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Protein

Homeobox protein Nkx-2.5

Gene

Nkx2-5

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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. Binds to the core DNA motif of NPPA promoter. 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.By similarity2 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi137 – 196HomeoboxPROSITE-ProRule annotationBy similarityAdd BLAST60

GO - Molecular functioni

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

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 by RNA polymerase II 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 by RNA polymerase II 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: MGI
  • pulmonary myocardium development Source: MGI
  • Purkinje myocyte differentiation Source: MGI
  • regulation of cardiac conduction Source: BHF-UCL
  • regulation of cardiac muscle cell proliferation Source: MGI
  • regulation of cardiac muscle contraction Source: BHF-UCL
  • regulation of transcription by RNA polymerase II Source: MGI
  • right ventricular cardiac muscle tissue morphogenesis Source: MGI
  • sarcomere organization Source: MGI
  • septum secundum development Source: MGI
  • spleen development Source: MGI
  • thyroid gland development Source: BHF-UCL
  • tongue development Source: BHF-UCL
  • 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

Keywordsi

Molecular functionDevelopmental protein, DNA-binding

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi

Organism-specific databases

MGIiMGI:97350 Nkx2-5

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000489381 – 318Homeobox protein Nkx-2.5Add BLAST318

Proteomic databases

PaxDbiP42582
PRIDEiP42582

PTM databases

iPTMnetiP42582
PhosphoSitePlusiP42582

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

BgeeiENSMUSG00000015579
ExpressionAtlasiP42582 baseline and differential
GenevisibleiP42582 MM

Interactioni

Subunit structurei

Homodimer (via the homeobox); binds DNA as homodimer. Interacts (via the homeobox) with TBX5 (via the T-box); this complex binds DNA (By similarity). Interacts with HIPK1 and HIPK2, but not HIPK3 (PubMed:9748262). Interacts with the C-terminal zinc finger of GATA4 through its homeobox domain (PubMed:9584153). Also interacts with JARID2 which represses its ability to activate transcription of ANF (PubMed:15542826). Interacts with FBLIM1 (PubMed:14757752). Interacts with TBX18 (PubMed:17584735).By similarity5 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein heterodimerization activity Source: MGI
  • protein homodimerization activity Source: UniProtKB
  • transcription factor binding Source: MGI

Protein-protein interaction databases

BioGridi201778, 12 interactors
CORUMiP42582
DIPiDIP-33031N
IntActiP42582, 5 interactors
STRINGi10090.ENSMUSP00000015723

Structurei

Secondary structure

1318
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi146 – 156Combined sources11
Helixi164 – 173Combined sources10
Helixi178 – 188Combined sources11
Helixi192 – 196Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5FLVX-ray3.00A/E/I/M134-197[»]
ProteinModelPortaliP42582
SMRiP42582
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi41 – 107Ala/Pro-richAdd BLAST67
Compositional biasi206 – 280Ala/Pro-richAdd BLAST75

Domaini

The homeobox domain binds to double-stranded DNA.By similarity

Sequence similaritiesi

Belongs to the NK-2 homeobox family.Curated

Keywords - Domaini

Homeobox

Phylogenomic databases

eggNOGiKOG0842 Eukaryota
ENOG410XR21 LUCA
GeneTreeiENSGT00910000144003
HOGENOMiHOG000231923
HOVERGENiHBG006689
InParanoidiP42582
KOiK09345
OMAiDKKELCA
OrthoDBiEOG091G0LZ2
PhylomeDBiP42582
TreeFamiTF351204

Family and domain databases

CDDicd00086 homeodomain, 1 hit
InterProiView protein in InterPro
IPR009057 Homeobox-like_sf
IPR017970 Homeobox_CS
IPR001356 Homeobox_dom
IPR020479 Homeobox_metazoa
IPR033629 NKX-2.5
PANTHERiPTHR24340:SF28 PTHR24340:SF28, 1 hit
PfamiView protein in Pfam
PF00046 Homeobox, 1 hit
PRINTSiPR00024 HOMEOBOX
SMARTiView protein in SMART
SM00389 HOX, 1 hit
SUPFAMiSSF46689 SSF46689, 1 hit
PROSITEiView protein in PROSITE
PS00027 HOMEOBOX_1, 1 hit
PS50071 HOMEOBOX_2, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti62A → R in L20300 (PubMed:7690144).Curated1
Sequence conflicti164 – 165AP → PA (PubMed:7904557).Curated2
Sequence conflicti234A → T (PubMed:9778505).Curated1
Sequence conflicti276 – 277QP → HA (PubMed:7904557).Curated2

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_006523797.3
UniGeneiMm.41974

Genome annotation databases

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

Similar proteinsi

Entry informationi

Entry nameiNKX25_MOUSE
AccessioniPrimary (citable) accession number: P42582
Secondary accession number(s): P97335
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: November 1, 1995
Last modified: April 25, 2018
This is version 158 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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

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