# Triadin > Mediated Wiki article. Canonical URL: https://mediated.wiki/source/Triadin > Markdown URL: https://mediated.wiki/source/Triadin.md > Source: https://en.wikipedia.org/wiki/Triadin > Source revision: 1300697332 > License: Creative Commons Attribution-ShareAlike 4.0 International (https://creativecommons.org/licenses/by-sa/4.0/) {{Short description|Protein-coding gene in humans}} {{Infobox gene}} '''Triadin''', also known as '''TRDN''', is a human [gene](/source/gene){{cite web | title = Entrez Gene: TRDN triadin| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=10345| access-date = }} associated with the release of calcium ions from the [sarcoplasmic reticulum](/source/sarcoplasmic_reticulum) triggering muscular contraction through [calcium-induced calcium release](/source/calcium-induced_calcium_release). Triadin is a multiprotein family, arising from different processing of the TRDN gene on [chromosome 6](/source/chromosome_6).{{cite journal |last1=Thevenon |first1=D. |last2=Smida-Rezgui |first2=S. |last3=Chevessier |first3=F. |last4=Groh |first4=S.|last5=Henry-Berger |first5=J. |last6=Romero |first6=N. B. |last7=Villaz |first7=M. |last8=De Waard |first8=M |last9=Marty |first9=I |year=2003 |title=Human skeletal muscle triadin: gene organization and cloning of the major isoform, Trisk 51 |journal=Biochem. Biophys. Res. Commun. |volume=303 |pages=669–675 |pmid=12659871 |issue=12 |doi=10.1016/s0006-291x(03)00406-6}} It is a transmembrane protein on the sarcoplasmic reticulum due to a well defined hydrophobic section{{cite journal |last1=Kobayashi |first1=Y. M. |first2=L. R. |last2=Jones |year=1999 |title=Identification of triadin 1 as the predominant triadin isoform expressed in mammalian myocardium |journal=J. Biol. Chem. |volume=274 |pages=28660–28668 |pmid=10497235 |issue=40 |doi=10.1074/jbc.274.40.28660|doi-access=free }}{{cite journal |last1=Jones |first1=L. R. |first2=L. |last2=Zhang |first3=K. |last3=Sanborn |first4=A. O. |last4=Jorgensen |first5=J. |last5=Kelley. |year=1995 |title=Purification, primary structure, and immunological characterization of the 26-kDa calsequestrin binding protein (junctin) from cardiac junctional sarcoplasmic reticulum |journal=J. Biol. Chem. |volume=270 |pages=30787–30796 |pmid=8530521 |issue=51 |doi=10.1074/jbc.270.51.30787|doi-access=free }} and it forms a quaternary complex with the cardiac [ryanodine receptor](/source/ryanodine_receptor) ([RYR2](/source/RYR2)), calsequestrin ([CASQ2](/source/CASQ2)) and [junctin](/source/junctin) proteins.{{cite journal |last1=Zhang |first1=L. |first2=J. |last2=Kelley |first3=G. |last3=Schmeisser |first4=Y. M. |last4=Kobayashi |first5=L. R. |last5=Jones |year=1997 |title=Complex formation between junctin, triadin, calsequestrin, and the ryanodine receptor. Proteins of the cardiac junctional sarcoplasmic reticulum membrane. |journal=J. Biol. Chem. |volume=272 |issue=37 |pages=23389–23397 |pmid=9287354 |doi=10.1074/jbc.272.37.23389|doi-access=free }}{{cite journal |last1=Kobayashi |first1=Y. M. |first2=B. A. |last2=Alseikhan |first3=L. R. |last3=Jones |year=2000 |title=Localization and characterization of the calsequestrin-binding domain of triadin 1. Evidence for a charged beta-strand in mediating the protein-protein interaction |journal=J. Biol. Chem. |volume=275 |issue=23 |pages=17639–17646 |pmid=10748065 |doi=10.1074/jbc.M002091200|doi-access=free }} The [luminal](/source/lumen_(anatomy)) (inner compartment of the sarcoplasmic reticulum) section of Triadin has areas of highly charged amino acid residues that act as luminal Ca2+ receptors. Triadin is also able to sense luminal Ca2+ concentrations by mediating interactions between RYR2 and CASQ2. Triadin has several [different forms](/source/isoform); Trisk 95 and Trisk 51, which are expressed in skeletal muscle, and Trisk 32 (CT1), which is mainly expressed in cardiac muscle.{{cite journal | last1 = Marty | first1 = I. | last2 = Fauré | first2 = J. | last3 = Fourest-Lieuvin | first3 = A. | last4 = Vassilopoulos | first4 = S. | last5 = Oddoux | first5 = S. | last6 = Brocard | first6 = J. | year = 2009 | title = Triadin: what possible function 20 years later? | journal = J. Physiol. | volume = 587 | issue = 13| pages = 3117–3121 | doi=10.1113/jphysiol.2009.171892| pmid = 19403623 | pmc = 2727022 }} ==Interactions== TRDN has been shown to [interact](/source/Protein-protein_interaction) with [RYR1](/source/RYR1).{{cite journal |last=Lee |first=Jae Man |author2=Rho Seong-Hwan |author3=Shin Dong Wook |author4=Cho Chunghee |author5=Park Woo Jin |author6=Eom Soo Hyun |author7=Ma Jianjie |author8=Kim Do Han |date=Feb 2004 |title=Negatively charged amino acids within the intraluminal loop of ryanodine receptor are involved in the interaction with triadin |journal=J. Biol. Chem. |volume=279 |issue=8 |pages=6994–7000 |location = United States| issn = 0021-9258| pmid = 14638677 |doi = 10.1074/jbc.M312446200 |doi-access=free }}{{cite journal |last=Caswell |first=A H |author2=Motoike H K |author3=Fan H |author4=Brandt N R |date=Jan 1999 |title=Location of ryanodine receptor binding site on skeletal muscle triadin |journal=Biochemistry |volume=38 |issue=1 |pages=90–7 |location = United States| issn = 0006-2960| pmid = 9890886 |doi = 10.1021/bi981306+}}{{cite journal |last=Guo |first=W |author2=Campbell K P |date=Apr 1995 |title=Association of triadin with the ryanodine receptor and calsequestrin in the lumen of the sarcoplasmic reticulum |journal=J. Biol. Chem. |volume=270 |issue=16 |pages=9027–30 |location = United States |issn = 0021-9258| pmid = 7721813 |doi=10.1074/jbc.270.16.9027 |doi-access=free }}{{cite journal |last=Groh |first=S |author2=Marty I |author3=Ottolia M |author4=Prestipino G |author5=Chapel A |author6=Villaz M |author7=Ronjat M |date=Apr 1999 |title=Functional interaction of the cytoplasmic domain of triadin with the skeletal ryanodine receptor |journal=J. Biol. Chem. |volume=274 |issue=18 |pages=12278–83 |location = United States |issn = 0021-9258| pmid = 10212196 |doi=10.1074/jbc.274.18.12278 |doi-access=free }} Triadin is required to physically link the [RYR2](/source/RYR2) and CASQ2 proteins, so that RYR2 channel activity can be regulated by CASQ2.{{cite journal |last1=Gyorke |first1=I. |last2=Hester |first2=N. |last3=Jones |first3=L. R. |last4=Gyorke |first4=S. |year=2004 |title=The Role of Calsequestrin, Triadin, and Junctin in Conferring Cardiac Ryanodine Receptor Responsiveness to Luminal Calcium |journal=Biophysical Journal |volume=86 |issue=4 |pages=2121–2128 |pmid=15041652 |doi=10.1016/S0006-3495(04)74271-X |pmc=1304063|bibcode=2004BpJ....86.2121G }} The linkage of RYR2 with CASQ2 occurs via highly charged luminal sections of Triadin that are characterized as alternating positively and negatively charged amino acids, known as the KEKE motif.{{cite journal |last1=Shin |first1=D. W. |first2=J. |last2=Ma |first3=D. H. |last3=Kim |year=2000 |title=The asp-rich region at the carboxyl-terminus of calsequestrin binds to Ca2+ and interacts with triadin |journal=FEBS Lett. |volume=486 |issue=2 |pages=178–182 |pmid=11113462 |doi=10.1016/S0014-5793(00)02246-8|s2cid=3135618 |doi-access= }} [Luminal](/source/Lumen_(anatomy)) concentration levels of Ca2+ are sensed by CSQ, and this information is transmitted to [RyR](/source/ryanodine) via Triadin. At low luminal Ca2+ concentrations, Triadin is bound to both RYR2 and CASQ2, so that CSQ prevents RYR2 from opening. At high luminal Ca2+ concentrations, Ca2+ binding sites on CASQ2 become occupied with Ca2+, leading to a weakened interaction between CASQ2 and Triadin. This removes CASQ2's ability to have an inhibitory effect on the RYR2 channel activity. As more Ca2+ binding sites on CASQ2 become occupied, there is an increasing probability of the RYR2 channel being able to open. Eventually, CASQ2 completely dissociates from Triadin and the RYR2 channel becomes completely uninhibited, although Triadin remains bound to RYR2 at all luminal concentrations of Ca2+. ==Relation to catecholaminergic polymorphic ventricular tachycardia== Most mutations that result in [CPVT](/source/Catecholaminergic_polymorphic_ventricular_tachycardia) are found in RYR2 or CASQ2 genes, however a third of CPVT patients have no mutations in either of these proteins, making a mutation in Triadin the most likely cause{{cite journal |last=Roux-Buisson |first=N. |author2=Cacheux, M. |author3=Fourest-Lieuvin, A. |author4=Fauconnier, J. |author5=Brocard, J. |author6=Denjoy, I. |author7=Durand, P. |author8=Guicheney, P. |author9=Kyndt, F. |author10=Leenhardt, A. |author11=Le Marec, H. |author12=Lucet, V. |author13=Mabo, P. |author14=Probst, V. |author15=Monnier, N. |author16=Ray, P. F. |author17=Santoni, E. |author18=Tremeaux, P. |author19=Lacampagne, A. |author20=Faure, J. |author21=Lunardi, J. |author22=Marty, I. |year=2012 |title=Absence of triadin, a protein of the calcium release complex, is responsible for cardiac arrhythmia with sudden death in human |journal=Human Molecular Genetics |volume=21 |issue=12 |pages=2759–2767 |pmid=22422768 |doi=10.1093/hmg/dds104 |pmc=3363337|url=http://www.hal.inserm.fr/inserm-00763211/document }} Because Triadin is necessary in the regulation of Ca2+ release by the RyR channel during cardiac contraction, a mutation that prevents Triadin from being formed will make CASQ2 unable to inhibit the RYR2 channel activity, allowing Ca2+ leaks and the development of [CPVT](/source/CPVT). A deletion of [amino acids](/source/amino_acids) in the TRDN gene can result in an early [stop codon](/source/stop_codon). A premature [stop codon](/source/stop_codon) can either prevent the [gene](/source/gene) from being translated into the Triadin protein, or can result in a shortened, nonfunctional Triadin protein. A replacement of the amino acid [Arginine](/source/Arginine) for the amino acid [Threonine](/source/Threonine) at position 59 of the TRDN gene (pT59R) causes instability of Triadin, leading to degradation of the protein. Any of these naturally occurring mutations result in an absence of functional Triadin protein, resulting in CPVT in patients. ==References== {{reflist}} ==Further reading== {{refbegin | 2}} *{{cite journal | author=Taske NL |title=Molecular cloning of the cDNA encoding human skeletal muscle triadin and its localisation to chromosome 6q22-6q23 |journal=Eur. J. Biochem. |volume=233 |issue= 1 |pages= 258–65 |year= 1995 |pmid= 7588753 |doi=10.1111/j.1432-1033.1995.258_1.x |name-list-style=vanc| author2=Eyre HJ | author3=O'Brien RO | display-authors=3 | last4=Sutherland | first4=Grant R. | last5=Denborough | first5=Michael A. | last6=Foster | first6=Paul S. }} *{{cite journal |vauthors=Guo W, Campbell KP |title=Association of triadin with the ryanodine receptor and calsequestrin in the lumen of the sarcoplasmic reticulum |journal=J. Biol. Chem. |volume=270 |issue= 16 |pages= 9027–30 |year= 1995 |pmid= 7721813 |doi=10.1074/jbc.270.16.9027 |doi-access=free }} *{{cite journal | author=Zhang L |title=Complex formation between junctin, triadin, calsequestrin, and the ryanodine receptor. Proteins of the cardiac junctional sarcoplasmic reticulum membrane |journal=J. Biol. Chem. |volume=272 |issue= 37 |pages= 23389–97 |year= 1997 |pmid= 9287354 |doi=10.1074/jbc.272.37.23389 |name-list-style=vanc| author2=Kelley J | author3=Schmeisser G | display-authors=3 | last4=Kobayashi | first4=YM | last5=Jones | first5=LR |doi-access=free }} *{{cite journal |vauthors=Caswell AH, Motoike HK, Fan H, Brandt NR |title=Location of ryanodine receptor binding site on skeletal muscle triadin |journal=Biochemistry |volume=38 |issue= 1 |pages= 90–7 |year= 1999 |pmid= 9890886 |doi= 10.1021/bi981306+}} *{{cite journal | author=Groh S |title=Functional interaction of the cytoplasmic domain of triadin with the skeletal ryanodine receptor |journal=J. Biol. Chem. |volume=274 |issue= 18 |pages= 12278–83 |year= 1999 |pmid= 10212196 |doi=10.1074/jbc.274.18.12278 |name-list-style=vanc| author2=Marty I | author3=Ottolia M | display-authors=3 | last4=Prestipino | first4=G | last5=Chapel | first5=A | last6=Villaz | first6=M | last7=Ronjat | first7=M | doi-access=free }} *{{cite journal |vauthors=Sacchetto R, Turcato F, Damiani E, Margreth A |title=Interaction of triadin with histidine-rich Ca2+-binding protein at the triadic junction in skeletal muscle fibers |journal=J. Muscle Res. Cell. Motil. |volume=20 |issue= 4 |pages= 403–15 |year= 1999 |pmid= 10531621 |doi=10.1023/A:1005580609414 |s2cid=21796512 }} *{{cite journal |vauthors=Kobayashi YM, Alseikhan BA, Jones LR |title=Localization and characterization of the calsequestrin-binding domain of triadin 1. Evidence for a charged beta-strand in mediating the protein-protein interaction |journal=J. Biol. Chem. |volume=275 |issue= 23 |pages= 17639–46 |year= 2000 |pmid= 10748065 |doi= 10.1074/jbc.M002091200 |doi-access= free }} *{{cite journal | author=Kirchhefer U |title=Cardiac hypertrophy and impaired relaxation in transgenic mice overexpressing triadin 1 |journal=J. Biol. Chem. |volume=276 |issue= 6 |pages= 4142–9 |year= 2001 |pmid= 11069905 |doi= 10.1074/jbc.M006443200 |name-list-style=vanc| author2=Neumann J | author3=Baba HA | display-authors=3 | last4=Begrow | first4=F | last5=Kobayashi | first5=YM | last6=Reinke | first6=U | last7=Schmitz | first7=W | last8=Jones | first8=LR | doi-access=free }} *{{cite journal |vauthors=Shin DW, Ma J, Kim DH |title=The asp-rich region at the carboxyl-terminus of calsequestrin binds to Ca2+ and interacts with triadin |journal=FEBS Lett. |volume=486 |issue= 2 |pages= 178–82 |year= 2001 |pmid= 11113462 |doi=10.1016/S0014-5793(00)02246-8 |s2cid=3135618 |doi-access= }} *{{cite journal |vauthors=Lee HG, Kang H, Kim DH, Park WJ |title=Interaction of HRC (histidine-rich Ca2+-binding protein) and triadin in the lumen of sarcoplasmic reticulum |journal=J. Biol. Chem. |volume=276 |issue= 43 |pages= 39533–8 |year= 2001 |pmid= 11504710 |doi= 10.1074/jbc.M010664200 |doi-access= free }} *{{cite journal | author=Hong CS |title=Molecular cloning and characterization of mouse cardiac triadin isoforms |journal=Gene |volume=278 |issue= 1–2 |pages= 193–9 |year= 2002 |pmid= 11707337 |doi=10.1016/S0378-1119(01)00718-1 |name-list-style=vanc| author2=Ji JH | author3=Kim JP | display-authors=3 | last4=Jung | first4=DH | last5=Kim | first5=DH }} *{{cite journal | author=Strausberg RL |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |name-list-style=vanc| author2=Feingold EA | author3=Grouse LH | display-authors=3 | last4=Derge | first4=JG | last5=Klausner | first5=RD | last6=Collins | first6=FS | last7=Wagner | first7=L | last8=Shenmen | first8=CM | last9=Schuler | first9=GD |bibcode=2002PNAS...9916899M |doi-access=free }} *{{cite journal | author=Kim E |title=Increased Ca2+ storage capacity in the sarcoplasmic reticulum by overexpression of HRC (histidine-rich Ca2+ binding protein) |journal=Biochem. Biophys. Res. Commun. |volume=300 |issue= 1 |pages= 192–6 |year= 2003 |pmid= 12480542 |doi=10.1016/S0006-291X(02)02829-2 |name-list-style=vanc| author2=Shin DW | author3=Hong CS | display-authors=3 | last4=Jeong | first4=Dongtak | last5=Kim | first5=Do Han | last6=Park | first6=Woo Jin }} *{{cite journal | author=Thevenon D |title=Human skeletal muscle triadin: gene organization and cloning of the major isoform, Trisk 51 |journal=Biochem. Biophys. Res. Commun. |volume=303 |issue= 2 |pages= 669–75 |year= 2003 |pmid= 12659871 |doi=10.1016/S0006-291X(03)00406-6 |name-list-style=vanc| author2=Smida-Rezgui S | author3=Chevessier F | display-authors=3 | last4=Groh | first4=Séverine | last5=Henry-Berger | first5=Joëlle | last6=Beatriz Romero | first6=Norma | last7=Villaz | first7=Michel | last8=Dewaard | first8=Michel | last9=Marty | first9=Isabelle }} *{{cite journal | author=Lee JM |title=Negatively charged amino acids within the intraluminal loop of ryanodine receptor are involved in the interaction with triadin |journal=J. Biol. Chem. |volume=279 |issue= 8 |pages= 6994–7000 |year= 2004 |pmid= 14638677 |doi= 10.1074/jbc.M312446200 |name-list-style=vanc| author2=Rho SH | author3=Shin DW | display-authors=3 | last4=Cho | first4=C | last5=Park | first5=WJ | last6=Eom | first6=SH | last7=Ma | first7=J | last8=Kim | first8=DH | doi-access=free }} *{{cite journal | author=Olsen JV |title=Global, in vivo, and site-specific phosphorylation dynamics in signaling networks |journal=Cell |volume=127 |issue= 3 |pages= 635–48 |year= 2006 |pmid= 17081983 |doi= 10.1016/j.cell.2006.09.026 |name-list-style=vanc| author2=Blagoev B | author3=Gnad F | display-authors=3 | last4=Macek | first4=Boris | last5=Kumar | first5=Chanchal | last6=Mortensen | first6=Peter | last7=Mann | first7=Matthias |s2cid=7827573 | doi-access=free }} *{{cite journal | author=Arvanitis DA |title=Histidine-rich Ca-binding protein interacts with sarcoplasmic reticulum Ca-ATPase |journal=Am. J. Physiol. Heart Circ. Physiol. |volume=293 |issue= 3 |pages= H1581–9 |year= 2007 |pmid= 17526652 |doi= 10.1152/ajpheart.00278.2007 |name-list-style=vanc| author2=Vafiadaki E | author3=Fan GC | display-authors=3 | last4=Mitton | first4=B. A. | last5=Gregory | first5=K. N. | last6=Del Monte | first6=F. | last7=Kontrogianni-Konstantopoulos | first7=A. | last8=Sanoudou | first8=D. | last9=Kranias | first9=E. G. |s2cid=12820507 }} {{refend}} ==External links== * {{UCSC genome browser|TRDN}} * {{UCSC gene details|TRDN}} --- Adapted from the Wikipedia article [Triadin](https://en.wikipedia.org/wiki/Triadin) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/Triadin?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.