CDX2_MESAU
ID CDX2_MESAU Reviewed; 313 AA.
AC Q04649;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1994, sequence version 1.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Homeobox protein CDX-2;
DE AltName: Full=Caudal-type homeobox protein 2;
GN Name=CDX2; Synonyms=CDX-3, CDX3;
OS Mesocricetus auratus (Golden hamster).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Mesocricetus.
OX NCBI_TaxID=10036;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=1358758; DOI=10.1101/gad.6.11.2165;
RA German M.S., Wang J., Chadwick R.B., Rutter W.J.;
RT "Synergistic activation of the insulin gene by a LIM-homeo domain protein
RT and a basic helix-loop-helix protein: building a functional insulin
RT minienhancer complex.";
RL Genes Dev. 6:2165-2176(1992).
RN [2]
RP FUNCTION.
RX PubMed=9148757; DOI=10.1042/bj3220833;
RA Troelsen J.T., Mitchelmore C., Spodsberg N., Jensen A.M., Noren O.,
RA Sjoestroem H.;
RT "Regulation of lactase-phlorizin hydrolase gene expression by the caudal-
RT related homoeodomain protein Cdx-2.";
RL Biochem. J. 322:833-838(1997).
CC -!- FUNCTION: Transcription factor which regulates the transcription of
CC multiple genes expressed in the intestinal epithelium (PubMed:1358758).
CC Binds to the promoter of the intestinal sucrase-isomaltase SI and
CC activates SI transcription (By similarity). Binds to the DNA sequence
CC 5'-ATAAAAACTTAT-3' in the promoter region of VDR and activates VDR
CC transcription (By similarity). Binds to and activates transcription of
CC LPH (PubMed:9148757). Activates transcription of CLDN2 and intestinal
CC mucin MUC2 (By similarity). Binds to the 5'-AATTTTTTACAACACCT-3' DNA
CC sequence in the promoter region of CA1 and activates CA1 transcription
CC (By similarity). Important in broad range of functions from early
CC differentiation to maintenance of the intestinal epithelial lining of
CC both the small and large intestine. Binds preferentially to methylated
CC DNA (By similarity). {ECO:0000250|UniProtKB:P43241,
CC ECO:0000250|UniProtKB:Q99626, ECO:0000269|PubMed:1358758,
CC ECO:0000269|PubMed:9148757}.
CC -!- SUBUNIT: Can bind DNA as a monomer or homodimer.
CC {ECO:0000250|UniProtKB:P43241}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P43241}.
CC -!- TISSUE SPECIFICITY: Expressed in the intestine.
CC {ECO:0000269|PubMed:1358758}.
CC -!- PTM: Ubiquitinated, leading to its degradation by the proteasome.
CC {ECO:0000250|UniProtKB:P43241}.
CC -!- PTM: Phosphorylation at Ser-60 reduces transactivation capacity.
CC Phosphorylation at Ser-283 reduces transactivation capacity and also
CC increases ubiquitin-dependent proteasome degradation.
CC {ECO:0000250|UniProtKB:P43241}.
CC -!- SIMILARITY: Belongs to the Caudal homeobox family. {ECO:0000305}.
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DR EMBL; X81404; CAA57162.1; -; mRNA.
DR PIR; A46233; A46233.
DR RefSeq; NP_001268630.1; NM_001281701.1.
DR AlphaFoldDB; Q04649; -.
DR SMR; Q04649; -.
DR STRING; 10036.XP_005083240.1; -.
DR GeneID; 101841392; -.
DR CTD; 1045; -.
DR eggNOG; KOG0848; Eukaryota.
DR OrthoDB; 1380804at2759; -.
DR Proteomes; UP000189706; Unplaced.
DR GO; GO:0000794; C:condensed nuclear chromosome; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0017053; C:transcription repressor complex; IEA:Ensembl.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IEA:Ensembl.
DR GO; GO:0008327; F:methyl-CpG binding; ISS:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IEA:Ensembl.
DR GO; GO:0001568; P:blood vessel development; IEA:Ensembl.
DR GO; GO:0008333; P:endosome to lysosome transport; IEA:Ensembl.
DR GO; GO:0045197; P:establishment or maintenance of epithelial cell apical/basal polarity; IEA:Ensembl.
DR GO; GO:0060575; P:intestinal epithelial cell differentiation; ISS:UniProtKB.
DR GO; GO:0060711; P:labyrinthine layer development; IEA:Ensembl.
DR GO; GO:0045597; P:positive regulation of cell differentiation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0014807; P:regulation of somitogenesis; ISS:UniProtKB.
DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl.
DR GO; GO:0048863; P:stem cell differentiation; IEA:Ensembl.
DR GO; GO:0001829; P:trophectodermal cell differentiation; IEA:Ensembl.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR006820; Caudal_activation_dom.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR020479; Homeobox_metazoa.
DR InterPro; IPR000047; HTH_motif.
DR Pfam; PF04731; Caudal_act; 1.
DR Pfam; PF00046; Homeodomain; 1.
DR PRINTS; PR00024; HOMEOBOX.
DR PRINTS; PR00031; HTHREPRESSR.
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 Activator; Developmental protein; DNA-binding; Homeobox; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..313
FT /note="Homeobox protein CDX-2"
FT /id="PRO_0000048850"
FT DNA_BIND 185..244
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 113..153
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 185..215
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250|UniProtKB:Q99626"
FT REGION 227..241
FT /note="Interaction with 5-mCpG DNA"
FT /evidence="ECO:0000250|UniProtKB:Q99626"
FT REGION 242..313
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 283..295
FT /note="4S motif; modulates transactivation activity and
FT protein stability"
FT /evidence="ECO:0000250|UniProtKB:P43241"
FT COMPBIAS 248..262
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 275..293
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 60
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43241"
FT MOD_RES 283
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P43241"
SQ SEQUENCE 313 AA; 33560 MW; 63C98A9C0DEFD05C CRC64;
MYVSYLLDKD VSMYPSSVRH SGGLNLAPQN FVSPPQYPDY GGYHVAAAAA AAANLDSAQS
PGPSWSTAYG APLREDWNGY PPGGAAAANA VAHGLNGGSP AAAMGYSSPA DYHAHHHPHH
HPHHPAAAPS CASGLLQTLN PGPPGPAATG AAEQLSPSGQ RRNLCEWMRK PAQPSLGSQV
KTRTKDKYRV VYTDHQRLEL EKEFHYSRYI TIRRKAELAA TLGLSERQVK IWFQNRRAKE
RKINKKKLQQ QQQQQQQQQL ASPPPQPSQP QPGSLRSVPE PLSPVSSLQG SVPGSVPGVL
GPAGGVLNPT VTQ