Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P42582

- NKX25_MOUSE

UniProt

P42582 - NKX25_MOUSE

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
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 123 (01 Oct 2014)
      Sequence version 1 (01 Nov 1995)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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 binding Source: UniProtKB
    4. protein heterodimerization activity Source: MGI
    5. protein homodimerization activity Source: UniProtKB
    6. RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity Source: MGI
    7. RNA polymerase II transcription cofactor activity Source: BHF-UCL
    8. RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription Source: BHF-UCL
    9. sequence-specific DNA binding Source: Ensembl
    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

    Keywords - Molecular functioni

    Developmental protein

    Keywords - Ligandi

    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 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

    Keywords - Cellular componenti

    Nucleus

    PTM / Processingi

    Molecule processing

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

    Proteomic databases

    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

    ArrayExpressiP42582.
    BgeeiP42582.
    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 FBLIM1.4 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

    MFPSPALTPT PFSVKDILNL EQQQRSLASG DLSARLEATL APASCMLAAF    50
    KPEAYSGPEA AASGLAELRA EMGPAPSPPK CSPAFPAAPT FYPGAYGDPD 100
    PAKDPRADKK ELCALQKAVE LDKAETDGAE RPRARRRRKP RVLFSQAQVY 150
    ELERRFKQQR YLSAPERDQL ASVLKLTSTQ VKIWFQNRRY KCKRQRQDQT 200
    LELLGPPPPP ARRIAVPVLV RDGKPCLGDP AAYAPAYGVG LNAYGYNAYP 250
    YPSYGGAACS PGYSCAAYPA APPAAQPPAA SANSNFVNFG VGDLNTVQSP 300
    GMPQGNSGVS TLHGIRAW 318
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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

    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.

    Miscellaneous databases

    ChiTaRSi NKX2-5. mouse.
    NextBioi 293235.
    PROi P42582.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P42582.
    Bgeei P42582.
    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. 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: October 1, 2014
    This is version 123 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