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P52952 (NKX25_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 153. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Homeobox protein Nkx-2.5
Alternative name(s):
Cardiac-specific homeobox
Homeobox protein CSX
Homeobox protein NK-2 homolog E
Gene names
Name:NKX2-5
Synonyms:CSX, NKX2.5, NKX2E
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length324 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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. It is transcriptionally controlled by PBX1 and acts as a transcriptional repressor of CDKN2B By similarity. It is required for spleen development. Ref.7

Subunit structure

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 By similarity.

Subcellular location

Nucleus Probable.

Tissue specificity

Expressed only in the heart.

Involvement in 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9 Ref.11 Ref.12 Ref.13

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9 Ref.10 Ref.11

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.
Note: The disease is caused by mutations affecting the gene represented in this entry.

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.14

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.15 Ref.16

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.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Asplenia, isolated congenital (ICAS) [MIM:271400]: A rare primary immunodeficiency and life-threatening condition, often presenting with pneumococcal sepsis. Most affected individuals die of severe bacterial infections in early childhood. Isolated asplenia is distinct from asplenia associated with other complex visceral defects, notably heterotaxy syndromes such as Ivemark syndrome.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7

Sequence similarities

Belongs to the NK-2 homeobox family.

Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseAtrial septal defect
Congenital hypothyroidism
Disease mutation
   DomainHomeobox
   LigandDNA-binding
   Molecular functionDevelopmental protein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processBMP signaling pathway

Inferred from electronic annotation. Source: Ensembl

Purkinje myocyte differentiation

Inferred from electronic annotation. Source: Ensembl

adult heart development

Inferred from mutant phenotype Ref.8. Source: BHF-UCL

apoptotic process involved in heart morphogenesis

Inferred from electronic annotation. Source: Ensembl

atrial cardiac muscle cell development

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

atrial septum morphogenesis

Inferred from mutant phenotype Ref.9Ref.8. Source: BHF-UCL

atrioventricular node cell development

Inferred from electronic annotation. Source: Ensembl

atrioventricular node cell fate commitment

Inferred from electronic annotation. Source: Ensembl

bundle of His development

Inferred from electronic annotation. Source: Ensembl

canonical Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

cardiac conduction system development

Inferred from mutant phenotype PubMed 15109497. Source: MGI

cardiac muscle cell differentiation

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

cardiac muscle cell proliferation

Inferred from electronic annotation. Source: Ensembl

cardiac muscle contraction

Inferred from electronic annotation. Source: Ensembl

cardiac muscle tissue morphogenesis

Inferred from mutant phenotype PubMed 11889119. Source: BHF-UCL

cardiac ventricle formation

Inferred from electronic annotation. Source: Ensembl

cell differentiation

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

embryonic heart tube development

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

embryonic heart tube left/right pattern formation

Inferred from electronic annotation. Source: Ensembl

heart looping

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

heart morphogenesis

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

heart trabecula formation

Inferred from electronic annotation. Source: Ensembl

hemopoiesis

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

negative regulation of apoptotic process

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

negative regulation of canonical Wnt signaling pathway

Inferred from sequence or structural similarity. Source: BHF-UCL

negative regulation of cardiac muscle cell apoptotic process

Inferred from mutant phenotype PubMed 11889119. Source: BHF-UCL

negative regulation of myotube differentiation

Inferred from mutant phenotype PubMed 15653675. Source: BHF-UCL

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 19479054. Source: BHF-UCL

negative regulation of transcription, DNA-templated

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

outflow tract septum morphogenesis

Inferred from mutant phenotype PubMed 20807224. Source: BHF-UCL

pharyngeal system development

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

positive regulation of cardioblast differentiation

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

positive regulation of cell proliferation

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

positive regulation of heart contraction

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of neuron differentiation

Inferred from mutant phenotype PubMed 15653675. Source: BHF-UCL

positive regulation of sodium ion transport

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 10948187. Source: BHF-UCL

positive regulation of transcription initiation from RNA polymerase II promoter

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

positive regulation of transcription via serum response element binding

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 11431700. Source: UniProtKB

positive regulation of voltage-gated calcium channel activity

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

proepicardium development

Inferred from electronic annotation. Source: Ensembl

pulmonary myocardium development

Inferred from electronic annotation. Source: Ensembl

regulation of cardiac muscle cell proliferation

Inferred from electronic annotation. Source: Ensembl

regulation of cardiac muscle contraction

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

right ventricular cardiac muscle tissue morphogenesis

Inferred from mutant phenotype PubMed 20807224. Source: BHF-UCL

sarcomere organization

Inferred from electronic annotation. Source: Ensembl

septum secundum development

Inferred from mutant phenotype Ref.9. Source: BHF-UCL

spleen development

Inferred from mutant phenotype Ref.7. Source: UniProtKB

thyroid gland development

Inferred from mutant phenotype Ref.14. Source: BHF-UCL

vasculogenesis

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

ventricular cardiac muscle cell development

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

ventricular cardiac myofibril assembly

Inferred from electronic annotation. Source: Ensembl

ventricular septum morphogenesis

Inferred from mutant phenotype Ref.9PubMed 20807224. Source: BHF-UCL

ventricular trabecula myocardium morphogenesis

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from direct assay PubMed 10948187PubMed 9858576. Source: BHF-UCL

transcription factor complex

Inferred by curator PubMed 9312027. Source: BHF-UCL

   Molecular_functionDNA binding

Inferred from direct assay PubMed 9858576. Source: BHF-UCL

RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity

Inferred from electronic annotation. Source: Ensembl

RNA polymerase II transcription cofactor activity

Inferred from electronic annotation. Source: Ensembl

RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription

Inferred from electronic annotation. Source: Ensembl

chromatin binding

Inferred from direct assay PubMed 16678093. Source: MGI

protein binding

Inferred from physical interaction PubMed 11431700PubMed 12499378PubMed 19797053. Source: UniProtKB

protein heterodimerization activity

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

sequence-specific DNA binding

Inferred from direct assay PubMed 10948187. Source: BHF-UCL

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 11431700. Source: UniProtKB

serum response element binding

Inferred from sequence or structural similarity Ref.1. Source: BHF-UCL

transcription factor binding

Inferred from physical interaction PubMed 11431700PubMed 9858576. Source: BHF-UCL

transcription regulatory region DNA binding

Inferred from direct assay PubMed 19479054. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

TBX5Q99593-16EBI-936601,EBI-304423

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P52952-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P52952-2)

The sequence of this isoform differs from the canonical sequence as follows:
     112-151: ELCALQKAVE...RVLFSQAQVY → GCELPRGQRP...CRWLPVHLAE
     152-324: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: P52952-3)

The sequence of this isoform differs from the canonical sequence as follows:
     112-112: E → A
     113-324: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 324324Homeobox protein Nkx-2.5
PRO_0000048937

Regions

DNA binding138 – 19760Homeobox
Compositional bias42 – 10867Ala/Pro-rich
Compositional bias208 – 28275Ala/Pro-rich

Natural variations

Alternative sequence112 – 15140ELCAL…QAQVY → GCELPRGQRPPVLFSSALSQ PDFLQMLSETCRWLPVHLAE in isoform 2.
VSP_043492
Alternative sequence1121E → A in isoform 3.
VSP_045481
Alternative sequence113 – 324212Missing in isoform 3.
VSP_045482
Alternative sequence152 – 324173Missing in isoform 2.
VSP_043493
Natural variant71L → P in ASD7; somatic mutation. Ref.12
VAR_038212
Natural variant151K → I in ASD7. Ref.11 Ref.13
VAR_038213
Natural variant161D → A.
Corresponds to variant rs17052019 [ dbSNP | Ensembl ].
VAR_049581
Natural variant191N → S in ASD7; somatic mutation. Ref.12
VAR_038214
Natural variant211E → Q in TOF and ASD7. Ref.10 Ref.11 Ref.13
VAR_038215
Natural variant221Q → P in ASD7 and TOF. Ref.11 Ref.13
VAR_038216
Natural variant251R → C in ASD7, TOF, CHNG5 and HLHS2; 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. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14
Corresponds to variant rs28936670 [ dbSNP | Ensembl ].
VAR_010116
Natural variant451S → P in ASD7; somatic mutation. Ref.12
VAR_038217
Natural variant511F → L in ASD7; somatic mutation. Ref.12
VAR_038218
Natural variant591P → A in VSD3; significantly reduced activation of NPPA gene compared to wild-type. Ref.16
VAR_067586
Natural variant631A → V in ASD7. Ref.11 Ref.13
VAR_038219
Natural variant691L → P in ASD7; somatic mutation. Ref.12
VAR_038220
Natural variant741G → D. Ref.3
Corresponds to variant rs201362118 [ dbSNP | Ensembl ].
VAR_069058
Natural variant771P → L in ASD7; somatic mutation. Ref.12
VAR_038221
Natural variant1141C → R in ASD7; somatic mutation. Ref.12
VAR_038222
Natural variant1141C → S in ASD7; somatic mutation. Ref.12
VAR_038223
Natural variant1181K → R in ASD7; somatic mutation. Ref.12
VAR_038224
Natural variant1191A → S in CHNG5; exhibits a significant functional impairment with reduction of transactivation properties and dominant-negative effect which was associated with reduced DNA binding. Ref.14
VAR_047869
Natural variant1241K → R in ASD7; somatic mutation. Ref.12
VAR_038225
Natural variant1261E → V in ASD7; somatic mutation. Ref.12
VAR_038226
Natural variant1271A → E in ASD7. Ref.11 Ref.13
VAR_038227
Natural variant1331P → S in ASD7; somatic mutation. Ref.12
VAR_038228
Natural variant1351A → T in ASD7; somatic mutation. Ref.12
VAR_038229
Natural variant1421R → C in ASD7. Ref.13
VAR_038230
Natural variant1441L → P in ASD7; somatic mutation. Ref.12
VAR_038231
Natural variant1611R → P in CHNG5; exhibits a significant functional impairment with reduction of transactivation properties and dominant-negative effect which was associated with reduced DNA binding. Ref.14
VAR_047870
Natural variant1781T → M in ASD7. Ref.8 Ref.12 Ref.13
VAR_003752
Natural variant1831K → E in ASD7; somatic mutation. Ref.12
VAR_038232
Natural variant1871Q → H in ASD7. Ref.13
VAR_038233
Natural variant1881N → K in ASD7. Ref.9 Ref.13
VAR_010117
Natural variant1891R → G in ASD7. Ref.9 Ref.13
VAR_010118
Natural variant1901R → C in ASD7. Ref.13
VAR_038234
Natural variant1911Y → C in ASD7. Ref.9 Ref.13
VAR_010119
Natural variant1921K → R in ASD7; somatic mutation. Ref.12
VAR_038235
Natural variant1921K → T in ASD7; somatic mutation. Ref.12
VAR_038236
Natural variant1941K → R in ASD7; somatic mutation. Ref.12
VAR_038237
Natural variant2051V → E in ASD7; somatic mutation. Ref.12
VAR_038238
Natural variant2161R → C in TOF and ASD7. Ref.10 Ref.11 Ref.13
VAR_038239
Natural variant2191A → V in ASD7 and TOF; somatic mutation. Ref.10 Ref.11 Ref.12 Ref.13
VAR_038240
Natural variant2261D → N in ASD7; somatic mutation. Ref.12
VAR_038241
Natural variant2361P → H in ICAS; does not affect DNA binding; impairs transactivation activity. Ref.7
VAR_069590
Natural variant2481Y → H in ASD7; somatic mutation. Ref.12
VAR_038242
Natural variant2751P → T in ASD7. Ref.11 Ref.13
VAR_038243
Natural variant2791S → F in ASD7; somatic mutation. Ref.12
VAR_038244
Natural variant2791S → P in ASD7; somatic mutation. Ref.12
VAR_038245
Natural variant2811A → V in ASD7; somatic mutation. Ref.12
VAR_038246
Natural variant2831P → Q in VSD3. Ref.15
VAR_067587
Natural variant2861A → V in ASD7; somatic mutation. Ref.12
VAR_038247
Natural variant2911Missing in CTMH. Ref.11
VAR_067588
Natural variant2941N → H in ASD7; somatic mutation. Ref.12
VAR_038248
Natural variant2991D → G in ASD7; somatic mutation. Ref.12
VAR_038249
Natural variant3051S → G in ASD7; somatic mutation. Ref.12
VAR_038250
Natural variant3201G → S in ASD7; somatic mutation. Ref.12
VAR_038251
Natural variant3221R → Q in ASD7; somatic mutation. Ref.12
VAR_038252
Natural variant3231A → T in ASD7 and TOF. Ref.11 Ref.13
VAR_038253

Secondary structure

....... 324
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: ACCC9C2F9C292586

FASTA32434,918
        10         20         30         40         50         60 
MFPSPALTPT PFSVKDILNL EQQQRSLAAA GELSARLEAT LAPSSCMLAA FKPEAYAGPE 

        70         80         90        100        110        120 
AAAPGLPELR AELGRAPSPA KCASAFPAAP AFYPRAYSDP DPAKDPRAEK KELCALQKAV 

       130        140        150        160        170        180 
ELEKTEADNA ERPRARRRRK PRVLFSQAQV YELERRFKQQ RYLSAPERDQ LASVLKLTST 

       190        200        210        220        230        240 
QVKIWFQNRR YKCKRQRQDQ TLELVGLPPP PPPPARRIAV PVLVRDGKPC LGDSAPYAPA 

       250        260        270        280        290        300 
YGVGLNPYGY NAYPAYPGYG GAACSPGYSC TAAYPAGPSP AQPATAAANN NFVNFGVGDL 

       310        320 
NAVQSPGIPQ SNSGVSTLHG IRAW 

« Hide

Isoform 2 [UniParc].

Checksum: FFBDEE031AFCB6AF
Show »

FASTA15116,102
Isoform 3 [UniParc].

Checksum: 1DED387CB9297E28
Show »

FASTA11211,681

References

« Hide 'large scale' references
[1]"Molecular cloning, chromosomal mapping, and characterization of the human cardiac-specific homeobox gene hCsx."
Turbay D., Wechsler S.B., Blanchard K.M., Izumo S.
Mol. Med. 2:86-96(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Heart.
[2]"Human Nkx-2.5 gene."
Tate G., Mitsuya T.
Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Fetal lung.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
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. expand/collapse author list , 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.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), VARIANT ASP-74.
Tissue: Heart.
[4]"The DNA sequence and comparative analysis of human chromosome 5."
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. expand/collapse author list , 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.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]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. expand/collapse author list , 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
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Pancreas and Spleen.
[7]"Congenital asplenia in mice and humans with mutations in a Pbx/Nkx2-5/p15 module."
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.
Dev. Cell 22:913-926(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, VARIANT ICAS HIS-236, CHARACTERIZATION OF VARIANT ICAS HIS-236.
[8]"Congenital heart disease caused by mutations in the transcription factor NKX2-5."
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.
Science 281:108-111(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ASD7 MET-178.
[9]"Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways."
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.
J. Clin. Invest. 104:1567-1573(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TOF CYS-25, VARIANTS ASD7 LYS-188; GLY-189 AND CYS-191.
[10]"NKX2.5 mutations in patients with tetralogy of fallot."
Goldmuntz E., Geiger E., Benson D.W.
Circulation 104:2565-2568(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS TOF GLN-21; CYS-25; CYS-216 AND VAL-219.
[11]"NKX2.5 mutations in patients with congenital heart disease."
McElhinney D.B., Geiger E., Blinder J., Benson D.W., Goldmuntz E.
J. Am. Coll. Cardiol. 42:1650-1655(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: 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.
[12]"Somatic NKX2-5 mutations as a novel mechanism of disease in complex congenital heart disease."
Reamon-Buettner S.M., Borlak J.
J. Med. Genet. 41:684-690(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: 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.
[13]"Phenotypes with GATA4 or NKX2.5 mutations in familial atrial septal defect."
Hirayama-Yamada K., Kamisago M., Akimoto K., Aotsuka H., Nakamura Y., Tomita H., Furutani M., Imamura S., Takao A., Nakazawa M., Matsuoka R.
Am. J. Med. Genet. A 135:47-52(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: 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.
[14]"Missense mutation in the transcription factor NKX2-5: a novel molecular event in the pathogenesis of thyroid dysgenesis."
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.
J. Clin. Endocrinol. Metab. 91:1428-1433(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CHNG5 CYS-25; SER-119 AND PRO-161, CHARACTERIZATION OF VARIANTS CHNG5 CYS-25; SER-119 AND PRO-161.
[15]"Mutations of the GATA4 and NKX2.5 genes in Chinese pediatric patients with non-familial congenital heart disease."
Peng T., Wang L., Zhou S.F., Li X.
Genetica 138:1231-1240(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VSD3 GLN-283.
[16]"A novel NKX2-5 mutation in familial ventricular septal defect."
Wang J., Xin Y.F., Liu X.Y., Liu Z.M., Wang X.Z., Yang Y.Q.
Int. J. Mol. Med. 27:369-375(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VSD3 ALA-59, CHARACTERIZATION OF VARIANT VSD3 ALA-59.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U34962 mRNA. Translation: AAC50470.1.
AB021133 mRNA. Translation: BAA35181.1.
AK297844 mRNA. Translation: BAG60178.1.
AK290615 mRNA. Translation: BAF83304.1.
AK309495 mRNA. No translation available.
AC008412 Genomic DNA. No translation available.
CH471062 Genomic DNA. Translation: EAW61404.1.
BC025711 mRNA. Translation: AAH25711.1.
CCDSCCDS4387.1. [P52952-1]
CCDS54949.1. [P52952-2]
CCDS54950.1. [P52952-3]
RefSeqNP_001159647.1. NM_001166175.1. [P52952-3]
NP_001159648.1. NM_001166176.1. [P52952-2]
NP_004378.1. NM_004387.3. [P52952-1]
UniGeneHs.54473.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3RKQX-ray1.70A/B138-192[»]
ProteinModelPortalP52952.
SMRP52952. Positions 138-192.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107864. 11 interactions.
IntActP52952. 2 interactions.
STRING9606.ENSP00000327758.

PTM databases

PhosphoSiteP52952.

Polymorphism databases

DMDM1708211.

Proteomic databases

PaxDbP52952.
PRIDEP52952.

Protocols and materials databases

DNASU1482.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000329198; ENSP00000327758; ENSG00000183072. [P52952-1]
ENST00000424406; ENSP00000395378; ENSG00000183072. [P52952-3]
ENST00000521848; ENSP00000427906; ENSG00000183072. [P52952-2]
GeneID1482.
KEGGhsa:1482.
UCSCuc003mcm.2. human. [P52952-1]
uc011dfe.2. human. [P52952-2]

Organism-specific databases

CTD1482.
GeneCardsGC05M172659.
HGNCHGNC:2488. NKX2-5.
MIM108900. phenotype.
187500. phenotype.
217095. phenotype.
225250. phenotype.
271400. phenotype.
600584. gene.
614432. phenotype.
614435. phenotype.
neXtProtNX_P52952.
Orphanet95713. Athyreosis.
1479. Atrial septal defect - atrioventricular conduction defects.
99103. Atrial septal defect, ostium secundum type.
334. Familial atrial fibrillation.
101351. Familial isolated congenital asplenia.
871. Familial progressive cardiac conduction defect.
2248. Hypoplastic left heart syndrome.
99097. Single ventricular septal defect.
3303. Tetralogy of Fallot.
95720. Thyroid hypoplasia.
PharmGKBPA24202.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG310976.
HOGENOMHOG000231923.
HOVERGENHBG006689.
InParanoidP52952.
KOK09345.
OMAAYGDPDP.
OrthoDBEOG769ZK0.
PhylomeDBP52952.
TreeFamTF351204.

Enzyme and pathway databases

SignaLinkP52952.

Gene expression databases

ArrayExpressP52952.
BgeeP52952.
CleanExHS_NKX2-5.
GenevestigatorP52952.

Family and domain databases

Gene3D1.10.10.60. 1 hit.
InterProIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR020479. Homeobox_metazoa.
IPR009057. Homeodomain-like.
[Graphical view]
PfamPF00046. Homeobox. 1 hit.
[Graphical view]
PRINTSPR00024. HOMEOBOX.
SMARTSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMSSF46689. SSF46689. 1 hit.
PROSITEPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiNKX2-5.
GenomeRNAi1482.
NextBio6089.
PROP52952.
SOURCESearch...

Entry information

Entry nameNKX25_HUMAN
AccessionPrimary (citable) accession number: P52952
Secondary accession number(s): A8K3K0, B4DNB6, E9PBU6
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: July 9, 2014
This is version 153 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM