Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P42582 (NKX25_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Homeobox protein Nkx-2.5
Alternative name(s):
Cardiac-specific homeobox
Homeobox protein CSX
Homeobox protein NK-2 homolog E
Gene names
Name:Nkx2-5
Synonyms:Csx, Nkx-2.5, Nkx2e
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length318 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Implicated in commitment to and/or differentiation of the myocardial lineage. Acts as a transcriptional activator of ANF in cooperation with GATA4. It is transcriptionally controlled by PBX1 and acts as a transcriptional repressor of CDKN2B. Together with PBX1, it is required for spleen development through a mechanism that involves CDKN2B repression. Ref.6 Ref.9

Subunit structure

Interacts with HIPK1 and HIPK2, but not HIPK3. Interacts with the C-terminal zinc finger of GATA4 through its homeobox domain. Also interacts with JARID2 which represses its ability to activate transcription of ANF. Interacts with FBLIM1. Ref.5 Ref.6 Ref.7 Ref.8

Subcellular location

Nucleus Probable.

Tissue specificity

Predominantly in the adult and embryonic heart, and to a lesser extent in lingual muscle, spleen and stomach.

Developmental stage

Expression preceeds the onset of myogenic differentiation, and continues in cardiomyocytes of embryonic, fetal and adult hearts. It is also expressed laterally in future pharyngeal endoderm which is believed to produce the heart inducer. After foregut closure expression in endoderm is limited to the pharyngeal floor, dorsal to the developing heart tube. The thyroid primordium a derivative of the pharyngeal floor continues to express the protein after its levels diminish in the rest of the pharynx.

Sequence similarities

Belongs to the NK-2 homeobox family.

Contains 1 homeobox DNA-binding domain.

Ontologies

Keywords
   Cellular componentNucleus
   DomainHomeobox
   LigandDNA-binding
   Molecular functionDevelopmental protein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processBMP signaling pathway

Inferred from direct assay PubMed 17360443. Source: MGI

Purkinje myocyte differentiation

Inferred from mutant phenotype PubMed 17250822. Source: MGI

adult heart development

Inferred from mutant phenotype PubMed 7628699. Source: MGI

apoptotic process involved in heart morphogenesis

Inferred from mutant phenotype PubMed 16510504. Source: MGI

atrial cardiac muscle cell development

Traceable author statement PubMed 9621431. Source: BHF-UCL

atrial septum morphogenesis

Inferred from electronic annotation. Source: Ensembl

atrioventricular node cell development

Inferred from mutant phenotype PubMed 19546853. Source: MGI

atrioventricular node cell fate commitment

Inferred from mutant phenotype PubMed 15109497. Source: MGI

atrioventricular node development

Inferred from mutant phenotype PubMed 18689573. Source: BHF-UCL

bundle of His development

Inferred from genetic interaction PubMed 17604724. Source: MGI

canonical Wnt signaling pathway

Inferred from direct assay PubMed 17360443. Source: MGI

cardiac conduction system development

Inferred from genetic interaction PubMed 21690310. Source: MGI

cardiac muscle cell differentiation

Inferred from direct assay PubMed 9857019. Source: UniProtKB

cardiac muscle cell proliferation

Inferred from genetic interaction PubMed 17350578. Source: MGI

cardiac muscle contraction

Inferred from mutant phenotype PubMed 19546853. Source: MGI

cardiac muscle tissue development

Inferred from mutant phenotype PubMed 7628699. Source: MGI

cardiac ventricle formation

Inferred from genetic interaction PubMed 19035347. Source: MGI

cardiac ventricle morphogenesis

Inferred from mutant phenotype PubMed 16510504. Source: MGI

cardiovascular system development

Inferred from genetic interaction PubMed 20457810. Source: MGI

cell differentiation

Inferred from genetic interaction PubMed 11390666. Source: MGI

embryonic heart tube development

Inferred from genetic interaction PubMed 15843414. Source: MGI

embryonic heart tube left/right pattern formation

Inferred from mutant phenotype PubMed 9192865. Source: MGI

endoderm development

Traceable author statement PubMed 9621431. Source: BHF-UCL

heart contraction

Inferred from genetic interaction PubMed 21690310. Source: MGI

heart development

Inferred from mutant phenotype PubMed 10021345PubMed 15085192. Source: MGI

heart looping

Inferred from mutant phenotype PubMed 16510504PubMed 7628699PubMed 9192865. Source: MGI

heart morphogenesis

Inferred from mutant phenotype PubMed 11784028. Source: MGI

heart trabecula formation

Inferred from mutant phenotype PubMed 16510504. Source: MGI

hemopoiesis

Inferred from mutant phenotype PubMed 10021345. Source: MGI

negative regulation of apoptotic process

Inferred from genetic interaction PubMed 11390666. Source: MGI

negative regulation of canonical Wnt signaling pathway

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

negative regulation of cardiac muscle cell apoptotic process

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

negative regulation of myotube differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 12023302. Source: MGI

outflow tract morphogenesis

Inferred from mutant phenotype PubMed 16510504. Source: MGI

outflow tract septum morphogenesis

Inferred from electronic annotation. Source: Ensembl

pharyngeal system development

Inferred from genetic interaction PubMed 11390666. Source: MGI

positive regulation of cardioblast differentiation

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

positive regulation of cell proliferation

Inferred from genetic interaction PubMed 11390666. Source: MGI

positive regulation of gene expression

Inferred from direct assay PubMed 9857019. Source: UniProtKB

positive regulation of heart contraction

Inferred from mutant phenotype PubMed 18689573. Source: BHF-UCL

positive regulation of neuron differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of sodium ion transport

Inferred from mutant phenotype PubMed 18689573. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 18689573. Source: BHF-UCL

positive regulation of transcription initiation from RNA polymerase II promoter

Inferred from direct assay PubMed 8887666. Source: BHF-UCL

positive regulation of transcription via serum response element binding

Inferred from direct assay PubMed 8887666. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 11572777PubMed 14978031. Source: MGI

positive regulation of voltage-gated calcium channel activity

Inferred from mutant phenotype PubMed 18689573. Source: BHF-UCL

proepicardium development

Inferred from mutant phenotype PubMed 18722343. Source: MGI

pulmonary myocardium development

Inferred from mutant phenotype PubMed 17823370. Source: MGI

regulation of cardiac muscle cell proliferation

Inferred from direct assay PubMed 20713518. Source: MGI

regulation of cardiac muscle contraction

Inferred from mutant phenotype PubMed 18689573. Source: BHF-UCL

regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 14645532. Source: MGI

right ventricular cardiac muscle tissue morphogenesis

Inferred from electronic annotation. Source: Ensembl

sarcomere organization

Inferred from genetic interaction PubMed 20457810. Source: MGI

septum secundum development

Inferred from electronic annotation. Source: Ensembl

spleen development

Traceable author statement PubMed 9621431. Source: BHF-UCL

thyroid gland development

Inferred from mutant phenotype PubMed 16418214. Source: BHF-UCL

tongue development

Traceable author statement PubMed 9621431. Source: BHF-UCL

transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 21379568. Source: GOC

vasculogenesis

Inferred from mutant phenotype PubMed 10021345. Source: MGI

ventricular cardiac muscle cell development

Traceable author statement PubMed 9621431. Source: BHF-UCL

ventricular cardiac myofibril assembly

Inferred from mutant phenotype PubMed 19546853. Source: MGI

ventricular septum morphogenesis

Inferred from electronic annotation. Source: Ensembl

ventricular trabecula myocardium morphogenesis

Inferred from mutant phenotype PubMed 15109497. Source: MGI

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 15653675. Source: BHF-UCL

nucleus

Inferred from direct assay PubMed 14550786PubMed 15653675. Source: BHF-UCL

transcription factor complex

Inferred from direct assay PubMed 12023302. Source: MGI

   Molecular_functionDNA binding

Inferred from direct assay PubMed 11042197. Source: UniProtKB

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

Inferred from direct assay PubMed 21379568. Source: MGI

RNA polymerase II transcription cofactor activity

Inferred from mutant phenotype PubMed 15363409. Source: BHF-UCL

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

Inferred from mutant phenotype PubMed 15363409. Source: BHF-UCL

chromatin binding

Inferred from direct assay PubMed 19483677PubMed 21379568. Source: MGI

protein heterodimerization activity

Inferred from physical interaction PubMed 12392994. Source: MGI

protein homodimerization activity

Inferred from direct assay PubMed 11042197. Source: UniProtKB

sequence-specific DNA binding

Inferred from electronic annotation. Source: Ensembl

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 11572777PubMed 16510504PubMed 8900044. Source: MGI

serum response element binding

Inferred from direct assay PubMed 8887666. Source: BHF-UCL

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CAMTA2O949832EBI-297021,EBI-936534From a different organism.
Gata4Q083694EBI-297021,EBI-297008
Jarid2Q623153EBI-297021,EBI-493592

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 318318Homeobox protein Nkx-2.5
PRO_0000048938

Regions

DNA binding137 – 19660Homeobox
Compositional bias41 – 10767Ala/Pro-rich
Compositional bias206 – 28075Ala/Pro-rich

Experimental info

Sequence conflict621A → R in L20300. Ref.4
Sequence conflict164 – 1652AP → PA Ref.1
Sequence conflict2341A → T Ref.3
Sequence conflict276 – 2772QP → HA Ref.1

Sequences

Sequence LengthMass (Da)Tools
P42582 [UniParc].

Last modified November 1, 1995. Version 1.
Checksum: 6A3E7859F46D4FA6

FASTA31834,163
        10         20         30         40         50         60 
MFPSPALTPT PFSVKDILNL EQQQRSLASG DLSARLEATL APASCMLAAF KPEAYSGPEA 

        70         80         90        100        110        120 
AASGLAELRA EMGPAPSPPK CSPAFPAAPT FYPGAYGDPD PAKDPRADKK ELCALQKAVE 

       130        140        150        160        170        180 
LDKAETDGAE RPRARRRRKP RVLFSQAQVY ELERRFKQQR YLSAPERDQL ASVLKLTSTQ 

       190        200        210        220        230        240 
VKIWFQNRRY KCKRQRQDQT LELLGPPPPP ARRIAVPVLV RDGKPCLGDP AAYAPAYGVG 

       250        260        270        280        290        300 
LNAYGYNAYP YPSYGGAACS PGYSCAAYPA APPAAQPPAA SANSNFVNFG VGDLNTVQSP 

       310 
GMPQGNSGVS TLHGIRAW 

« Hide

References

[1]"Nkx-2.5: a novel murine homeobox gene expressed in early heart progenitor cells and their myogenic descendants."
Lints T.J., Parsons L.M., Hartley L., Lyons I., Harvey R.P.
Development 119:419-431(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE.
Tissue: Heart.
[2]Erratum
Lints T.J., Parsons L.M., Hartley L., Lyons I., Harvey R.P.
Development 119:969-969(1993) [PubMed] [Europe PMC] [Abstract]
[3]"A GATA-dependent nkx-2.5 regulatory element activates early cardiac gene expression in transgenic mice."
Searcy R.D., Vincent E.B., Liberatore C.M., Yutzey K.E.
Development 125:4461-4470(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Strain: 129/J.
[4]"Csx: a murine homeobox-containing gene specifically expressed in the developing heart."
Komuro I., Izumo S.
Proc. Natl. Acad. Sci. U.S.A. 90:8145-8149(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 17-318.
[5]"Homeodomain-interacting protein kinases, a novel family of co-repressors for homeodomain transcription factors."
Kim Y.H., Choi C.Y., Lee S.-J., Conti M.A., Kim Y.
J. Biol. Chem. 273:25875-25879(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIPK1 AND HIPK2.
Strain: BALB/c.
[6]"The cardiac tissue-restricted homeobox protein Csx/Nkx2.5 physically associates with the zinc finger protein GATA4 and cooperatively activates atrial natriuretic factor gene expression."
Lee Y., Shioi T., Kasahara H., Jobe S.M., Wiese R.J., Markham B.E., Izumo S.
Mol. Cell. Biol. 18:3120-3129(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH GATA4.
[7]"A novel LIM protein Cal promotes cardiac differentiation by association with CSX/NKX2-5."
Akazawa H., Kudoh S., Mochizuki N., Takekoshi N., Takano H., Nagai T., Komuro I.
J. Cell Biol. 164:395-405(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FBLIM1.
[8]"Jumonji represses atrial natriuretic factor gene expression by inhibiting transcriptional activities of cardiac transcription factors."
Kim T.-G., Chen J., Sadoshima J., Lee Y.
Mol. Cell. Biol. 24:10151-10160(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH JARID2.
[9]"Congenital asplenia in mice and humans with mutations in a Pbx/Nkx2-5/p15 module."
Koss M., Bolze A., Brendolan A., Saggese M., Capellini T.D., Bojilova E., Boisson B., Prall O.W., Elliott D.A., Solloway M., Lenti E., Hidaka C., Chang C.P., Mahlaoui N., Harvey R.P., Casanova J.L., Selleri L.
Dev. Cell 22:913-926(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L20300 mRNA. No translation available.
AF091351 Genomic DNA. Translation: AAC97934.1.
X75415 mRNA. Translation: CAA53169.1.
RefSeqNP_032726.1. NM_008700.2.
XP_006523860.1. XM_006523797.1.
UniGeneMm.41974.

3D structure databases

ProteinModelPortalP42582.
SMRP42582. Positions 137-191.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201778. 10 interactions.
DIPDIP-33031N.
IntActP42582. 4 interactions.

PTM databases

PhosphoSiteP42582.

Proteomic databases

PRIDEP42582.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000015723; ENSMUSP00000015723; ENSMUSG00000015579.
GeneID18091.
KEGGmmu:18091.
UCSCuc008beo.1. mouse.

Organism-specific databases

CTD1482.
MGIMGI:97350. Nkx2-5.

Phylogenomic databases

eggNOGNOG310976.
HOGENOMHOG000231923.
HOVERGENHBG006689.
InParanoidP42582.
KOK09345.
OMAYGGAACS.
OrthoDBEOG769ZK0.
PhylomeDBP42582.
TreeFamTF351204.

Gene expression databases

ArrayExpressP42582.
BgeeP42582.
GenevestigatorP42582.

Family and domain databases

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

Other

ChiTaRSNKX2-5. mouse.
NextBio293235.
PROP42582.
SOURCESearch...

Entry information

Entry nameNKX25_MOUSE
AccessionPrimary (citable) accession number: P42582
Secondary accession number(s): P97335
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: April 16, 2014
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot