NKX25_RAT
ID NKX25_RAT Reviewed; 318 AA.
AC O35767;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Homeobox protein Nkx-2.5;
DE Short=rNKx-2.5;
DE AltName: Full=Homeobox protein NK-2 homolog E;
GN Name=Nkx2-5; Synonyms=Csx, Nkx-2.5, Nkx2e;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Heart;
RA Fu Y., Ruiz-Lozano P., Evans S.M.;
RT "A rat homeobox gene, rNKx-2.5, is a homologue of the tinman gene in
RT Drosophila and is mainly expressed during heart development.";
RL Dev. Genes Evol. 207:352-358(1997).
CC -!- FUNCTION: Transcription factor required for the development of the
CC heart and the spleen (By similarity). During heart development, acts as
CC a transcriptional activator of NPPA/ANF in cooperation with GATA4 (By
CC similarity). May cooperate with TBX2 to negatively modulate expression
CC of NPPA/ANF in the atrioventricular canal (By similarity). Binds to the
CC core DNA motif of NPPA promoter. Together with PBX1, required for
CC spleen development through a mechanism that involves CDKN2B repression
CC (By similarity). {ECO:0000250|UniProtKB:P42582,
CC ECO:0000250|UniProtKB:P52952}.
CC -!- SUBUNIT: Homodimer (via the homeobox); binds DNA as homodimer.
CC Interacts (via the homeobox) with TBX5 (via the T-box); this complex
CC binds DNA. Interacts with HIPK1 and HIPK2, but not HIPK3. Interacts
CC with the C-terminal zinc finger of GATA4 through its homeobox domain.
CC Also interacts with JARID2 which represses its ability to activate
CC transcription of ANF. Interacts with FBLIM1. Interacts with TBX18.
CC Interacts with histone methyltransferase NSD2 (via HMG box) (By
CC similarity). {ECO:0000250|UniProtKB:P42582,
CC ECO:0000250|UniProtKB:P52952}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P42582}.
CC -!- DOMAIN: The homeobox domain binds to double-stranded DNA.
CC {ECO:0000250|UniProtKB:P52952}.
CC -!- SIMILARITY: Belongs to the NK-2 homeobox family. {ECO:0000305}.
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DR EMBL; AF006664; AAB62696.1; -; mRNA.
DR RefSeq; NP_446103.1; NM_053651.1.
DR AlphaFoldDB; O35767; -.
DR SMR; O35767; -.
DR STRING; 10116.ENSRNOP00000028155; -.
DR ChEMBL; CHEMBL4105991; -.
DR PhosphoSitePlus; O35767; -.
DR PaxDb; O35767; -.
DR GeneID; 114109; -.
DR KEGG; rno:114109; -.
DR UCSC; RGD:620520; rat.
DR CTD; 1482; -.
DR RGD; 620520; Nkx2-5.
DR eggNOG; KOG0842; Eukaryota.
DR InParanoid; O35767; -.
DR OrthoDB; 1191455at2759; -.
DR PhylomeDB; O35767; -.
DR PRO; PR:O35767; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISS:UniProtKB.
DR GO; GO:0032993; C:protein-DNA complex; ISS:UniProtKB.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; ISO:RGD.
DR GO; GO:0005667; C:transcription regulator complex; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0001216; F:DNA-binding transcription activator activity; ISO:RGD.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0042826; F:histone deacetylase binding; IPI:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:RGD.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:RGD.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR GO; GO:0007512; P:adult heart development; ISO:RGD.
DR GO; GO:0003278; P:apoptotic process involved in heart morphogenesis; ISO:RGD.
DR GO; GO:0003228; P:atrial cardiac muscle tissue development; ISO:RGD.
DR GO; GO:0060413; P:atrial septum morphogenesis; ISO:RGD.
DR GO; GO:0060928; P:atrioventricular node cell development; ISO:RGD.
DR GO; GO:0060929; P:atrioventricular node cell fate commitment; ISO:RGD.
DR GO; GO:0003162; P:atrioventricular node development; ISO:RGD.
DR GO; GO:0003166; P:bundle of His development; ISO:RGD.
DR GO; GO:0003161; P:cardiac conduction system development; ISO:RGD.
DR GO; GO:0055013; P:cardiac muscle cell development; ISO:RGD.
DR GO; GO:0055007; P:cardiac muscle cell differentiation; IEP:RGD.
DR GO; GO:0060038; P:cardiac muscle cell proliferation; ISO:RGD.
DR GO; GO:0060048; P:cardiac muscle contraction; ISO:RGD.
DR GO; GO:0048738; P:cardiac muscle tissue development; ISO:RGD.
DR GO; GO:0055008; P:cardiac muscle tissue morphogenesis; ISO:RGD.
DR GO; GO:0003211; P:cardiac ventricle formation; ISO:RGD.
DR GO; GO:0003208; P:cardiac ventricle morphogenesis; ISO:RGD.
DR GO; GO:0030154; P:cell differentiation; ISO:RGD.
DR GO; GO:0071363; P:cellular response to growth factor stimulus; IEP:RGD.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEP:RGD.
DR GO; GO:0072359; P:circulatory system development; ISO:RGD.
DR GO; GO:0035050; P:embryonic heart tube development; ISO:RGD.
DR GO; GO:0060971; P:embryonic heart tube left/right pattern formation; ISO:RGD.
DR GO; GO:0060047; P:heart contraction; ISO:RGD.
DR GO; GO:0007507; P:heart development; ISO:RGD.
DR GO; GO:0001947; P:heart looping; ISO:RGD.
DR GO; GO:0003007; P:heart morphogenesis; ISO:RGD.
DR GO; GO:0060347; P:heart trabecula formation; ISO:RGD.
DR GO; GO:0030097; P:hemopoiesis; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; ISO:RGD.
DR GO; GO:0010832; P:negative regulation of myotube differentiation; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:RGD.
DR GO; GO:0003151; P:outflow tract morphogenesis; ISO:RGD.
DR GO; GO:0003148; P:outflow tract septum morphogenesis; ISO:RGD.
DR GO; GO:0060037; P:pharyngeal system development; ISO:RGD.
DR GO; GO:0051891; P:positive regulation of cardioblast differentiation; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0045823; P:positive regulation of heart contraction; ISO:RGD.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; ISO:RGD.
DR GO; GO:0010765; P:positive regulation of sodium ion transport; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0060261; P:positive regulation of transcription initiation from RNA polymerase II promoter; ISO:RGD.
DR GO; GO:0010735; P:positive regulation of transcription via serum response element binding; ISO:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0003342; P:proepicardium development; ISO:RGD.
DR GO; GO:0003350; P:pulmonary myocardium development; ISO:RGD.
DR GO; GO:0003168; P:Purkinje myocyte differentiation; ISO:RGD.
DR GO; GO:1903779; P:regulation of cardiac conduction; ISO:RGD.
DR GO; GO:0060043; P:regulation of cardiac muscle cell proliferation; ISO:RGD.
DR GO; GO:0055117; P:regulation of cardiac muscle contraction; ISO:RGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0003221; P:right ventricular cardiac muscle tissue morphogenesis; ISO:RGD.
DR GO; GO:0045214; P:sarcomere organization; ISO:RGD.
DR GO; GO:0003285; P:septum secundum development; ISO:RGD.
DR GO; GO:0048536; P:spleen development; ISS:UniProtKB.
DR GO; GO:0030878; P:thyroid gland development; ISO:RGD.
DR GO; GO:0001570; P:vasculogenesis; ISO:RGD.
DR GO; GO:0055005; P:ventricular cardiac myofibril assembly; ISO:RGD.
DR GO; GO:0060412; P:ventricular septum morphogenesis; ISO:RGD.
DR GO; GO:0003222; P:ventricular trabecula myocardium morphogenesis; ISO:RGD.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR020479; Homeobox_metazoa.
DR InterPro; IPR033629; NKX-2.5.
DR PANTHER; PTHR24340:SF28; PTHR24340:SF28; 1.
DR Pfam; PF00046; Homeodomain; 1.
DR PRINTS; PR00024; HOMEOBOX.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 2: Evidence at transcript level;
KW Developmental protein; DNA-binding; Homeobox; Nucleus; Reference proteome.
FT CHAIN 1..318
FT /note="Homeobox protein Nkx-2.5"
FT /id="PRO_0000048939"
FT DNA_BIND 137..196
FT /note="Homeobox"
FT /evidence="ECO:0000250|UniProtKB:P52952,
FT ECO:0000255|PROSITE-ProRule:PRU00108"
SQ SEQUENCE 318 AA; 34336 MW; FCF845D4C41DA87C CRC64;
MFPSPALTHT PFSVKDILNL EQQQRSLAAG DLSARLEATL APASCMLAAF KPDGYSGPEA
AAPGLAELRA ELGPAPSPPK CSPAFPTAPT FYPRAYGDPD PAKDPRADKK ELCALQKAVE
LDKAETDGAE RRRPRRRRKP RVLFSQAQVY ELERRFKQQR YLSPAERDQL ASVLKLTSTQ
VKIWFQNRRY KCKRQRQDQT LELLGPPPPP ARRIAVPVLV RDGKPCLGDS AAYAPAYGLG
LNAYGYNAYP YPGYGGAACS PAYSCAAYPA APPAAHAPAA SANSNFVNFG VGDLNTVQSP
GMPQGNSGVS TLHGIRAW
