CDX2_HUMAN
ID CDX2_HUMAN Reviewed; 313 AA.
AC Q99626; O00503; Q5VTU7; Q969L8; Q9UD92;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 3.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Homeobox protein CDX-2;
DE AltName: Full=CDX-3;
DE AltName: Full=Caudal-type homeobox protein 2;
GN Name=CDX2; Synonyms=CDX3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-293.
RX PubMed=9459001; DOI=10.1046/j.1469-1809.1997.6150393.x;
RA Drummond F.J., Putt W., Fox M., Edwards Y.H.;
RT "Cloning and chromosome assignment of the human CDX2 gene.";
RL Ann. Hum. Genet. 61:393-400(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT SER-293.
RC TISSUE=Colon carcinoma;
RX PubMed=9036867;
RX DOI=10.1002/(sici)1097-0215(19970220)74:1<35::aid-ijc7>3.0.co;2-1;
RA Mallo G.V., Rechreche H., Frigerio J.-M., Rocha D., Zweibaum A., Lacasa M.,
RA Jordan B.R., Dusetti N.J., Dagorn J.-C., Iovanna J.L.;
RT "Molecular cloning, sequencing and expression of the mRNA encoding human
RT Cdx1 and Cdx2 homeobox. Down-regulation of Cdx1 and Cdx2 mRNA expression
RT during colorectal carcinogenesis.";
RL Int. J. Cancer 74:35-44(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-293.
RX PubMed=11161380; DOI=10.1054/bjoc.2000.1544;
RA Sivagnanasundaram S., Islam I., Talbot I., Drummond F., Walters J.R.,
RA Edwards Y.H.;
RT "The homeobox gene CDX2 in colorectal carcinoma: a genetic analysis.";
RL Br. J. Cancer 84:218-225(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-293.
RA Tanizawa Y., Ueda K., Inoue H., Ayame H., Aoki M., Kuwano A., German M.S.,
RA Liu L., Donis-Keller H., Permutt M.A., Oka Y.;
RT "Isolation, characterization, and linkage mapping of the human caudal-type
RT homeobox gene, CDX2/3.";
RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT SER-293.
RC TISSUE=Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 205-232.
RC TISSUE=T-cell;
RX PubMed=8105782; DOI=10.1006/bbrc.1993.2235;
RA Inamori K., Takeshita K., Chiba S., Yazaki Y., Hirai H.;
RT "Identification of homeobox genes expressed in human T-lymphocytes.";
RL Biochem. Biophys. Res. Commun. 196:203-208(1993).
RN [8]
RP TISSUE SPECIFICITY.
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 [9] {ECO:0007744|PDB:5LTY}
RP X-RAY CRYSTALLOGRAPHY (2.66 ANGSTROMS) OF 185-255 IN COMPLEX WITH
RP METHYLATED DNA, AND DNA-BINDING.
RX PubMed=28473536; DOI=10.1126/science.aaj2239;
RA Yin Y., Morgunova E., Jolma A., Kaasinen E., Sahu B., Khund-Sayeed S.,
RA Das P.K., Kivioja T., Dave K., Zhong F., Nitta K.R., Taipale M., Popov A.,
RA Ginno P.A., Domcke S., Yan J., Schubeler D., Vinson C., Taipale J.;
RT "Impact of cytosine methylation on DNA binding specificities of human
RT transcription factors.";
RL Science 356:0-0(2017).
CC -!- FUNCTION: Transcription factor which regulates the transcription of
CC multiple genes expressed in the intestinal epithelium (By similarity).
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 (By similarity). 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 (PubMed:28473536). {ECO:0000250|UniProtKB:P43241,
CC ECO:0000250|UniProtKB:Q04649, ECO:0000269|PubMed:28473536}.
CC -!- SUBUNIT: Can bind DNA as a monomer or homodimer.
CC {ECO:0000250|UniProtKB:P43241}.
CC -!- INTERACTION:
CC Q99626; Q8IYR0: CFAP206; NbExp=3; IntAct=EBI-10899513, EBI-749051;
CC Q99626; Q9BQ66: KRTAP4-12; NbExp=3; IntAct=EBI-10899513, EBI-739863;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P43241}.
CC -!- TISSUE SPECIFICITY: Detected in small intestine, colon and pancreas.
CC {ECO:0000269|PubMed:9933478}.
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}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CDX2ID326.html";
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DR EMBL; Y13709; CAA74038.1; -; mRNA.
DR EMBL; U51096; AAB40603.1; -; mRNA.
DR EMBL; AJ278431; CAB94779.1; -; Genomic_DNA.
DR EMBL; AJ278432; CAB94779.1; JOINED; Genomic_DNA.
DR EMBL; AJ278434; CAB94779.1; JOINED; Genomic_DNA.
DR EMBL; AF007886; AAD05200.1; -; Genomic_DNA.
DR EMBL; AF007884; AAD05200.1; JOINED; Genomic_DNA.
DR EMBL; AF007885; AAD05200.1; JOINED; Genomic_DNA.
DR EMBL; AL591024; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC014461; AAH14461.1; -; mRNA.
DR CCDS; CCDS9328.1; -.
DR PIR; PN0625; PN0625.
DR RefSeq; NP_001256.3; NM_001265.4.
DR PDB; 5LTY; X-ray; 2.66 A; K/M=185-255.
DR PDB; 6ES2; X-ray; 2.95 A; K/L=186-256.
DR PDB; 6ES3; X-ray; 2.57 A; K/M=184-255.
DR PDBsum; 5LTY; -.
DR PDBsum; 6ES2; -.
DR PDBsum; 6ES3; -.
DR AlphaFoldDB; Q99626; -.
DR SMR; Q99626; -.
DR BioGRID; 107475; 22.
DR CORUM; Q99626; -.
DR IntAct; Q99626; 4.
DR MINT; Q99626; -.
DR STRING; 9606.ENSP00000370408; -.
DR iPTMnet; Q99626; -.
DR PhosphoSitePlus; Q99626; -.
DR BioMuta; CDX2; -.
DR DMDM; 311033469; -.
DR jPOST; Q99626; -.
DR MassIVE; Q99626; -.
DR MaxQB; Q99626; -.
DR PaxDb; Q99626; -.
DR PeptideAtlas; Q99626; -.
DR PRIDE; Q99626; -.
DR ProteomicsDB; 78366; -.
DR Antibodypedia; 3700; 1195 antibodies from 49 providers.
DR DNASU; 1045; -.
DR Ensembl; ENST00000381020.8; ENSP00000370408.6; ENSG00000165556.10.
DR GeneID; 1045; -.
DR KEGG; hsa:1045; -.
DR MANE-Select; ENST00000381020.8; ENSP00000370408.6; NM_001265.6; NP_001256.4.
DR UCSC; uc001urv.5; human.
DR CTD; 1045; -.
DR DisGeNET; 1045; -.
DR GeneCards; CDX2; -.
DR HGNC; HGNC:1806; CDX2.
DR HPA; ENSG00000165556; Tissue enriched (intestine).
DR MIM; 600297; gene.
DR neXtProt; NX_Q99626; -.
DR OpenTargets; ENSG00000165556; -.
DR PharmGKB; PA26352; -.
DR VEuPathDB; HostDB:ENSG00000165556; -.
DR eggNOG; KOG0848; Eukaryota.
DR GeneTree; ENSGT00940000161261; -.
DR HOGENOM; CLU_073177_1_0_1; -.
DR InParanoid; Q99626; -.
DR OMA; CSAGVMQ; -.
DR OrthoDB; 1380804at2759; -.
DR PhylomeDB; Q99626; -.
DR TreeFam; TF351605; -.
DR PathwayCommons; Q99626; -.
DR Reactome; R-HSA-381771; Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1).
DR SignaLink; Q99626; -.
DR SIGNOR; Q99626; -.
DR BioGRID-ORCS; 1045; 47 hits in 1094 CRISPR screens.
DR ChiTaRS; CDX2; human.
DR GeneWiki; CDX2; -.
DR GenomeRNAi; 1045; -.
DR Pharos; Q99626; Tbio.
DR PRO; PR:Q99626; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q99626; protein.
DR Bgee; ENSG00000165556; Expressed in mucosa of transverse colon and 47 other tissues.
DR Genevisible; Q99626; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0000794; C:condensed nuclear chromosome; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0017053; C:transcription repressor complex; IEA:Ensembl.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IBA:GO_Central.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:NTNU_SB.
DR GO; GO:0008327; F:methyl-CpG binding; IDA:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
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:0001568; P:blood vessel development; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
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:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0045597; P:positive regulation of cell differentiation; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; 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:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
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 1: Evidence at protein level;
KW 3D-structure; Activator; Developmental protein; DNA-binding; Homeobox;
KW Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..313
FT /note="Homeobox protein CDX-2"
FT /id="PRO_0000048849"
FT DNA_BIND 186..245
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 186..216
FT /note="Interaction with DNA"
FT /evidence="ECO:0000305|PubMed:28473536"
FT REGION 228..242
FT /note="Interaction with 5-mCpG DNA"
FT /evidence="ECO:0000305|PubMed:28473536"
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 255..279
FT /note="Pro 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"
FT VARIANT 293
FT /note="P -> S (in dbSNP:rs1805107)"
FT /evidence="ECO:0000269|PubMed:11161380,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9036867,
FT ECO:0000269|PubMed:9459001, ECO:0000269|Ref.4"
FT /id="VAR_014530"
FT CONFLICT 52..53
FT /note="AA -> Q (in Ref. 2; AAB40603)"
FT /evidence="ECO:0000305"
FT CONFLICT 89
FT /note="Missing (in Ref. 2; AAB40603)"
FT /evidence="ECO:0000305"
FT CONFLICT 95
FT /note="G -> A (in Ref. 2; AAB40603)"
FT /evidence="ECO:0000305"
FT STRAND 187..189
FT /evidence="ECO:0007829|PDB:6ES3"
FT HELIX 195..207
FT /evidence="ECO:0007829|PDB:6ES3"
FT HELIX 213..223
FT /evidence="ECO:0007829|PDB:6ES3"
FT HELIX 227..254
FT /evidence="ECO:0007829|PDB:6ES3"
SQ SEQUENCE 313 AA; 33520 MW; B5724F1F7CA569AF CRC64;
MYVSYLLDKD VSMYPSSVRH SGGLNLAPQN FVSPPQYPDY GGYHVAAAAA AAANLDSAQS
PGPSWPAAYG APLREDWNGY APGGAAAAAN AVAHGLNGGS PAAAMGYSSP ADYHPHHHPH
HHPHHPAAAP SCASGLLQTL NPGPPGPAAT AAAEQLSPGG QRRNLCEWMR KPAQQSLGSQ
VKTRTKDKYR VVYTDHQRLE LEKEFHYSRY ITIRRKAELA ATLGLSERQV KIWFQNRRAK
ERKINKKKLQ QQQQQQPPQP PPPPPQPPQP QPGPLRSVPE PLSPVSSLQA SVPGSVPGVL
GPTGGVLNPT VTQ
