DLX1_HUMAN
ID DLX1_HUMAN Reviewed; 255 AA.
AC P56177; D3DPD7; Q53ZU4; Q7Z724; Q8IYB2;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 3.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Homeobox protein DLX-1;
GN Name=DLX1;
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] (ISOFORM 1), FUNCTION, INTERACTION WITH SMAD4,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DOMAIN.
RX PubMed=14671321; DOI=10.1073/pnas.2536757100;
RA Chiba S., Takeshita K., Imai Y., Kumano K., Kurokawa M., Masuda S.,
RA Shimizu K., Nakamura S., Ruddle F.H., Hirai H.;
RT "Homeoprotein DLX-1 interacts with Smad4 and blocks a signaling pathway
RT from activin A in hematopoietic cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:15577-15582(2003).
RN [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP CYS-136.
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 128-193 (ISOFORM 1).
RC TISSUE=Embryo;
RX PubMed=7907794; DOI=10.1073/pnas.91.6.2250;
RA Simeone A., Acampora D., Pannese M., D'Esposito M., Stornaiuolo A.,
RA Gulisano M., Mallamaci A., Kastury K., Druck T., Huebner K., Boncinelli E.;
RT "Cloning and characterization of two members of the vertebrate Dlx gene
RT family.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:2250-2254(1994).
CC -!- FUNCTION: Plays a role as a transcriptional activator or repressor
CC (PubMed:14671321). Inhibits several cytokine signaling pathways, such
CC as TGFB1, activin-A/INHBA and BMP4 by interfering with the
CC transcriptional stimulatory activity of transcription factors, such as
CC MSX2, FAST2, SMAD2 and SMAD3 during hematopoietic cell differentiation
CC (PubMed:14671321). Plays a role in terminal differentiation of
CC interneurons, such as amacrine and bipolar cells in the developing
CC retina (By similarity). Likely to play a regulatory role in the
CC development of the ventral forebrain (By similarity). May play a role
CC in craniofacial patterning and morphogenesis and may be involved in the
CC early development of diencephalic subdivisions (By similarity).
CC {ECO:0000250|UniProtKB:Q64317, ECO:0000269|PubMed:14671321}.
CC -!- SUBUNIT: Interacts with SMAD4 (via homeobox DNA-binding domain)
CC (PubMed:14671321). Interacts (via homeobox DNA-binding domain) with
CC POU4F2; this interaction suppresses DLX1-mediated transcriptional
CC activity in postnatal retina and enhances retinal ganglion cell (RGC)
CC differentiation (By similarity). {ECO:0000250|UniProtKB:Q64317,
CC ECO:0000269|PubMed:14671321}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14671321}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P56177-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P56177-2; Sequence=VSP_043589;
CC -!- TISSUE SPECIFICITY: Expressed in hematopoietic cell lines.
CC {ECO:0000269|PubMed:14671321}.
CC -!- DOMAIN: The homeobox DNA-binding domain is necessary for its nuclear
CC localization, transcriptional and erythroid differentiation activities
CC (PubMed:14671321). {ECO:0000269|PubMed:14671321}.
CC -!- SIMILARITY: Belongs to the distal-less 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; AY257976; AAO91939.1; -; mRNA.
DR EMBL; AC015976; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471058; EAX11185.1; -; Genomic_DNA.
DR EMBL; CH471058; EAX11187.1; -; Genomic_DNA.
DR EMBL; BC036189; AAH36189.2; -; mRNA.
DR EMBL; BC053351; AAH53351.1; -; mRNA.
DR CCDS; CCDS2247.2; -. [P56177-1]
DR CCDS; CCDS33328.1; -. [P56177-2]
DR PIR; A53495; A53495.
DR RefSeq; NP_001033582.1; NM_001038493.1. [P56177-2]
DR RefSeq; NP_835221.2; NM_178120.4. [P56177-1]
DR AlphaFoldDB; P56177; -.
DR SMR; P56177; -.
DR BioGRID; 108089; 6.
DR IntAct; P56177; 2.
DR MINT; P56177; -.
DR STRING; 9606.ENSP00000354478; -.
DR GlyGen; P56177; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P56177; -.
DR PhosphoSitePlus; P56177; -.
DR BioMuta; DLX1; -.
DR DMDM; 116241335; -.
DR MassIVE; P56177; -.
DR PaxDb; P56177; -.
DR PeptideAtlas; P56177; -.
DR PRIDE; P56177; -.
DR ProteomicsDB; 56890; -. [P56177-1]
DR ABCD; P56177; 1 sequenced antibody.
DR Antibodypedia; 33859; 365 antibodies from 33 providers.
DR DNASU; 1745; -.
DR Ensembl; ENST00000341900.6; ENSP00000341786.6; ENSG00000144355.15. [P56177-2]
DR Ensembl; ENST00000361725.5; ENSP00000354478.4; ENSG00000144355.15. [P56177-1]
DR GeneID; 1745; -.
DR KEGG; hsa:1745; -.
DR MANE-Select; ENST00000361725.5; ENSP00000354478.4; NM_178120.5; NP_835221.2.
DR UCSC; uc002uhm.4; human. [P56177-1]
DR CTD; 1745; -.
DR DisGeNET; 1745; -.
DR GeneCards; DLX1; -.
DR HGNC; HGNC:2914; DLX1.
DR HPA; ENSG00000144355; Tissue enriched (brain).
DR MIM; 600029; gene.
DR neXtProt; NX_P56177; -.
DR OpenTargets; ENSG00000144355; -.
DR PharmGKB; PA27369; -.
DR VEuPathDB; HostDB:ENSG00000144355; -.
DR eggNOG; KOG0850; Eukaryota.
DR GeneTree; ENSGT00940000160029; -.
DR HOGENOM; CLU_2170222_0_0_1; -.
DR InParanoid; P56177; -.
DR OMA; MEFGPPG; -.
DR PhylomeDB; P56177; -.
DR TreeFam; TF315720; -.
DR PathwayCommons; P56177; -.
DR SignaLink; P56177; -.
DR BioGRID-ORCS; 1745; 13 hits in 1105 CRISPR screens.
DR GeneWiki; DLX1; -.
DR GenomeRNAi; 1745; -.
DR Pharos; P56177; Tbio.
DR PRO; PR:P56177; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P56177; protein.
DR Bgee; ENSG00000144355; Expressed in middle temporal gyrus and 110 other tissues.
DR ExpressionAtlas; P56177; baseline and differential.
DR Genevisible; P56177; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
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:1990837; F:sequence-specific double-stranded DNA binding; IDA:ARUK-UCL.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0071773; P:cellular response to BMP stimulus; IMP:UniProtKB.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IMP:UniProtKB.
DR GO; GO:0021893; P:cerebral cortex GABAergic interneuron fate commitment; IEA:Ensembl.
DR GO; GO:0048706; P:embryonic skeletal system development; IEA:Ensembl.
DR GO; GO:0021879; P:forebrain neuron differentiation; IEA:Ensembl.
DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IMP:UniProtKB.
DR GO; GO:1903845; P:negative regulation of cellular response to transforming growth factor beta stimulus; IMP:UniProtKB.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0045746; P:negative regulation of Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0048715; P:negative regulation of oligodendrocyte differentiation; IEA:Ensembl.
DR GO; GO:0046533; P:negative regulation of photoreceptor cell differentiation; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0014016; P:neuroblast differentiation; IEA:Ensembl.
DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IEA:Ensembl.
DR GO; GO:1902871; P:positive regulation of amacrine cell differentiation; ISS:UniProtKB.
DR GO; GO:0045597; P:positive regulation of cell differentiation; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0009954; P:proximal/distal pattern formation; IEA:Ensembl.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0021544; P:subpallium development; IEA:Ensembl.
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; IPR000047; HTH_motif.
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 Activator; Alternative splicing; Developmental protein; Differentiation;
KW DNA-binding; Homeobox; Nucleus; Reference proteome; Repressor;
KW Transcription; Transcription regulation.
FT CHAIN 1..255
FT /note="Homeobox protein DLX-1"
FT /id="PRO_0000049020"
FT DNA_BIND 128..187
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 1..38
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 95..118
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 204..230
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 106..255
FT /note="ADSEKSTVVEGGEVRFNGKGKKIRKPRTIYSSLQLQALNRRFQQTQYLALPE
FT RAELAASLGLTQTQVKIWFQNKRSKFKKLMKQGGAALEGSALANGRALSAGSPPVPPGW
FT NPNSSSGKGSGGNAGSYIPSYTSWYPSAHQEAMQQPQLM -> QDLVPKQAIQVQEADE
FT AGWGGSGG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_043589"
FT VARIANT 136
FT /note="S -> C (in dbSNP:rs17853565)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_028443"
SQ SEQUENCE 255 AA; 27320 MW; 99B468315FBFE7BD CRC64;
MTMTTMPESL NSPVSGKAVF MEFGPPNQQM SPSPMSHGHY SMHCLHSAGH SQPDGAYSSA
SSFSRPLGYP YVNSVSSHAS SPYISSVQSY PGSASLAQSR LEDPGADSEK STVVEGGEVR
FNGKGKKIRK PRTIYSSLQL QALNRRFQQT QYLALPERAE LAASLGLTQT QVKIWFQNKR
SKFKKLMKQG GAALEGSALA NGRALSAGSP PVPPGWNPNS SSGKGSGGNA GSYIPSYTSW
YPSAHQEAMQ QPQLM
