TLX2_HUMAN
ID TLX2_HUMAN Reviewed; 284 AA.
AC O43763; Q9UD56; Q9UQ48;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2002, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=T-cell leukemia homeobox protein 2;
DE AltName: Full=Homeobox protein Hox-11L1;
DE AltName: Full=Neural crest homeobox protein;
GN Name=TLX2; Synonyms=HOX11L1, NCX;
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].
RX PubMed=10446220; DOI=10.1074/jbc.274.34.24401;
RA Iitsuka Y., Shimizu H., Kang M.M., Sasagawa K., Sekiya S., Tokuhisa T.,
RA Hatano M.;
RT "An enhancer element for expression of the Ncx (Enx, Hox11L1) gene in
RT neural crest-derived cells.";
RL J. Biol. Chem. 274:24401-24407(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Delgado P., Rodriguez R.E., Gonzalez-Sarmiento R.;
RT "Genomic characterization and chromosomal location of the human homeobox
RT gene HOX11L1.";
RL Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 NUCLEOTIDE SEQUENCE [MRNA] OF 165-203.
RC TISSUE=Bone marrow;
RX PubMed=7518789; DOI=10.1016/0378-1119(94)90380-8;
RA Moretti P., Simmons P., Thomas P., Haylock D., Rathjen P., Vadas M.,
RA D'Andrea R.;
RT "Identification of homeobox genes expressed in human haemopoietic
RT progenitor cells.";
RL Gene 144:213-219(1994).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.54 ANGSTROMS) OF 162-216, AND DNA-BINDING.
RX PubMed=20389279; DOI=10.1038/emboj.2010.53;
RA Miyazono K., Zhi Y., Takamura Y., Nagata K., Saigo K., Kojima T.,
RA Tanokura M.;
RT "Cooperative DNA-binding and sequence-recognition mechanism of aristaless
RT and clawless.";
RL EMBO J. 29:1613-1623(2010).
CC -!- FUNCTION: Transcription activator that binds DNA elements with the
CC consensus sequence 5'-CGGTAATTGG-3'. Binds DNA via its homeobox.
CC Required for normal cell death of enteric neurons in the
CC gastrointestinal tract. Required for normal development of the enteric
CC nervous system, and for proper development of normal motility of the
CC gastrointestinal tract (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC O43763; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-6101484, EBI-11962084;
CC O43763; P78424: POU6F2; NbExp=3; IntAct=EBI-6101484, EBI-12029004;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB008501; BAA83463.1; -; mRNA.
DR EMBL; AJ002607; CAA05636.1; -; Genomic_DNA.
DR EMBL; AJ002608; CAA05636.1; JOINED; Genomic_DNA.
DR EMBL; AJ002609; CAA05636.1; JOINED; Genomic_DNA.
DR EMBL; AC005041; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC006356; AAH06356.1; -; mRNA.
DR CCDS; CCDS1947.1; -.
DR RefSeq; NP_057254.1; NM_016170.4.
DR PDB; 3A03; X-ray; 1.54 A; A=162-216.
DR PDBsum; 3A03; -.
DR AlphaFoldDB; O43763; -.
DR SMR; O43763; -.
DR BioGRID; 109436; 139.
DR ELM; O43763; -.
DR IntAct; O43763; 135.
DR STRING; 9606.ENSP00000233638; -.
DR iPTMnet; O43763; -.
DR PhosphoSitePlus; O43763; -.
DR BioMuta; TLX2; -.
DR MassIVE; O43763; -.
DR PaxDb; O43763; -.
DR PeptideAtlas; O43763; -.
DR PRIDE; O43763; -.
DR Antibodypedia; 16736; 74 antibodies from 21 providers.
DR DNASU; 3196; -.
DR Ensembl; ENST00000233638.8; ENSP00000233638.6; ENSG00000115297.11.
DR GeneID; 3196; -.
DR KEGG; hsa:3196; -.
DR MANE-Select; ENST00000233638.8; ENSP00000233638.6; NM_016170.5; NP_057254.1.
DR UCSC; uc002smb.3; human.
DR CTD; 3196; -.
DR DisGeNET; 3196; -.
DR GeneCards; TLX2; -.
DR HGNC; HGNC:5057; TLX2.
DR HPA; ENSG00000115297; Tissue enhanced (adrenal gland, retina).
DR MIM; 604240; gene.
DR neXtProt; NX_O43763; -.
DR OpenTargets; ENSG00000115297; -.
DR PharmGKB; PA35096; -.
DR VEuPathDB; HostDB:ENSG00000115297; -.
DR eggNOG; KOG0488; Eukaryota.
DR GeneTree; ENSGT00940000162452; -.
DR HOGENOM; CLU_053409_1_0_1; -.
DR InParanoid; O43763; -.
DR OMA; QGHGEST; -.
DR OrthoDB; 1391465at2759; -.
DR PhylomeDB; O43763; -.
DR TreeFam; TF325347; -.
DR PathwayCommons; O43763; -.
DR SignaLink; O43763; -.
DR BioGRID-ORCS; 3196; 7 hits in 1090 CRISPR screens.
DR EvolutionaryTrace; O43763; -.
DR GeneWiki; TLX2; -.
DR GenomeRNAi; 3196; -.
DR Pharos; O43763; Tbio.
DR PRO; PR:O43763; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O43763; protein.
DR Bgee; ENSG00000115297; Expressed in transverse colon and 57 other tissues.
DR ExpressionAtlas; O43763; baseline and differential.
DR Genevisible; O43763; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
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:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISA:NTNU_SB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:NTNU_SB.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0048513; P:animal organ development; IBA:GO_Central.
DR GO; GO:0048484; P:enteric nervous system development; IEA:Ensembl.
DR GO; GO:0001707; P:mesoderm formation; IEA:Ensembl.
DR GO; GO:0050774; P:negative regulation of dendrite morphogenesis; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:NTNU_SB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR020479; Homeobox_metazoa.
DR InterPro; IPR042247; TLX1/2/3.
DR PANTHER; PTHR45921; PTHR45921; 1.
DR Pfam; PF00046; Homeodomain; 1.
DR PRINTS; PR00024; HOMEOBOX.
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; Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..284
FT /note="T-cell leukemia homeobox protein 2"
FT /id="PRO_0000049336"
FT DNA_BIND 157..216
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 1..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 78..106
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 139..166
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 86..100
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CONFLICT 16
FT /note="P -> A (in Ref. 2; CAA05636)"
FT /evidence="ECO:0000305"
FT CONFLICT 30..32
FT /note="TPG -> PR (in Ref. 2; CAA05636)"
FT /evidence="ECO:0000305"
FT CONFLICT 37..48
FT /note="LGRGGQGHGENG -> WVAGQVIGEWA (in Ref. 2; CAA05636)"
FT /evidence="ECO:0000305"
FT CONFLICT 100..102
FT /note="Missing (in Ref. 2; CAA05636)"
FT /evidence="ECO:0000305"
FT CONFLICT 131..136
FT /note="RLTAAL -> PAV (in Ref. 2; CAA05636)"
FT /evidence="ECO:0000305"
FT CONFLICT 196
FT /note="M -> T (in Ref. 5; no nucleotide entry)"
FT /evidence="ECO:0000305"
FT CONFLICT 219
FT /note="Missing (in Ref. 2; CAA05636)"
FT /evidence="ECO:0000305"
FT CONFLICT 241
FT /note="R -> T (in Ref. 2; CAA05636)"
FT /evidence="ECO:0000305"
FT CONFLICT 274
FT /note="V -> A (in Ref. 2; CAA05636)"
FT /evidence="ECO:0000305"
FT HELIX 166..178
FT /evidence="ECO:0007829|PDB:3A03"
FT HELIX 184..194
FT /evidence="ECO:0007829|PDB:3A03"
FT HELIX 198..215
FT /evidence="ECO:0007829|PDB:3A03"
SQ SEQUENCE 284 AA; 30251 MW; 794B07A9E7817939 CRC64;
MEPGMLGPHN LPHHEPISFG IDQILSGPET PGGGLGLGRG GQGHGENGAF SGGYHGASGY
GPAGSLAPLP GSSGVGPGGV IRVPAHRPLP VPPPAGGAPA VPGPSGLGGA GGLAGLTFPW
MDSGRRFAKD RLTAALSPFS GTRRIGHPYQ NRTPPKRKKP RTSFSRSQVL ELERRFLRQK
YLASAERAAL AKALRMTDAQ VKTWFQNRRT KWRRQTAEER EAERHRAGRL LLHLQQDALP
RPLRPPLPPD PLCLHNSSLF ALQNLQPWAE DNKVASVSGL ASVV
