LEUTX_HUMAN
ID LEUTX_HUMAN Reviewed; 198 AA.
AC A8MZ59; A0A1W2PQ33;
DT 22-JUL-2008, integrated into UniProtKB/Swiss-Prot.
DT 22-APR-2020, sequence version 4.
DT 03-AUG-2022, entry version 104.
DE RecName: Full=Paired-like homeodomain transcription factor LEUTX;
DE AltName: Full=Leucine-twenty homeobox;
DE AltName: Full=Paired-like homeobox transcription factor LEUTX {ECO:0000303|PubMed:27578796};
DE Short=PRD-LIKE homeobox transcription factor LEUTX {ECO:0000303|PubMed:27578796};
GN Name=LEUTX {ECO:0000312|HGNC:HGNC:31953};
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 [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Stevens M., Wei C., Gross S.S., McPherson J., Brent M.R.;
RT "Exhaustive RT-PCR and sequencing of all novel TWINSCAN predictions in
RT human.";
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP IDENTIFICATION OF ISOFORM 2.
RX PubMed=17963489; DOI=10.1186/1741-7007-5-47;
RA Holland P.W.H., Booth H.A.F., Bruford E.A.;
RT "Classification and nomenclature of all human homeobox genes.";
RL BMC Biol. 5:47-47(2007).
RN [5]
RP FUNCTION, CHARACTERIZATION OF ISOFORM 1, DEVELOPMENTAL STAGE, SUBCELLULAR
RP LOCATION, AND DOMAIN.
RX PubMed=27578796; DOI=10.1242/dev.134510;
RA Jouhilahti E.M., Madissoon E., Vesterlund L., Toehoenen V., Krjutskov K.,
RA Plaza Reyes A., Petropoulos S., Maansson R., Linnarsson S., Buerglin T.,
RA Lanner F., Hovatta O., Katayama S., Kere J.;
RT "The human PRD-like homeobox gene LEUTX has a central role in embryo genome
RT activation.";
RL Development 143:3459-3469(2016).
RN [6]
RP FUNCTION, CHARACTERIZATION OF ISOFORM 1, MUTAGENESIS OF ILE-54 AND ALA-61,
RP AND DOMAIN.
RX PubMed=30479355; DOI=10.1038/s41598-018-35547-5;
RA Katayama S., Ranga V., Jouhilahti E.M., Airenne T.T., Johnson M.S.,
RA Mukherjee K., Buerglin T.R., Kere J.;
RT "Phylogenetic and mutational analyses of human LEUTX, a homeobox gene
RT implicated in embryogenesis.";
RL Sci. Rep. 8:17421-17421(2018).
CC -!- FUNCTION: [Isoform 1]: Paired-like homeobox transcription factor
CC involved in embryogenesis (PubMed:27578796, PubMed:30479355). May act
CC as a regulator of embryo genome activation (PubMed:27578796). Binds to
CC a 36 bp DNA elements containing a 5'-TAATCC-3' sequence motif, referred
CC to as EEA motif (EGA-enriched Alu-motif), present in the promoters of
CC target genes activated in early embryos (PubMed:27578796,
CC PubMed:30479355). {ECO:0000269|PubMed:27578796,
CC ECO:0000269|PubMed:30479355}.
CC -!- FUNCTION: [Isoform 2]: Inactive transcriptional activity.
CC {ECO:0000269|PubMed:27578796}.
CC -!- INTERACTION:
CC A8MZ59; Q9NRZ5: AGPAT4; NbExp=3; IntAct=EBI-17490413, EBI-1754287;
CC A8MZ59; Q9NVV5-2: AIG1; NbExp=3; IntAct=EBI-17490413, EBI-11957045;
CC A8MZ59; P41181: AQP2; NbExp=3; IntAct=EBI-17490413, EBI-12701138;
CC A8MZ59; Q92482: AQP3; NbExp=3; IntAct=EBI-17490413, EBI-2808854;
CC A8MZ59; P07306: ASGR1; NbExp=3; IntAct=EBI-17490413, EBI-1172335;
CC A8MZ59; Q86Z23: C1QL4; NbExp=3; IntAct=EBI-17490413, EBI-12062109;
CC A8MZ59; O95674: CDS2; NbExp=3; IntAct=EBI-17490413, EBI-3913685;
CC A8MZ59; Q96MX0: CMTM3; NbExp=3; IntAct=EBI-17490413, EBI-7247651;
CC A8MZ59; Q96DZ9-2: CMTM5; NbExp=3; IntAct=EBI-17490413, EBI-11522780;
CC A8MZ59; O95406: CNIH1; NbExp=3; IntAct=EBI-17490413, EBI-12172273;
CC A8MZ59; Q8TBE1: CNIH3; NbExp=3; IntAct=EBI-17490413, EBI-12208021;
CC A8MZ59; Q07325: CXCL9; NbExp=3; IntAct=EBI-17490413, EBI-3911467;
CC A8MZ59; P54852: EMP3; NbExp=3; IntAct=EBI-17490413, EBI-3907816;
CC A8MZ59; O75355-2: ENTPD3; NbExp=3; IntAct=EBI-17490413, EBI-12279764;
CC A8MZ59; Q8N5W8: FAM24B; NbExp=3; IntAct=EBI-17490413, EBI-13383724;
CC A8MZ59; O75084: FZD7; NbExp=3; IntAct=EBI-17490413, EBI-746917;
CC A8MZ59; O14653: GOSR2; NbExp=3; IntAct=EBI-17490413, EBI-4401517;
CC A8MZ59; P43628: KIR2DL3; NbExp=3; IntAct=EBI-17490413, EBI-8632435;
CC A8MZ59; O43561-2: LAT; NbExp=3; IntAct=EBI-17490413, EBI-8070286;
CC A8MZ59; Q9BQC6: MRPL57; NbExp=3; IntAct=EBI-17490413, EBI-1055359;
CC A8MZ59; P11836: MS4A1; NbExp=3; IntAct=EBI-17490413, EBI-2808234;
CC A8MZ59; Q9H115: NAPB; NbExp=3; IntAct=EBI-17490413, EBI-3921185;
CC A8MZ59; Q9ULP0-2: NDRG4; NbExp=3; IntAct=EBI-17490413, EBI-11978907;
CC A8MZ59; Q6UX06: OLFM4; NbExp=3; IntAct=EBI-17490413, EBI-2804156;
CC A8MZ59; P60201-2: PLP1; NbExp=3; IntAct=EBI-17490413, EBI-12188331;
CC A8MZ59; P54315: PNLIPRP1; NbExp=3; IntAct=EBI-17490413, EBI-8652812;
CC A8MZ59; A5D903: PRB1; NbExp=3; IntAct=EBI-17490413, EBI-10173935;
CC A8MZ59; Q8WWT9: SLC13A3; NbExp=3; IntAct=EBI-17490413, EBI-12938720;
CC A8MZ59; Q8IWU4: SLC30A8; NbExp=3; IntAct=EBI-17490413, EBI-10262251;
CC A8MZ59; Q96JW4: SLC41A2; NbExp=3; IntAct=EBI-17490413, EBI-10290130;
CC A8MZ59; P02808: STATH; NbExp=3; IntAct=EBI-17490413, EBI-738687;
CC A8MZ59; P02787: TF; NbExp=3; IntAct=EBI-17490413, EBI-714319;
CC A8MZ59; Q5BJH2-2: TMEM128; NbExp=3; IntAct=EBI-17490413, EBI-10694905;
CC A8MZ59; Q9BVK8: TMEM147; NbExp=3; IntAct=EBI-17490413, EBI-348587;
CC A8MZ59; Q14656: TMEM187; NbExp=3; IntAct=EBI-17490413, EBI-13046724;
CC A8MZ59; Q8TBM7: TMEM254; NbExp=3; IntAct=EBI-17490413, EBI-11956809;
CC A8MZ59; Q9H2L4: TMEM60; NbExp=3; IntAct=EBI-17490413, EBI-2852148;
CC A8MZ59; Q5BJF2: TMEM97; NbExp=3; IntAct=EBI-17490413, EBI-12111910;
CC A8MZ59; P30536: TSPO; NbExp=3; IntAct=EBI-17490413, EBI-6623146;
CC A8MZ59; Q5BVD1: TTMP; NbExp=3; IntAct=EBI-17490413, EBI-10243654;
CC A8MZ59; P49638: TTPA; NbExp=3; IntAct=EBI-17490413, EBI-10210710;
CC A8MZ59; Q9H1C4: UNC93B1; NbExp=3; IntAct=EBI-17490413, EBI-4401271;
CC A8MZ59; O75379: VAMP4; NbExp=3; IntAct=EBI-17490413, EBI-744953;
CC A8MZ59; O95159: ZFPL1; NbExp=3; IntAct=EBI-17490413, EBI-718439;
CC A8MZ59; O15015: ZNF646; NbExp=3; IntAct=EBI-17490413, EBI-745608;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:27578796}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=1; Synonyms=LEUTX.n {ECO:0000303|PubMed:27578796};
CC IsoId=A8MZ59-2; Sequence=Displayed;
CC Name=2; Synonyms=LEUTX.R;
CC IsoId=A8MZ59-1; Sequence=VSP_060567;
CC -!- DEVELOPMENTAL STAGE: [Isoform 1]: During early embryo development, its
CC expression is restricted to the 4-cell to 8-cell stage of the
CC preimplantation embryo. {ECO:0000269|PubMed:27578796}.
CC -!- DOMAIN: [Isoform 1]: The homeobox contain essential residues (Ile-54,
CC Lys-57, Ala-61) for binding to the 5'-TAATCC-3' motif of the targe gene
CC promoters. {ECO:0000269|PubMed:30479355}.
CC -!- DOMAIN: [Isoform 2]: The homeobox is incomplete and cannot bind to the
CC 36 bp motif found in the promoters of the target genes.
CC {ECO:0000269|PubMed:27578796}.
CC -!- DOMAIN: The 9aaTAD motif is a conserved putative nine amino acid
CC transactivation motifs in C-terminus of the LEUTX region.
CC {ECO:0000305|PubMed:30479355}.
CC -!- SIMILARITY: Belongs to the paired homeobox family. {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; AC005393; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CR746510; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; DY655817; -; NOT_ANNOTATED_CDS; mRNA.
DR RefSeq; NP_001137304.1; NM_001143832.1. [A8MZ59-1]
DR AlphaFoldDB; A8MZ59; -.
DR SMR; A8MZ59; -.
DR BioGRID; 131206; 46.
DR IntAct; A8MZ59; 45.
DR STRING; 9606.ENSP00000380053; -.
DR GlyGen; A8MZ59; 1 site, 1 O-linked glycan (1 site).
DR BioMuta; LEUTX; -.
DR PaxDb; A8MZ59; -.
DR PRIDE; A8MZ59; -.
DR Antibodypedia; 48021; 8 antibodies from 5 providers.
DR DNASU; 342900; -.
DR Ensembl; ENST00000396841.4; ENSP00000380053.3; ENSG00000213921.8. [A8MZ59-1]
DR Ensembl; ENST00000629267.1; ENSP00000486698.1; ENSG00000280774.2. [A8MZ59-1]
DR Ensembl; ENST00000638280.2; ENSP00000491740.1; ENSG00000213921.8. [A8MZ59-2]
DR Ensembl; ENST00000640845.1; ENSP00000491781.1; ENSG00000280774.2. [A8MZ59-2]
DR GeneID; 342900; -.
DR KEGG; hsa:342900; -.
DR MANE-Select; ENST00000638280.2; ENSP00000491740.1; NM_001382345.1; NP_001369274.1.
DR UCSC; uc010xvg.3; human. [A8MZ59-2]
DR CTD; 342900; -.
DR DisGeNET; 342900; -.
DR GeneCards; LEUTX; -.
DR HGNC; HGNC:31953; LEUTX.
DR HPA; ENSG00000213921; Not detected.
DR MIM; 618701; gene.
DR neXtProt; NX_A8MZ59; -.
DR OpenTargets; ENSG00000213921; -.
DR VEuPathDB; HostDB:ENSG00000213921; -.
DR eggNOG; KOG2251; Eukaryota.
DR GeneTree; ENSGT00950000183093; -.
DR HOGENOM; CLU_124748_0_0_1; -.
DR InParanoid; A8MZ59; -.
DR OMA; DSDPPWA; -.
DR OrthoDB; 1417936at2759; -.
DR PhylomeDB; A8MZ59; -.
DR PathwayCommons; A8MZ59; -.
DR SignaLink; A8MZ59; -.
DR BioGRID-ORCS; 342900; 4 hits in 272 CRISPR screens.
DR GenomeRNAi; 342900; -.
DR Pharos; A8MZ59; Tdark.
DR PRO; PR:A8MZ59; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; A8MZ59; protein.
DR Bgee; ENSG00000213921; Expressed in cell and 10 other tissues.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
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: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 Pfam; PF00046; Homeodomain; 1.
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 Alternative initiation; DNA-binding; Homeobox; Nucleus; Reference proteome.
FT CHAIN 1..198
FT /note="Paired-like homeodomain transcription factor LEUTX"
FT /id="PRO_0000343891"
FT DNA_BIND 33..67
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 65..133
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 79..190
FT /note="LEUTX region"
FT /evidence="ECO:0000303|PubMed:30479355"
FT MOTIF 125..136
FT /note="9aaTAD"
FT /evidence="ECO:0000303|PubMed:30479355"
FT MOTIF 153..161
FT /note="9aaTAD"
FT /evidence="ECO:0000303|PubMed:30479355"
FT MOTIF 163..171
FT /note="9aaTAD"
FT /evidence="ECO:0000303|PubMed:30479355"
FT MOTIF 178..186
FT /note="9aaTAD"
FT /evidence="ECO:0000303|PubMed:30479355"
FT COMPBIAS 65..104
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 54
FT /note="Required for binding to the 5'-TAATCC-3' sequence"
FT /evidence="ECO:0000269|PubMed:30479355"
FT SITE 57
FT /note="Required for binding to the 5'-TAATCC-3' sequence"
FT /evidence="ECO:0000269|PubMed:30479355"
FT SITE 61
FT /note="Required for binding to the 5'-TAATCC-3' sequence"
FT /evidence="ECO:0000269|PubMed:30479355"
FT VAR_SEQ 1..30
FT /note="Missing (in isoform 2)"
FT /id="VSP_060567"
FT MUTAGEN 54
FT /note="I->T: Increased transcriptional activity; when
FT associated with Ala-61-Val, restores wild-type
FT transcriptional activity."
FT /evidence="ECO:0000269|PubMed:30479355"
FT MUTAGEN 61
FT /note="A->V: Abolished catalytic activity; when assiociated
FT with Ile-54-Thr, restores wild-type transcriptional
FT activity."
FT /evidence="ECO:0000269|PubMed:30479355"
FT CONFLICT 103
FT /note="V -> E (in Ref. 3; DY655817)"
FT /evidence="ECO:0000305"
FT CONFLICT 128
FT /note="S -> T (in Ref. 3; DY655817)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 198 AA; 22358 MW; F9D921B42E6ED11F CRC64;
MFEGPRRYRR PRTRFLSKQL TALRELLEKT MHPSLATMGK LASKLQLDLS VVKIWFKNQR
AKWKRQQRQQ MQTRPSLGPA NQTTSVKKEE TPSAITTANI RPVSPGISDA NDHDLREPSG
IKNPGGASAS ARVSSWDSQS YDIEQICLGA SNPPWASTLF EIDEFVKIYD LPGEDDTSSL
NQYLFPVCLE YDQLQSSV
