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P42582

- NKX25_MOUSE

UniProt

P42582 - NKX25_MOUSE

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Protein

Homeobox protein Nkx-2.5

Gene

Nkx2-5

Organism
Mus musculus (Mouse)
Status
Reviewed - 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

  1. chromatin binding Source: MGI
  2. DNA binding Source: UniProtKB
  3. protein heterodimerization activity Source: MGI
  4. protein homodimerization activity Source: UniProtKB
  5. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: Ensembl
  6. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: Ensembl
  7. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: MGI
  8. RNA polymerase II transcription cofactor activity Source: BHF-UCL
  9. RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription Source: BHF-UCL
  10. sequence-specific DNA binding transcription factor activity Source: MGI
  11. serum response element binding Source: BHF-UCL

GO - Biological processi

  1. adult heart development Source: MGI
  2. apoptotic process involved in heart morphogenesis Source: MGI
  3. atrial cardiac muscle cell development Source: BHF-UCL
  4. atrial septum morphogenesis Source: Ensembl
  5. atrioventricular node cell development Source: MGI
  6. atrioventricular node cell fate commitment Source: MGI
  7. atrioventricular node development Source: BHF-UCL
  8. BMP signaling pathway Source: MGI
  9. bundle of His development Source: MGI
  10. canonical Wnt signaling pathway Source: MGI
  11. cardiac conduction system development Source: MGI
  12. cardiac muscle cell differentiation Source: UniProtKB
  13. cardiac muscle cell proliferation Source: MGI
  14. cardiac muscle contraction Source: MGI
  15. cardiac muscle tissue development Source: MGI
  16. cardiac ventricle formation Source: MGI
  17. cardiac ventricle morphogenesis Source: MGI
  18. cardiovascular system development Source: MGI
  19. cell differentiation Source: MGI
  20. embryonic heart tube development Source: MGI
  21. embryonic heart tube left/right pattern formation Source: MGI
  22. endoderm development Source: BHF-UCL
  23. heart contraction Source: MGI
  24. heart development Source: MGI
  25. heart looping Source: MGI
  26. heart morphogenesis Source: MGI
  27. heart trabecula formation Source: MGI
  28. hemopoiesis Source: MGI
  29. negative regulation of apoptotic process Source: MGI
  30. negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
  31. negative regulation of cardiac muscle cell apoptotic process Source: BHF-UCL
  32. negative regulation of myotube differentiation Source: Ensembl
  33. negative regulation of transcription from RNA polymerase II promoter Source: MGI
  34. outflow tract morphogenesis Source: MGI
  35. outflow tract septum morphogenesis Source: Ensembl
  36. pharyngeal system development Source: MGI
  37. positive regulation of cardioblast differentiation Source: BHF-UCL
  38. positive regulation of cell proliferation Source: MGI
  39. positive regulation of gene expression Source: UniProtKB
  40. positive regulation of heart contraction Source: BHF-UCL
  41. positive regulation of neuron differentiation Source: Ensembl
  42. positive regulation of sodium ion transport Source: BHF-UCL
  43. positive regulation of transcription, DNA-templated Source: MGI
  44. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  45. positive regulation of transcription initiation from RNA polymerase II promoter Source: BHF-UCL
  46. positive regulation of transcription via serum response element binding Source: BHF-UCL
  47. positive regulation of voltage-gated calcium channel activity Source: BHF-UCL
  48. proepicardium development Source: MGI
  49. pulmonary myocardium development Source: MGI
  50. Purkinje myocyte differentiation Source: MGI
  51. regulation of cardiac muscle cell proliferation Source: MGI
  52. regulation of cardiac muscle contraction Source: BHF-UCL
  53. regulation of transcription from RNA polymerase II promoter Source: MGI
  54. right ventricular cardiac muscle tissue morphogenesis Source: Ensembl
  55. sarcomere organization Source: MGI
  56. septum secundum development Source: Ensembl
  57. spleen development Source: BHF-UCL
  58. thyroid gland development Source: BHF-UCL
  59. tongue development Source: BHF-UCL
  60. transcription from RNA polymerase II promoter Source: GOC
  61. vasculogenesis Source: MGI
  62. ventricular cardiac muscle cell development Source: BHF-UCL
  63. ventricular cardiac myofibril assembly Source: MGI
  64. ventricular septum morphogenesis Source: Ensembl
  65. ventricular trabecula myocardium morphogenesis Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_196516. 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: Chromosome 17

Organism-specific databases

MGIiMGI:97350. Nkx2-5.

Subcellular locationi

Nucleus Curated

GO - Cellular componenti

  1. cytoplasm Source: BHF-UCL
  2. nucleus Source: BHF-UCL
  3. 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.
GenevestigatoriP42582.

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 TBX18.5 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.

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.
OMAiAYGDPDP.
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_006523797.1.
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 .
CCDSi CCDS28556.1.
RefSeqi NP_032726.1. NM_008700.2.
XP_006523860.1. XM_006523797.1.
UniGenei Mm.41974.

3D structure databases

ProteinModelPortali P42582.
SMRi P42582. Positions 137-191.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 201778. 10 interactions.
DIPi DIP-33031N.
IntActi P42582. 4 interactions.

PTM databases

PhosphoSitei P42582.

Proteomic databases

MaxQBi P42582.
PRIDEi P42582.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000015723 ; ENSMUSP00000015723 ; ENSMUSG00000015579 .
GeneIDi 18091.
KEGGi mmu:18091.
UCSCi uc008beo.1. mouse.

Organism-specific databases

CTDi 1482.
MGIi MGI:97350. Nkx2-5.

Phylogenomic databases

eggNOGi NOG310976.
HOGENOMi HOG000231923.
HOVERGENi HBG006689.
InParanoidi P42582.
KOi K09345.
OMAi AYGDPDP.
OrthoDBi EOG769ZK0.
PhylomeDBi P42582.
TreeFami TF351204.

Enzyme and pathway databases

Reactomei REACT_196516. YAP1- and WWTR1 (TAZ)-stimulated gene expression.

Miscellaneous databases

ChiTaRSi Nkx2-5. mouse.
NextBioi 293235.
PROi P42582.
SOURCEi Search...

Gene expression databases

Bgeei P42582.
ExpressionAtlasi P42582. baseline and differential.
Genevestigatori P42582.

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. "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: November 26, 2014
This is version 125 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