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Homeobox protein Nkx-2.5 (Cardiac-specific homeobox) (Homeobox protein CSX) (Homeobox protein NK-2 homolog E)

 NKX25_HUMAN             Reviewed;         324 AA.
P52952; A8K3K0; B4DNB6; E9PBU6;
01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
01-OCT-1996, sequence version 1.
25-OCT-2017, entry version 185.
RecName: Full=Homeobox protein Nkx-2.5;
AltName: Full=Cardiac-specific homeobox;
AltName: Full=Homeobox protein CSX;
AltName: Full=Homeobox protein NK-2 homolog E;
Name=NKX2-5; Synonyms=CSX, NKX2.5, NKX2E;
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 1).
TISSUE=Heart;
PubMed=8900537;
Turbay D., Wechsler S.B., Blanchard K.M., Izumo S.;
"Molecular cloning, chromosomal mapping, and characterization of the
human cardiac-specific homeobox gene hCsx.";
Mol. Med. 2:86-96(1996).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
TISSUE=Fetal lung;
Tate G., Mitsuya T.;
"Human Nkx-2.5 gene.";
Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND
VARIANT ASP-74.
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).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=15372022; DOI=10.1038/nature02919;
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
"The DNA sequence and comparative analysis of human chromosome 5.";
Nature 431:268-274(2004).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
Venter J.C.;
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
TISSUE=Pancreas, and Spleen;
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).
[7]
FUNCTION, VARIANT HIS-236, AND CHARACTERIZATION OF VARIANT HIS-236.
PubMed=22560297; DOI=10.1016/j.devcel.2012.02.009;
Koss M., Bolze A., Brendolan A., Saggese M., Capellini T.D.,
Bojilova E., Boisson B., Prall O.W., Elliott D.A., Solloway M.,
Lenti E., Hidaka C., Chang C.P., Mahlaoui N., Harvey R.P.,
Casanova J.L., Selleri L.;
"Congenital asplenia in mice and humans with mutations in a Pbx/Nkx2-
5/p15 module.";
Dev. Cell 22:913-926(2012).
[8]
X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 138-194 OF MUTANT SER-193 OF
HOMODIMER IN COMPLEX WITH DNA, SUBUNIT, AND DNA-BINDING.
PubMed=22849347; DOI=10.1021/bi300849c;
Pradhan L., Genis C., Scone P., Weinberg E.O., Kasahara H., Nam H.J.;
"Crystal structure of the human NKX2.5 homeodomain in complex with DNA
target.";
Biochemistry 51:6312-6319(2012).
[9]
X-RAY CRYSTALLOGRAPHY (2.82 ANGSTROMS) OF 142-194 IN COMPLEX WITH TBX5
AND DNA, INTERACTION WITH TBX5, AND DNA-BINDING.
PubMed=26926761; DOI=10.1021/acs.biochem.6b00171;
Pradhan L., Gopal S., Li S., Ashur S., Suryanarayanan S., Kasahara H.,
Nam H.J.;
"Intermolecular interactions of cardiac transcription factors NKX2.5
and TBX5.";
Biochemistry 55:1702-1710(2016).
[10]
VARIANT ASD7 MET-178.
PubMed=9651244; DOI=10.1126/science.281.5373.108;
Schott J.-J., Benson D.W., Basson C.T., Pease W., Silberbach G.M.,
Moak J.P., Maron B.J., Seidman C.E., Seidman J.G.;
"Congenital heart disease caused by mutations in the transcription
factor NKX2-5.";
Science 281:108-111(1998).
[11]
VARIANT TOF CYS-25, AND VARIANTS ASD7 LYS-188; GLY-189 AND CYS-191.
PubMed=10587520; DOI=10.1172/JCI8154;
Benson D.W., Silberbach G.M., Kavanaugh-McHugh A., Cottrill C.,
Zhang Y., Riggs S., Smalls O., Johnson M.C., Watson M.S.,
Seidman J.G., Seidman C.E., Plowden J., Kugler J.D.;
"Mutations in the cardiac transcription factor NKX2.5 affect diverse
cardiac developmental pathways.";
J. Clin. Invest. 104:1567-1573(1999).
[12]
VARIANTS TOF GLN-21; CYS-25; CYS-216 AND VAL-219.
PubMed=11714651; DOI=10.1161/hc4601.098427;
Goldmuntz E., Geiger E., Benson D.W.;
"NKX2.5 mutations in patients with tetralogy of fallot.";
Circulation 104:2565-2568(2001).
[13]
VARIANTS ASD7 ILE-15; VAL-63; GLU-127 AND THR-275, VARIANTS TOF
GLN-21; PRO-22; CYS-25; CYS-216; VAL-219 AND THR-323, VARIANT CTMH
ASN-291 DEL, VARIANT HLHS2 CYS-25, AND INVOLVEMENT IN CONGENITAL HEART
MALFORMATIONS.
PubMed=14607454; DOI=10.1016/j.jacc.2003.05.004;
McElhinney D.B., Geiger E., Blinder J., Benson D.W., Goldmuntz E.;
"NKX2.5 mutations in patients with congenital heart disease.";
J. Am. Coll. Cardiol. 42:1650-1655(2003).
[14]
VARIANTS ASD7 PRO-7; SER-19; CYS-25; PRO-45; LEU-51; PRO-69; LEU-77;
SER-114; ARG-114; ARG-118; ARG-124; VAL-126; SER-133; THR-135;
PRO-144; MET-178; GLU-183; THR-192; ARG-192; ARG-194; GLU-205;
VAL-219; ASN-226; HIS-248; PRO-279; PHE-279; VAL-281; VAL-286;
HIS-294; GLY-299; GLY-305; SER-320 AND GLN-322.
PubMed=15342699; DOI=10.1136/jmg.2003.017483;
Reamon-Buettner S.M., Borlak J.;
"Somatic NKX2-5 mutations as a novel mechanism of disease in complex
congenital heart disease.";
J. Med. Genet. 41:684-690(2004).
[15]
VARIANTS ASD7 ILE-15; GLN-21; PRO-22; CYS-25; VAL-63; GLU-127;
CYS-142; MET-178; HIS-187; LYS-188; GLY-189; CYS-190; CYS-191;
CYS-216; VAL-219; THR-275 AND THR-323, AND VARIANT HLHS2 CYS-25.
PubMed=15810002; DOI=10.1002/ajmg.a.30684;
Hirayama-Yamada K., Kamisago M., Akimoto K., Aotsuka H., Nakamura Y.,
Tomita H., Furutani M., Imamura S., Takao A., Nakazawa M.,
Matsuoka R.;
"Phenotypes with GATA4 or NKX2.5 mutations in familial atrial septal
defect.";
Am. J. Med. Genet. A 135:47-52(2005).
[16]
VARIANTS CHNG5 CYS-25; SER-119 AND PRO-161, AND CHARACTERIZATION OF
VARIANTS CHNG5 CYS-25; SER-119 AND PRO-161.
PubMed=16418214; DOI=10.1210/jc.2005-1350;
Dentice M., Cordeddu V., Rosica A., Ferrara A.M., Santarpia L.,
Salvatore D., Chiovato L., Perri A., Moschini L., Fazzini C.,
Olivieri A., Costa P., Stoppioni V., Baserga M., De Felice M.,
Sorcini M., Fenzi G., Di Lauro R., Tartaglia M., Macchia P.E.;
"Missense mutation in the transcription factor NKX2-5: a novel
molecular event in the pathogenesis of thyroid dysgenesis.";
J. Clin. Endocrinol. Metab. 91:1428-1433(2006).
[17]
VARIANT CTHM CYS-25.
PubMed=17891434; DOI=10.1007/s00246-007-9058-2;
Akcaboy M.I., Cengiz F.B., Inceoglu B., Ucar T., Atalay S., Tutar E.,
Tekin M.;
"The effect of p.Arg25Cys alteration in NKX2-5 on conotruncal heart
anomalies: mutation or polymorphism?";
Pediatr. Cardiol. 29:126-129(2008).
[18]
VARIANT VSD3 GLN-283.
PubMed=21110066; DOI=10.1007/s10709-010-9522-4;
Peng T., Wang L., Zhou S.F., Li X.;
"Mutations of the GATA4 and NKX2.5 genes in Chinese pediatric patients
with non-familial congenital heart disease.";
Genetica 138:1231-1240(2010).
[19]
VARIANT VSD3 ALA-59, AND CHARACTERIZATION OF VARIANT VSD3 ALA-59.
PubMed=21165553; DOI=10.3892/ijmm.2010.585;
Wang J., Xin Y.F., Liu X.Y., Liu Z.M., Wang X.Z., Yang Y.Q.;
"A novel NKX2-5 mutation in familial ventricular septal defect.";
Int. J. Mol. Med. 27:369-375(2011).
-!- FUNCTION: Implicated in commitment to and/or differentiation of
the myocardial lineage. Acts as a transcriptional activator of ANF
in cooperation with GATA4 (By similarity). Binds to the core DNA
motif of NPPA promoter (PubMed:22849347, PubMed:26926761). It is
transcriptionally controlled by PBX1 and acts as a transcriptional
repressor of CDKN2B (By similarity). It is required for spleen
development. {ECO:0000250|UniProtKB:P42582,
ECO:0000269|PubMed:22560297, ECO:0000269|PubMed:22849347,
ECO:0000269|PubMed:26926761}.
-!- SUBUNIT: Homodimer (via the homeobox); binds DNA as homodimer
(PubMed:22849347). Interacts (via the homeobox) with TBX5 (via the
T-box); this complex binds DNA (PubMed:26926761). Interacts with
HIPK1 and HIPK2, but not HIPK3. Interacts with the C-terminal zinc
finger of GATA4 through its homeobox domain. Also interacts with
JARID2 which represses its ability to activate transcription of
ANF. Interacts with FBLIM1. Interacts with TBX18 (By similarity).
{ECO:0000250|UniProtKB:P42582, ECO:0000269|PubMed:22849347,
ECO:0000269|PubMed:26926761}.
-!- INTERACTION:
Q99593-1:TBX5; NbExp=6; IntAct=EBI-936601, EBI-304423;
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=3;
Name=1;
IsoId=P52952-1; Sequence=Displayed;
Name=2;
IsoId=P52952-2; Sequence=VSP_043492, VSP_043493;
Note=No experimental confirmation available.;
Name=3;
IsoId=P52952-3; Sequence=VSP_045481, VSP_045482;
Note=No experimental confirmation available.;
-!- TISSUE SPECIFICITY: Expressed only in the heart.
-!- DOMAIN: The homeobox domain binds to double-stranded DNA
(PubMed:22849347). {ECO:0000269|PubMed:22849347}.
-!- DISEASE: Atrial septal defect 7, with or without atrioventricular
conduction defects (ASD7) [MIM:108900]: A congenital heart
malformation characterized by incomplete closure of the wall
between the atria resulting in blood flow from the left to the
right atria, and atrioventricular conduction defects in some
cases. {ECO:0000269|PubMed:10587520, ECO:0000269|PubMed:14607454,
ECO:0000269|PubMed:15342699, ECO:0000269|PubMed:15810002,
ECO:0000269|PubMed:9651244}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- DISEASE: Tetralogy of Fallot (TOF) [MIM:187500]: A congenital
heart anomaly which consists of pulmonary stenosis, ventricular
septal defect, dextroposition of the aorta (aorta is on the right
side instead of the left) and hypertrophy of the right ventricle.
In this condition, blood from both ventricles (oxygen-rich and
oxygen-poor) is pumped into the body often causing cyanosis.
{ECO:0000269|PubMed:10587520, ECO:0000269|PubMed:11714651,
ECO:0000269|PubMed:14607454}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- DISEASE: Conotruncal heart malformations (CTHM) [MIM:217095]: A
group of congenital heart defects involving the outflow tracts.
Examples include truncus arteriosus communis, double-outlet right
ventricle and transposition of great arteries. Truncus arteriosus
communis is characterized by a single outflow tract instead of a
separate aorta and pulmonary artery. In transposition of the great
arteries, the aorta arises from the right ventricle and the
pulmonary artery from the left ventricle. In double outlet of the
right ventricle, both the pulmonary artery and aorta arise from
the right ventricle. {ECO:0000269|PubMed:14607454,
ECO:0000269|PubMed:17891434}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- DISEASE: Hypothyroidism, congenital, non-goitrous, 5 (CHNG5)
[MIM:225250]: A non-autoimmune condition characterized by
resistance to thyroid-stimulating hormone (TSH) leading to
increased levels of plasma TSH and low levels of thyroid hormone.
CHNG5 presents variable severity depending on the completeness of
the defect. Most patients are euthyroid and asymptomatic, with a
normal sized thyroid gland. Only a subset of patients develop
hypothyroidism and present a hypoplastic thyroid gland.
{ECO:0000269|PubMed:16418214}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- DISEASE: Ventricular septal defect 3 (VSD3) [MIM:614432]: A common
form of congenital cardiovascular anomaly that may occur alone or
in combination with other cardiac malformations. It can affect any
portion of the ventricular septum, resulting in abnormal
communications between the two lower chambers of the heart.
Classification is based on location of the communication, such as
perimembranous, inlet, outlet (infundibular), central muscular,
marginal muscular, or apical muscular defect. Large defects that
go unrepaired may give rise to cardiac enlargement, congestive
heart failure, pulmonary hypertension, Eisenmenger's syndrome,
delayed fetal brain development, arrhythmias, and even sudden
cardiac death. {ECO:0000269|PubMed:21110066,
ECO:0000269|PubMed:21165553}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- DISEASE: Hypoplastic left heart syndrome 2 (HLHS2) [MIM:614435]: A
syndrome due to defective development of the aorta proximal to the
entrance of the ductus arteriosus, and hypoplasia of the left
ventricle and mitral valve. As a result of the abnormal
circulation, the ductus arteriosus and foramen ovale are patent
and the right atrium, right ventricle, and pulmonary artery are
enlarged. {ECO:0000269|PubMed:14607454,
ECO:0000269|PubMed:15810002}. Note=The disease is caused by
mutations affecting the gene represented in this entry.
-!- SIMILARITY: Belongs to the NK-2 homeobox family. {ECO:0000305}.
-!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
and Haematology;
URL="http://atlasgeneticsoncology.org/Genes/NKX25ID42958ch5q35.html";
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EMBL; U34962; AAC50470.1; -; mRNA.
EMBL; AB021133; BAA35181.1; -; mRNA.
EMBL; AK297844; BAG60178.1; -; mRNA.
EMBL; AK290615; BAF83304.1; -; mRNA.
EMBL; AK309495; -; NOT_ANNOTATED_CDS; mRNA.
EMBL; AC008412; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH471062; EAW61404.1; -; Genomic_DNA.
EMBL; BC025711; AAH25711.1; -; mRNA.
CCDS; CCDS4387.1; -. [P52952-1]
CCDS; CCDS54949.1; -. [P52952-2]
CCDS; CCDS54950.1; -. [P52952-3]
RefSeq; NP_001159647.1; NM_001166175.1. [P52952-3]
RefSeq; NP_001159648.1; NM_001166176.1. [P52952-2]
RefSeq; NP_004378.1; NM_004387.3. [P52952-1]
UniGene; Hs.54473; -.
PDB; 3RKQ; X-ray; 1.70 A; A/B=138-192.
PDB; 4S0H; X-ray; 2.82 A; B/F=142-192.
PDBsum; 3RKQ; -.
PDBsum; 4S0H; -.
ProteinModelPortal; P52952; -.
SMR; P52952; -.
BioGrid; 107864; 20.
IntAct; P52952; 11.
STRING; 9606.ENSP00000327758; -.
iPTMnet; P52952; -.
PhosphoSitePlus; P52952; -.
BioMuta; NKX2-5; -.
DMDM; 1708211; -.
PaxDb; P52952; -.
PeptideAtlas; P52952; -.
PRIDE; P52952; -.
DNASU; 1482; -.
Ensembl; ENST00000329198; ENSP00000327758; ENSG00000183072. [P52952-1]
Ensembl; ENST00000424406; ENSP00000395378; ENSG00000183072. [P52952-3]
Ensembl; ENST00000521848; ENSP00000427906; ENSG00000183072. [P52952-2]
GeneID; 1482; -.
KEGG; hsa:1482; -.
UCSC; uc003mcm.3; human. [P52952-1]
CTD; 1482; -.
DisGeNET; 1482; -.
EuPathDB; HostDB:ENSG00000183072.9; -.
GeneCards; NKX2-5; -.
HGNC; HGNC:2488; NKX2-5.
HPA; HPA065034; -.
MalaCards; NKX2-5; -.
MIM; 108900; phenotype.
MIM; 187500; phenotype.
MIM; 217095; phenotype.
MIM; 225250; phenotype.
MIM; 600584; gene.
MIM; 614432; phenotype.
MIM; 614435; phenotype.
neXtProt; NX_P52952; -.
OpenTargets; ENSG00000183072; -.
Orphanet; 95713; Athyreosis.
Orphanet; 1479; Atrial septal defect - atrioventricular conduction defects.
Orphanet; 99103; Atrial septal defect, ostium secundum type.
Orphanet; 334; Familial atrial fibrillation.
Orphanet; 101351; Familial isolated congenital asplenia.
Orphanet; 871; Familial progressive cardiac conduction defect.
Orphanet; 2248; Hypoplastic left heart syndrome.
Orphanet; 99097; Single ventricular septal defect.
Orphanet; 3303; Tetralogy of Fallot.
Orphanet; 95720; Thyroid hypoplasia.
PharmGKB; PA24202; -.
eggNOG; KOG0842; Eukaryota.
eggNOG; ENOG410XR21; LUCA.
GeneTree; ENSGT00900000140771; -.
HOGENOM; HOG000231923; -.
HOVERGEN; HBG006689; -.
InParanoid; P52952; -.
KO; K09345; -.
OMA; DKKELCA; -.
OrthoDB; EOG091G0LZ2; -.
PhylomeDB; P52952; -.
TreeFam; TF351204; -.
Reactome; R-HSA-2032785; YAP1- and WWTR1 (TAZ)-stimulated gene expression.
Reactome; R-HSA-5578768; Physiological factors.
SignaLink; P52952; -.
SIGNOR; P52952; -.
GeneWiki; NKX2-5; -.
GenomeRNAi; 1482; -.
PRO; PR:P52952; -.
Proteomes; UP000005640; Chromosome 5.
Bgee; ENSG00000183072; -.
CleanEx; HS_NKX2-5; -.
ExpressionAtlas; P52952; baseline and differential.
Genevisible; P52952; HS.
GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
GO; GO:0032991; C:macromolecular complex; IDA:UniProtKB.
GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
GO; GO:0032993; C:protein-DNA complex; IDA:UniProtKB.
GO; GO:0090575; C:RNA polymerase II transcription factor complex; IDA:BHF-UCL.
GO; GO:0005667; C:transcription factor complex; IC:BHF-UCL.
GO; GO:0003682; F:chromatin binding; IDA:MGI.
GO; GO:0003677; F:DNA binding; IDA:BHF-UCL.
GO; GO:0046982; F:protein heterodimerization activity; ISS:BHF-UCL.
GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IDA:UniProtKB.
GO; GO:0001104; F:RNA polymerase II transcription cofactor activity; IEA:Ensembl.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:BHF-UCL.
GO; GO:0010736; F:serum response element binding; ISS:BHF-UCL.
GO; GO:0003705; F:transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding; IEA:Ensembl.
GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:UniProtKB.
GO; GO:0008134; F:transcription factor binding; IPI:BHF-UCL.
GO; GO:0044212; F:transcription regulatory region DNA binding; IDA:BHF-UCL.
GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; IMP:NTNU_SB.
GO; GO:0001190; F:transcriptional activator activity, RNA polymerase II transcription factor binding; IEA:Ensembl.
GO; GO:0001228; F:transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding; IDA:BHF-UCL.
GO; GO:0007512; P:adult heart development; IMP:BHF-UCL.
GO; GO:0003278; P:apoptotic process involved in heart morphogenesis; IEA:Ensembl.
GO; GO:0055014; P:atrial cardiac muscle cell development; ISS:BHF-UCL.
GO; GO:0060413; P:atrial septum morphogenesis; IMP:BHF-UCL.
GO; GO:0060928; P:atrioventricular node cell development; IEA:Ensembl.
GO; GO:0060929; P:atrioventricular node cell fate commitment; IEA:Ensembl.
GO; GO:0030509; P:BMP signaling pathway; IEA:Ensembl.
GO; GO:0003166; P:bundle of His development; IEA:Ensembl.
GO; GO:0060070; P:canonical Wnt signaling pathway; IEA:Ensembl.
GO; GO:0003161; P:cardiac conduction system development; IMP:BHF-UCL.
GO; GO:0055007; P:cardiac muscle cell differentiation; ISS:BHF-UCL.
GO; GO:0060038; P:cardiac muscle cell proliferation; IEA:Ensembl.
GO; GO:0060048; P:cardiac muscle contraction; IEA:Ensembl.
GO; GO:0055008; P:cardiac muscle tissue morphogenesis; IMP:BHF-UCL.
GO; GO:0003211; P:cardiac ventricle formation; IEA:Ensembl.
GO; GO:0030154; P:cell differentiation; ISS:BHF-UCL.
GO; GO:0035050; P:embryonic heart tube development; ISS:BHF-UCL.
GO; GO:0060971; P:embryonic heart tube left/right pattern formation; IEA:Ensembl.
GO; GO:0001947; P:heart looping; ISS:BHF-UCL.
GO; GO:0003007; P:heart morphogenesis; ISS:BHF-UCL.
GO; GO:0060347; P:heart trabecula formation; IEA:Ensembl.
GO; GO:0030097; P:hemopoiesis; ISS:BHF-UCL.
GO; GO:0043066; P:negative regulation of apoptotic process; ISS:BHF-UCL.
GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISS:BHF-UCL.
GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IMP:BHF-UCL.
GO; GO:0010832; P:negative regulation of myotube differentiation; IMP:BHF-UCL.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL.
GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:BHF-UCL.
GO; GO:0003148; P:outflow tract septum morphogenesis; IMP:BHF-UCL.
GO; GO:0060037; P:pharyngeal system development; ISS:BHF-UCL.
GO; GO:0051891; P:positive regulation of cardioblast differentiation; ISS:BHF-UCL.
GO; GO:0008284; P:positive regulation of cell proliferation; ISS:BHF-UCL.
GO; GO:0045823; P:positive regulation of heart contraction; ISS:BHF-UCL.
GO; GO:0045666; P:positive regulation of neuron differentiation; IMP:BHF-UCL.
GO; GO:0010765; P:positive regulation of sodium ion transport; ISS:BHF-UCL.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
GO; GO:0060261; P:positive regulation of transcription initiation from RNA polymerase II promoter; ISS:BHF-UCL.
GO; GO:0010735; P:positive regulation of transcription via serum response element binding; ISS:BHF-UCL.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
GO; GO:0003342; P:proepicardium development; IEA:Ensembl.
GO; GO:0003350; P:pulmonary myocardium development; IEA:Ensembl.
GO; GO:0003168; P:Purkinje myocyte differentiation; IEA:Ensembl.
GO; GO:1903779; P:regulation of cardiac conduction; ISS:BHF-UCL.
GO; GO:0060043; P:regulation of cardiac muscle cell proliferation; IEA:Ensembl.
GO; GO:0055117; P:regulation of cardiac muscle contraction; ISS:BHF-UCL.
GO; GO:0003221; P:right ventricular cardiac muscle tissue morphogenesis; IMP:BHF-UCL.
GO; GO:0045214; P:sarcomere organization; IEA:Ensembl.
GO; GO:0003285; P:septum secundum development; IMP:BHF-UCL.
GO; GO:0048536; P:spleen development; IMP:UniProtKB.
GO; GO:0030878; P:thyroid gland development; IMP:BHF-UCL.
GO; GO:0001570; P:vasculogenesis; ISS:BHF-UCL.
GO; GO:0055015; P:ventricular cardiac muscle cell development; ISS:BHF-UCL.
GO; GO:0055005; P:ventricular cardiac myofibril assembly; IEA:Ensembl.
GO; GO:0060412; P:ventricular septum morphogenesis; IMP:BHF-UCL.
GO; GO:0003222; P:ventricular trabecula myocardium morphogenesis; IEA:Ensembl.
CDD; cd00086; homeodomain; 1.
InterPro; IPR009057; Homeobox-like.
InterPro; IPR017970; Homeobox_CS.
InterPro; IPR001356; Homeobox_dom.
InterPro; IPR020479; Homeobox_metazoa.
InterPro; IPR033629; NKX-2.5.
PANTHER; PTHR24340:SF28; PTHR24340:SF28; 1.
Pfam; PF00046; Homeobox; 1.
PRINTS; PR00024; HOMEOBOX.
SMART; SM00389; HOX; 1.
SUPFAM; SSF46689; SSF46689; 1.
PROSITE; PS00027; HOMEOBOX_1; 1.
PROSITE; PS50071; HOMEOBOX_2; 1.
1: Evidence at protein level;
3D-structure; Alternative splicing; Atrial septal defect;
Complete proteome; Congenital hypothyroidism; Developmental protein;
Disease mutation; DNA-binding; Homeobox; Nucleus; Polymorphism;
Reference proteome.
CHAIN 1 324 Homeobox protein Nkx-2.5.
/FTId=PRO_0000048937.
DNA_BIND 138 197 Homeobox. {ECO:0000255|PROSITE-
ProRule:PRU00108,
ECO:0000269|PubMed:22849347,
ECO:0000269|PubMed:26926761}.
COMPBIAS 42 108 Ala/Pro-rich.
COMPBIAS 208 282 Ala/Pro-rich.
VAR_SEQ 112 151 ELCALQKAVELEKTEADNAERPRARRRRKPRVLFSQAQVY
-> GCELPRGQRPPVLFSSALSQPDFLQMLSETCRWLPVHL
AE (in isoform 2).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_043492.
VAR_SEQ 112 112 E -> A (in isoform 3).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_045481.
VAR_SEQ 113 324 Missing (in isoform 3).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_045482.
VAR_SEQ 152 324 Missing (in isoform 2).
{ECO:0000303|PubMed:14702039}.
/FTId=VSP_043493.
VARIANT 7 7 L -> P (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038212.
VARIANT 15 15 K -> I (in ASD7; dbSNP:rs387906773).
{ECO:0000269|PubMed:14607454,
ECO:0000269|PubMed:15810002}.
/FTId=VAR_038213.
VARIANT 16 16 D -> A (in dbSNP:rs17052019).
/FTId=VAR_049581.
VARIANT 19 19 N -> S (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038214.
VARIANT 21 21 E -> Q (in TOF and ASD7;
dbSNP:rs104893904).
{ECO:0000269|PubMed:11714651,
ECO:0000269|PubMed:14607454,
ECO:0000269|PubMed:15810002}.
/FTId=VAR_038215.
VARIANT 22 22 Q -> P (in ASD7 and TOF).
{ECO:0000269|PubMed:14607454,
ECO:0000269|PubMed:15810002}.
/FTId=VAR_038216.
VARIANT 25 25 R -> C (in ASD7, TOF, CHNG5, HLHS2 and
CTHM; unknown pathological significance;
exhibits significant functional
impairment with reduction of
transactivation properties and dominant-
negative effect; the mutant protein
activity on the DIO2, TG and TPO
promoters is significantly impaired;
dbSNP:rs28936670).
{ECO:0000269|PubMed:10587520,
ECO:0000269|PubMed:11714651,
ECO:0000269|PubMed:14607454,
ECO:0000269|PubMed:15342699,
ECO:0000269|PubMed:15810002,
ECO:0000269|PubMed:16418214,
ECO:0000269|PubMed:17891434}.
/FTId=VAR_010116.
VARIANT 45 45 S -> P (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038217.
VARIANT 51 51 F -> L (in ASD7; somatic mutation;
dbSNP:rs753937287).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038218.
VARIANT 59 59 P -> A (in VSD3; significantly reduced
activation of NPPA gene compared to wild-
type; dbSNP:rs387906775).
{ECO:0000269|PubMed:21165553}.
/FTId=VAR_067586.
VARIANT 63 63 A -> V (in ASD7; dbSNP:rs530270916).
{ECO:0000269|PubMed:14607454,
ECO:0000269|PubMed:15810002}.
/FTId=VAR_038219.
VARIANT 69 69 L -> P (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038220.
VARIANT 74 74 G -> D (in dbSNP:rs201362118).
{ECO:0000269|PubMed:14702039}.
/FTId=VAR_069058.
VARIANT 77 77 P -> L (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038221.
VARIANT 114 114 C -> R (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038222.
VARIANT 114 114 C -> S (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038223.
VARIANT 118 118 K -> R (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038224.
VARIANT 119 119 A -> S (in CHNG5; exhibits a significant
functional impairment with reduction of
transactivation properties and dominant-
negative effect which was associated with
reduced DNA binding; dbSNP:rs137852684).
{ECO:0000269|PubMed:16418214}.
/FTId=VAR_047869.
VARIANT 124 124 K -> R (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038225.
VARIANT 126 126 E -> V (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038226.
VARIANT 127 127 A -> E (in ASD7; dbSNP:rs387906774).
{ECO:0000269|PubMed:14607454,
ECO:0000269|PubMed:15810002}.
/FTId=VAR_038227.
VARIANT 133 133 P -> S (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038228.
VARIANT 135 135 A -> T (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038229.
VARIANT 142 142 R -> C (in ASD7).
{ECO:0000269|PubMed:15810002}.
/FTId=VAR_038230.
VARIANT 144 144 L -> P (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038231.
VARIANT 161 161 R -> P (in CHNG5; exhibits a significant
functional impairment with reduction of
transactivation properties and dominant-
negative effect which was associated with
reduced DNA binding; dbSNP:rs137852685).
{ECO:0000269|PubMed:16418214}.
/FTId=VAR_047870.
VARIANT 178 178 T -> M (in ASD7; dbSNP:rs104893900).
{ECO:0000269|PubMed:15342699,
ECO:0000269|PubMed:15810002,
ECO:0000269|PubMed:9651244}.
/FTId=VAR_003752.
VARIANT 183 183 K -> E (in ASD7; somatic mutation;
dbSNP:rs137852686).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038232.
VARIANT 187 187 Q -> H (in ASD7).
{ECO:0000269|PubMed:15810002}.
/FTId=VAR_038233.
VARIANT 188 188 N -> K (in ASD7).
{ECO:0000269|PubMed:10587520,
ECO:0000269|PubMed:15810002}.
/FTId=VAR_010117.
VARIANT 189 189 R -> G (in ASD7).
{ECO:0000269|PubMed:10587520,
ECO:0000269|PubMed:15810002}.
/FTId=VAR_010118.
VARIANT 190 190 R -> C (in ASD7; dbSNP:rs104893906).
{ECO:0000269|PubMed:15810002}.
/FTId=VAR_038234.
VARIANT 191 191 Y -> C (in ASD7).
{ECO:0000269|PubMed:10587520,
ECO:0000269|PubMed:15810002}.
/FTId=VAR_010119.
VARIANT 192 192 K -> R (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038235.
VARIANT 192 192 K -> T (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038236.
VARIANT 194 194 K -> R (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038237.
VARIANT 205 205 V -> E (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038238.
VARIANT 216 216 R -> C (in TOF and ASD7;
dbSNP:rs104893905).
{ECO:0000269|PubMed:11714651,
ECO:0000269|PubMed:14607454,
ECO:0000269|PubMed:15810002}.
/FTId=VAR_038239.
VARIANT 219 219 A -> V (in ASD7 and TOF; somatic
mutation; dbSNP:rs104893902).
{ECO:0000269|PubMed:11714651,
ECO:0000269|PubMed:14607454,
ECO:0000269|PubMed:15342699,
ECO:0000269|PubMed:15810002}.
/FTId=VAR_038240.
VARIANT 226 226 D -> N (in ASD7; somatic mutation;
dbSNP:rs760528062).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038241.
VARIANT 236 236 P -> H (found in patients with isolated
congenital asplenia; unknown pathological
significance; does not affect DNA
binding; impairs transactivation
activity; dbSNP:rs397515399).
{ECO:0000269|PubMed:22560297}.
/FTId=VAR_069590.
VARIANT 248 248 Y -> H (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038242.
VARIANT 275 275 P -> T (in ASD7; dbSNP:rs368366482).
{ECO:0000269|PubMed:14607454,
ECO:0000269|PubMed:15810002}.
/FTId=VAR_038243.
VARIANT 279 279 S -> F (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038244.
VARIANT 279 279 S -> P (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038245.
VARIANT 281 281 A -> V (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038246.
VARIANT 283 283 P -> Q (in VSD3; dbSNP:rs375086983).
{ECO:0000269|PubMed:21110066}.
/FTId=VAR_067587.
VARIANT 286 286 A -> V (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038247.
VARIANT 291 291 Missing (in CTMH).
{ECO:0000269|PubMed:14607454}.
/FTId=VAR_067588.
VARIANT 294 294 N -> H (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038248.
VARIANT 299 299 D -> G (in ASD7; somatic mutation;
dbSNP:rs137852683).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038249.
VARIANT 305 305 S -> G (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038250.
VARIANT 320 320 G -> S (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038251.
VARIANT 322 322 R -> Q (in ASD7; somatic mutation).
{ECO:0000269|PubMed:15342699}.
/FTId=VAR_038252.
VARIANT 323 323 A -> T (in ASD7 and TOF).
{ECO:0000269|PubMed:14607454,
ECO:0000269|PubMed:15810002}.
/FTId=VAR_038253.
HELIX 147 157 {ECO:0000244|PDB:3RKQ}.
HELIX 165 175 {ECO:0000244|PDB:3RKQ}.
HELIX 179 192 {ECO:0000244|PDB:3RKQ}.
SEQUENCE 324 AA; 34918 MW; ACCC9C2F9C292586 CRC64;
MFPSPALTPT PFSVKDILNL EQQQRSLAAA GELSARLEAT LAPSSCMLAA FKPEAYAGPE
AAAPGLPELR AELGRAPSPA KCASAFPAAP AFYPRAYSDP DPAKDPRAEK KELCALQKAV
ELEKTEADNA ERPRARRRRK PRVLFSQAQV YELERRFKQQ RYLSAPERDQ LASVLKLTST
QVKIWFQNRR YKCKRQRQDQ TLELVGLPPP PPPPARRIAV PVLVRDGKPC LGDSAPYAPA
YGVGLNPYGY NAYPAYPGYG GAACSPGYSC TAAYPAGPSP AQPATAAANN NFVNFGVGDL
NAVQSPGIPQ SNSGVSTLHG IRAW


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