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   24-JAN-2024, entry version 184.
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}.
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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; 140.
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; 9606-ENSP00000233638; -.
DR   PeptideAtlas; O43763; -.
DR   Antibodypedia; 16736; 89 antibodies from 22 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   AGR; HGNC:5057; -.
DR   CTD; 3196; -.
DR   DisGeNET; 3196; -.
DR   GeneCards; TLX2; -.
DR   HGNC; HGNC:5057; TLX2.
DR   HPA; ENSG00000115297; Tissue enhanced (adrenal gland, retina, testis).
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; 380905at2759; -.
DR   PhylomeDB; O43763; -.
DR   TreeFam; TF325347; -.
DR   PathwayCommons; O43763; -.
DR   SignaLink; O43763; -.
DR   BioGRID-ORCS; 3196; 9 hits in 1166 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 primordial germ cell in gonad and 58 other cell types or tissues.
DR   ExpressionAtlas; O43763; baseline and differential.
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   Gene3D; 1.10.10.60; Homeodomain-like; 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; IP01054P; 1.
DR   PANTHER; PTHR45921:SF3; T-CELL LEUKEMIA HOMEOBOX PROTEIN 2; 1.
DR   Pfam; PF00046; Homeodomain; 1.
DR   PRINTS; PR00024; HOMEOBOX.
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; O43763; HS.
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
//