Titin

Ttn
Dostupne strukture
PDB	Pretraga Human UniProta: A2ASS6 PDBe A2ASS6 RCSB
Spisak PDB ID kodova
	4UOW, 1BPV, 1G1C, 1NCT, 1NCU, 1TIT, 1TIU, 1TKI, 1TNM, 1TNN, 1WAA, 1YA5, 2A38, 2BK8, 2F8V, 2ILL, 2J8H, 2J8O, 2NZI, 2RQ8, 2WP3, 2WWK, 2WWM, 2Y9R, 3KNB, 3LCY, 3LPW, 3PUC, 3Q5O, 3QP3, 4C4K, 4JNW, 4O00, 4QEG, 5BS0
Identifikatori
Aliasi
Vanjski ID-jevi	HomoloGene: 130650 GeneCards: [1]
EC broj	2.7.11.1
Lokacija gena (čovjek)
Hrom.	Hromosom 2 (čovjek)
Kraj	76,982,547 bp
Ontologija gena
Molekularna funkcija	• aktivnost sa transferazom; • nucleotide binding; • calcium ion binding; • protein kinase activity; • actinin binding; • muscle alpha-actinin binding; • structural molecule activity conferring elasticity; • vezivanje iona metala; • telethonin binding; • protease binding; • protein self-association; • actin filament binding; • protein serine/threonine kinase activity; • kinase activity; • GO:0001948, GO:0016582 vezivanje za proteine; • vezivanje identičnih proteina; • vezivanje enzima; • protein tyrosine kinase activity; • structural constituent of muscle; • ATP binding; • protein kinase binding; • calmodulin binding; • structural constituent of cytoskeleton; • ankyrin binding;
Ćelijska komponenta	• citoplazma; • citosol; • I band; • striated muscle thin filament; • kondenzovani nuklearni hromosom; • extracellular region; • Z discdkac; • muscle myosin complex; • Egzosom; • jedro; • M band; • Sarkomera; • A band; • Miofibril;
Biološki proces	• sarcomerogenesis; • Mišićna kontrakcija; • mitotic chromosome condensation; • cardiac muscle contraction; • Fosforilacija; • cardiac muscle hypertrophy; • platelet degranulation; • cardiac muscle tissue morphogenesis; • skeletal muscle thin filament assembly; • detection of muscle stretch; • response to calcium ion; • cardiac myofibril assembly; • protein phosphorylation; • muscle filament sliding; • regulation of protein kinase activity; • GO:0048552 regulation of catalytic activity; • sarcomere organization; • skeletal muscle myosin thick filament assembly; • striated muscle contraction; • peptidyl-tyrosine phosphorylation; • GO:1901313 positive regulation of gene expression; • protein kinase A signaling; • positive regulation of protein secretion; • somitogenesis; • ventricular system development; • in utero embryonic development; • heart morphogenesis; • striated muscle cell development; • heart growth; • adult heart development; • forward locomotion; • heart development; • regulation of relaxation of cardiac muscle; • actin filament organization; • striated muscle myosin thick filament assembly;
	Izvori:Amigo / QuickGO
Ortolozi
	22138
	n/a
	ENSMUSG00000051747
	n/a
	Q8WZ42
	n/a
	NM_011652; NM_028004
	n/a
NP_001243779; NP_001254479; NP_003310; NP_596869; NP_596870;
	NP_597676; NP_597681; NP_035782; NP_082280; NP_001372637
	n/a
	Wikipodaci
Pogledaj/uredi – čovjek

Titin – poznat i kao konektin – je protein kojeg kod čovjeka kodira genTTN.^[2]^[3] Titin je džinovski protein, dužine veće od 1 µm,^[4] koja funkcionira kao molekularna opruga koja je odgovorna za pasivnu elastičnost mišića, uz to što održava molekule miozina na mjestu. Sastoji se od 244 pojedinačno presavijenih domena proteina povezanih nestrukturiranim peptidnim sekvencama.^[5] Ovi domeni se opružaju kada se protein proteže i ponovo se savijaju kada prestane napetost.^[6]

Titin je važan u kontrakciji prugastog mišićnog tkiva . Povezuje Z-linije sa M linijamq u sarkomerama. Protein doprinosi prenošenju sile na liniji Z i napetosti u mirovanju u regiji I pruge.^[7] Ograničava opseg pokreta sarkomera u napetosti, pridonoseći tako pasivnoj krutosti mišića. Varijacije u sekvenci titina između različitih vrsta mišića (npr. srčanog ili skeletnog) povezane su sa razlikama u mehaničkim svojstvima tih mišića.^[2]^[8]

Titin je treći najzastupljeniji protein u mišićima (nakon miozina i aktina), a odrasli čovjek sadrži otprilike 0,5 kg titina.^[9] Sa svojom dužinom od ~27.000 do ~35.000 aminokiselina (ovisno o izomorfnom spoju), titin je najveći poznati protein.^[10] Gen za titin sadrži najveći broj egzona (363) otkrivenih u bilo kojem jedinom genu,^[11] kao i najduži pojedinačni egzon (17.106 bp).

Izoforme

Brojne izoforme titina formiraju se u različitim prugastim mišićnim tkivima kao rezultat alternativnog spajanja u rasponu od ~ 27.000 do ~ 36.000 aminokiselinskih ostataka u dužini. Izuzetak je mala srčana izoforma novex-3, ćija je dužina samo 5.604 aminokiselina. Slijedeća tabela navodi poznate titinske izoforme:

Izoforma	Alias/Opise	Dužina	Molekulska težina
Q8WZ42-1	"Kanonska" sekvenca	34.350	3,816.030
Q8WZ42-2		34.258	3,805.708
Q8WZ42-3	Mala srčana N2-B	26.926	2,992.939
Q8WZ42-4	M. soleus	33.445	3,716.027
Q8WZ42-5		32.900	3,653.085
Q8WZ42-6	Mala srčana novex-3	5.604	631.567
Q8WZ42-7	Srčana novex-2	33.615	3,734.648
Q8WZ42-8	Srčana 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

Struktura

Titin je najveći poznati protein; njegova varijanta kod čovjeka sastoji se od 34.350 aminokiselina , pri čemu je molekularna težina zrele "kanonske" izoforme proteina približno 3.816.188,13 Da. Njegov mišji homolog je još veći i sadrži 35.213 aminokiselina sa molekulskom masom od 3.906.487,6 Da.^[12] Izoelektrična tačka mi je na 6,01.^[13] Empireijska hemijska formula proteina je: C_169,719H_270,466N_45,688O_52,238S₉₁₁.^[13]

Ima teorijski indeks nestabilnosti (II) od 42,41, klasificirajući protein kao nestabilan.^[13] Proteinski poluživot in vivo, prije nego što se polovina količine proteina u ćeliji, razgradi nakon njegove sinteze, iznosi približno 30 sati (u sisarskim retikulocitima).^[14]

Titinski protein smješten je između miozinskog debelog vlakna i Z diska.^[16] Titin se sastoji uglavnom od linearnog niza od dvije vrste modula, koji se također nazivaju domen proteina (ukupno 244 kopije): tip I domen fibronektina tipa III (132 kopije) i tip II domen imunoglobulina (112 kopija).^[5]^[9] Međutim, tačan broj ovih domena razlikuje se kod različitih vrsta. Ovaj linearni niz je dalje organiziran u dvije regije:

N-terminalna I-pruga: djeluje kao elastični dio molekule i sastoji se uglavnom od modula tipa II. Preciznije, pruga I sadrži dve regije imunglobulinskih domena tandemskog tipa II na obje strane PEVK regije koja je bogata prolinom (P), glutamatom (E), valinom (V) i lizinom .
C-kraj A-pruga: smatra se da djeluje kao ravnalo proteina i sastoji se od naizmjeničnih modula tipa I (Fn3) i II (Ig) sa superponovljenim segmentima. Pokazalo se da se oni poklapaju sa 43 nm aksijalnim ponavljanjima debelih filamenata miozina s imunoglobulinskim domenima koji se odnose na miozinske krune.^[17]

Područje C-kraja sadrži i domen serin kinaza,^[18] što je prije svega poznato po prilagođavanju mišića mehaničkom naprezanju.^[19]„Osetljiv je na rastezanje“ i pomaže u popravljanju prekomernog istezanja sarkomera.^[20] N-kraj (kraj Z-diska) sadrži "Z ponavljanje" koje prepoznaje Aktinin alfa 2.^[21]

Proteinski domeni titinske A-pruge. Bijele pruge su domeni Fn3, crvene domeni Ig, žute su Fn3 domeni sa -AVNKYG- sekvencom, a crni je domen protein kinaze .^[22]

Elastičnost PEVK regije ima i entropijski i entalpijski doprinos, a karakteriziraju je polimerna perzistentna dužina i modul rastezanja.^[23] Pri malom do umjerenom produženju PEVK-a, elastičnost se može predstaviti standardnim modelom crvolikog lanca (WLC), modelom entropijske elastičnosti. Pri visokim produženjima PEVK, istezanje se može modelirati s modificiranim WLC, koji uključuje entalpijskiu elastičnost. Razlika između elastičnosti niskog i visokog rastezanja je zbog elektrostatskog ukrućenja i hidrofobnih efekata.

Funkcija

Model klizećih filamenata u mišićnoj kontrakciji.
(Titin je označen gore desno.)

Titin je veliki i česti protein prugastih mišića. Njegove primarne funkcije su stabiliziranje debelih niti, centriranje između tankih niti, sprečavanje prekomernog istezanja sarkomera i vraćanje sarkomera poput opruge nakon što se istežu.^[24] Regija Z-diska N-kraja i M-linija C-kraja vežu se na Z-liniju i M-liniju sarkomere, tako da jedan molekul titina proteže polovinu dužine sarkomera . Titin također sadrži vezna mesta za proteine povezane sa mišićima pa služi kao adhezivni obrazac za sklapanje kontraktilnih mašinerija u mišićnim ćelijama. Također je identificiran kao strukturni protein hromosoma.^[25] Značajna varijabilnost postoji u I-pugama, M-liniji i Z-diskovima u regionima titina. Promjenjivost u regiji I-pruga doprinosi razlikama u elastičnosti različitih titinskih izoformi i, prema tome, razlici elastičnosti različitih tipova mišića. Od mnogih identificiranih inačica titina, pet je opisano sa dostupnim cjelovitim informacijama o transkriptu.^[2]^[3]

Titin interaktivno djeluje sa mnogim sarkomernim proteinima, uključujući:^[11]

Regiju Z linije: teletonin i alfa-aktinin
Regija pruge I: kalpain-3 i opskurin
Regija M linije: miozin-vežući protein C, kalmodulin 1, CAPN3 i MURF1

Reference

^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b ^c "Entrez Gene: TTN titin".
^ ^a ^b Labeit S, Barlow DP, Gautel M, Gibson T, Holt J, Hsieh CL, Francke U, Leonard K, Wardale J, Whiting A (maj 1990). "A regular pattern of two types of 100-residue motif in the sequence of titin". Nature. 345 (6272): 273–6. doi:10.1038/345273a0. PMID 2129545.
^ Eric H. Lee. "The Chain-like Elasticity of Titin". Theoretical and Computational Biophysics Group, University of Illinois. Pristupljeno 25. 9. 2014.
^ ^a ^b Labeit S, Kolmerer B (oktobar 1995). "Titins: giant proteins in charge of muscle ultrastructure and elasticity". Science. 270 (5234): 293–6. doi:10.1126/science.270.5234.293. PMID 7569978.
^ Minajeva A, Kulke M, Fernandez JM, Linke WA (mart 2001). "Unfolding of titin domains explains the viscoelastic behavior of skeletal myofibrils". Biophysical Journal. 80 (3): 1442–51. doi:10.1016/S0006-3495(01)76116-4. PMC 1301335. PMID 11222304.
^ 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 (februar 2002). "Titin mutations as the molecular basis for dilated cardiomyopathy". Biochemical and Biophysical Research Communications. 291 (2): 385–93. doi:10.1006/bbrc.2002.6448. PMID 11846417.
^ OMIM: 188840
^ ^a ^b Labeit S, Kolmerer B, Linke WA (februar 1997). "The giant protein titin. Emerging roles in physiology and pathophysiology". Circulation Research. 80 (2): 290–4. doi:10.1161/01.RES.80.2.290. PMID 9012751.
^ Opitz CA, Kulke M, Leake MC, Neagoe C, Hinssen H, Hajjar RJ, Linke WA (oktobar 2003). "Damped elastic recoil of the titin spring in myofibrils of human myocardium". Proceedings of the National Academy of Sciences of the United States of America. 100 (22): 12688–93. doi:10.1073/pnas.2133733100. PMC 240679. PMID 14563922.
^ ^a ^b Bang ML, Centner T, Fornoff F, Geach AJ, Gotthardt M, McNabb M, Witt CC, Labeit D, Gregorio CC, Granzier H, Labeit S (novembar 2001). "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". Circulation Research. 89 (11): 1065–72. doi:10.1161/hh2301.100981. PMID 11717165.
^ "ProtParam for mouse titin". ExPASy Proteomics Server. Swiss Institute of Bioinformatics. Pristupljeno 6. 5. 2010.
^ ^a ^b ^c "ProtParam for human titin". ExPASy Proteomics Server. Swiss Institute of Bioinformatics. Pristupljeno 25. 7. 2011.
^ "Titin - Homo sapiens (Human)". Universal Protein Resource. UniProt Consortium. 5. 10. 2010. Pristupljeno 15. 10. 2010.
^ Giganti D, Yan K, Badilla CL, Fernandez JM, Alegre-Cebollada J (januar 2018). "Disulfide isomerization reactions in titin immunoglobulin domains enable a mode of protein elasticity". Nature Communications. 9 (1): 185. doi:10.1038/s41467-017-02528-7. PMC 5766482. PMID 29330363.
^ Wang K, McCarter R, Wright J, Beverly J, Ramirez-Mitchell R (august 1991). "Regulation of skeletal muscle stiffness and elasticity by titin isoforms: a test of the segmental extension model of resting tension". Proceedings of the National Academy of Sciences of the United States of America. 88 (16): 7101–5. doi:10.1073/pnas.88.16.7101. PMC 52241. PMID 1714586.
^ Bennett PM, Gautel M (juni 1996). "Titin domain patterns correlate with the axial disposition of myosin at the end of the thick filament". Journal of Molecular Biology. 259 (5): 896–903. doi:10.1006/jmbi.1996.0367. PMID 8683592.
^ Higgins DG, Labeit S, Gautel M, Gibson TJ (april 1994). "The evolution of titin and related giant muscle proteins". Journal of Molecular Evolution. 38 (4): 395–404. doi:10.1007/BF00163156. PMID 8007007.
^ Puchner EM, Alexandrovich A, Kho AL, Hensen U, Schäfer LV, Brandmeier B, Gräter F, Grubmüller H, Gaub HE, Gautel M (septembar 2008). "Mechanoenzymatics of titin kinase". Proceedings of the National Academy of Sciences of the United States of America. 105 (36): 13385–90. doi:10.1073/pnas.0805034105. PMC 2527993. PMID 18765796.
^ Myhre JL, Pilgrim D (septembar 2014). "A Titan but not necessarily a ruler: assessing the role of titin during thick filament patterning and assembly". Anatomical Record. 297 (9): 1604–14. doi:10.1002/ar.22987. PMID 25125174.
^ "Titin, Z repeat (IPR015129) < InterPro < EMBL-EBI". Pristupljeno 13. 3. 2019.
^ Mikelsaar AV, Sünter A, Mikelsaar R, Toomik P, Kõiveer A, Mikelsaar I, Juronen E (septembar 2012). "Epitope of titin A-band-specific monoclonal antibody Tit1 5 H1.1 is highly conserved in several Fn3 domains of the titin molecule. Centriole staining in human, mouse and zebrafish cells". Cell Division. 7 (1): 21. doi:10.1186/1747-1028-7-21. PMC 3541999. PMID 22985877.
^ Linke WA, Ivemeyer M, Mundel P, Stockmeier MR, Kolmerer B (juli 1998). "Nature of PEVK-titin elasticity in skeletal muscle". Proceedings of the National Academy of Sciences of the United States of America. 95 (14): 8052–7. doi:10.1073/pnas.95.14.8052. PMC 20927. PMID 9653138.
^ Saladin, Kenneth (2015). Anatomy & Physiology (7th izd.). McGraw Hill. str. 401. ISBN 978-0-07-340371-7. Nepoznati parametar |name-list-format= zanemaren (prijedlog zamjene: |name-list-style=) (pomoć)
^ Machado C, Andrew DJ (2000). Titin as a chromosomal protein. Advances in Experimental Medicine and Biology. 481. str. 221–32, discussion 232–6. doi:10.1007/978-1-4615-4267-4_13. ISBN 978-1-4613-6916-5. PMID 10987075.

Dopunska literatura

Tskhovrebova L, Trinick J (septembar 2003). "Titin: properties and family relationships". Nature Reviews Molecular Cell Biology. 4 (9): 679–89. doi:10.1038/nrm1198. PMID 14506471.
Kinbara K, Sorimachi H, Ishiura S, Suzuki K (august 1998). "Skeletal muscle-specific calpain, p49: structure and physiological function". Biochemical Pharmacology. 56 (4): 415–20. doi:10.1016/S0006-2952(98)00095-1. PMID 9763216.
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 (1999). "The titin cDNA sequence and partial genomic sequences: insights into the molecular genetics, cell biology and physiology of the titin filament system". Reviews of Physiology, Biochemistry and Pharmacology. 138: 19–55. doi:10.1007/BF02346659. PMID 10396137.
Trinick J, Tskhovrebova L (oktobar 1999). "Titin: a molecular control freak". Trends in Cell Biology. 9 (10): 377–80. doi:10.1016/S0962-8924(99)01641-4. PMID 10481174.
Sorimachi H, Ono Y, Suzuki K (2000). Skeletal muscle-specific calpain, p94, and connectin/titin: their physiological functions and relationship to limb-girdle muscular dystrophy type 2A. Advances in Experimental Medicine and Biology. 481. str. 383–95, discussion 395–7. doi:10.1007/978-1-4615-4267-4_23. ISBN 978-1-4613-6916-5. PMID 10987085.
Tskhovrebova L, Trinick J (februar 2002). "Role of titin in vertebrate striated muscle". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 357 (1418): 199–206. doi:10.1098/rstb.2001.1028. PMC 1692937. PMID 11911777.
Sela BA (juli 2002). "[Titin: some aspects of the largest protein in the body]". Harefuah. 141 (7): 631–5, 665. PMID 12187564.
Tskhovrebova L, Trinick J (novembar 2004). "Properties of titin immunoglobulin and fibronectin-3 domains". The Journal of Biological Chemistry. 279 (45): 46351–4. doi:10.1074/jbc.R400023200. PMID 15322090.
Wu Y, Labeit S, Lewinter MM, Granzier H (decembar 2002). "Titin: an endosarcomeric protein that modulates myocardial stiffness in DCM". Journal of Cardiac Failure. 8 (6 Suppl): S276–86. doi:10.1054/jcaf.2002.129278. PMID 12555133.

Vanjski linkovi

[1] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[Entrez_7273-2] "Entrez Gene: TTN titin".

[Labeit_1990-3] Labeit S, Barlow DP, Gautel M, Gibson T, Holt J, Hsieh CL, Francke U, Leonard K, Wardale J, Whiting A (maj 1990). "A regular pattern of two types of 100-residue motif in the sequence of titin". Nature. 345 (6272): 273–6. doi:10.1038/345273a0. PMID 2129545.

[4] Eric H. Lee. "The Chain-like Elasticity of Titin". Theoretical and Computational Biophysics Group, University of Illinois. Pristupljeno 25. 9. 2014.

[Labeit_1995-5] Labeit S, Kolmerer B (oktobar 1995). "Titins: giant proteins in charge of muscle ultrastructure and elasticity". Science. 270 (5234): 293–6. doi:10.1126/science.270.5234.293. PMID 7569978.

[Minajeva_2001-6] Minajeva A, Kulke M, Fernandez JM, Linke WA (mart 2001). "Unfolding of titin domains explains the viscoelastic behavior of skeletal myofibrils". Biophysical Journal. 80 (3): 1442–51. doi:10.1016/S0006-3495(01)76116-4. PMC 1301335. PMID 11222304.

[Itoh-Satoh_2002-7] 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 (februar 2002). "Titin mutations as the molecular basis for dilated cardiomyopathy". Biochemical and Biophysical Research Communications. 291 (2): 385–93. doi:10.1006/bbrc.2002.6448. PMID 11846417.

[8] OMIM: 188840

[Labeit_1997-9] Labeit S, Kolmerer B, Linke WA (februar 1997). "The giant protein titin. Emerging roles in physiology and pathophysiology". Circulation Research. 80 (2): 290–4. doi:10.1161/01.RES.80.2.290. PMID 9012751.

[Opitz_2003-10] Opitz CA, Kulke M, Leake MC, Neagoe C, Hinssen H, Hajjar RJ, Linke WA (oktobar 2003). "Damped elastic recoil of the titin spring in myofibrils of human myocardium". Proceedings of the National Academy of Sciences of the United States of America. 100 (22): 12688–93. doi:10.1073/pnas.2133733100. PMC 240679. PMID 14563922.

[Bang_2001-11] Bang ML, Centner T, Fornoff F, Geach AJ, Gotthardt M, McNabb M, Witt CC, Labeit D, Gregorio CC, Granzier H, Labeit S (novembar 2001). "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". Circulation Research. 89 (11): 1065–72. doi:10.1161/hh2301.100981. PMID 11717165.

[urlExPASy_mouse-12] "ProtParam for mouse titin". ExPASy Proteomics Server. Swiss Institute of Bioinformatics. Pristupljeno 6. 5. 2010.

[urlExPASy_human-13] "ProtParam for human titin". ExPASy Proteomics Server. Swiss Institute of Bioinformatics. Pristupljeno 25. 7. 2011.

[url_UniProt_Q8WZ42)-14] "Titin - Homo sapiens (Human)". Universal Protein Resource. UniProt Consortium. 5. 10. 2010. Pristupljeno 15. 10. 2010.

[15] Giganti D, Yan K, Badilla CL, Fernandez JM, Alegre-Cebollada J (januar 2018). "Disulfide isomerization reactions in titin immunoglobulin domains enable a mode of protein elasticity". Nature Communications. 9 (1): 185. doi:10.1038/s41467-017-02528-7. PMC 5766482. PMID 29330363.

[Wang_1991-16] Wang K, McCarter R, Wright J, Beverly J, Ramirez-Mitchell R (august 1991). "Regulation of skeletal muscle stiffness and elasticity by titin isoforms: a test of the segmental extension model of resting tension". Proceedings of the National Academy of Sciences of the United States of America. 88 (16): 7101–5. doi:10.1073/pnas.88.16.7101. PMC 52241. PMID 1714586.

[Bennett_1996-17] Bennett PM, Gautel M (juni 1996). "Titin domain patterns correlate with the axial disposition of myosin at the end of the thick filament". Journal of Molecular Biology. 259 (5): 896–903. doi:10.1006/jmbi.1996.0367. PMID 8683592.

[Higgins_1994-18] Higgins DG, Labeit S, Gautel M, Gibson TJ (april 1994). "The evolution of titin and related giant muscle proteins". Journal of Molecular Evolution. 38 (4): 395–404. doi:10.1007/BF00163156. PMID 8007007.

[Puchner_2008-19] Puchner EM, Alexandrovich A, Kho AL, Hensen U, Schäfer LV, Brandmeier B, Gräter F, Grubmüller H, Gaub HE, Gautel M (septembar 2008). "Mechanoenzymatics of titin kinase". Proceedings of the National Academy of Sciences of the United States of America. 105 (36): 13385–90. doi:10.1073/pnas.0805034105. PMC 2527993. PMID 18765796.

[Myhre_2014-20] Myhre JL, Pilgrim D (septembar 2014). "A Titan but not necessarily a ruler: assessing the role of titin during thick filament patterning and assembly". Anatomical Record. 297 (9): 1604–14. doi:10.1002/ar.22987. PMID 25125174.

[21] "Titin, Z repeat (IPR015129) < InterPro < EMBL-EBI". Pristupljeno 13. 3. 2019.

[22] Mikelsaar AV, Sünter A, Mikelsaar R, Toomik P, Kõiveer A, Mikelsaar I, Juronen E (septembar 2012). "Epitope of titin A-band-specific monoclonal antibody Tit1 5 H1.1 is highly conserved in several Fn3 domains of the titin molecule. Centriole staining in human, mouse and zebrafish cells". Cell Division. 7 (1): 21. doi:10.1186/1747-1028-7-21. PMC 3541999. PMID 22985877.

[23] Linke WA, Ivemeyer M, Mundel P, Stockmeier MR, Kolmerer B (juli 1998). "Nature of PEVK-titin elasticity in skeletal muscle". Proceedings of the National Academy of Sciences of the United States of America. 95 (14): 8052–7. doi:10.1073/pnas.95.14.8052. PMC 20927. PMID 9653138.

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p r u Enzimi
Teme	Aktivno mjesto Alosterna regulacija Difuzijski limitirani enzim EC broj Enzimska kataliza Inhibicija enzimskih reakcija Kinetika enzima Koenzim Kooperativnost Lineweaver–Burkov dijagram Michaelis–Mentenova kinetika Mjesto vezanja Spisak enzima
Tipovi	EC1 Oksidoreduktaze/spisak EC2 Transferaze/spisak EC3 Hidrolaze/spisak EC4 Lijaze/spisak EC5 Izomeraze/spisak EC6 Ligaze/spisak