CDX2_MOUSE
ID CDX2_MOUSE Reviewed; 311 AA.
AC P43241;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Homeobox protein CDX-2;
DE AltName: Full=Caudal-type homeobox protein 2;
GN Name=Cdx2; Synonyms=Cdx-2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=BALB/cJ;
RX PubMed=7910823; DOI=10.1016/s0021-9258(17)36596-1;
RA James R.J., Erler T., Kazenwadel J.;
RT "Structure of the murine homeobox gene cdx-2. Expression in embryonic and
RT adult intestinal epithelium.";
RL J. Biol. Chem. 269:15229-15237(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBUNIT, AND TISSUE SPECIFICITY.
RC TISSUE=Small intestine;
RX PubMed=7935448; DOI=10.1128/mcb.14.11.7340-7351.1994;
RA Suh E., Chen L., Taylor J., Traber P.G.;
RT "A homeodomain protein related to caudal regulates intestine-specific gene
RT transcription.";
RL Mol. Cell. Biol. 14:7340-7351(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE OF 204-229, AND TISSUE SPECIFICITY.
RX PubMed=1671571; DOI=10.1016/s0021-9258(18)49981-4;
RA James R.J., Kazenwadel J.;
RT "Homeobox gene expression in the intestinal epithelium of adult mice.";
RL J. Biol. Chem. 266:3246-3251(1991).
RN [4]
RP FUNCTION.
RX PubMed=9512360; DOI=10.1016/s0014-5793(98)00103-3;
RA Drummond F.J., Sowden J., Morrison K., Edwards Y.H.;
RT "Colon carbonic anhydrase 1: transactivation of gene expression by the
RT homeodomain protein Cdx2.";
RL FEBS Lett. 423:218-222(1998).
RN [5]
RP FUNCTION.
RX PubMed=9933478; DOI=10.1359/jbmr.1999.14.2.240;
RA Yamamoto H., Miyamoto K., Li B., Taketani Y., Kitano M., Inoue Y.,
RA Morita K., Pike J.W., Takeda E.;
RT "The caudal-related homeodomain protein Cdx-2 regulates vitamin D receptor
RT gene expression in the small intestine.";
RL J. Bone Miner. Res. 14:240-247(1999).
RN [6]
RP SUBUNIT, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, PHOSPHORYLATION AT
RP SER-60, AND MUTAGENESIS OF SER-60.
RX PubMed=11729123; DOI=10.1053/gast.2001.29618;
RA Rings E.H., Boudreau F., Taylor J.K., Moffett J., Suh E.R., Traber P.G.;
RT "Phosphorylation of the serine 60 residue within the Cdx2 activation domain
RT mediates its transactivation capacity.";
RL Gastroenterology 121:1437-1450(2001).
RN [7]
RP FUNCTION, TISSUE SPECIFICITY, UBIQUITINATION, MOTIF, AND PHOSPHORYLATION AT
RP SER-281.
RX PubMed=16027724; DOI=10.1038/sj.onc.1208945;
RA Gross I., Lhermitte B., Domon-Dell C., Duluc I., Martin E., Gaiddon C.,
RA Kedinger M., Freund J.N.;
RT "Phosphorylation of the homeotic tumor suppressor Cdx2 mediates its
RT ubiquitin-dependent proteasome degradation.";
RL Oncogene 24:7955-7963(2005).
CC -!- FUNCTION: Transcription factor which regulates the transcription of
CC multiple genes expressed in the intestinal epithelium (PubMed:9933478,
CC PubMed:16027724). Binds to the promoter of the intestinal sucrase-
CC isomaltase SI and activates SI transcription (PubMed:7935448). Binds to
CC the DNA sequence 5'-ATAAAAACTTAT-3' in the promoter region of VDR and
CC activates VDR transcription (PubMed:9933478). Binds to and activates
CC transcription of LPH (By similarity). Activates transcription of CLDN2
CC and intestinal mucin MUC2 (PubMed:16027724). Binds to the 5'-
CC AATTTTTTACAACACCT-3' DNA sequence in the promoter region of CA1 and
CC activates CA1 transcription (PubMed:9512360). Important in broad range
CC of functions from early differentiation to maintenance of the
CC intestinal epithelial lining of both the small and large intestine.
CC Binds preferentially to methylated DNA (By similarity).
CC {ECO:0000250|UniProtKB:Q04649, ECO:0000250|UniProtKB:Q99626,
CC ECO:0000269|PubMed:16027724, ECO:0000269|PubMed:7935448,
CC ECO:0000269|PubMed:9512360, ECO:0000269|PubMed:9933478}.
CC -!- SUBUNIT: Can bind DNA as a monomer or homodimer.
CC {ECO:0000269|PubMed:11729123, ECO:0000269|PubMed:7935448}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11729123,
CC ECO:0000269|PubMed:7910823}.
CC -!- TISSUE SPECIFICITY: In the intestine, detected in ileum and proximal
CC and distal colon (at protein level) (PubMed:16027724). In adult small
CC intestine, predominantly localized in crypt and lower villus cells of
CC the epithelium (at protein level) (PubMed:11729123). Expressed in the
CC intestine but not detected in other tissues including stomach, liver,
CC kidney, spleen, brain, heart, lung, pancreas, skeletal muscle and
CC testis (PubMed:7935448). Expressed specifically in gut epithelium where
CC it is not restricted to a particular cell lineage. Abundant expression
CC is seen in the proximal colon with slightly lower levels in distal
CC colon (PubMed:7910823, PubMed:1671571). Expression in the proximal
CC colon is not restricted either to a particular cell lineage or stage of
CC differentiation while in the distal colon it is more abundant in the
CC differentiated cells towards the top of the crypt.
CC {ECO:0000269|PubMed:11729123, ECO:0000269|PubMed:16027724,
CC ECO:0000269|PubMed:1671571, ECO:0000269|PubMed:7910823,
CC ECO:0000269|PubMed:7935448}.
CC -!- PTM: Ubiquitinated, leading to its degradation by the proteasome.
CC {ECO:0000269|PubMed:16027724}.
CC -!- PTM: Phosphorylation at Ser-60 reduces transactivation capacity
CC (PubMed:11729123). Phosphorylation at Ser-281 reduces transactivation
CC capacity and increases ubiquitin-dependent proteasome degradation
CC (PubMed:16027724). {ECO:0000269|PubMed:11729123,
CC ECO:0000269|PubMed:16027724}.
CC -!- SIMILARITY: Belongs to the Caudal homeobox family. {ECO:0000305}.
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DR EMBL; U00454; AAA19645.1; -; Unassigned_DNA.
DR EMBL; S74520; AAB32251.1; -; mRNA.
DR CCDS; CCDS19878.1; -.
DR PIR; A53808; A53808.
DR RefSeq; NP_031699.2; NM_007673.3.
DR AlphaFoldDB; P43241; -.
DR SMR; P43241; -.
DR BioGRID; 198664; 57.
DR IntAct; P43241; 4.
DR STRING; 10090.ENSMUSP00000031650; -.
DR iPTMnet; P43241; -.
DR PhosphoSitePlus; P43241; -.
DR PaxDb; P43241; -.
DR PeptideAtlas; P43241; -.
DR PRIDE; P43241; -.
DR ProteomicsDB; 281523; -.
DR Antibodypedia; 3700; 1195 antibodies from 49 providers.
DR DNASU; 12591; -.
DR Ensembl; ENSMUST00000031650; ENSMUSP00000031650; ENSMUSG00000029646.
DR GeneID; 12591; -.
DR KEGG; mmu:12591; -.
DR UCSC; uc009anz.1; mouse.
DR CTD; 1045; -.
DR MGI; MGI:88361; Cdx2.
DR VEuPathDB; HostDB:ENSMUSG00000029646; -.
DR eggNOG; KOG0848; Eukaryota.
DR GeneTree; ENSGT00940000161261; -.
DR HOGENOM; CLU_073177_1_0_1; -.
DR InParanoid; P43241; -.
DR OMA; CSAGVMQ; -.
DR OrthoDB; 1380804at2759; -.
DR PhylomeDB; P43241; -.
DR TreeFam; TF351605; -.
DR BioGRID-ORCS; 12591; 3 hits in 74 CRISPR screens.
DR PRO; PR:P43241; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; P43241; protein.
DR Bgee; ENSMUSG00000029646; Expressed in paneth cell and 45 other tissues.
DR ExpressionAtlas; P43241; baseline and differential.
DR Genevisible; P43241; MM.
DR GO; GO:0000794; C:condensed nuclear chromosome; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0017053; C:transcription repressor complex; IDA:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISO:MGI.
DR GO; GO:0003690; F:double-stranded DNA binding; ISO:MGI.
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; IDA:UniProtKB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR GO; GO:0009948; P:anterior/posterior axis specification; IBA:GO_Central.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IGI:MGI.
DR GO; GO:0001824; P:blastocyst development; IMP:MGI.
DR GO; GO:0001568; P:blood vessel development; IGI:MGI.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0008333; P:endosome to lysosome transport; IMP:MGI.
DR GO; GO:0045197; P:establishment or maintenance of epithelial cell apical/basal polarity; IMP:MGI.
DR GO; GO:0060575; P:intestinal epithelial cell differentiation; IMP:UniProtKB.
DR GO; GO:0060711; P:labyrinthine layer development; IGI:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0007389; P:pattern specification process; IMP:MGI.
DR GO; GO:0001890; P:placenta development; IGI:MGI.
DR GO; GO:0045597; P:positive regulation of cell differentiation; IDA:MGI.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0014807; P:regulation of somitogenesis; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0035019; P:somatic stem cell population maintenance; IMP:MGI.
DR GO; GO:0048863; P:stem cell differentiation; IMP:MGI.
DR GO; GO:0001829; P:trophectodermal cell differentiation; IDA:MGI.
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 1: Evidence at protein level;
KW Activator; Developmental protein; DNA-binding; Homeobox; Nucleus;
KW Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..311
FT /note="Homeobox protein CDX-2"
FT /id="PRO_0000048851"
FT DNA_BIND 185..244
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 111..151
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 239..311
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 281..293
FT /note="4S motif; modulates transactivation activity and
FT protein stability"
FT /evidence="ECO:0000269|PubMed:16027724"
FT COMPBIAS 256..272
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 60
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:11729123"
FT MOD_RES 281
FT /note="Phosphoserine; by CDK2"
FT /evidence="ECO:0000269|PubMed:16027724"
FT MUTAGEN 60
FT /note="S->A: Reduced phosphorylation. Does not affect
FT nuclear localization."
FT /evidence="ECO:0000269|PubMed:11729123"
FT CONFLICT 69
FT /note="Y -> H (in Ref. 2; AAB32251)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 311 AA; 33476 MW; 71FFC4C263462FF3 CRC64;
MYVSYLLDKD VSMYPSSVRH SGGLNLAPQN FVSPPQYPDY GGYHVAAAAA ATANLDSAQS
PGPSWPTAYG APLREDWNGY APGGAAAANA VAHGLNGGSP AAAMGYSSPA EYHAHHHPHH
HPHHPAASPS CASGLLQTLN LGPPGPAATA AAEQLSPSGQ RRNLCEWMRK PAQQSLGSQV
KTRTKDKYRV VYTDHQRLEL EKEFHFSRYI TIRRKSELAA TLGLSERQVK IWFQNRRAKE
RKIKKKQQQQ QQQQQQQPPQ PPPQPSQPQP GALRSVPEPL SPVTSLQGSV PGSVPGVLGP
AGGVLNSTVT Q
