 76 | issue = 8 | pages = 3698–702 | date = August 1979 | pmid = 291034 | pmc = 383900 | doi = 10.1073/pnas.76.8.3698 }}</ref><ref name="pmid8011942">{{cite journal | vauthors = Maruyama K | title = Connectin, an elastic protein of striated muscle | journal = Biophysical Chemistry | volume = 50 | issue = 1–2 | pages = 73–85 | date = May 1994 | pmid = 8011942 | doi = 10.1016/0301-4622(94)85021-6 }}</ref>
[[Labeit]] pada tahun 1990 mengisolasi sebagian [[cDNA]] kloning titin.<ref name="pmid2129545"/> Pada tahun 1995, Labeit dan [[Kolmerer]] menentukan urutan cDNA dari titin jantung manusia.<ref name="pmid7569978"/> Bang and colleagues in 2001 determined the complete sequence of the human titin gene.<ref name="pmid11717165"/><ref name = "OMIM" >{{OMIM|188840|Titin}}</ref>
== Genomik ==
Gen manusia yang mengkodekan titin terletak pada lengan panjang kromosom 2 dan mengandung 363 ekson, yang bersama-sama mengkodekan 38.138 residu (4200 kDa).<ref name="pmid11717165"/> Dalam gen tersebut ditemukan sejumlah besar eksplan PEVK yang berjumlah 84 sampai 99 nukleotida yang memperjelas motif residu 28 sampai 33-residu yang dapat mewakili unit struktural dari pegas PEVK titin. Jumlah motif PEVK dalam gen titin tampaknya meningkat selama evolusi, yang tampaknya memodifikasi daerah genom yang bertanggung jawab untuk sifat pegas titin.<ref>{{cite journal | vauthors = Freiburg A, Trombitas K, Hell W, Cazorla O, Fougerousse F, Centner T, Kolmerer B, Witt C, Beckmann JS, Gregorio CC, Granzier H, Labeit S | title = Series of exon-skipping events in the elastic spring region of titin as the structural basis for myofibrillar elastic diversity }}</ref>
== Isoform ==
Sejumlah [[isoform protein|isoform]] diproduksi di jaringan otot lurik yang berbeda sebagai hasil dari [[sambungan alternatif]].<ref name="url_UniProt_Q8WZ42)"/> Semua kecuali satu dari isoform ini berada dalam kisaran ~27.000 sampai ~36.000 residu asam amino. Pengecualian adalah inoform jantung kecil ''novex-3'' yang hanya 5.604 residu amino panjangnya. Tabel berikut mencantumkan isoform titin yang diketahui:
{| class="wikitable"
|-
! Isoform !! alias/deskripsi !! panjang !! MW
|-
| Q8WZ42-1 || The "canonical" sequence || 34,350 || 3,816,030
|-
| Q8WZ42-2 || || 34,258 || 3,805,708
|-
| Q8WZ42-3 || Small cardiac N2-B || 26,926 || 2,992,939
|-
| Q8WZ42-4 || Soleus || 33,445 || 3,716,027
|-
| Q8WZ42-5 || || 32,900 || 3,653,085
|-
| Q8WZ42-6 || Small cardiac novex-3 || 5,604 || 631,567
|-
| Q8WZ42-7 || Cardiac novex-2 || 33,615 || 3,734,648
|-
| Q8WZ42-8 || Cardiac novex-1 || 34,475 || 3,829,846
|-
| Q8WZ42-9 || || 27,118 || 3,013,957
|-
| Q8WZ42-10 || || 27,051 || 3,006,755
|-
| Q8WZ42-11 || || 33,423 || 3,713,600
|-
| Q8WZ42-12 || || 35,991 || 3,994,625
|-
| Q8WZ42-13 || || 34,484 || 3,831,069
|}
== Struktur ==
Titin adalah protein terbesar yang diketahui; varian manusianya terdiri dari 34.350 [[asam amino]], dengan berat molekul isoform "kanonik" dewasa dari protein sekitar 3.816.188,13 [[unit massa atom|Da]].<ref name="urlExPASy_human"/> Homolog protein ini pada tikus bahkan lebih besar lagi, terdiri dari 35.213 asam amino dengan MW 3.906.487,6 [[unit massa atom|Da]].<ref name="urlExPASy_mouse">{{cite web|url= http://www.expasy.org/cgi-bin/protparam1?A2ASS6@noft@ |title= ProtParam for mouse titin |work= ExPASy Proteomics Server |publisher= Swiss Institute of Bioinformatics |accessdate=2010-05-06}}</ref> Protein ini memiliki [[titik isoelektrik]] teoritis 6,01.<ref name="urlExPASy_human"/> [[Rumus kimia]] empiris proteinnya adalah C<sub>169,719</sub>H<sub>270,464</sub>N<sub>45,688</sub>O<sub>52,237</sub>S<sub>911</sub>.<ref name="urlExPASy_human">{{cite web|url= http://web.expasy.org/cgi-bin/protparam/protparam1?Q8WZ42@1-34350@ |title= ProtParam for human titin |work= ExPASy Proteomics Server |publisher= Swiss Institute of Bioinformatics |accessdate=2011-07-25}}</ref> Ini memiliki teori [[indeks ketidakstabilan]] (II) 42,41, dan karena itu diklasifikasikan sebagai protein tidak stabil.<ref name="urlExPASy_human"/> [[Paruh waktu]] protein [[in vivo]], waktu yang dibutuhkan setengah dari jumlah protein dalam sel untuk dipecah setelah sintesisnya di dalam sel, diperkirakan sekitar 30 jam (pada [[reticulocyte]] [[mamalia]]).<ref name="url_UniProt_Q8WZ42)">{{cite web|url= http://www.uniprot.org/uniprot/Q8WZ42 |title= Titin - Homo sapiens (Human) | work = Universal Protein Resource | publisher = UniProt Consortium | date=2010-10-05 |accessdate=2010-10-15}}</ref>
Protein titin terletak di antara filamen tebal [[myosin]] dan cakram Z.<ref name="Wang_1991">{{cite journal | vauthors = Wang K, McCarter R, Wright J, Beverly J, Ramirez-Mitchell R | title = Regulation of skeletal muscle stiffness and elasticity by titin isoforms: a test of the segmental extension model of resting tension | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 88 | issue = 16 | pages = 7101–5 | date = August 1991 | pmid = 1714586 | pmc = 52241 | doi = 10.1073/pnas.88.16.7101 }}</ref> Titin terdiri dari rangkaian linear dua jenis modul (juga disebut sebagai [[domain protein]]; 244 total salinan): tipe I ([[domain fibronektin tipe III]]; 132 salinan) dan tipe II ([[domain imunoglobulin]]; 112 salinan).<ref name="pmid7569978"/> Array linier ini selanjutnya disusun menjadi dua wilayah:
* [[N-terminus|N-terminal]] I-band: bertindak sebagai bagian elastis dari molekul dan sebagian besar terdiri dari modul tipe II. Lebih khusus lagi, I-band berisi dua wilayah domain imunoglobulin tandem tipe II di kedua sisi wilayah PEVK yang kaya akan prolin, glutamat, valin dan lisin<ref name="Wang_1991"/> Elastisitas PVK memiliki sifat entropik dan enthalpic yang dapat dikarakterisasi oleh panjang ketekunan polimer dan modulus regangan.<ref>{{cite journal | vauthors = Linke WA, Ivemeyer M, Mundel P, Stockmeier MR, Kolmerer B | title = Nature of PEVK-titin elasticity in skeletal muscle | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 14 | pages = 8052–7 | date = July 1998 | pmid = 9653138 | doi=10.1073/pnas.95.14.8052 | pmc=20927}}</ref> Pada elastisitas ekstensi PEVK yang rendah sampai sedang dapat dimodelkan dengan model elastisitas entropik tipe wormlike (rantai cacing). Pada ekstensi PEVK yang tinggi dapat dimodelkan dengan model WLC yang dimodifikasi yang menggabungkan elastisitas enthalpic. Perbedaan antara elastisitas elastisitas rendah dan tinggi adalah karena penguatan kaku dan efek hidrofobik elektrostatik.
* [[C-terminus|C-terminal]] A-band: dianggap bertindak sebagai penguasa protein dan memiliki aktivitas [[kinase]]. A-band terdiri dari modul tipe I dan II bergantian dengan segmen pengulang-super. Hal ini telah ditunjukkan untuk menyelaraskan pengulangan miosin aksial berketebalan 43 nm dengan domain imunoglobulin yang berkorelasi dengan mahkota miosin.<ref name="pmid8683592">{{cite journal | vauthors = Bennett PM, Gautel M | title = Titin domain patterns correlate with the axial disposition of myosin at the end of the thick filament | journal = Journal of Molecular Biology | volume = 259 | issue = 5 | pages = 896–903 | date = June 1996 | pmid = 8683592 | doi = 10.1006/jmbi.1996.0367 }}</ref>
== Fugsi ==
[[File:Sarcomere.svg|thumb|370px|Model filamen geser kontraksi otot. (Titin berlabel di kanan atas.)]]
Titin adalah protein otot lurik yang melimpah. Fungsi utama Titin adalah menstabilkan filamen tebal, memusatkannya di antara filamen tipis, mencegah perenggangan sarkomer yang berlebihan, dan untuk melepaskan sarkomer seperti pegas setelah diregangkan.<ref>{{cite book | last1 = Saladin | first1 = Kenneth | name-list-format = vanc | title = Anatomy & Physiology | date = 2015 | publisher = McGraw Hill | page = 401 | edition = 7 | accessdate=14 November 2016 }}</ref> Daerah ''N-terminal'' ''Z-disc'' dan daerah ''C-terminal M-line'' masing-masing terikat ke ''Z-line'' dan ''M-line'' [[sarkomer]], sehingga satu molekul titin membentang setengah panjang sarkomer . Titin juga mengandung situs pengikat untuk protein yang berhubungan dengan otot sehingga berfungsi sebagai templat penempel untuk perakitan mesin kontraktil pada sel otot. Ini juga telah diidentifikasi sebagai protein struktural untuk [[kromosom]].<ref name="Machado_1998"/><ref name = "Machado_2000">{{cite journal | vauthors = Machado C, Andrew DJ | title = Titin as a chromosomal protein | journal = Advances in Experimental Medicine and Biology | volume = 481 | issue = | pages = 221–32; discussion 232–6 | year = 2000 | pmid = 10987075 | doi = 10.1007/978-1-4615-4267-4_13 }}</ref> Considerable variability exists in the I-band, the M-line and the Z-disc regions of titin. Variability in the I-band region contributes to the differences in elasticity of different titin isoforms and, therefore, to the differences in elasticity of different muscle types. Of the many titin variants identified, five are described with complete transcript information available.<ref name= "Entrez_ 7273"/><ref name="pmid2129545" />
Titin interacts with many [[sarcomere|sarcomeric]] proteins including:<ref name="pmid11717165"/>
* Z line region: [[TCAP (gene)|telethonin]] and [[ACTN1|alpha-actinin]]
* I band region: [[CAPN3|calpain-3]] and [[OBSCN|obscurin]]
* M line region: [[MYBPC3|myosin-binding protein C]], [[calmodulin 1]], [[CAPN3]], and [[TRIM63|MURF1]]
== Clinical relevance ==
[[Mutation]]s anywhere within the unusually long sequence of this gene can cause [[premature stop codon]]s or other defects. Titin mutations are associated with hereditary myopathy with early respiratory failure, early-onset myopathy with fatal cardiomyopathy, core myopathy with heart disease, centronuclear myopathy, Limb-girdle muscular dystrophy type 2J, [[family|familial]] [[dilated cardiomyopathy]] 9,<ref name="pmid11846417"/><ref name="pmid10051295">{{cite journal | vauthors = Siu BL, Niimura H, Osborne JA, Fatkin D, MacRae C, Solomon S, Benson DW, Seidman JG, Seidman CE | title = Familial dilated cardiomyopathy locus maps to chromosome 2q31 | journal = Circulation | volume = 99 | issue = 8 | pages = 1022–6 | date = March 1999 | pmid = 10051295 | doi = 10.1161/01.cir.99.8.1022 | url = http://circ.ahajournals.org/cgi/content/abstract/99/8/1022 }}</ref> hypertrophic cardiomyopathy and [[distal muscular dystrophy|tibial muscular dystrophy]].<ref name="pmid12145747">{{cite journal | vauthors = Hackman P, Vihola A, Haravuori H, Marchand S, Sarparanta J, De Seze J, Labeit S, Witt C, Peltonen L, Richard I, Udd B | title = Tibial muscular dystrophy is a titinopathy caused by mutations in TTN, the gene encoding the giant skeletal-muscle protein titin | journal = American Journal of Human Genetics | volume = 71 | issue = 3 | pages = 492–500 | date = September 2002 | pmid = 12145747 | pmc = 379188 | doi = 10.1086/342380 }}</ref> Further research also suggests that no genetically linked form of any [[wikt:Special:Search/dystrophy|dystrophy]] or [[myopathy]] can be safely excluded from being caused by a mutation on the TTN gene.<ref name="pmid15728284">{{cite journal | vauthors = Udd B, Vihola A, Sarparanta J, Richard I, Hackman P | title = Titinopathies and extension of the M-line mutation phenotype beyond distal myopathy and LGMD2J | journal = Neurology | volume = 64 | issue = 4 | pages = 636–42 | date = February 2005 | pmid = 15728284 | doi = 10.1212/01.WNL.0000151853.50144.82 }}</ref> Truncating mutations in dilated cardiomyopathy patients are most commonly found in the A region; although truncations in the upstream I region might be expected to prevent translation of the A region entirely, [[alternative splicing]] creates some transcripts that do not encounter the premature stop codon, ameliorating its effect.<ref name="pmid26315439">{{cite journal | vauthors = Hinson JT, Chopra A, Nafissi N, Polacheck WJ, Benson CC, Swist S, Gorham J, Yang L, Schafer S, Sheng CC, Haghighi A, Homsy J, Hubner N, Church G, Cook SA, Linke WA, Chen CS, Seidman JG, Seidman CE | title = HEART DISEASE. Titin mutations in iPS cells define sarcomere insufficiency as a cause of dilated cardiomyopathy | journal = Science | volume = 349 | issue = 6251 | pages = 982–6 | date = August 2015 | pmid = 26315439 | doi = 10.1126/science.aaa5458 | pmc=4618316}}</ref>
Autoantibodies to titin are produced in patients with the autoimmune disease [[scleroderma]].<ref name="Machado_1998">{{cite journal | vauthors = Machado C, Sunkel CE, Andrew DJ | title = Human autoantibodies reveal titin as a chromosomal protein | journal = The Journal of Cell Biology | volume = 141 | issue = 2 | pages = 321–33 | date = April 1998 | pmid = 9548712 | pmc = 2148454 | doi = 10.1083/jcb.141.2.321 }}</ref>
== Interactions ==
Titin has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[ANK1]],<ref name="pmid12444090">{{cite journal | vauthors = Kontrogianni-Konstantopoulos A, Bloch RJ | title = The hydrophilic domain of small ankyrin-1 interacts with the two N-terminal immunoglobulin domains of titin | journal = The Journal of Biological Chemistry | volume = 278 | issue = 6 | pages = 3985–91 | date = February 2003 | pmid = 12444090 | doi = 10.1074/jbc.M209012200 }}</ref>
* [[ANKRD1]],<ref name="pmid14583192">{{cite journal | vauthors = Miller MK, Bang ML, Witt CC, Labeit D, Trombitas C, Watanabe K, Granzier H, McElhinny AS, Gregorio CC, Labeit S | title = The muscle ankyrin repeat proteins: CARP, ankrd2/Arpp and DARP as a family of titin filament-based stress response molecules | journal = Journal of Molecular Biology | volume = 333 | issue = 5 | pages = 951–64 | date = November 2003 | pmid = 14583192 | doi = 10.1016/j.jmb.2003.09.012 }}</ref>
* [[ANKRD23]]<ref name=pmid14583192/>
* [[CAPN3]],<ref name="pmid9642272">{{cite journal | vauthors = Ono Y, Shimada H, Sorimachi H, Richard I, Saido TC, Beckmann JS, Ishiura S, Suzuki K | title = Functional defects of a muscle-specific calpain, p94, caused by mutations associated with limb-girdle muscular dystrophy type 2A | journal = The Journal of Biological Chemistry | volume = 273 | issue = 27 | pages = 17073–8 | date = July 1998 | pmid = 9642272 | doi = 10.1074/jbc.273.27.17073 }}</ref><ref name="pmid8537379">{{cite journal | vauthors = Sorimachi H, Kinbara K, Kimura S, Takahashi M, Ishiura S, Sasagawa N, Sorimachi N, Shimada H, Tagawa K, Maruyama K | title = Muscle-specific calpain, p94, responsible for limb girdle muscular dystrophy type 2A, associates with connectin through IS2, a p94-specific sequence | journal = The Journal of Biological Chemistry | volume = 270 | issue = 52 | pages = 31158–62 | date = December 1995 | pmid = 8537379 | doi = 10.1074/jbc.270.52.31158 }}</ref>
* [[FHL2]],<ref name="pmid12432079">{{cite journal | vauthors = Lange S, Auerbach D, McLoughlin P, Perriard E, Schäfer BW, Perriard JC, Ehler E | title = Subcellular targeting of metabolic enzymes to titin in heart muscle may be mediated by DRAL/FHL-2 | journal = Journal of Cell Science | volume = 115 | issue = Pt 24 | pages = 4925–36 | date = December 2002 | pmid = 12432079 | doi = 10.1242/jcs.00181 }}</ref>
* [[OBSCN]],<ref name="pmid11448995">{{cite journal | vauthors = Young P, Ehler E, Gautel M | title = Obscurin, a giant sarcomeric Rho guanine nucleotide exchange factor protein involved in sarcomere assembly | journal = The Journal of Cell Biology | volume = 154 | issue = 1 | pages = 123–36 | date = July 2001 | pmid = 11448995 | pmc = 2196875 | doi = 10.1083/jcb.200102110 }}</ref>
* [[Telethonin|TCAP]],<ref name="pmid9817758">{{cite journal | vauthors = Gregorio CC, Trombitás K, Centner T, Kolmerer B, Stier G, Kunke K, Suzuki K, Obermayr F, Herrmann B, Granzier H, Sorimachi H, Labeit S | title = The NH2 terminus of titin spans the Z-disc: its interaction with a novel 19-kD ligand (T-cap) is required for sarcomeric integrity | journal = The Journal of Cell Biology | volume = 143 | issue = 4 | pages = 1013–27 | date = November 1998 | pmid = 9817758 | pmc = 2132961 | doi = 10.1083/jcb.143.4.1013 }}</ref><ref name="pmid9804419">{{cite journal | vauthors = Mayans O, van der Ven PF, Wilm M, Mues A, Young P, Fürst DO, Wilmanns M, Gautel M | title = Structural basis for activation of the titin kinase domain during myofibrillogenesis | journal = Nature | volume = 395 | issue = 6705 | pages = 863–9 | date = October 1998 | pmid = 9804419 | doi = 10.1038/27603 }}</ref><ref name="pmid12446666">{{cite journal | vauthors = Zou P, Gautel M, Geerlof A, Wilmanns M, Koch MH, Svergun DI | title = Solution scattering suggests cross-linking function of telethonin in the complex with titin | journal = The Journal of Biological Chemistry | volume = 278 | issue = 4 | pages = 2636–44 | date = January 2003 | pmid = 12446666 | doi = 10.1074/jbc.M210217200 }}</ref><ref name="pmid9645487">{{cite journal | vauthors = Mues A, van der Ven PF, Young P, Fürst DO, Gautel M | title = Two immunoglobulin-like domains of the Z-disc portion of titin interact in a conformation-dependent way with telethonin | journal = FEBS Letters | volume = 428 | issue = 1–2 | pages = 111–4 | date = May 1998 | pmid = 9645487 | doi = 10.1016/S0014-5793(98)00501-8 }}</ref> and
* [[TRIM63]].<ref name="pmid11243782">{{cite journal | vauthors = Centner T, Yano J, Kimura E, McElhinny AS, Pelin K, Witt CC, Bang ML, Trombitas K, Granzier H, Gregorio CC, Sorimachi H, Labeit S | title = Identification of muscle specific ring finger proteins as potential regulators of the titin kinase domain | journal = Journal of Molecular Biology | volume = 306 | issue = 4 | pages = 717–26 | date = March 2001 | pmid = 11243782 | doi = 10.1006/jmbi.2001.4448 }}</ref>
{{Div col end}}
== Linguistic significance ==
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DO NOT ADD THE FULL CHEMICAL NAME OF TITIN TO THIS ARTICLE
This has been discussed extensively on this article's talk page and the consensus is to *not* provide the full chemical name of titin here. Please see the talk page for details.
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The name titin is derived from the Greek [[Titan (mythology)|Titan]] (a giant deity, anything of great size).<ref name="pmid291034"/>
As the largest known protein, titin also has the longest [[International Union of Pure and Applied Chemistry nomenclature|IUPAC name]] of a protein. The full chemical name of the human canonical form of titin, which starts ''[[Methionine|methionyl]]...'' and ends ''...[[isoleucine]]'', contains 189,819 letters and is sometimes stated to be the [[Longest word in English|longest word in the English language]], or [[longest words|any language]].<ref name="urlSarah McCulloch">{{cite web | url = http://www.sarahmcculloch.com/luminary-uprise/2009/longest-word/ | title = Longest word in English | vauthors = McCulloch S | work = Sarah McCulloch.com |archiveurl=https://web.archive.org/web/20100114221953/http://www.sarahmcculloch.com/luminaryuprise/longest-word.html |archivedate=2010-01-14 | accessdate = 2016-10-12 }}</ref> However, [[List of lexicographers|lexicographers]] regard generic names of [[chemical compound]]s as ''verbal [[Chemical formula|formulae]]'' rather than English words.<ref>{{cite web | author = Oxford Word and Language Service team | title = Ask the experts - What is the longest English word? | publisher = AskOxford.com / [[Oxford University Press]] | url = http://www.askoxford.com/asktheexperts/faq/aboutwords/longestword | accessdate = 2008-01-13 | archive-url = https://web.archive.org/web/20080913173417/http://www.askoxford.com/asktheexperts/faq/aboutwords/longestword | archive-date = 2008-09-13 | dead-url = yes}}</ref>
==See also==
*[[Longest word in English]]
== Referensi ==
{{Reflist|35em}}
== Bacaan lanjutan ==
{{refbegin|35em}}
* {{cite journal | vauthors = Tskhovrebova L, Trinick J | title = Titin: properties and family relationships | journal = Nature Reviews Molecular Cell Biology | volume = 4 | issue = 9 | pages = 679–89 | date = September 2003 | pmid = 14506471 | doi = 10.1038/nrm1198 }}
* {{cite journal | vauthors = Kinbara K, Sorimachi H, Ishiura S, Suzuki K | title = Skeletal muscle-specific calpain, p49: structure and physiological function | journal = Biochemical Pharmacology | volume = 56 | issue = 4 | pages = 415–20 | date = August 1998 | pmid = 9763216 | doi = 10.1016/S0006-2952(98)00095-1 }}
* {{cite journal | vauthors = Kolmerer B, Witt CC, Freiburg A, Millevoi S, Stier G, Sorimachi H, Pelin K, Carrier L, Schwartz K, Labeit D, Gregorio CC, Linke WA, Labeit S | title = The titin cDNA sequence and partial genomic sequences: insights into the molecular genetics, cell biology and physiology of the titin filament system | journal = Reviews of Physiology, Biochemistry and Pharmacology | volume = 138 | issue = | pages = 19–55 | year = 1999 | pmid = 10396137 | doi = 10.1007/BF02346659 }}
* {{cite journal | vauthors = Trinick J, Tskhovrebova L | title = Titin: a molecular control freak | journal = Trends in Cell Biology | volume = 9 | issue = 10 | pages = 377–80 | date = October 1999 | pmid = 10481174 | doi = 10.1016/S0962-8924(99)01641-4 }}
* {{cite journal | vauthors = Sorimachi H, Ono Y, Suzuki K | title = Skeletal muscle-specific calpain, p94, and connectin/titin: their physiological functions and relationship to limb-girdle muscular dystrophy type 2A | journal = Advances in Experimental Medicine and Biology | volume = 481 | issue = | pages = 383–95; discussion 395–7 | year = 2000 | pmid = 10987085 | doi = 10.1007/978-1-4615-4267-4_23 }}
* {{cite journal | vauthors = Tskhovrebova L, Trinick J | title = Role of titin in vertebrate striated muscle | journal = Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences | volume = 357 |issue = 1418 | pages = 199–206 | date = February 2002 | pmid = 11911777 | pmc = 1692937 | doi = 10.1098/rstb.2001.1028 }}
* {{cite journal | vauthors = Sela BA | title = [Titin: some aspects of the largest protein in the body] | journal = Harefuah | volume = 141 | issue = 7 | pages = 631–5, 665 | date = July 2002 | pmid = 12187564 | doi = }}
* {{cite journal | vauthors = Tskhovrebova L, Trinick J | title = Properties of titin immunoglobulin and fibronectin-3 domains | journal = The Journal of Biological Chemistry | volume = 279 | issue = 45 | pages = 46351–4 | date = November 2004 | pmid = 15322090 | doi = 10.1074/jbc.R400023200 }}
* {{cite journal | vauthors = Wu Y, Labeit S, Lewinter MM, Granzier H | title = Titin: an endosarcomeric protein that modulates myocardial stiffness in DCM | journal = Journal of Cardiac Failure | volume = 8 | issue = 6 Suppl | pages = S276-86 | date = December 2002 | pmid = 12555133 | doi = 10.1054/jcaf.2002.129278 }}
{{refend}}
== Pranala luar ==
{{Wiktionary pipe|Appendix:List of protologisms/Long words/Titin|the full chemical name of titin}}
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=hyper-card GeneReviews/NIH/NCBI/UW entry on Familial Hypertrophic Cardiomyopathy Overview]
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=udd GeneReviews/NCBI/NIH/UW entry on Udd Distal Myopathy, Tibial Muscular Dystrophy, Udd Myopathy]
* [https://www.ncbi.nlm.nih.gov/books/NBK83297/ GeneReviews/NIH/NCBI/UW entry on Salih Myopathy or Early-Onset Myopathy with Fatal Cardiomyopathy]
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[[Category:Protein struktural]]
[[Category:EC 2.7.11]]
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