CDX1_HUMAN
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 03-AUG-2022, entry version 187.
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 PDBsum; 5LUX; -.
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 iPTMnet; P47902; -.
DR PhosphoSitePlus; P47902; -.
DR BioMuta; CDX1; -.
DR DMDM; 116241291; -.
DR jPOST; P47902; -.
DR MassIVE; P47902; -.
DR MaxQB; P47902; -.
DR PaxDb; P47902; -.
DR PeptideAtlas; P47902; -.
DR PRIDE; P47902; -.
DR ProteomicsDB; 55820; -. [P47902-1]
DR ProteomicsDB; 55821; -. [P47902-2]
DR Antibodypedia; 27929; 505 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 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; DKDTNMY; -.
DR OrthoDB; 1380804at2759; -.
DR PhylomeDB; P47902; -.
DR TreeFam; TF351605; -.
DR PathwayCommons; P47902; -.
DR SignaLink; P47902; -.
DR SIGNOR; P47902; -.
DR BioGRID-ORCS; 1044; 7 hits in 1087 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 104 other tissues.
DR ExpressionAtlas; P47902; baseline and differential.
DR Genevisible; P47902; HS.
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 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; 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
