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P52952

- NKX25_HUMAN

UniProt

P52952 - NKX25_HUMAN

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Protein

Homeobox protein Nkx-2.5

Gene

NKX2-5

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.By similarity1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi138 – 19760HomeoboxPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. chromatin binding Source: MGI
  2. DNA binding Source: BHF-UCL
  3. protein heterodimerization activity Source: BHF-UCL
  4. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  5. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: NTNU_SB
  6. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: Ensembl
  7. RNA polymerase II transcription cofactor activity Source: Ensembl
  8. RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription Source: Ensembl
  9. sequence-specific DNA binding Source: BHF-UCL
  10. sequence-specific DNA binding transcription factor activity Source: UniProtKB
  11. serum response element binding Source: BHF-UCL
  12. transcription factor binding Source: BHF-UCL
  13. transcription regulatory region DNA binding Source: BHF-UCL

GO - Biological processi

  1. adult heart development Source: BHF-UCL
  2. apoptotic process involved in heart morphogenesis Source: Ensembl
  3. atrial cardiac muscle cell development Source: BHF-UCL
  4. atrial septum morphogenesis Source: BHF-UCL
  5. atrioventricular node cell development Source: Ensembl
  6. atrioventricular node cell fate commitment Source: Ensembl
  7. BMP signaling pathway Source: Ensembl
  8. bundle of His development Source: Ensembl
  9. canonical Wnt signaling pathway Source: Ensembl
  10. cardiac conduction system development Source: MGI
  11. cardiac muscle cell differentiation Source: BHF-UCL
  12. cardiac muscle cell proliferation Source: Ensembl
  13. cardiac muscle contraction Source: Ensembl
  14. cardiac muscle tissue morphogenesis Source: BHF-UCL
  15. cardiac ventricle formation Source: Ensembl
  16. cell differentiation Source: BHF-UCL
  17. embryonic heart tube development Source: BHF-UCL
  18. embryonic heart tube left/right pattern formation Source: Ensembl
  19. heart looping Source: BHF-UCL
  20. heart morphogenesis Source: BHF-UCL
  21. heart trabecula formation Source: Ensembl
  22. hemopoiesis Source: BHF-UCL
  23. negative regulation of apoptotic process Source: BHF-UCL
  24. negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
  25. negative regulation of cardiac muscle cell apoptotic process Source: BHF-UCL
  26. negative regulation of myotube differentiation Source: BHF-UCL
  27. negative regulation of transcription, DNA-templated Source: BHF-UCL
  28. negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  29. outflow tract septum morphogenesis Source: BHF-UCL
  30. pharyngeal system development Source: BHF-UCL
  31. positive regulation of cardioblast differentiation Source: BHF-UCL
  32. positive regulation of cell proliferation Source: BHF-UCL
  33. positive regulation of heart contraction Source: BHF-UCL
  34. positive regulation of neuron differentiation Source: BHF-UCL
  35. positive regulation of sodium ion transport Source: BHF-UCL
  36. positive regulation of transcription, DNA-templated Source: UniProtKB
  37. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  38. positive regulation of transcription initiation from RNA polymerase II promoter Source: BHF-UCL
  39. positive regulation of transcription via serum response element binding Source: BHF-UCL
  40. positive regulation of voltage-gated calcium channel activity Source: BHF-UCL
  41. proepicardium development Source: Ensembl
  42. pulmonary myocardium development Source: Ensembl
  43. Purkinje myocyte differentiation Source: Ensembl
  44. regulation of cardiac muscle cell proliferation Source: Ensembl
  45. regulation of cardiac muscle contraction Source: BHF-UCL
  46. right ventricular cardiac muscle tissue morphogenesis Source: BHF-UCL
  47. sarcomere organization Source: Ensembl
  48. septum secundum development Source: BHF-UCL
  49. spleen development Source: UniProtKB
  50. thyroid gland development Source: BHF-UCL
  51. vasculogenesis Source: BHF-UCL
  52. ventricular cardiac muscle cell development Source: BHF-UCL
  53. ventricular cardiac myofibril assembly Source: Ensembl
  54. ventricular septum morphogenesis Source: BHF-UCL
  55. ventricular trabecula myocardium morphogenesis Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

SignaLinkiP52952.

Names & Taxonomyi

Protein namesi
Recommended name:
Homeobox protein Nkx-2.5
Alternative name(s):
Cardiac-specific homeobox
Homeobox protein CSX
Homeobox protein NK-2 homolog E
Gene namesi
Name:NKX2-5
Synonyms:CSX, NKX2.5, NKX2E
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 5

Organism-specific databases

HGNCiHGNC:2488. NKX2-5.

Subcellular locationi

Nucleus Curated

GO - Cellular componenti

  1. cytoplasm Source: Ensembl
  2. nucleus Source: BHF-UCL
  3. transcription factor complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

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.5 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti7 – 71L → P in ASD7; somatic mutation. 1 Publication
VAR_038212
Natural varianti15 – 151K → I in ASD7. 2 Publications
VAR_038213
Natural varianti19 – 191N → S in ASD7; somatic mutation. 1 Publication
VAR_038214
Natural varianti21 – 211E → Q in TOF and ASD7. 3 Publications
VAR_038215
Natural varianti22 – 221Q → P in ASD7 and TOF. 2 Publications
VAR_038216
Natural varianti25 – 251R → 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. 6 Publications
Corresponds to variant rs28936670 [ dbSNP | Ensembl ].
VAR_010116
Natural varianti45 – 451S → P in ASD7; somatic mutation. 1 Publication
VAR_038217
Natural varianti51 – 511F → L in ASD7; somatic mutation. 1 Publication
VAR_038218
Natural varianti63 – 631A → V in ASD7. 2 Publications
VAR_038219
Natural varianti69 – 691L → P in ASD7; somatic mutation. 1 Publication
VAR_038220
Natural varianti77 – 771P → L in ASD7; somatic mutation. 1 Publication
VAR_038221
Natural varianti114 – 1141C → R in ASD7; somatic mutation. 1 Publication
VAR_038222
Natural varianti114 – 1141C → S in ASD7; somatic mutation. 1 Publication
VAR_038223
Natural varianti118 – 1181K → R in ASD7; somatic mutation. 1 Publication
VAR_038224
Natural varianti124 – 1241K → R in ASD7; somatic mutation. 1 Publication
VAR_038225
Natural varianti126 – 1261E → V in ASD7; somatic mutation. 1 Publication
VAR_038226
Natural varianti127 – 1271A → E in ASD7. 2 Publications
VAR_038227
Natural varianti133 – 1331P → S in ASD7; somatic mutation. 1 Publication
VAR_038228
Natural varianti135 – 1351A → T in ASD7; somatic mutation. 1 Publication
VAR_038229
Natural varianti142 – 1421R → C in ASD7. 1 Publication
VAR_038230
Natural varianti144 – 1441L → P in ASD7; somatic mutation. 1 Publication
VAR_038231
Natural varianti178 – 1781T → M in ASD7. 3 Publications
VAR_003752
Natural varianti183 – 1831K → E in ASD7; somatic mutation. 1 Publication
VAR_038232
Natural varianti187 – 1871Q → H in ASD7. 1 Publication
VAR_038233
Natural varianti188 – 1881N → K in ASD7. 2 Publications
VAR_010117
Natural varianti189 – 1891R → G in ASD7. 2 Publications
VAR_010118
Natural varianti190 – 1901R → C in ASD7. 1 Publication
VAR_038234
Natural varianti191 – 1911Y → C in ASD7. 2 Publications
VAR_010119
Natural varianti192 – 1921K → R in ASD7; somatic mutation. 1 Publication
VAR_038235
Natural varianti192 – 1921K → T in ASD7; somatic mutation. 1 Publication
VAR_038236
Natural varianti194 – 1941K → R in ASD7; somatic mutation. 1 Publication
VAR_038237
Natural varianti205 – 2051V → E in ASD7; somatic mutation. 1 Publication
VAR_038238
Natural varianti216 – 2161R → C in TOF and ASD7. 3 Publications
VAR_038239
Natural varianti219 – 2191A → V in ASD7 and TOF; somatic mutation. 4 Publications
VAR_038240
Natural varianti226 – 2261D → N in ASD7; somatic mutation. 1 Publication
VAR_038241
Natural varianti248 – 2481Y → H in ASD7; somatic mutation. 1 Publication
VAR_038242
Natural varianti275 – 2751P → T in ASD7. 2 Publications
VAR_038243
Natural varianti279 – 2791S → F in ASD7; somatic mutation. 1 Publication
VAR_038244
Natural varianti279 – 2791S → P in ASD7; somatic mutation. 1 Publication
VAR_038245
Natural varianti281 – 2811A → V in ASD7; somatic mutation. 1 Publication
VAR_038246
Natural varianti286 – 2861A → V in ASD7; somatic mutation. 1 Publication
VAR_038247
Natural varianti294 – 2941N → H in ASD7; somatic mutation. 1 Publication
VAR_038248
Natural varianti299 – 2991D → G in ASD7; somatic mutation. 1 Publication
VAR_038249
Natural varianti305 – 3051S → G in ASD7; somatic mutation. 1 Publication
VAR_038250
Natural varianti320 – 3201G → S in ASD7; somatic mutation. 1 Publication
VAR_038251
Natural varianti322 – 3221R → Q in ASD7; somatic mutation. 1 Publication
VAR_038252
Natural varianti323 – 3231A → T in ASD7 and TOF. 2 Publications
VAR_038253
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.3 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti21 – 211E → Q in TOF and ASD7. 3 Publications
VAR_038215
Natural varianti22 – 221Q → P in ASD7 and TOF. 2 Publications
VAR_038216
Natural varianti25 – 251R → 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. 6 Publications
Corresponds to variant rs28936670 [ dbSNP | Ensembl ].
VAR_010116
Natural varianti216 – 2161R → C in TOF and ASD7. 3 Publications
VAR_038239
Natural varianti219 – 2191A → V in ASD7 and TOF; somatic mutation. 4 Publications
VAR_038240
Natural varianti323 – 3231A → T in ASD7 and TOF. 2 Publications
VAR_038253
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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti25 – 251R → 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. 6 Publications
Corresponds to variant rs28936670 [ dbSNP | Ensembl ].
VAR_010116
Natural varianti119 – 1191A → S in CHNG5; exhibits a significant functional impairment with reduction of transactivation properties and dominant-negative effect which was associated with reduced DNA binding. 1 Publication
VAR_047869
Natural varianti161 – 1611R → P in CHNG5; exhibits a significant functional impairment with reduction of transactivation properties and dominant-negative effect which was associated with reduced DNA binding. 1 Publication
VAR_047870
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.2 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti59 – 591P → A in VSD3; significantly reduced activation of NPPA gene compared to wild-type. 1 Publication
VAR_067586
Natural varianti283 – 2831P → Q in VSD3. 1 Publication
VAR_067587
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.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti25 – 251R → 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. 6 Publications
Corresponds to variant rs28936670 [ dbSNP | Ensembl ].
VAR_010116
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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti236 – 2361P → H in ICAS; does not affect DNA binding; impairs transactivation activity. 1 Publication
VAR_069590

Keywords - Diseasei

Atrial septal defect, Congenital hypothyroidism, Disease mutation

Organism-specific databases

MIMi108900. phenotype.
187500. phenotype.
217095. phenotype.
225250. phenotype.
271400. phenotype.
614432. phenotype.
614435. phenotype.
Orphaneti95713. 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.
PharmGKBiPA24202.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 324324Homeobox protein Nkx-2.5PRO_0000048937Add
BLAST

Proteomic databases

PaxDbiP52952.
PRIDEiP52952.

PTM databases

PhosphoSiteiP52952.

Expressioni

Tissue specificityi

Expressed only in the heart.

Gene expression databases

BgeeiP52952.
CleanExiHS_NKX2-5.
ExpressionAtlasiP52952. baseline and differential.
GenevestigatoriP52952.

Interactioni

Subunit structurei

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

Binary interactionsi

WithEntry#Exp.IntActNotes
TBX5Q99593-16EBI-936601,EBI-304423

Protein-protein interaction databases

BioGridi107864. 11 interactions.
IntActiP52952. 2 interactions.
STRINGi9606.ENSP00000327758.

Structurei

Secondary structure

1
324
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi147 – 15711Combined sources
Helixi165 – 17511Combined sources
Helixi179 – 19214Combined sources

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3RKQX-ray1.70A/B138-192[»]
ProteinModelPortaliP52952.
SMRiP52952. Positions 138-192.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi42 – 10867Ala/Pro-richAdd
BLAST
Compositional biasi208 – 28275Ala/Pro-richAdd
BLAST

Sequence similaritiesi

Belongs to the NK-2 homeobox family.Curated
Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiNOG310976.
GeneTreeiENSGT00760000118779.
HOGENOMiHOG000231923.
HOVERGENiHBG006689.
InParanoidiP52952.
KOiK09345.
OMAiAYGDPDP.
OrthoDBiEOG769ZK0.
PhylomeDBiP52952.
TreeFamiTF351204.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR020479. Homeobox_metazoa.
IPR009057. Homeodomain-like.
[Graphical view]
PfamiPF00046. Homeobox. 1 hit.
[Graphical view]
PRINTSiPR00024. HOMEOBOX.
SMARTiSM00389. HOX. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: P52952-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MFPSPALTPT PFSVKDILNL EQQQRSLAAA GELSARLEAT LAPSSCMLAA
60 70 80 90 100
FKPEAYAGPE AAAPGLPELR AELGRAPSPA KCASAFPAAP AFYPRAYSDP
110 120 130 140 150
DPAKDPRAEK KELCALQKAV ELEKTEADNA ERPRARRRRK PRVLFSQAQV
160 170 180 190 200
YELERRFKQQ RYLSAPERDQ LASVLKLTST QVKIWFQNRR YKCKRQRQDQ
210 220 230 240 250
TLELVGLPPP PPPPARRIAV PVLVRDGKPC LGDSAPYAPA YGVGLNPYGY
260 270 280 290 300
NAYPAYPGYG GAACSPGYSC TAAYPAGPSP AQPATAAANN NFVNFGVGDL
310 320
NAVQSPGIPQ SNSGVSTLHG IRAW
Length:324
Mass (Da):34,918
Last modified:October 1, 1996 - v1
Checksum:iACCC9C2F9C292586
GO
Isoform 2 (identifier: P52952-2) [UniParc]FASTAAdd to Basket

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.

Show »
Length:151
Mass (Da):16,102
Checksum:iFFBDEE031AFCB6AF
GO
Isoform 3 (identifier: P52952-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     112-112: E → A
     113-324: Missing.

Note: No experimental confirmation available.

Show »
Length:112
Mass (Da):11,681
Checksum:i1DED387CB9297E28
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti7 – 71L → P in ASD7; somatic mutation. 1 Publication
VAR_038212
Natural varianti15 – 151K → I in ASD7. 2 Publications
VAR_038213
Natural varianti16 – 161D → A.
Corresponds to variant rs17052019 [ dbSNP | Ensembl ].
VAR_049581
Natural varianti19 – 191N → S in ASD7; somatic mutation. 1 Publication
VAR_038214
Natural varianti21 – 211E → Q in TOF and ASD7. 3 Publications
VAR_038215
Natural varianti22 – 221Q → P in ASD7 and TOF. 2 Publications
VAR_038216
Natural varianti25 – 251R → 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. 6 Publications
Corresponds to variant rs28936670 [ dbSNP | Ensembl ].
VAR_010116
Natural varianti45 – 451S → P in ASD7; somatic mutation. 1 Publication
VAR_038217
Natural varianti51 – 511F → L in ASD7; somatic mutation. 1 Publication
VAR_038218
Natural varianti59 – 591P → A in VSD3; significantly reduced activation of NPPA gene compared to wild-type. 1 Publication
VAR_067586
Natural varianti63 – 631A → V in ASD7. 2 Publications
VAR_038219
Natural varianti69 – 691L → P in ASD7; somatic mutation. 1 Publication
VAR_038220
Natural varianti74 – 741G → D.1 Publication
Corresponds to variant rs201362118 [ dbSNP | Ensembl ].
VAR_069058
Natural varianti77 – 771P → L in ASD7; somatic mutation. 1 Publication
VAR_038221
Natural varianti114 – 1141C → R in ASD7; somatic mutation. 1 Publication
VAR_038222
Natural varianti114 – 1141C → S in ASD7; somatic mutation. 1 Publication
VAR_038223
Natural varianti118 – 1181K → R in ASD7; somatic mutation. 1 Publication
VAR_038224
Natural varianti119 – 1191A → S in CHNG5; exhibits a significant functional impairment with reduction of transactivation properties and dominant-negative effect which was associated with reduced DNA binding. 1 Publication
VAR_047869
Natural varianti124 – 1241K → R in ASD7; somatic mutation. 1 Publication
VAR_038225
Natural varianti126 – 1261E → V in ASD7; somatic mutation. 1 Publication
VAR_038226
Natural varianti127 – 1271A → E in ASD7. 2 Publications
VAR_038227
Natural varianti133 – 1331P → S in ASD7; somatic mutation. 1 Publication
VAR_038228
Natural varianti135 – 1351A → T in ASD7; somatic mutation. 1 Publication
VAR_038229
Natural varianti142 – 1421R → C in ASD7. 1 Publication
VAR_038230
Natural varianti144 – 1441L → P in ASD7; somatic mutation. 1 Publication
VAR_038231
Natural varianti161 – 1611R → P in CHNG5; exhibits a significant functional impairment with reduction of transactivation properties and dominant-negative effect which was associated with reduced DNA binding. 1 Publication
VAR_047870
Natural varianti178 – 1781T → M in ASD7. 3 Publications
VAR_003752
Natural varianti183 – 1831K → E in ASD7; somatic mutation. 1 Publication
VAR_038232
Natural varianti187 – 1871Q → H in ASD7. 1 Publication
VAR_038233
Natural varianti188 – 1881N → K in ASD7. 2 Publications
VAR_010117
Natural varianti189 – 1891R → G in ASD7. 2 Publications
VAR_010118
Natural varianti190 – 1901R → C in ASD7. 1 Publication
VAR_038234
Natural varianti191 – 1911Y → C in ASD7. 2 Publications
VAR_010119
Natural varianti192 – 1921K → R in ASD7; somatic mutation. 1 Publication
VAR_038235
Natural varianti192 – 1921K → T in ASD7; somatic mutation. 1 Publication
VAR_038236
Natural varianti194 – 1941K → R in ASD7; somatic mutation. 1 Publication
VAR_038237
Natural varianti205 – 2051V → E in ASD7; somatic mutation. 1 Publication
VAR_038238
Natural varianti216 – 2161R → C in TOF and ASD7. 3 Publications
VAR_038239
Natural varianti219 – 2191A → V in ASD7 and TOF; somatic mutation. 4 Publications
VAR_038240
Natural varianti226 – 2261D → N in ASD7; somatic mutation. 1 Publication
VAR_038241
Natural varianti236 – 2361P → H in ICAS; does not affect DNA binding; impairs transactivation activity. 1 Publication
VAR_069590
Natural varianti248 – 2481Y → H in ASD7; somatic mutation. 1 Publication
VAR_038242
Natural varianti275 – 2751P → T in ASD7. 2 Publications
VAR_038243
Natural varianti279 – 2791S → F in ASD7; somatic mutation. 1 Publication
VAR_038244
Natural varianti279 – 2791S → P in ASD7; somatic mutation. 1 Publication
VAR_038245
Natural varianti281 – 2811A → V in ASD7; somatic mutation. 1 Publication
VAR_038246
Natural varianti283 – 2831P → Q in VSD3. 1 Publication
VAR_067587
Natural varianti286 – 2861A → V in ASD7; somatic mutation. 1 Publication
VAR_038247
Natural varianti291 – 2911Missing in CTMH. 1 Publication
VAR_067588
Natural varianti294 – 2941N → H in ASD7; somatic mutation. 1 Publication
VAR_038248
Natural varianti299 – 2991D → G in ASD7; somatic mutation. 1 Publication
VAR_038249
Natural varianti305 – 3051S → G in ASD7; somatic mutation. 1 Publication
VAR_038250
Natural varianti320 – 3201G → S in ASD7; somatic mutation. 1 Publication
VAR_038251
Natural varianti322 – 3221R → Q in ASD7; somatic mutation. 1 Publication
VAR_038252
Natural varianti323 – 3231A → T in ASD7 and TOF. 2 Publications
VAR_038253

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei112 – 15140ELCAL…QAQVY → GCELPRGQRPPVLFSSALSQ PDFLQMLSETCRWLPVHLAE in isoform 2. 1 PublicationVSP_043492Add
BLAST
Alternative sequencei112 – 1121E → A in isoform 3. 1 PublicationVSP_045481
Alternative sequencei113 – 324212Missing in isoform 3. 1 PublicationVSP_045482Add
BLAST
Alternative sequencei152 – 324173Missing in isoform 2. 1 PublicationVSP_043493Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS4387.1. [P52952-1]
CCDS54949.1. [P52952-2]
CCDS54950.1. [P52952-3]
RefSeqiNP_001159647.1. NM_001166175.1. [P52952-3]
NP_001159648.1. NM_001166176.1. [P52952-2]
NP_004378.1. NM_004387.3. [P52952-1]
UniGeneiHs.54473.

Genome annotation databases

EnsembliENST00000329198; ENSP00000327758; ENSG00000183072. [P52952-1]
ENST00000424406; ENSP00000395378; ENSG00000183072. [P52952-3]
ENST00000521848; ENSP00000427906; ENSG00000183072. [P52952-2]
GeneIDi1482.
KEGGihsa:1482.
UCSCiuc003mcm.2. human. [P52952-1]
uc011dfe.2. human. [P52952-2]

Polymorphism databases

DMDMi1708211.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS4387.1. [P52952-1 ]
CCDS54949.1. [P52952-2 ]
CCDS54950.1. [P52952-3 ]
RefSeqi NP_001159647.1. NM_001166175.1. [P52952-3 ]
NP_001159648.1. NM_001166176.1. [P52952-2 ]
NP_004378.1. NM_004387.3. [P52952-1 ]
UniGenei Hs.54473.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
3RKQ X-ray 1.70 A/B 138-192 [» ]
ProteinModelPortali P52952.
SMRi P52952. Positions 138-192.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 107864. 11 interactions.
IntActi P52952. 2 interactions.
STRINGi 9606.ENSP00000327758.

PTM databases

PhosphoSitei P52952.

Polymorphism databases

DMDMi 1708211.

Proteomic databases

PaxDbi P52952.
PRIDEi P52952.

Protocols and materials databases

DNASUi 1482.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000329198 ; ENSP00000327758 ; ENSG00000183072 . [P52952-1 ]
ENST00000424406 ; ENSP00000395378 ; ENSG00000183072 . [P52952-3 ]
ENST00000521848 ; ENSP00000427906 ; ENSG00000183072 . [P52952-2 ]
GeneIDi 1482.
KEGGi hsa:1482.
UCSCi uc003mcm.2. human. [P52952-1 ]
uc011dfe.2. human. [P52952-2 ]

Organism-specific databases

CTDi 1482.
GeneCardsi GC05M172659.
HGNCi HGNC:2488. NKX2-5.
MIMi 108900. phenotype.
187500. phenotype.
217095. phenotype.
225250. phenotype.
271400. phenotype.
600584. gene.
614432. phenotype.
614435. phenotype.
neXtProti NX_P52952.
Orphaneti 95713. 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.
PharmGKBi PA24202.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG310976.
GeneTreei ENSGT00760000118779.
HOGENOMi HOG000231923.
HOVERGENi HBG006689.
InParanoidi P52952.
KOi K09345.
OMAi AYGDPDP.
OrthoDBi EOG769ZK0.
PhylomeDBi P52952.
TreeFami TF351204.

Enzyme and pathway databases

SignaLinki P52952.

Miscellaneous databases

GeneWikii NKX2-5.
GenomeRNAii 1482.
NextBioi 6089.
PROi P52952.
SOURCEi Search...

Gene expression databases

Bgeei P52952.
CleanExi HS_NKX2-5.
ExpressionAtlasi P52952. baseline and differential.
Genevestigatori P52952.

Family and domain databases

Gene3Di 1.10.10.60. 1 hit.
InterProi IPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR020479. Homeobox_metazoa.
IPR009057. Homeodomain-like.
[Graphical view ]
Pfami PF00046. Homeobox. 1 hit.
[Graphical view ]
PRINTSi PR00024. HOMEOBOX.
SMARTi SM00389. HOX. 1 hit.
[Graphical view ]
SUPFAMi SSF46689. SSF46689. 1 hit.
PROSITEi PS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.
    , 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. 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. 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. 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. 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. 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, VARIANT HLHS2 CYS-25.
  14. 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.

Entry informationi

Entry nameiNKX25_HUMAN
AccessioniPrimary (citable) accession number: P52952
Secondary accession number(s): A8K3K0, B4DNB6, E9PBU6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: October 29, 2014
This is version 155 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3