ID   CDX1_HUMAN              Reviewed;         265 AA.
AC   P47902; Q4VAU4; Q9NYK8;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   17-OCT-2006, sequence version 2.
DT   24-JAN-2024, entry version 195.
DE   RecName: Full=Homeobox protein CDX-1;
DE   AltName: Full=Caudal-type homeobox protein 1;
GN   Name=CDX1;
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 [GENOMIC DNA / MRNA] (ISOFORM 1).
RC   TISSUE=Small intestine;
RX   PubMed=8530027; DOI=10.1006/geno.1995.1132;
RA   Bonner C.A., Lofus S.K., Wasmuth J.J.;
RT   "Isolation, characterization, and precise physical localization of human
RT   CDX1, a caudal-type homeobox gene.";
RL   Genomics 28:206-211(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
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 [MRNA] (ISOFORM 1).
RA   Malakooti J.;
RT   "Molecular cloning and sequencing of the human CDX1 homeobox gene.";
RL   Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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   [5]
RP   FUNCTION, AND DNA-BINDING.
RX   PubMed=24623306; DOI=10.7554/elife.02313;
RA   Serra R.W., Fang M., Park S.M., Hutchinson L., Green M.R.;
RT   "A KRAS-directed transcriptional silencing pathway that mediates the CpG
RT   island methylator phenotype.";
RL   Elife 3:E02313-E02313(2014).
RN   [6] {ECO:0007744|PDB:5LUX}
RP   X-RAY CRYSTALLOGRAPHY (3.23 ANGSTROMS) OF 153-215 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: Plays a role in transcriptional regulation (PubMed:24623306).
CC       Involved in activated KRAS-mediated transcriptional activation of PRKD1
CC       in colorectal cancer (CRC) cells (PubMed:24623306). Binds to the PRKD1
CC       promoter in colorectal cancer (CRC) cells (PubMed:24623306). Could play
CC       a role in the terminal differentiation of the intestine. Binds
CC       preferentially to methylated DNA (PubMed:28473536).
CC       {ECO:0000269|PubMed:24623306, ECO:0000269|PubMed:28473536}.
CC   -!- INTERACTION:
CC       P47902; P49715: CEBPA; NbExp=3; IntAct=EBI-8514176, EBI-1172054;
CC   -!- SUBCELLULAR LOCATION: Nucleus.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=P47902-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=P47902-2; Sequence=VSP_021030;
CC   -!- TISSUE SPECIFICITY: Intestinal epithelium.
CC   -!- SIMILARITY: Belongs to the Caudal homeobox family. {ECO:0000305}.
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DR   EMBL; U16360; AAA80284.1; -; Genomic_DNA.
DR   EMBL; U15212; AAC50237.1; -; mRNA.
DR   EMBL; U51095; AAB40602.1; -; mRNA.
DR   EMBL; AF239666; AAF61234.1; -; mRNA.
DR   EMBL; BC096251; AAH96251.1; -; mRNA.
DR   CCDS; CCDS4304.1; -. [P47902-1]
DR   PIR; I38868; I38868.
DR   PIR; I38881; I38881.
DR   RefSeq; NP_001795.2; NM_001804.2. [P47902-1]
DR   PDB; 5LUX; X-ray; 3.23 A; K/L=153-215.
DR   PDB; 7Q3O; X-ray; 2.78 A; C/E/G/K=151-215.
DR   PDBsum; 5LUX; -.
DR   PDBsum; 7Q3O; -.
DR   AlphaFoldDB; P47902; -.
DR   SMR; P47902; -.
DR   BioGRID; 107474; 74.
DR   ELM; P47902; -.
DR   IntAct; P47902; 63.
DR   MINT; P47902; -.
DR   STRING; 9606.ENSP00000231656; -.
DR   GlyGen; P47902; 2 sites, 1 O-linked glycan (2 sites).
DR   iPTMnet; P47902; -.
DR   PhosphoSitePlus; P47902; -.
DR   BioMuta; CDX1; -.
DR   DMDM; 116241291; -.
DR   jPOST; P47902; -.
DR   MassIVE; P47902; -.
DR   MaxQB; P47902; -.
DR   PaxDb; 9606-ENSP00000231656; -.
DR   PeptideAtlas; P47902; -.
DR   ProteomicsDB; 55820; -. [P47902-1]
DR   ProteomicsDB; 55821; -. [P47902-2]
DR   Antibodypedia; 27929; 558 antibodies from 32 providers.
DR   DNASU; 1044; -.
DR   Ensembl; ENST00000231656.13; ENSP00000231656.7; ENSG00000113722.18. [P47902-1]
DR   GeneID; 1044; -.
DR   KEGG; hsa:1044; -.
DR   MANE-Select; ENST00000231656.13; ENSP00000231656.7; NM_001804.3; NP_001795.2.
DR   UCSC; uc003lrq.4; human. [P47902-1]
DR   AGR; HGNC:1805; -.
DR   CTD; 1044; -.
DR   DisGeNET; 1044; -.
DR   GeneCards; CDX1; -.
DR   HGNC; HGNC:1805; CDX1.
DR   HPA; ENSG00000113722; Tissue enriched (intestine).
DR   MIM; 600746; gene.
DR   neXtProt; NX_P47902; -.
DR   OpenTargets; ENSG00000113722; -.
DR   PharmGKB; PA26351; -.
DR   VEuPathDB; HostDB:ENSG00000113722; -.
DR   eggNOG; KOG0848; Eukaryota.
DR   GeneTree; ENSGT00940000162069; -.
DR   HOGENOM; CLU_073177_1_0_1; -.
DR   InParanoid; P47902; -.
DR   OMA; VDKDTNM; -.
DR   OrthoDB; 728401at2759; -.
DR   PhylomeDB; P47902; -.
DR   TreeFam; TF351605; -.
DR   PathwayCommons; P47902; -.
DR   SignaLink; P47902; -.
DR   SIGNOR; P47902; -.
DR   BioGRID-ORCS; 1044; 7 hits in 1163 CRISPR screens.
DR   GeneWiki; CDX1; -.
DR   GenomeRNAi; 1044; -.
DR   Pharos; P47902; Tbio.
DR   PRO; PR:P47902; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   RNAct; P47902; Protein.
DR   Bgee; ENSG00000113722; Expressed in mucosa of transverse colon and 106 other cell types or tissues.
DR   ExpressionAtlas; P47902; baseline and differential.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:NTNU_SB.
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: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:0000976; F:transcription cis-regulatory region binding; IDA:UniProtKB.
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:0060349; P:bone morphogenesis; IEA:Ensembl.
DR   GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
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   CDD; cd00086; homeodomain; 1.
DR   Gene3D; 1.10.10.60; Homeodomain-like; 1.
DR   InterPro; IPR006820; Caudal_activation_dom.
DR   InterPro; IPR047152; Caudal_homeobox.
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   PANTHER; PTHR24332; HOMEOBOX PROTEIN CDX; 1.
DR   PANTHER; PTHR24332:SF16; HOMEOBOX PROTEIN CDX-1; 1.
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; Homeodomain-like; 1.
DR   PROSITE; PS00027; HOMEOBOX_1; 1.
DR   PROSITE; PS50071; HOMEOBOX_2; 1.
DR   Genevisible; P47902; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Activator; Alternative splicing; Developmental protein;
KW   DNA-binding; Homeobox; Nucleus; Reference proteome; Transcription;
KW   Transcription regulation.
FT   CHAIN           1..265
FT                   /note="Homeobox protein CDX-1"
FT                   /id="PRO_0000048846"
FT   DNA_BIND        154..213
FT                   /note="Homeobox"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          9..153
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          157..178
FT                   /note="Interaction with DNA"
FT                   /evidence="ECO:0000305|PubMed:28473536"
FT   REGION          196..207
FT                   /note="Interaction with 5-mCpG DNA"
FT                   /evidence="ECO:0000305|PubMed:28473536"
FT   REGION          207..265
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        29..43
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        89..112
FT                   /note="Pro residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        241..255
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         1..135
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_021030"
FT   VARIANT         130
FT                   /note="P -> R (in dbSNP:rs2302275)"
FT                   /id="VAR_020149"
FT   CONFLICT        28..29
FT                   /note="QA -> AN (in Ref. 1; AAA80284/AAC50237 and 2;
FT                   AAB40602)"
FT                   /evidence="ECO:0000305"
FT   HELIX           163..175
FT                   /evidence="ECO:0007829|PDB:5LUX"
FT   HELIX           181..191
FT                   /evidence="ECO:0007829|PDB:5LUX"
FT   HELIX           195..214
FT                   /evidence="ECO:0007829|PDB:5LUX"
SQ   SEQUENCE   265 AA;  28138 MW;  484CB284E3357BC6 CRC64;
     MYVGYVLDKD SPVYPGPARP ASLGLGPQAY GPPAPPPAPP QYPDFSSYSH VEPAPAPPTA
     WGAPFPAPKD DWAAAYGPGP AAPAASPASL AFGPPPDFSP VPAPPGPGPG LLAQPLGGPG
     TPSSPGAQRP TPYEWMRRSV AAGGGGGSGK TRTKDKYRVV YTDHQRLELE KEFHYSRYIT
     IRRKSELAAN LGLTERQVKI WFQNRRAKER KVNKKKQQQQ QPPQPPMAHD ITATPAGPSL
     GGLCPSNTSL LATSSPMPVK EEFLP
//