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P52952

- NKX25_HUMAN

UniProt

P52952 - NKX25_HUMAN

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
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    • History
      Entry version 154 (01 Oct 2014)
      Sequence version 1 (01 Oct 1996)
      Previous versions | rss
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    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 binding Source: UniProtKB
    4. protein heterodimerization activity Source: BHF-UCL
    5. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
    6. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: NTNU_SB
    7. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: Ensembl
    8. RNA polymerase II transcription cofactor activity Source: Ensembl
    9. RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription Source: Ensembl
    10. sequence-specific DNA binding Source: BHF-UCL
    11. sequence-specific DNA binding transcription factor activity Source: UniProtKB
    12. serum response element binding Source: BHF-UCL
    13. transcription factor binding Source: BHF-UCL
    14. 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

    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

    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

    ArrayExpressiP52952.
    BgeeiP52952.
    CleanExiHS_NKX2-5.
    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 By similarity.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 – 15711
    Helixi165 – 17511
    Helixi179 – 19214

    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.
    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

    MFPSPALTPT PFSVKDILNL EQQQRSLAAA GELSARLEAT LAPSSCMLAA    50
    FKPEAYAGPE AAAPGLPELR AELGRAPSPA KCASAFPAAP AFYPRAYSDP 100
    DPAKDPRAEK KELCALQKAV ELEKTEADNA ERPRARRRRK PRVLFSQAQV 150
    YELERRFKQQ RYLSAPERDQ LASVLKLTST QVKIWFQNRR YKCKRQRQDQ 200
    TLELVGLPPP PPPPARRIAV PVLVRDGKPC LGDSAPYAPA YGVGLNPYGY 250
    NAYPAYPGYG GAACSPGYSC TAAYPAGPSP AQPATAAANN NFVNFGVGDL 300
    NAVQSPGIPQ SNSGVSTLHG IRAW 324
    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.
    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

    ArrayExpressi P52952.
    Bgeei P52952.
    CleanExi HS_NKX2-5.
    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

    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.
    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 1, 2014
    This is version 154 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