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Protein

Homeobox protein Nkx-2.5

Gene

NKX2-5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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)DescriptionActionsGraphical viewLength
DNA bindingi138 – 197HomeoboxPROSITE-ProRule annotationAdd BLAST60

GO - Molecular functioni

  • chromatin binding Source: MGI
  • DNA binding Source: BHF-UCL
  • protein heterodimerization activity Source: BHF-UCL
  • RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: NTNU_SB
  • RNA polymerase II transcription cofactor activity Source: Ensembl
  • sequence-specific DNA binding Source: BHF-UCL
  • serum response element binding Source: BHF-UCL
  • transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding Source: NTNU_SB
  • transcriptional activator activity, RNA polymerase II transcription factor binding Source: Ensembl
  • transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding Source: BHF-UCL
  • transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding Source: Ensembl
  • transcription factor activity, sequence-specific DNA binding Source: UniProtKB
  • transcription factor binding Source: BHF-UCL
  • transcription regulatory region DNA binding Source: BHF-UCL

GO - Biological processi

  • adult heart development Source: BHF-UCL
  • apoptotic process involved in heart morphogenesis Source: Ensembl
  • atrial cardiac muscle cell development Source: BHF-UCL
  • atrial septum morphogenesis Source: BHF-UCL
  • atrioventricular node cell development Source: Ensembl
  • atrioventricular node cell fate commitment Source: Ensembl
  • BMP signaling pathway Source: Ensembl
  • bundle of His development Source: Ensembl
  • canonical Wnt signaling pathway Source: Ensembl
  • cardiac conduction system development Source: MGI
  • cardiac muscle cell differentiation Source: BHF-UCL
  • cardiac muscle cell proliferation Source: Ensembl
  • cardiac muscle contraction Source: Ensembl
  • cardiac muscle tissue morphogenesis Source: BHF-UCL
  • cardiac ventricle formation Source: Ensembl
  • cell differentiation Source: BHF-UCL
  • embryonic heart tube development Source: BHF-UCL
  • embryonic heart tube left/right pattern formation Source: Ensembl
  • heart looping Source: BHF-UCL
  • heart morphogenesis Source: BHF-UCL
  • heart trabecula formation Source: Ensembl
  • hemopoiesis Source: BHF-UCL
  • negative regulation of apoptotic process Source: BHF-UCL
  • negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
  • negative regulation of cardiac muscle cell apoptotic process Source: BHF-UCL
  • negative regulation of myotube differentiation Source: BHF-UCL
  • negative regulation of transcription, DNA-templated Source: BHF-UCL
  • negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • outflow tract septum morphogenesis Source: BHF-UCL
  • pharyngeal system development Source: BHF-UCL
  • positive regulation of cardioblast differentiation Source: BHF-UCL
  • positive regulation of cell proliferation Source: BHF-UCL
  • positive regulation of heart contraction Source: BHF-UCL
  • positive regulation of neuron differentiation Source: BHF-UCL
  • positive regulation of sodium ion transport Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of transcription initiation from RNA polymerase II promoter Source: BHF-UCL
  • positive regulation of transcription via serum response element binding Source: BHF-UCL
  • proepicardium development Source: Ensembl
  • pulmonary myocardium development Source: Ensembl
  • Purkinje myocyte differentiation Source: Ensembl
  • regulation of cardiac conduction Source: BHF-UCL
  • regulation of cardiac muscle cell proliferation Source: Ensembl
  • regulation of cardiac muscle contraction Source: BHF-UCL
  • right ventricular cardiac muscle tissue morphogenesis Source: BHF-UCL
  • sarcomere organization Source: Ensembl
  • septum secundum development Source: BHF-UCL
  • spleen development Source: UniProtKB
  • thyroid gland development Source: BHF-UCL
  • vasculogenesis Source: BHF-UCL
  • ventricular cardiac muscle cell development Source: BHF-UCL
  • ventricular cardiac myofibril assembly Source: Ensembl
  • ventricular septum morphogenesis Source: BHF-UCL
  • ventricular trabecula myocardium morphogenesis Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:G66-31271-MONOMER.
ReactomeiR-HSA-2032785. YAP1- and WWTR1 (TAZ)-stimulated gene expression.
R-HSA-5578768. Physiological factors.
SignaLinkiP52952.
SIGNORiP52952.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:2488. NKX2-5.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: Ensembl
  • nucleus Source: BHF-UCL
  • RNA polymerase II transcription factor complex Source: BHF-UCL
  • 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)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:108900
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0382127L → P in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_03821315K → I in ASD7. 2 PublicationsCorresponds to variant rs387906773dbSNPEnsembl.1
Natural variantiVAR_03821419N → S in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_03821521E → Q in TOF and ASD7. 3 PublicationsCorresponds to variant rs104893904dbSNPEnsembl.1
Natural variantiVAR_03821622Q → P in ASD7 and TOF. 2 Publications1
Natural variantiVAR_01011625R → C in ASD7, TOF, CHNG5, HLHS2 and CTHM; unknown pathological significance; exhibits significant functional impairment with reduction of transactivation properties and dominant-negative effect; the mutant protein activity on the DIO2, TG and TPO promoters is significantly impaired. 7 PublicationsCorresponds to variant rs28936670dbSNPEnsembl.1
Natural variantiVAR_03821745S → P in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_03821851F → L in ASD7; somatic mutation. 1 PublicationCorresponds to variant rs753937287dbSNPEnsembl.1
Natural variantiVAR_03821963A → V in ASD7. 2 PublicationsCorresponds to variant rs530270916dbSNPEnsembl.1
Natural variantiVAR_03822069L → P in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_03822177P → L in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038222114C → R in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038223114C → S in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038224118K → R in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038225124K → R in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038226126E → V in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038227127A → E in ASD7. 2 PublicationsCorresponds to variant rs387906774dbSNPEnsembl.1
Natural variantiVAR_038228133P → S in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038229135A → T in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038230142R → C in ASD7. 1 Publication1
Natural variantiVAR_038231144L → P in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_003752178T → M in ASD7. 3 PublicationsCorresponds to variant rs104893900dbSNPEnsembl.1
Natural variantiVAR_038232183K → E in ASD7; somatic mutation. 1 PublicationCorresponds to variant rs137852686dbSNPEnsembl.1
Natural variantiVAR_038233187Q → H in ASD7. 1 Publication1
Natural variantiVAR_010117188N → K in ASD7. 2 Publications1
Natural variantiVAR_010118189R → G in ASD7. 2 Publications1
Natural variantiVAR_038234190R → C in ASD7. 1 PublicationCorresponds to variant rs104893906dbSNPEnsembl.1
Natural variantiVAR_010119191Y → C in ASD7. 2 Publications1
Natural variantiVAR_038235192K → R in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038236192K → T in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038237194K → R in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038238205V → E in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038239216R → C in TOF and ASD7. 3 PublicationsCorresponds to variant rs104893905dbSNPEnsembl.1
Natural variantiVAR_038240219A → V in ASD7 and TOF; somatic mutation. 4 PublicationsCorresponds to variant rs104893902dbSNPEnsembl.1
Natural variantiVAR_038241226D → N in ASD7; somatic mutation. 1 PublicationCorresponds to variant rs760528062dbSNPEnsembl.1
Natural variantiVAR_038242248Y → H in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038243275P → T in ASD7. 2 PublicationsCorresponds to variant rs368366482dbSNPEnsembl.1
Natural variantiVAR_038244279S → F in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038245279S → P in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038246281A → V in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038247286A → V in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038248294N → H in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038249299D → G in ASD7; somatic mutation. 1 PublicationCorresponds to variant rs137852683dbSNPEnsembl.1
Natural variantiVAR_038250305S → G in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038251320G → S in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038252322R → Q in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038253323A → T in ASD7 and TOF. 2 Publications1
Tetralogy of Fallot (TOF)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:187500
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03821521E → Q in TOF and ASD7. 3 PublicationsCorresponds to variant rs104893904dbSNPEnsembl.1
Natural variantiVAR_03821622Q → P in ASD7 and TOF. 2 Publications1
Natural variantiVAR_01011625R → C in ASD7, TOF, CHNG5, HLHS2 and CTHM; unknown pathological significance; exhibits significant functional impairment with reduction of transactivation properties and dominant-negative effect; the mutant protein activity on the DIO2, TG and TPO promoters is significantly impaired. 7 PublicationsCorresponds to variant rs28936670dbSNPEnsembl.1
Natural variantiVAR_038239216R → C in TOF and ASD7. 3 PublicationsCorresponds to variant rs104893905dbSNPEnsembl.1
Natural variantiVAR_038240219A → V in ASD7 and TOF; somatic mutation. 4 PublicationsCorresponds to variant rs104893902dbSNPEnsembl.1
Natural variantiVAR_038253323A → T in ASD7 and TOF. 2 Publications1
Conotruncal heart malformations (CTHM)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:217095
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01011625R → C in ASD7, TOF, CHNG5, HLHS2 and CTHM; unknown pathological significance; exhibits significant functional impairment with reduction of transactivation properties and dominant-negative effect; the mutant protein activity on the DIO2, TG and TPO promoters is significantly impaired. 7 PublicationsCorresponds to variant rs28936670dbSNPEnsembl.1
Hypothyroidism, congenital, non-goitrous, 5 (CHNG5)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:225250
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01011625R → C in ASD7, TOF, CHNG5, HLHS2 and CTHM; unknown pathological significance; exhibits significant functional impairment with reduction of transactivation properties and dominant-negative effect; the mutant protein activity on the DIO2, TG and TPO promoters is significantly impaired. 7 PublicationsCorresponds to variant rs28936670dbSNPEnsembl.1
Natural variantiVAR_047869119A → 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 PublicationCorresponds to variant rs137852684dbSNPEnsembl.1
Natural variantiVAR_047870161R → 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 PublicationCorresponds to variant rs137852685dbSNPEnsembl.1
Ventricular septal defect 3 (VSD3)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:614432
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06758659P → A in VSD3; significantly reduced activation of NPPA gene compared to wild-type. 1 PublicationCorresponds to variant rs387906775dbSNPEnsembl.1
Natural variantiVAR_067587283P → Q in VSD3. 1 PublicationCorresponds to variant rs375086983dbSNPEnsembl.1
Hypoplastic left heart syndrome 2 (HLHS2)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:614435
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01011625R → C in ASD7, TOF, CHNG5, HLHS2 and CTHM; unknown pathological significance; exhibits significant functional impairment with reduction of transactivation properties and dominant-negative effect; the mutant protein activity on the DIO2, TG and TPO promoters is significantly impaired. 7 PublicationsCorresponds to variant rs28936670dbSNPEnsembl.1

Keywords - Diseasei

Atrial septal defect, Congenital hypothyroidism, Disease mutation

Organism-specific databases

DisGeNETi1482.
MalaCardsiNKX2-5.
MIMi108900. phenotype.
187500. phenotype.
217095. phenotype.
225250. phenotype.
614432. phenotype.
614435. phenotype.
OpenTargetsiENSG00000183072.
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.

Polymorphism and mutation databases

BioMutaiNKX2-5.
DMDMi1708211.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000489371 – 324Homeobox protein Nkx-2.5Add BLAST324

Proteomic databases

PaxDbiP52952.
PeptideAtlasiP52952.
PRIDEiP52952.

PTM databases

iPTMnetiP52952.
PhosphoSitePlusiP52952.

Expressioni

Tissue specificityi

Expressed only in the heart.

Gene expression databases

BgeeiENSG00000183072.
CleanExiHS_NKX2-5.
ExpressionAtlasiP52952. baseline and differential.
GenevisibleiP52952. HS.

Organism-specific databases

HPAiHPA065034.

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

GO - Molecular functioni

  • protein heterodimerization activity Source: BHF-UCL
  • transcription factor binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi107864. 18 interactors.
IntActiP52952. 8 interactors.
STRINGi9606.ENSP00000327758.

Structurei

Secondary structure

1324
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi147 – 157Combined sources11
Helixi165 – 175Combined sources11
Helixi179 – 192Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3RKQX-ray1.70A/B138-192[»]
4S0HX-ray2.82B/F142-192[»]
ProteinModelPortaliP52952.
SMRiP52952.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi42 – 108Ala/Pro-richAdd BLAST67
Compositional biasi208 – 282Ala/Pro-richAdd BLAST75

Sequence similaritiesi

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

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiKOG0842. Eukaryota.
ENOG410XR21. LUCA.
GeneTreeiENSGT00860000133666.
HOGENOMiHOG000231923.
HOVERGENiHBG006689.
InParanoidiP52952.
KOiK09345.
OMAiCNANYNC.
OrthoDBiEOG091G0LZ2.
PhylomeDBiP52952.
TreeFamiTF351204.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR020479. Homeobox_metazoa.
IPR009057. Homeodomain-like.
IPR033629. NKX-2.5.
[Graphical view]
PANTHERiPTHR24340:SF28. PTHR24340:SF28. 1 hit.
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. AlignAdd to basket

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_0382127L → P in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_03821315K → I in ASD7. 2 PublicationsCorresponds to variant rs387906773dbSNPEnsembl.1
Natural variantiVAR_04958116D → A.Corresponds to variant rs17052019dbSNPEnsembl.1
Natural variantiVAR_03821419N → S in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_03821521E → Q in TOF and ASD7. 3 PublicationsCorresponds to variant rs104893904dbSNPEnsembl.1
Natural variantiVAR_03821622Q → P in ASD7 and TOF. 2 Publications1
Natural variantiVAR_01011625R → C in ASD7, TOF, CHNG5, HLHS2 and CTHM; unknown pathological significance; exhibits significant functional impairment with reduction of transactivation properties and dominant-negative effect; the mutant protein activity on the DIO2, TG and TPO promoters is significantly impaired. 7 PublicationsCorresponds to variant rs28936670dbSNPEnsembl.1
Natural variantiVAR_03821745S → P in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_03821851F → L in ASD7; somatic mutation. 1 PublicationCorresponds to variant rs753937287dbSNPEnsembl.1
Natural variantiVAR_06758659P → A in VSD3; significantly reduced activation of NPPA gene compared to wild-type. 1 PublicationCorresponds to variant rs387906775dbSNPEnsembl.1
Natural variantiVAR_03821963A → V in ASD7. 2 PublicationsCorresponds to variant rs530270916dbSNPEnsembl.1
Natural variantiVAR_03822069L → P in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_06905874G → D.1 PublicationCorresponds to variant rs201362118dbSNPEnsembl.1
Natural variantiVAR_03822177P → L in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038222114C → R in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038223114C → S in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038224118K → R in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_047869119A → 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 PublicationCorresponds to variant rs137852684dbSNPEnsembl.1
Natural variantiVAR_038225124K → R in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038226126E → V in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038227127A → E in ASD7. 2 PublicationsCorresponds to variant rs387906774dbSNPEnsembl.1
Natural variantiVAR_038228133P → S in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038229135A → T in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038230142R → C in ASD7. 1 Publication1
Natural variantiVAR_038231144L → P in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_047870161R → 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 PublicationCorresponds to variant rs137852685dbSNPEnsembl.1
Natural variantiVAR_003752178T → M in ASD7. 3 PublicationsCorresponds to variant rs104893900dbSNPEnsembl.1
Natural variantiVAR_038232183K → E in ASD7; somatic mutation. 1 PublicationCorresponds to variant rs137852686dbSNPEnsembl.1
Natural variantiVAR_038233187Q → H in ASD7. 1 Publication1
Natural variantiVAR_010117188N → K in ASD7. 2 Publications1
Natural variantiVAR_010118189R → G in ASD7. 2 Publications1
Natural variantiVAR_038234190R → C in ASD7. 1 PublicationCorresponds to variant rs104893906dbSNPEnsembl.1
Natural variantiVAR_010119191Y → C in ASD7. 2 Publications1
Natural variantiVAR_038235192K → R in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038236192K → T in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038237194K → R in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038238205V → E in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038239216R → C in TOF and ASD7. 3 PublicationsCorresponds to variant rs104893905dbSNPEnsembl.1
Natural variantiVAR_038240219A → V in ASD7 and TOF; somatic mutation. 4 PublicationsCorresponds to variant rs104893902dbSNPEnsembl.1
Natural variantiVAR_038241226D → N in ASD7; somatic mutation. 1 PublicationCorresponds to variant rs760528062dbSNPEnsembl.1
Natural variantiVAR_069590236P → H Found in patients with isolated congenital asplenia; unknown pathological significance; does not affect DNA binding; impairs transactivation activity. 1 PublicationCorresponds to variant rs397515399dbSNPEnsembl.1
Natural variantiVAR_038242248Y → H in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038243275P → T in ASD7. 2 PublicationsCorresponds to variant rs368366482dbSNPEnsembl.1
Natural variantiVAR_038244279S → F in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038245279S → P in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038246281A → V in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_067587283P → Q in VSD3. 1 PublicationCorresponds to variant rs375086983dbSNPEnsembl.1
Natural variantiVAR_038247286A → V in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_067588291Missing in CTMH. 1 Publication1
Natural variantiVAR_038248294N → H in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038249299D → G in ASD7; somatic mutation. 1 PublicationCorresponds to variant rs137852683dbSNPEnsembl.1
Natural variantiVAR_038250305S → G in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038251320G → S in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038252322R → Q in ASD7; somatic mutation. 1 Publication1
Natural variantiVAR_038253323A → T in ASD7 and TOF. 2 Publications1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_043492112 – 151ELCAL…QAQVY → GCELPRGQRPPVLFSSALSQ PDFLQMLSETCRWLPVHLAE in isoform 2. 1 PublicationAdd BLAST40
Alternative sequenceiVSP_045481112E → A in isoform 3. 1 Publication1
Alternative sequenceiVSP_045482113 – 324Missing in isoform 3. 1 PublicationAdd BLAST212
Alternative sequenceiVSP_043493152 – 324Missing in isoform 2. 1 PublicationAdd BLAST173

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.3. human. [P52952-1]

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:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3RKQX-ray1.70A/B138-192[»]
4S0HX-ray2.82B/F142-192[»]
ProteinModelPortaliP52952.
SMRiP52952.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107864. 18 interactors.
IntActiP52952. 8 interactors.
STRINGi9606.ENSP00000327758.

PTM databases

iPTMnetiP52952.
PhosphoSitePlusiP52952.

Polymorphism and mutation databases

BioMutaiNKX2-5.
DMDMi1708211.

Proteomic databases

PaxDbiP52952.
PeptideAtlasiP52952.
PRIDEiP52952.

Protocols and materials databases

DNASUi1482.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi1482.
DisGeNETi1482.
GeneCardsiNKX2-5.
HGNCiHGNC:2488. NKX2-5.
HPAiHPA065034.
MalaCardsiNKX2-5.
MIMi108900. phenotype.
187500. phenotype.
217095. phenotype.
225250. phenotype.
600584. gene.
614432. phenotype.
614435. phenotype.
neXtProtiNX_P52952.
OpenTargetsiENSG00000183072.
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.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0842. Eukaryota.
ENOG410XR21. LUCA.
GeneTreeiENSGT00860000133666.
HOGENOMiHOG000231923.
HOVERGENiHBG006689.
InParanoidiP52952.
KOiK09345.
OMAiCNANYNC.
OrthoDBiEOG091G0LZ2.
PhylomeDBiP52952.
TreeFamiTF351204.

Enzyme and pathway databases

BioCyciZFISH:G66-31271-MONOMER.
ReactomeiR-HSA-2032785. YAP1- and WWTR1 (TAZ)-stimulated gene expression.
R-HSA-5578768. Physiological factors.
SignaLinkiP52952.
SIGNORiP52952.

Miscellaneous databases

GeneWikiiNKX2-5.
GenomeRNAii1482.
PROiP52952.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000183072.
CleanExiHS_NKX2-5.
ExpressionAtlasiP52952. baseline and differential.
GenevisibleiP52952. HS.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
InterProiIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR020479. Homeobox_metazoa.
IPR009057. Homeodomain-like.
IPR033629. NKX-2.5.
[Graphical view]
PANTHERiPTHR24340:SF28. PTHR24340:SF28. 1 hit.
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]
ProtoNetiSearch...

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: November 30, 2016
This is version 177 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.