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Troponin T, cardiac muscle (TnTc) (Cardiac muscle troponin T) (cTnT)

 TNNT2_HUMAN             Reviewed;         298 AA.
P45379; A2TDB9; A8K3K6; O60214; Q99596; Q99597; Q9BUF6; Q9UM96;
01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
23-JAN-2007, sequence version 3.
27-SEP-2017, entry version 178.
RecName: Full=Troponin T, cardiac muscle;
Short=TnTc;
AltName: Full=Cardiac muscle troponin T;
Short=cTnT;
Name=TNNT2;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6).
TISSUE=Heart;
PubMed=8344420; DOI=10.1016/0014-5793(93)80981-Y;
Mesnard L., Samson F., Espinasse I., Durand J., Neveux J.-Y.,
Mercadier J.-J.;
"Molecular cloning and developmental expression of human cardiac
troponin T.";
FEBS Lett. 328:139-144(1993).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 6 AND 12).
TISSUE=Heart muscle;
PubMed=8088824; DOI=10.1006/geno.1994.1271;
Townsend P.J., Farza H., Macgeoch C., Spurr N.K., Wade R., Gahlman R.,
Yacoub M.H., Barton P.J.R.;
"Human cardiac troponin T: identification of fetal isoforms and
assignment of the TNNT2 locus to chromosome 1q.";
Genomics 21:311-316(1994).
[3]
NUCLEOTIDE SEQUENCE [MRNA], AND ALTERNATIVE SPLICING.
TISSUE=Fetal heart;
PubMed=8576938; DOI=10.1016/S0022-2828(95)91587-7;
Townsend P.J., Barton P.J.R., Yacoub M.H., Farza H.;
"Molecular cloning of human cardiac troponin T isoforms: expression in
developing and failing heart.";
J. Mol. Cell. Cardiol. 27:2223-2236(1995).
[4]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 6; 7 AND 8).
TISSUE=Heart;
PubMed=7534662; DOI=10.1161/01.RES.76.4.681;
Anderson P.A., Greig A., Mark T.M., Malouf N.N., Oakeley A.E.,
Ungerleider R.M., Allen P.D., Kay B.K.;
"Molecular basis of human cardiac troponin T isoforms expressed in the
developing, adult, and failing heart.";
Circ. Res. 76:681-686(1995).
[5]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2; 3; 4; 5; 6 AND 10).
TISSUE=Fetal heart;
PubMed=7895342; DOI=10.1161/01.RES.76.4.687;
Mesnard L., Logeart D., Taviaux S., Diriong S., Mercadier J.-J.,
Samson F.;
"Human cardiac troponin T: cloning and expression of new isoforms in
the normal and failing heart.";
Circ. Res. 76:687-692(1995).
[6]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 6), AND VARIANT CMH2
ILE-120.
TISSUE=Heart muscle;
PubMed=9482583;
DOI=10.1002/(SICI)1098-1004(1998)11:2<179::AID-HUMU12>3.0.CO;2-W;
Gerull B., Osterziel K.-J., Witt C., Dietz R., Thierfelder L.;
"A rapid protocol for cardiac troponin T gene mutation detection in
familial hypertrophic cardiomyopathy.";
Hum. Mutat. 11:179-182(1998).
[7]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 6).
D'Cruz L.G., Oberoi J., Mughal F., Steffensen U., Steffensen M.,
Kubo T., Mogensen J., McKoy G., O'Donnoghue A., Pondel M.,
McKenna W.J., Carter N.D., Baboonian C.;
"Genomic organization of the human cardiac troponin T gene (TNNT2) and
characterization of the candidate promoter region.";
Submitted (JUN-2001) to the EMBL/GenBank/DDBJ databases.
[8]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 6).
TISSUE=Heart;
PubMed=14702039; DOI=10.1038/ng1285;
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
"Complete sequencing and characterization of 21,243 full-length human
cDNAs.";
Nat. Genet. 36:40-45(2004).
[9]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
NHLBI resequencing and genotyping service (RS&G);
Submitted (DEC-2006) to the EMBL/GenBank/DDBJ databases.
[10]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=16710414; DOI=10.1038/nature04727;
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D.,
Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A.,
Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F.,
McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C.,
Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P.,
Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K.,
Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G.,
Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G.,
Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J.,
Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R.,
Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D.,
Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G.,
Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M.,
Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J.,
Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S.,
Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C.,
Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z.,
Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E.,
Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A.,
Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R.,
Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
Beck S., Rogers J., Bentley D.R.;
"The DNA sequence and biological annotation of human chromosome 1.";
Nature 441:315-321(2006).
[11]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 11).
TISSUE=Uterus;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[12]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 191-229 AND 231-288, ALTERNATIVE
SPLICING, AND VARIANT ARG-263.
TISSUE=Blood;
PubMed=9689598; DOI=10.1006/jmcc.1998.0698;
Farza H., Townsend P.J., Carrier L., Barton P.J., Mesnard L.,
Bahrend E., Forissier J.F., Fiszman M., Yacoub M.H., Schwartz K.;
"Genomic organisation, alternative splicing and polymorphisms of the
human cardiac troponin T gene.";
J. Mol. Cell. Cardiol. 30:1247-1253(1998).
[13]
PROTEIN SEQUENCE OF 70-76 AND 177-182.
TISSUE=Heart;
PubMed=7498159; DOI=10.1002/elps.11501601192;
Kovalyov L.I., Shishkin S.S., Efimochkin A.S., Kovalyova M.A.,
Ershova E.S., Egorov T.A., Musalyamov A.K.;
"The major protein expression profile and two-dimensional protein
database of human heart.";
Electrophoresis 16:1160-1169(1995).
[14]
X-RAY CRYSTALLOGRAPHY (2.61 ANGSTROMS) OF 193-298.
PubMed=12840750; DOI=10.1038/nature01780;
Takeda S., Yamashita A., Maeda K., Maeda Y.;
"Structure of the core domain of human cardiac troponin in the Ca(2+)-
saturated form.";
Nature 424:35-41(2003).
[15]
VARIANTS CMH2 ASN-89 AND GLN-102.
PubMed=8205619; DOI=10.1016/0092-8674(94)90054-X;
Thierfelder L., Watkins H., Macrae C., Lamas R., McKenna W.J.,
Vosberg H.-P., Seidman J.G., Seidman C.E.;
"Alpha-tropomyosin and cardiac troponin T mutations cause familial
hypertrophic cardiomyopathy: a disease of the sarcomere.";
Cell 77:701-712(1994).
[16]
VARIANTS CMH2 ILE-120; LYS-173; ASP-254 AND CYS-288.
PubMed=7898523; DOI=10.1056/NEJM199504203321603;
Watkins H., McKenna W.J., Thierfelder L., Suk H.J., Anan R.,
O'Donoghue A., Spirito P., Matsumori A., Moravec C.S., Seidman J.G.,
Seidman C.E.;
"Mutations in the genes for cardiac troponin T and alpha-tropomyosin
in hypertrophic cardiomyopathy.";
N. Engl. J. Med. 332:1058-1064(1995).
[17]
VARIANT CMH2 LEU-102.
PubMed=8989109; DOI=10.1161/01.CIR.94.12.3069;
Forissier J.F., Carrier L., Farza H., Bonne G., Bercovici J.,
Richard P., Hainque B., Townsend P.J., Yacoub M.H., Faure S.,
Dubourg O., Millaire A., Hagege A.A., Desnos M., Komajda M.,
Schwartz K.;
"Codon 102 of the cardiac troponin T gene is a putative hot spot for
mutations in familial hypertrophic cardiomyopathy.";
Circulation 94:3069-3073(1996).
[18]
VARIANT CMH2 TRP-102.
PubMed=9060892; DOI=10.1016/S0735-1097(96)00530-X;
Moolman J.C., Corfield V.A., Posen B., Ngumbela K., Seidman C.,
Brink P.A., Watkins H.;
"Sudden death due to troponin T mutations.";
J. Am. Coll. Cardiol. 29:549-555(1997).
[19]
VARIANT CMH2 PRO-288.
Erdmann J., Wischke S., Kallisch H., Riedel K., Heidenreich M.,
Fleck E., Regitz-Zagrosek V.;
"A novel missense Arg 278 Pro mutation in the troponin T gene
(TNNT2).";
Hum. Mutat. 12:364-364(1998).
[20]
VARIANT CMH2 LEU-104.
PubMed=10525521;
Varnava A., Baboonian C., Davison F., de Cruz L., Elliott P.M.,
Davies M.J., McKenna W.J.;
"A new mutation of the cardiac troponin T gene causing familial
hypertrophic cardiomyopathy without left ventricular hypertrophy.";
Heart 82:621-624(1999).
[21]
VARIANT CMH2 VAL-114.
PubMed=9140840; DOI=10.1006/jmcc.1996.0322;
Nakajima-Taniguchi C., Matsui H., Fujio Y., Nagata S., Kishimoto T.,
Yamauchi-Takihara K.;
"Novel missense mutation in cardiac troponin T gene found in Japanese
patient with hypertrophic cardiomyopathy.";
J. Mol. Cell. Cardiol. 29:839-843(1997).
[22]
VARIANT CMH2 PHE-189.
PubMed=11034944; DOI=10.1161/01.CIR.102.16.1950;
Ho C.Y., Lever H.M., DeSanctis R., Farver C.F., Seidman J.G.,
Seidman C.E.;
"Homozygous mutation in cardiac troponin T: implications for
hypertrophic cardiomyopathy.";
Circulation 102:1950-1955(2000).
[23]
VARIANT CMD1D LYS-210 DEL.
PubMed=11106718; DOI=10.1056/NEJM200012073432304;
Kamisago M., Sharma S.D., DePalma S.R., Solomon S., Sharma P.,
McDonough B., Smoot L., Mullen M.P., Woolf P.K., Wigle E.D.,
Seidman J.G., Seidman C.E.;
"Mutations in sarcomere protein genes as a cause of dilated
cardiomyopathy.";
N. Engl. J. Med. 343:1688-1696(2000).
[24]
VARIANT CMD1D TRP-151.
PubMed=11684629; DOI=10.1161/hc4301.098285;
Li D., Czernuszewicz G.Z., Gonzalez O., Tapscott T., Karibe A.,
Durand J.B., Brugada R., Hill R., Gregoritch J.M., Anderson J.L.,
Quinones M., Bachinski L.L., Roberts R.;
"Novel cardiac troponin T mutation as a cause of familial dilated
cardiomyopathy.";
Circulation 104:2188-2193(2001).
[25]
VARIANTS CMH2 LEU-80; VAL-120; ILE-281 AND CYS-296.
PubMed=12707239; DOI=10.1161/01.CIR.0000066323.15244.54;
Richard P., Charron P., Carrier L., Ledeuil C., Cheav T.,
Pichereau C., Benaiche A., Isnard R., Dubourg O., Burban M.,
Gueffet J.-P., Millaire A., Desnos M., Schwartz K., Hainque B.,
Komajda M.;
"Hypertrophic cardiomyopathy: distribution of disease genes, spectrum
of mutations, and implications for a molecular diagnosis strategy.";
Circulation 107:2227-2232(2003).
[26]
ERRATUM.
Richard P., Charron P., Carrier L., Ledeuil C., Cheav T.,
Pichereau C., Benaiche A., Isnard R., Dubourg O., Burban M.,
Gueffet J.-P., Millaire A., Desnos M., Schwartz K., Hainque B.,
Komajda M.;
Circulation 109:3258-3258(2004).
[27]
VARIANT CMH2 PRO-288.
PubMed=12974739; DOI=10.1034/j.1399-0004.2003.00151.x;
Erdmann J., Daehmlow S., Wischke S., Senyuva M., Werner U., Raible J.,
Tanis N., Dyachenko S., Hummel M., Hetzer R., Regitz-Zagrosek V.;
"Mutation spectrum in a large cohort of unrelated consecutive patients
with hypertrophic cardiomyopathy.";
Clin. Genet. 64:339-349(2003).
[28]
VARIANTS CMD1D TRP-141; LEU-215 AND LYS-220 DEL.
PubMed=15542288; DOI=10.1016/j.jacc.2004.08.027;
Mogensen J., Murphy R.T., Shaw T., Bahl A., Redwood C., Watkins H.,
Burke M., Elliott P.M., McKenna W.J.;
"Severe disease expression of cardiac troponin C and T mutations in
patients with idiopathic dilated cardiomyopathy.";
J. Am. Coll. Cardiol. 44:2033-2040(2004).
[29]
VARIANT CMH2 CYS-140.
PubMed=15563892; DOI=10.1016/j.cccn.2004.09.016;
Song L., Zou Y., Wang J., Wang Z., Zhen Y., Lou K., Zhang Q., Wang X.,
Wang H., Li J., Hui R.;
"Mutations profile in Chinese patients with hypertrophic
cardiomyopathy.";
Clin. Chim. Acta 351:209-216(2005).
[30]
VARIANT CMD1D TRP-151.
PubMed=15769782; DOI=10.1093/eurheartj/ehi193;
Villard E., Duboscq-Bidot L., Charron P., Benaiche A., Conraads V.,
Sylvius N., Komajda M.;
"Mutation screening in dilated cardiomyopathy: prominent role of the
beta myosin heavy chain gene.";
Eur. Heart J. 26:794-803(2005).
[31]
VARIANT CMH2 CYS-288.
PubMed=16199542; DOI=10.1136/jmg.2005.033886;
Ingles J., Doolan A., Chiu C., Seidman J., Seidman C., Semsarian C.;
"Compound and double mutations in patients with hypertrophic
cardiomyopathy: implications for genetic testing and counselling.";
J. Med. Genet. 42:E59-E59(2005).
[32]
INVOLVEMENT IN RCM3.
PubMed=16651346; DOI=10.1542/peds.2005-2301;
Peddy S.B., Vricella L.A., Crosson J.E., Oswald G.L., Cohn R.D.,
Cameron D.E., Valle D., Loeys B.L.;
"Infantile restrictive cardiomyopathy resulting from a mutation in the
cardiac troponin T gene.";
Pediatrics 117:1830-1833(2006).
[33]
VARIANTS CMH2 VAL-38 AND CYS-288, AND VARIANTS CMD1D TRP-141 AND
LYS-220 DEL.
PubMed=21846512; DOI=10.1016/j.ejmg.2011.07.005;
Millat G., Bouvagnet P., Chevalier P., Sebbag L., Dulac A.,
Dauphin C., Jouk P.S., Delrue M.A., Thambo J.B., Le Metayer P.,
Seronde M.F., Faivre L., Eicher J.C., Rousson R.;
"Clinical and mutational spectrum in a cohort of 105 unrelated
patients with dilated cardiomyopathy.";
Eur. J. Med. Genet. 54:E570-E575(2011).
-!- FUNCTION: Troponin T is the tropomyosin-binding subunit of
troponin, the thin filament regulatory complex which confers
calcium-sensitivity to striated muscle actomyosin ATPase activity.
-!- INTERACTION:
Q15014:MORF4L2; NbExp=3; IntAct=EBI-8485957, EBI-399257;
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=12;
Comment=Additional isoforms seem to exist. Experimental
confirmation may be lacking for some isoforms.;
Name=1; Synonyms=TNT1;
IsoId=P45379-1; Sequence=Displayed;
Name=2;
IsoId=P45379-2; Sequence=VSP_006644;
Name=3;
IsoId=P45379-3; Sequence=VSP_006645;
Name=4;
IsoId=P45379-4; Sequence=VSP_006644, VSP_006645;
Name=5;
IsoId=P45379-5; Sequence=VSP_006647;
Name=6; Synonyms=TNT3;
IsoId=P45379-6; Sequence=VSP_006643;
Name=7; Synonyms=TNT4;
IsoId=P45379-7; Sequence=VSP_006642;
Name=8; Synonyms=TNT2;
IsoId=P45379-8; Sequence=VSP_006641;
Name=9;
IsoId=P45379-9; Sequence=VSP_006646;
Name=10;
IsoId=P45379-10; Sequence=VSP_006648;
Name=11;
IsoId=P45379-11; Sequence=VSP_006643, VSP_006648;
Note=No experimental confirmation available.;
Name=12;
IsoId=P45379-12; Sequence=VSP_006645, VSP_006646, VSP_006648;
-!- TISSUE SPECIFICITY: Heart. The fetal heart shows a greater
expression in the atrium than in the ventricle, while the adult
heart shows a greater expression in the ventricle than in the
atrium. Isoform 6 predominates in normal adult heart. Isoforms 1,
7 and 8 are expressed in fetal heart. Isoform 7 is also expressed
in failing adult heart.
-!- PTM: Phosphorylation at Thr-213 by PRKCA induces significant
reduction in myofilament calcium sensitivity and actomyosin ATPase
activity. {ECO:0000250}.
-!- DISEASE: Cardiomyopathy, familial hypertrophic 2 (CMH2)
[MIM:115195]: A hereditary heart disorder characterized by
ventricular hypertrophy, which is usually asymmetric and often
involves the interventricular septum. The symptoms include
dyspnea, syncope, collapse, palpitations, and chest pain. They can
be readily provoked by exercise. The disorder has inter- and
intrafamilial variability ranging from benign to malignant forms
with high risk of cardiac failure and sudden cardiac death.
{ECO:0000269|PubMed:10525521, ECO:0000269|PubMed:11034944,
ECO:0000269|PubMed:12707239, ECO:0000269|PubMed:12974739,
ECO:0000269|PubMed:15563892, ECO:0000269|PubMed:16199542,
ECO:0000269|PubMed:21846512, ECO:0000269|PubMed:7898523,
ECO:0000269|PubMed:8205619, ECO:0000269|PubMed:8989109,
ECO:0000269|PubMed:9060892, ECO:0000269|PubMed:9140840,
ECO:0000269|PubMed:9482583, ECO:0000269|Ref.19}. Note=The disease
is caused by mutations affecting the gene represented in this
entry.
-!- DISEASE: Cardiomyopathy, dilated 1D (CMD1D) [MIM:601494]: A
disorder characterized by ventricular dilation and impaired
systolic function, resulting in congestive heart failure and
arrhythmia. Patients are at risk of premature death.
{ECO:0000269|PubMed:11106718, ECO:0000269|PubMed:11684629,
ECO:0000269|PubMed:15542288, ECO:0000269|PubMed:15769782,
ECO:0000269|PubMed:21846512}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- DISEASE: Cardiomyopathy, familial restrictive 3 (RCM3)
[MIM:612422]: A heart disorder characterized by impaired filling
of the ventricles with reduced diastolic volume, in the presence
of normal or near normal wall thickness and systolic function.
{ECO:0000269|PubMed:16651346}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- SIMILARITY: Belongs to the troponin T family. {ECO:0000305}.
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EMBL; S64668; AAB27731.1; ALT_SEQ; mRNA.
EMBL; X74819; CAA52818.1; -; mRNA.
EMBL; L40162; AAA67422.1; -; mRNA.
EMBL; X79855; CAA56235.1; -; mRNA.
EMBL; X79856; CAA56236.1; -; mRNA.
EMBL; X79857; CAA56237.1; -; mRNA.
EMBL; X79858; CAA56238.1; -; mRNA.
EMBL; AF004422; AAC39590.1; -; Genomic_DNA.
EMBL; AF004409; AAC39590.1; JOINED; Genomic_DNA.
EMBL; AF004410; AAC39590.1; JOINED; Genomic_DNA.
EMBL; AF004411; AAC39590.1; JOINED; Genomic_DNA.
EMBL; AF004412; AAC39590.1; JOINED; Genomic_DNA.
EMBL; AF004413; AAC39590.1; JOINED; Genomic_DNA.
EMBL; AF004414; AAC39590.1; JOINED; Genomic_DNA.
EMBL; AF004415; AAC39590.1; JOINED; Genomic_DNA.
EMBL; AF004416; AAC39590.1; JOINED; Genomic_DNA.
EMBL; AF004417; AAC39590.1; JOINED; Genomic_DNA.
EMBL; AF004418; AAC39590.1; JOINED; Genomic_DNA.
EMBL; AF004419; AAC39590.1; JOINED; Genomic_DNA.
EMBL; AF004420; AAC39590.1; JOINED; Genomic_DNA.
EMBL; AF004421; AAC39590.1; JOINED; Genomic_DNA.
EMBL; AY044273; AAK92231.1; -; Genomic_DNA.
EMBL; AK290621; BAF83310.1; -; mRNA.
EMBL; EF179183; ABN05286.1; -; Genomic_DNA.
EMBL; AC119427; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; BC002653; AAH02653.1; -; mRNA.
EMBL; Y09626; CAA70839.1; -; Genomic_DNA.
EMBL; Y09627; CAA70840.1; -; Genomic_DNA.
EMBL; Y09628; CAA70841.1; -; Genomic_DNA.
EMBL; S71126; AAB30956.1; -; mRNA.
EMBL; S71127; AAB30957.1; -; Genomic_DNA.
EMBL; S71128; AAB30957.1; JOINED; Genomic_DNA.
CCDS; CCDS30968.1; -. [P45379-11]
CCDS; CCDS30969.1; -. [P45379-6]
CCDS; CCDS60390.1; -. [P45379-12]
CCDS; CCDS73003.1; -. [P45379-1]
PIR; A54671; TPHUTC.
RefSeq; NP_000355.2; NM_000364.3. [P45379-10]
RefSeq; NP_001001430.1; NM_001001430.2. [P45379-6]
RefSeq; NP_001001431.1; NM_001001431.2. [P45379-11]
RefSeq; NP_001001432.1; NM_001001432.2.
RefSeq; NP_001263274.1; NM_001276345.1. [P45379-1]
RefSeq; NP_001263275.1; NM_001276346.1. [P45379-12]
RefSeq; NP_001263276.1; NM_001276347.1. [P45379-6]
RefSeq; XP_006711571.1; XM_006711508.3. [P45379-6]
RefSeq; XP_011508240.1; XM_011509938.2. [P45379-1]
RefSeq; XP_011508241.1; XM_011509939.1. [P45379-3]
RefSeq; XP_011508242.1; XM_011509940.2. [P45379-5]
RefSeq; XP_011508244.1; XM_011509942.2. [P45379-7]
RefSeq; XP_011508245.1; XM_011509943.2. [P45379-7]
RefSeq; XP_016857706.1; XM_017002217.1. [P45379-11]
UniGene; Hs.533613; -.
PDB; 1J1D; X-ray; 2.61 A; B/E=193-298.
PDB; 1J1E; X-ray; 3.30 A; B/E=193-298.
PDB; 4Y99; X-ray; 2.00 A; B=193-298.
PDBsum; 1J1D; -.
PDBsum; 1J1E; -.
PDBsum; 4Y99; -.
ProteinModelPortal; P45379; -.
SMR; P45379; -.
BioGrid; 112993; 8.
IntAct; P45379; 3.
MINT; MINT-3015968; -.
STRING; 9606.ENSP00000356286; -.
ChEMBL; CHEMBL2095202; -.
iPTMnet; P45379; -.
PhosphoSitePlus; P45379; -.
DMDM; 21264536; -.
UCD-2DPAGE; P45379; -.
PaxDb; P45379; -.
PeptideAtlas; P45379; -.
PRIDE; P45379; -.
DNASU; 7139; -.
Ensembl; ENST00000236918; ENSP00000236918; ENSG00000118194. [P45379-1]
Ensembl; ENST00000360372; ENSP00000353535; ENSG00000118194. [P45379-12]
Ensembl; ENST00000367318; ENSP00000356287; ENSG00000118194. [P45379-6]
Ensembl; ENST00000367320; ENSP00000356289; ENSG00000118194. [P45379-12]
Ensembl; ENST00000367322; ENSP00000356291; ENSG00000118194. [P45379-11]
Ensembl; ENST00000509001; ENSP00000422031; ENSG00000118194. [P45379-6]
GeneID; 7139; -.
KEGG; hsa:7139; -.
UCSC; uc001gwg.5; human. [P45379-1]
CTD; 7139; -.
DisGeNET; 7139; -.
EuPathDB; HostDB:ENSG00000118194.18; -.
GeneCards; TNNT2; -.
GeneReviews; TNNT2; -.
HGNC; HGNC:11949; TNNT2.
HPA; CAB015371; -.
HPA; HPA015774; -.
HPA; HPA017888; -.
MalaCards; TNNT2; -.
MIM; 115195; phenotype.
MIM; 191045; gene.
MIM; 601494; phenotype.
MIM; 612422; phenotype.
neXtProt; NX_P45379; -.
OpenTargets; ENSG00000118194; -.
Orphanet; 154; Familial isolated dilated cardiomyopathy.
Orphanet; 155; Familial isolated hypertrophic cardiomyopathy.
Orphanet; 75249; Familial isolated restrictive cardiomyopathy.
Orphanet; 54260; Left ventricular noncompaction.
PharmGKB; PA36638; -.
eggNOG; KOG3634; Eukaryota.
eggNOG; ENOG410XS6A; LUCA.
GeneTree; ENSGT00390000013611; -.
HOGENOM; HOG000231049; -.
HOVERGEN; HBG052790; -.
InParanoid; P45379; -.
KO; K12045; -.
OMA; EVHFESR; -.
OrthoDB; EOG091G0U67; -.
PhylomeDB; P45379; -.
TreeFam; TF313321; -.
Reactome; R-HSA-390522; Striated Muscle Contraction.
SIGNOR; P45379; -.
ChiTaRS; TNNT2; human.
EvolutionaryTrace; P45379; -.
GeneWiki; TNNT2; -.
GenomeRNAi; 7139; -.
PRO; PR:P45379; -.
Proteomes; UP000005640; Chromosome 1.
Bgee; ENSG00000118194; -.
CleanEx; HS_TNNT2; -.
ExpressionAtlas; P45379; baseline and differential.
Genevisible; P45379; HS.
GO; GO:0097512; C:cardiac myofibril; IDA:CAFA.
GO; GO:1990584; C:cardiac Troponin complex; IDA:CAFA.
GO; GO:0005829; C:cytosol; TAS:Reactome.
GO; GO:0030017; C:sarcomere; TAS:BHF-UCL.
GO; GO:0005865; C:striated muscle thin filament; IDA:UniProtKB.
GO; GO:0005861; C:troponin complex; IDA:UniProtKB.
GO; GO:0003779; F:actin binding; IDA:UniProtKB.
GO; GO:0030674; F:protein binding, bridging; IEA:Ensembl.
GO; GO:0005523; F:tropomyosin binding; IDA:UniProtKB.
GO; GO:0030172; F:troponin C binding; IPI:UniProtKB.
GO; GO:0031013; F:troponin I binding; IPI:UniProtKB.
GO; GO:0051764; P:actin crosslink formation; IEA:Ensembl.
GO; GO:0060048; P:cardiac muscle contraction; IDA:CAFA.
GO; GO:0030049; P:muscle filament sliding; IDA:UniProtKB.
GO; GO:0032780; P:negative regulation of ATPase activity; IDA:UniProtKB.
GO; GO:0032781; P:positive regulation of ATPase activity; IDA:UniProtKB.
GO; GO:0051291; P:protein heterooligomerization; IEA:Ensembl.
GO; GO:0008016; P:regulation of heart contraction; IMP:UniProtKB.
GO; GO:0032972; P:regulation of muscle filament sliding speed; IEA:Ensembl.
GO; GO:0051592; P:response to calcium ion; IDA:UniProtKB.
GO; GO:0055010; P:ventricular cardiac muscle tissue morphogenesis; IMP:BHF-UCL.
InterPro; IPR027707; TNNT.
InterPro; IPR001978; Troponin.
PANTHER; PTHR11521; PTHR11521; 1.
Pfam; PF00992; Troponin; 2.
1: Evidence at protein level;
3D-structure; Acetylation; Alternative splicing; Cardiomyopathy;
Complete proteome; Direct protein sequencing; Disease mutation;
Muscle protein; Phosphoprotein; Polymorphism; Reference proteome.
INIT_MET 1 1 Removed. {ECO:0000250|UniProtKB:P09741}.
CHAIN 2 298 Troponin T, cardiac muscle.
/FTId=PRO_0000186173.
MOD_RES 2 2 N-acetylserine.
{ECO:0000250|UniProtKB:P09741}.
MOD_RES 2 2 Phosphoserine; by CK2.
{ECO:0000250|UniProtKB:P13789}.
MOD_RES 204 204 Phosphothreonine; by PKC/PRKCA.
{ECO:0000250|UniProtKB:P50752}.
MOD_RES 208 208 Phosphoserine; by PKC/PRKCA.
{ECO:0000250|UniProtKB:P50752}.
MOD_RES 213 213 Phosphothreonine; by PKC/PRKCA and RAF1.
{ECO:0000250}.
MOD_RES 294 294 Phosphothreonine; by PKC/PRKCA.
{ECO:0000250|UniProtKB:P50752}.
VAR_SEQ 18 32 Missing (in isoform 7).
{ECO:0000303|PubMed:7534662}.
/FTId=VSP_006642.
VAR_SEQ 18 22 Missing (in isoform 8).
{ECO:0000303|PubMed:7534662}.
/FTId=VSP_006641.
VAR_SEQ 23 32 Missing (in isoform 6 and isoform 11).
{ECO:0000303|PubMed:14702039,
ECO:0000303|PubMed:15489334,
ECO:0000303|PubMed:7534662,
ECO:0000303|PubMed:7895342,
ECO:0000303|PubMed:8088824,
ECO:0000303|PubMed:8344420}.
/FTId=VSP_006643.
VAR_SEQ 23 23 Missing (in isoform 2 and isoform 4).
{ECO:0000303|PubMed:7895342}.
/FTId=VSP_006644.
VAR_SEQ 54 54 Missing (in isoform 3, isoform 4 and
isoform 12). {ECO:0000303|PubMed:7895342,
ECO:0000303|PubMed:8088824}.
/FTId=VSP_006645.
VAR_SEQ 99 137 Missing (in isoform 9 and isoform 12).
{ECO:0000303|PubMed:8088824}.
/FTId=VSP_006646.
VAR_SEQ 201 203 Missing (in isoform 10, isoform 11 and
isoform 12).
{ECO:0000303|PubMed:15489334,
ECO:0000303|PubMed:7895342,
ECO:0000303|PubMed:8088824}.
/FTId=VSP_006648.
VAR_SEQ 201 201 Missing (in isoform 5).
{ECO:0000303|PubMed:7895342}.
/FTId=VSP_006647.
VARIANT 38 38 A -> V (in CMH2; dbSNP:rs200754249).
{ECO:0000269|PubMed:21846512}.
/FTId=VAR_067259.
VARIANT 80 80 F -> L (in CMH2).
{ECO:0000269|PubMed:12707239}.
/FTId=VAR_019877.
VARIANT 89 89 I -> N (in CMH2; dbSNP:rs121964855).
{ECO:0000269|PubMed:8205619}.
/FTId=VAR_007605.
VARIANT 102 102 R -> L (in CMH2; dbSNP:rs121964856).
{ECO:0000269|PubMed:8989109}.
/FTId=VAR_016195.
VARIANT 102 102 R -> Q (in CMH2; dbSNP:rs121964856).
{ECO:0000269|PubMed:8205619}.
/FTId=VAR_007606.
VARIANT 102 102 R -> W (in CMH2; dbSNP:rs397516456).
{ECO:0000269|PubMed:9060892}.
/FTId=VAR_016196.
VARIANT 104 104 R -> L (in CMH2; dbSNP:rs397516457).
{ECO:0000269|PubMed:10525521}.
/FTId=VAR_009194.
VARIANT 114 114 A -> V (in CMH2; dbSNP:rs727504245).
{ECO:0000269|PubMed:9140840}.
/FTId=VAR_016197.
VARIANT 120 120 F -> I (in CMH2; dbSNP:rs121964858).
{ECO:0000269|PubMed:7898523,
ECO:0000269|PubMed:9482583}.
/FTId=VAR_007607.
VARIANT 120 120 F -> V (in CMH2; dbSNP:rs121964858).
{ECO:0000269|PubMed:12707239}.
/FTId=VAR_019878.
VARIANT 139 139 R -> K (in dbSNP:rs2996496).
/FTId=VAR_013021.
VARIANT 140 140 R -> C (in CMH2; dbSNP:rs397516463).
{ECO:0000269|PubMed:15563892}.
/FTId=VAR_042747.
VARIANT 140 140 R -> K (in dbSNP:rs2996496).
/FTId=VAR_029450.
VARIANT 141 141 R -> W (in CMD1D; dbSNP:rs74315380).
{ECO:0000269|PubMed:15542288,
ECO:0000269|PubMed:21846512}.
/FTId=VAR_043983.
VARIANT 151 151 R -> W (in CMD1D; dbSNP:rs74315379).
{ECO:0000269|PubMed:11684629,
ECO:0000269|PubMed:15769782}.
/FTId=VAR_016198.
VARIANT 170 170 Missing (in CMH2).
/FTId=VAR_007608.
VARIANT 173 173 E -> K (in CMH2).
{ECO:0000269|PubMed:7898523}.
/FTId=VAR_007609.
VARIANT 189 189 S -> F (in CMH2; dbSNP:rs727504246).
{ECO:0000269|PubMed:11034944}.
/FTId=VAR_016199.
VARIANT 210 210 Missing (in CMD1D).
{ECO:0000269|PubMed:11106718}.
/FTId=VAR_022931.
VARIANT 215 215 R -> L (in CMD1D; dbSNP:rs121964860).
{ECO:0000269|PubMed:15542288}.
/FTId=VAR_043984.
VARIANT 220 220 Missing (in CMD1D).
{ECO:0000269|PubMed:15542288,
ECO:0000269|PubMed:21846512}.
/FTId=VAR_043985.
VARIANT 221 221 I -> T (in dbSNP:rs45520032).
/FTId=VAR_042748.
VARIANT 231 231 I -> T (in dbSNP:rs45520032).
/FTId=VAR_057310.
VARIANT 249 249 S -> T (in dbSNP:rs2996495).
/FTId=VAR_013022.
VARIANT 254 254 E -> D (in CMH2; dbSNP:rs45466197).
{ECO:0000269|PubMed:7898523}.
/FTId=VAR_007610.
VARIANT 263 263 K -> R (in dbSNP:rs3730238).
{ECO:0000269|PubMed:9689598}.
/FTId=VAR_007611.
VARIANT 279 279 N -> Y (in dbSNP:rs4523540).
/FTId=VAR_029451.
VARIANT 281 281 N -> I (in CMH2; dbSNP:rs863225119).
{ECO:0000269|PubMed:12707239}.
/FTId=VAR_019879.
VARIANT 288 288 R -> C (in CMH2; dbSNP:rs121964857).
{ECO:0000269|PubMed:16199542,
ECO:0000269|PubMed:21846512,
ECO:0000269|PubMed:7898523}.
/FTId=VAR_007612.
VARIANT 288 288 R -> P (in CMH2; dbSNP:rs397516484).
{ECO:0000269|PubMed:12974739,
ECO:0000269|Ref.19}.
/FTId=VAR_007613.
VARIANT 296 296 R -> C (in CMH2; dbSNP:rs367785431).
{ECO:0000269|PubMed:12707239}.
/FTId=VAR_019880.
CONFLICT 242 242 K -> E (in Ref. 12; CAA70840).
{ECO:0000305}.
HELIX 210 225 {ECO:0000244|PDB:4Y99}.
HELIX 236 280 {ECO:0000244|PDB:4Y99}.
SEQUENCE 298 AA; 35924 MW; 69974F2200CD5BEF CRC64;
MSDIEEVVEE YEEEEQEEAA VEEEEDWRED EDEQEEAAEE DAEAEAETEE TRAEEDEEEE
EAKEAEDGPM EESKPKPRSF MPNLVPPKIP DGERVDFDDI HRKRMEKDLN ELQALIEAHF
ENRKKEEEEL VSLKDRIERR RAERAEQQRI RNEREKERQN RLAEERARRE EEENRRKAED
EARKKKALSN MMHFGGYIQK QAQTERKSGK RQTEREKKKK ILAERRKVLA IDHLNEDQLR
EKAKELWQSI YNLEAEKFDL QEKFKQQKYE INVLRNRIND NQKVSKTRGK AKVTGRWK


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