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Protein

Homeobox protein Nkx-2.5

Gene

Nkx2-5

Organism
Mus musculus (Mouse)
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. 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.2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi137 – 19660HomeoboxPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

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

Keywords - Molecular functioni

Developmental protein

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_287523. YAP1- and WWTR1 (TAZ)-stimulated gene expression.

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, Nkx-2.5, Nkx2e
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:97350. Nkx2-5.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: BHF-UCL
  • nucleus Source: BHF-UCL
  • RNA polymerase II transcription factor complex Source: MGI
  • transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 318318Homeobox protein Nkx-2.5PRO_0000048938Add
BLAST

Proteomic databases

MaxQBiP42582.
PRIDEiP42582.

PTM databases

PhosphoSiteiP42582.

Expressioni

Tissue specificityi

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

Developmental stagei

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.

Gene expression databases

BgeeiP42582.
ExpressionAtlasiP42582. baseline and differential.
GenevisibleiP42582. MM.

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 similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CAMTA2O949832EBI-297021,EBI-936534From a different organism.
Gata4Q083694EBI-297021,EBI-297008
Jarid2Q623153EBI-297021,EBI-493592

Protein-protein interaction databases

BioGridi201778. 10 interactions.
DIPiDIP-33031N.
IntActiP42582. 4 interactions.
STRINGi10090.ENSMUSP00000015723.

Structurei

3D structure databases

ProteinModelPortaliP42582.
SMRiP42582. Positions 137-191.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi41 – 10767Ala/Pro-richAdd
BLAST
Compositional biasi206 – 28075Ala/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.
InParanoidiP42582.
KOiK09345.
OMAiGYGSAAC.
OrthoDBiEOG769ZK0.
PhylomeDBiP42582.
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]

Sequencei

Sequence statusi: Complete.

P42582-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MFPSPALTPT PFSVKDILNL EQQQRSLASG DLSARLEATL APASCMLAAF
60 70 80 90 100
KPEAYSGPEA AASGLAELRA EMGPAPSPPK CSPAFPAAPT FYPGAYGDPD
110 120 130 140 150
PAKDPRADKK ELCALQKAVE LDKAETDGAE RPRARRRRKP RVLFSQAQVY
160 170 180 190 200
ELERRFKQQR YLSAPERDQL ASVLKLTSTQ VKIWFQNRRY KCKRQRQDQT
210 220 230 240 250
LELLGPPPPP ARRIAVPVLV RDGKPCLGDP AAYAPAYGVG LNAYGYNAYP
260 270 280 290 300
YPSYGGAACS PGYSCAAYPA APPAAQPPAA SANSNFVNFG VGDLNTVQSP
310
GMPQGNSGVS TLHGIRAW
Length:318
Mass (Da):34,163
Last modified:November 1, 1995 - v1
Checksum:i6A3E7859F46D4FA6
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti62 – 621A → R in L20300 (PubMed:7690144).Curated
Sequence conflicti164 – 1652AP → PA (PubMed:7904557).Curated
Sequence conflicti234 – 2341A → T (PubMed:9778505).Curated
Sequence conflicti276 – 2772QP → HA (PubMed:7904557).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L20300 mRNA. No translation available.
AF091351 Genomic DNA. Translation: AAC97934.1.
X75415 mRNA. Translation: CAA53169.1.
CCDSiCCDS28556.1.
RefSeqiNP_032726.1. NM_008700.2.
XP_006523860.1. XM_006523797.2.
UniGeneiMm.41974.

Genome annotation databases

EnsembliENSMUST00000015723; ENSMUSP00000015723; ENSMUSG00000015579.
GeneIDi18091.
KEGGimmu:18091.
UCSCiuc008beo.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L20300 mRNA. No translation available.
AF091351 Genomic DNA. Translation: AAC97934.1.
X75415 mRNA. Translation: CAA53169.1.
CCDSiCCDS28556.1.
RefSeqiNP_032726.1. NM_008700.2.
XP_006523860.1. XM_006523797.2.
UniGeneiMm.41974.

3D structure databases

ProteinModelPortaliP42582.
SMRiP42582. Positions 137-191.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201778. 10 interactions.
DIPiDIP-33031N.
IntActiP42582. 4 interactions.
STRINGi10090.ENSMUSP00000015723.

PTM databases

PhosphoSiteiP42582.

Proteomic databases

MaxQBiP42582.
PRIDEiP42582.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000015723; ENSMUSP00000015723; ENSMUSG00000015579.
GeneIDi18091.
KEGGimmu:18091.
UCSCiuc008beo.1. mouse.

Organism-specific databases

CTDi1482.
MGIiMGI:97350. Nkx2-5.

Phylogenomic databases

eggNOGiNOG310976.
HOGENOMiHOG000231923.
HOVERGENiHBG006689.
InParanoidiP42582.
KOiK09345.
OMAiGYGSAAC.
OrthoDBiEOG769ZK0.
PhylomeDBiP42582.
TreeFamiTF351204.

Enzyme and pathway databases

ReactomeiREACT_287523. YAP1- and WWTR1 (TAZ)-stimulated gene expression.

Miscellaneous databases

ChiTaRSiNkx2-5. mouse.
NextBioi293235.
PROiP42582.
SOURCEiSearch...

Gene expression databases

BgeeiP42582.
ExpressionAtlasiP42582. baseline and differential.
GenevisibleiP42582. MM.

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]
ProtoNetiSearch...

Publicationsi

  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. "Transcriptional repression by the T-box proteins Tbx18 and Tbx15 depends on Groucho corepressors."
    Farin H.F., Bussen M., Schmidt M.K., Singh M.K., Schuster-Gossler K., Kispert A.
    J. Biol. Chem. 282:25748-25759(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TBX18.
  10. Cited for: FUNCTION.

Entry informationi

Entry nameiNKX25_MOUSE
AccessioniPrimary (citable) accession number: P42582
Secondary accession number(s): P97335
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: June 24, 2015
This is version 132 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.