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Homeobox protein Nkx-2.5 (Cardiac-specific homeobox) (Homeobox protein CSX) (Homeobox protein NK-2 homolog E)

 NKX25_MOUSE             Reviewed;         318 AA.
P42582; P97335;
01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
01-NOV-1995, sequence version 1.
22-NOV-2017, entry version 154.
RecName: Full=Homeobox protein Nkx-2.5;
AltName: Full=Cardiac-specific homeobox;
AltName: Full=Homeobox protein CSX;
AltName: Full=Homeobox protein NK-2 homolog E;
Name=Nkx2-5; Synonyms=Csx, Nkx-2.5, Nkx2e;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE.
TISSUE=Heart;
PubMed=7904557;
Lints T.J., Parsons L.M., Hartley L., Lyons I., Harvey R.P.;
"Nkx-2.5: a novel murine homeobox gene expressed in early heart
progenitor cells and their myogenic descendants.";
Development 119:419-431(1993).
[2]
ERRATUM.
PubMed=7910553;
Lints T.J., Parsons L.M., Hartley L., Lyons I., Harvey R.P.;
Development 119:969-969(1993).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
STRAIN=129/J;
PubMed=9778505;
Searcy R.D., Vincent E.B., Liberatore C.M., Yutzey K.E.;
"A GATA-dependent nkx-2.5 regulatory element activates early cardiac
gene expression in transgenic mice.";
Development 125:4461-4470(1998).
[4]
NUCLEOTIDE SEQUENCE [MRNA] OF 17-318.
PubMed=7690144; DOI=10.1073/pnas.90.17.8145;
Komuro I., Izumo S.;
"Csx: a murine homeobox-containing gene specifically expressed in the
developing heart.";
Proc. Natl. Acad. Sci. U.S.A. 90:8145-8149(1993).
[5]
INTERACTION WITH HIPK1 AND HIPK2.
STRAIN=BALB/cJ;
PubMed=9748262; DOI=10.1074/jbc.273.40.25875;
Kim Y.H., Choi C.Y., Lee S.-J., Conti M.A., Kim Y.;
"Homeodomain-interacting protein kinases, a novel family of co-
repressors for homeodomain transcription factors.";
J. Biol. Chem. 273:25875-25879(1998).
[6]
FUNCTION, AND INTERACTION WITH GATA4.
PubMed=9584153; DOI=10.1128/MCB.18.6.3120;
Lee Y., Shioi T., Kasahara H., Jobe S.M., Wiese R.J., Markham B.E.,
Izumo S.;
"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.";
Mol. Cell. Biol. 18:3120-3129(1998).
[7]
INTERACTION WITH FBLIM1.
PubMed=14757752; DOI=10.1083/jcb.200309159;
Akazawa H., Kudoh S., Mochizuki N., Takekoshi N., Takano H., Nagai T.,
Komuro I.;
"A novel LIM protein Cal promotes cardiac differentiation by
association with CSX/NKX2-5.";
J. Cell Biol. 164:395-405(2004).
[8]
INTERACTION WITH JARID2.
PubMed=15542826; DOI=10.1128/MCB.24.23.10151-10160.2004;
Kim T.-G., Chen J., Sadoshima J., Lee Y.;
"Jumonji represses atrial natriuretic factor gene expression by
inhibiting transcriptional activities of cardiac transcription
factors.";
Mol. Cell. Biol. 24:10151-10160(2004).
[9]
INTERACTION WITH TBX18.
PubMed=17584735; DOI=10.1074/jbc.M703724200;
Farin H.F., Bussen M., Schmidt M.K., Singh M.K., Schuster-Gossler K.,
Kispert A.;
"Transcriptional repression by the T-box proteins Tbx18 and Tbx15
depends on Groucho corepressors.";
J. Biol. Chem. 282:25748-25759(2007).
[10]
FUNCTION.
PubMed=22560297; DOI=10.1016/j.devcel.2012.02.009;
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.;
"Congenital asplenia in mice and humans with mutations in a Pbx/Nkx2-
5/p15 module.";
Dev. Cell 22:913-926(2012).
-!- FUNCTION: 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. {ECO:0000250|UniProtKB:P52952,
ECO:0000269|PubMed:22560297, ECO:0000269|PubMed:9584153}.
-!- SUBUNIT: 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).
{ECO:0000250|UniProtKB:P52952, ECO:0000269|PubMed:14757752,
ECO:0000269|PubMed:15542826, ECO:0000269|PubMed:17584735,
ECO:0000269|PubMed:9584153, ECO:0000269|PubMed:9748262}.
-!- INTERACTION:
Q9Z277:Baz1b; NbExp=2; IntAct=EBI-297021, EBI-927576;
O94983:CAMTA2 (xeno); NbExp=2; IntAct=EBI-297021, EBI-936534;
Q08369:Gata4; NbExp=4; IntAct=EBI-297021, EBI-297008;
Q62315:Jarid2; NbExp=3; IntAct=EBI-297021, EBI-493592;
Q8BVE8-2:Nsd2; NbExp=2; IntAct=EBI-297021, EBI-11518042;
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
-!- 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.
-!- DOMAIN: The homeobox domain binds to double-stranded DNA.
{ECO:0000250|UniProtKB:P52952}.
-!- SIMILARITY: Belongs to the NK-2 homeobox family. {ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; L20300; -; NOT_ANNOTATED_CDS; mRNA.
EMBL; AF091351; AAC97934.1; -; Genomic_DNA.
EMBL; X75415; CAA53169.1; -; mRNA.
CCDS; CCDS28556.1; -.
RefSeq; NP_032726.1; NM_008700.2.
RefSeq; XP_006523860.1; XM_006523797.3.
UniGene; Mm.41974; -.
PDB; 5FLV; X-ray; 3.00 A; A/E/I/M=134-197.
PDBsum; 5FLV; -.
ProteinModelPortal; P42582; -.
SMR; P42582; -.
BioGrid; 201778; 12.
CORUM; P42582; -.
DIP; DIP-33031N; -.
IntAct; P42582; 6.
STRING; 10090.ENSMUSP00000015723; -.
iPTMnet; P42582; -.
PhosphoSitePlus; P42582; -.
PaxDb; P42582; -.
PRIDE; P42582; -.
Ensembl; ENSMUST00000015723; ENSMUSP00000015723; ENSMUSG00000015579.
GeneID; 18091; -.
KEGG; mmu:18091; -.
UCSC; uc008beo.1; mouse.
CTD; 1482; -.
MGI; MGI:97350; Nkx2-5.
eggNOG; KOG0842; Eukaryota.
eggNOG; ENOG410XR21; LUCA.
GeneTree; ENSGT00900000140771; -.
HOGENOM; HOG000231923; -.
HOVERGEN; HBG006689; -.
InParanoid; P42582; -.
KO; K09345; -.
OMA; DKKELCA; -.
OrthoDB; EOG091G0LZ2; -.
PhylomeDB; P42582; -.
TreeFam; TF351204; -.
ChiTaRS; Nkx2-5; mouse.
PRO; PR:P42582; -.
Proteomes; UP000000589; Chromosome 17.
Bgee; ENSMUSG00000015579; -.
ExpressionAtlas; P42582; baseline and differential.
Genevisible; P42582; MM.
GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
GO; GO:0032991; C:macromolecular complex; ISO:MGI.
GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
GO; GO:0032993; C:protein-DNA complex; ISS:UniProtKB.
GO; GO:0090575; C:RNA polymerase II transcription factor complex; ISO:MGI.
GO; GO:0005667; C:transcription factor complex; IDA:MGI.
GO; GO:0003682; F:chromatin binding; IDA:MGI.
GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
GO; GO:0046982; F:protein heterodimerization activity; IPI:MGI.
GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; ISS:UniProtKB.
GO; GO:0001104; F:RNA polymerase II transcription cofactor activity; IMP:BHF-UCL.
GO; GO:0043565; F:sequence-specific DNA binding; ISO:MGI.
GO; GO:0010736; F:serum response element binding; IDA:BHF-UCL.
GO; GO:0003705; F:transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding; IDA:MGI.
GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:MGI.
GO; GO:0008134; F:transcription factor binding; ISO:MGI.
GO; GO:0044212; F:transcription regulatory region DNA binding; ISO:MGI.
GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; ISO:MGI.
GO; GO:0001190; F:transcriptional activator activity, RNA polymerase II transcription factor binding; IMP:BHF-UCL.
GO; GO:0001228; F:transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding; IDA:BHF-UCL.
GO; GO:0007512; P:adult heart development; IMP:MGI.
GO; GO:0003278; P:apoptotic process involved in heart morphogenesis; IMP:MGI.
GO; GO:0055014; P:atrial cardiac muscle cell development; TAS:BHF-UCL.
GO; GO:0060413; P:atrial septum morphogenesis; ISO:MGI.
GO; GO:0060928; P:atrioventricular node cell development; IMP:MGI.
GO; GO:0060929; P:atrioventricular node cell fate commitment; IMP:MGI.
GO; GO:0003162; P:atrioventricular node development; IMP:BHF-UCL.
GO; GO:0030509; P:BMP signaling pathway; IDA:MGI.
GO; GO:0003166; P:bundle of His development; IGI:MGI.
GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:MGI.
GO; GO:0003161; P:cardiac conduction system development; IGI:MGI.
GO; GO:0055007; P:cardiac muscle cell differentiation; IDA:UniProtKB.
GO; GO:0060038; P:cardiac muscle cell proliferation; IGI:MGI.
GO; GO:0060048; P:cardiac muscle contraction; IMP:MGI.
GO; GO:0048738; P:cardiac muscle tissue development; IMP:MGI.
GO; GO:0055008; P:cardiac muscle tissue morphogenesis; ISO:MGI.
GO; GO:0003211; P:cardiac ventricle formation; IGI:MGI.
GO; GO:0003208; P:cardiac ventricle morphogenesis; IMP:MGI.
GO; GO:0072358; P:cardiovascular system development; IGI:MGI.
GO; GO:0030154; P:cell differentiation; IGI:MGI.
GO; GO:0035050; P:embryonic heart tube development; IGI:MGI.
GO; GO:0060971; P:embryonic heart tube left/right pattern formation; IMP:MGI.
GO; GO:0007492; P:endoderm development; TAS:BHF-UCL.
GO; GO:0060047; P:heart contraction; IGI:MGI.
GO; GO:0007507; P:heart development; IMP:MGI.
GO; GO:0001947; P:heart looping; IMP:MGI.
GO; GO:0003007; P:heart morphogenesis; IMP:MGI.
GO; GO:0060347; P:heart trabecula formation; IMP:MGI.
GO; GO:0030097; P:hemopoiesis; IMP:MGI.
GO; GO:0043066; P:negative regulation of apoptotic process; IGI:MGI.
GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:BHF-UCL.
GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IMP:BHF-UCL.
GO; GO:0010832; P:negative regulation of myotube differentiation; ISO:MGI.
GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IDA:MGI.
GO; GO:0003151; P:outflow tract morphogenesis; IMP:MGI.
GO; GO:0003148; P:outflow tract septum morphogenesis; ISO:MGI.
GO; GO:0060037; P:pharyngeal system development; IGI:MGI.
GO; GO:0051891; P:positive regulation of cardioblast differentiation; IMP:BHF-UCL.
GO; GO:0008284; P:positive regulation of cell proliferation; IGI:MGI.
GO; GO:0010628; P:positive regulation of gene expression; IDA:UniProtKB.
GO; GO:0045823; P:positive regulation of heart contraction; IMP:BHF-UCL.
GO; GO:0045666; P:positive regulation of neuron differentiation; ISO:MGI.
GO; GO:0010765; P:positive regulation of sodium ion transport; IMP:BHF-UCL.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL.
GO; GO:0060261; P:positive regulation of transcription initiation from RNA polymerase II promoter; IDA:BHF-UCL.
GO; GO:0010735; P:positive regulation of transcription via serum response element binding; IDA:BHF-UCL.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MGI.
GO; GO:0003342; P:proepicardium development; IMP:MGI.
GO; GO:0003350; P:pulmonary myocardium development; IMP:MGI.
GO; GO:0003168; P:Purkinje myocyte differentiation; IMP:MGI.
GO; GO:1903779; P:regulation of cardiac conduction; IMP:BHF-UCL.
GO; GO:0060043; P:regulation of cardiac muscle cell proliferation; IDA:MGI.
GO; GO:0055117; P:regulation of cardiac muscle contraction; IMP:BHF-UCL.
GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; IDA:MGI.
GO; GO:0003221; P:right ventricular cardiac muscle tissue morphogenesis; ISO:MGI.
GO; GO:0045214; P:sarcomere organization; IGI:MGI.
GO; GO:0003285; P:septum secundum development; ISO:MGI.
GO; GO:0048536; P:spleen development; IGI:MGI.
GO; GO:0030878; P:thyroid gland development; IMP:BHF-UCL.
GO; GO:0043586; P:tongue development; TAS:BHF-UCL.
GO; GO:0001570; P:vasculogenesis; IMP:MGI.
GO; GO:0055015; P:ventricular cardiac muscle cell development; TAS:BHF-UCL.
GO; GO:0055005; P:ventricular cardiac myofibril assembly; IMP:MGI.
GO; GO:0060412; P:ventricular septum morphogenesis; ISO:MGI.
GO; GO:0003222; P:ventricular trabecula myocardium morphogenesis; IMP:MGI.
CDD; cd00086; homeodomain; 1.
InterPro; IPR009057; Homeobox-like_sf.
InterPro; IPR017970; Homeobox_CS.
InterPro; IPR001356; Homeobox_dom.
InterPro; IPR020479; Homeobox_metazoa.
InterPro; IPR033629; NKX-2.5.
PANTHER; PTHR24340:SF28; PTHR24340:SF28; 1.
Pfam; PF00046; Homeobox; 1.
PRINTS; PR00024; HOMEOBOX.
SMART; SM00389; HOX; 1.
SUPFAM; SSF46689; SSF46689; 1.
PROSITE; PS00027; HOMEOBOX_1; 1.
PROSITE; PS50071; HOMEOBOX_2; 1.
1: Evidence at protein level;
3D-structure; Complete proteome; Developmental protein; DNA-binding;
Homeobox; Nucleus; Reference proteome.
CHAIN 1 318 Homeobox protein Nkx-2.5.
/FTId=PRO_0000048938.
DNA_BIND 137 196 Homeobox. {ECO:0000250|UniProtKB:P52952,
ECO:0000255|PROSITE-ProRule:PRU00108}.
COMPBIAS 41 107 Ala/Pro-rich.
COMPBIAS 206 280 Ala/Pro-rich.
CONFLICT 62 62 A -> R (in Ref. 4; L20300).
{ECO:0000305}.
CONFLICT 164 165 AP -> PA (in Ref. 1). {ECO:0000305}.
CONFLICT 234 234 A -> T (in Ref. 3). {ECO:0000305}.
CONFLICT 276 277 QP -> HA (in Ref. 1). {ECO:0000305}.
HELIX 146 156 {ECO:0000244|PDB:5FLV}.
HELIX 164 173 {ECO:0000244|PDB:5FLV}.
HELIX 178 188 {ECO:0000244|PDB:5FLV}.
HELIX 192 196 {ECO:0000244|PDB:5FLV}.
SEQUENCE 318 AA; 34163 MW; 6A3E7859F46D4FA6 CRC64;
MFPSPALTPT PFSVKDILNL EQQQRSLASG DLSARLEATL APASCMLAAF KPEAYSGPEA
AASGLAELRA EMGPAPSPPK CSPAFPAAPT FYPGAYGDPD PAKDPRADKK ELCALQKAVE
LDKAETDGAE RPRARRRRKP RVLFSQAQVY ELERRFKQQR YLSAPERDQL ASVLKLTSTQ
VKIWFQNRRY KCKRQRQDQT LELLGPPPPP ARRIAVPVLV RDGKPCLGDP AAYAPAYGVG
LNAYGYNAYP YPSYGGAACS PGYSCAAYPA APPAAQPPAA SANSNFVNFG VGDLNTVQSP
GMPQGNSGVS TLHGIRAW


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