ID   DLX2_HUMAN              Reviewed;         328 AA.
AC   Q07687; B4DMK4; B7ZA14;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 2.
DT   24-JAN-2024, entry version 188.
DE   RecName: Full=Homeobox protein DLX-2;
GN   Name=DLX2;
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].
RX   PubMed=8812481; DOI=10.1006/geno.1996.0387;
RA   McGuinness T., Porteus M.H., Smiga S., Bulfone A., Kingsley C., Qiu M.,
RA   Liu J.K., Long J.E., Xu D., Rubenstein J.L.R.;
RT   "Sequence, organization, and transcription of the Dlx-1 and Dlx-2 locus.";
RL   Genomics 35:473-485(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Brain, and Tongue;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
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] (ISOFORM 1).
RC   TISSUE=Duodenum;
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 85-328 (ISOFORM 1).
RC   TISSUE=Brain;
RX   PubMed=7901126; DOI=10.1016/0378-1119(93)90212-l;
RA   Selski D.J., Thomas N.E., Coleman P.D., Rogers K.E.;
RT   "The human brain homeogene, DLX-2: cDNA sequence and alignment with the
RT   murine homologue.";
RL   Gene 132:301-303(1993).
RN   [6]
RP   NUCLEOTIDE SEQUENCE OF 152-217.
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).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-232, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18220336; DOI=10.1021/pr0705441;
RA   Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT   "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT   phosphoproteomic analysis.";
RL   J. Proteome Res. 7:1346-1351(2008).
RN   [8]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
CC   -!- FUNCTION: Acts as a transcriptional activator (By similarity).
CC       Activates transcription of CGA/alpha-GSU, via binding to the downstream
CC       activin regulatory element (DARE) in the gene promoter (By similarity).
CC       Plays a role in terminal differentiation of interneurons, such as
CC       amacrine and bipolar cells in the developing retina. Likely to play a
CC       regulatory role in the development of the ventral forebrain (By
CC       similarity). May play a role in craniofacial patterning and
CC       morphogenesis (By similarity). {ECO:0000250|UniProtKB:P40764}.
CC   -!- SUBUNIT: Interacts (via homeobox DNA-binding domain) with POU4F2; this
CC       interaction enhances retinal ganglion cell (RGC) differentiation.
CC       {ECO:0000250|UniProtKB:P40764}.
CC   -!- INTERACTION:
CC       Q07687; P28799: GRN; NbExp=3; IntAct=EBI-3908234, EBI-747754;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q07687-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q07687-2; Sequence=VSP_054287, VSP_054288;
CC   -!- SIMILARITY: Belongs to the distal-less homeobox family. {ECO:0000305}.
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DR   EMBL; U51003; AAB40902.1; -; Genomic_DNA.
DR   EMBL; AK297503; BAG59916.1; -; mRNA.
DR   EMBL; AK316129; BAH14500.1; -; mRNA.
DR   EMBL; AC104801; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC032558; AAH32558.1; -; mRNA.
DR   EMBL; L07919; AAA19663.1; -; mRNA.
DR   CCDS; CCDS2248.1; -. [Q07687-1]
DR   PIR; B53495; B53495.
DR   PIR; G02469; G02469.
DR   RefSeq; NP_004396.1; NM_004405.3. [Q07687-1]
DR   AlphaFoldDB; Q07687; -.
DR   SMR; Q07687; -.
DR   BioGRID; 108090; 16.
DR   IntAct; Q07687; 12.
DR   MINT; Q07687; -.
DR   STRING; 9606.ENSP00000234198; -.
DR   iPTMnet; Q07687; -.
DR   PhosphoSitePlus; Q07687; -.
DR   BioMuta; DLX2; -.
DR   DMDM; 2506529; -.
DR   jPOST; Q07687; -.
DR   MassIVE; Q07687; -.
DR   PaxDb; 9606-ENSP00000234198; -.
DR   PeptideAtlas; Q07687; -.
DR   ProteomicsDB; 58526; -. [Q07687-1]
DR   Pumba; Q07687; -.
DR   Antibodypedia; 19409; 390 antibodies from 32 providers.
DR   DNASU; 1746; -.
DR   Ensembl; ENST00000234198.9; ENSP00000234198.4; ENSG00000115844.11. [Q07687-1]
DR   Ensembl; ENST00000466293.2; ENSP00000446904.1; ENSG00000115844.11. [Q07687-2]
DR   GeneID; 1746; -.
DR   KEGG; hsa:1746; -.
DR   MANE-Select; ENST00000234198.9; ENSP00000234198.4; NM_004405.4; NP_004396.1.
DR   UCSC; uc010zdx.2; human. [Q07687-1]
DR   AGR; HGNC:2915; -.
DR   CTD; 1746; -.
DR   DisGeNET; 1746; -.
DR   GeneCards; DLX2; -.
DR   HGNC; HGNC:2915; DLX2.
DR   HPA; ENSG00000115844; Tissue enhanced (brain).
DR   MIM; 126255; gene.
DR   neXtProt; NX_Q07687; -.
DR   OpenTargets; ENSG00000115844; -.
DR   PharmGKB; PA27370; -.
DR   VEuPathDB; HostDB:ENSG00000115844; -.
DR   eggNOG; KOG0850; Eukaryota.
DR   GeneTree; ENSGT00940000160127; -.
DR   HOGENOM; CLU_074733_1_1_1; -.
DR   InParanoid; Q07687; -.
DR   OMA; WYHQASS; -.
DR   OrthoDB; 2969529at2759; -.
DR   PhylomeDB; Q07687; -.
DR   TreeFam; TF350606; -.
DR   PathwayCommons; Q07687; -.
DR   SignaLink; Q07687; -.
DR   SIGNOR; Q07687; -.
DR   BioGRID-ORCS; 1746; 19 hits in 1184 CRISPR screens.
DR   GeneWiki; DLX2; -.
DR   GenomeRNAi; 1746; -.
DR   Pharos; Q07687; Tbio.
DR   PRO; PR:Q07687; -.
DR   Proteomes; UP000005640; Chromosome 2.
DR   RNAct; Q07687; Protein.
DR   Bgee; ENSG00000115844; Expressed in primordial germ cell in gonad and 75 other cell types or tissues.
DR   ExpressionAtlas; Q07687; baseline and differential.
DR   GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR   GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR   GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IEA:Ensembl.
DR   GO; GO:0003700; F:DNA-binding transcription factor activity; TAS:ProtInc.
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:0003727; F:single-stranded RNA binding; IEA:Ensembl.
DR   GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR   GO; GO:0007420; P:brain development; TAS:ProtInc.
DR   GO; GO:0048755; P:branching morphogenesis of a nerve; IEA:Ensembl.
DR   GO; GO:0051216; P:cartilage development; IEA:Ensembl.
DR   GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR   GO; GO:0021893; P:cerebral cortex GABAergic interneuron fate commitment; IEA:Ensembl.
DR   GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IEA:Ensembl.
DR   GO; GO:0021879; P:forebrain neuron differentiation; IEA:Ensembl.
DR   GO; GO:0021766; P:hippocampus development; 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; IBA:GO_Central.
DR   GO; GO:0014016; P:neuroblast differentiation; 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:0021772; P:olfactory bulb development; 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; ISS:UniProtKB.
DR   GO; GO:0009954; P:proximal/distal pattern formation; IEA:Ensembl.
DR   GO; GO:0021544; P:subpallium development; IEA:Ensembl.
DR   CDD; cd00086; homeodomain; 1.
DR   Gene3D; 1.10.10.60; Homeodomain-like; 1.
DR   InterPro; IPR022135; Distal-less_N.
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   PANTHER; PTHR24327; HOMEOBOX PROTEIN; 1.
DR   PANTHER; PTHR24327:SF23; HOMEOBOX PROTEIN DLX-2; 1.
DR   Pfam; PF12413; DLL_N; 1.
DR   Pfam; PF00046; Homeodomain; 1.
DR   PRINTS; PR00024; HOMEOBOX.
DR   PRINTS; PR00031; HTHREPRESSR.
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; Q07687; HS.
PE   1: Evidence at protein level;
KW   Activator; Alternative splicing; Developmental protein; Differentiation;
KW   DNA-binding; Homeobox; Nucleus; Phosphoprotein; Reference proteome;
KW   Transcription; Transcription regulation.
FT   CHAIN           1..328
FT                   /note="Homeobox protein DLX-2"
FT                   /id="PRO_0000049023"
FT   DNA_BIND        152..211
FT                   /note="Homeobox"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT   REGION          16..81
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          211..270
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          300..328
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        16..72
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         232
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:18220336"
FT   VAR_SEQ         197..217
FT                   /note="KIWFQNRRSKFKKMWKSGEIP -> GLAPCRGEESAGLRWLGSRRV (in
FT                   isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_054287"
FT   VAR_SEQ         218..328
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_054288"
FT   CONFLICT        178
FT                   /note="A -> V (in Ref. 2; BAG59916)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   328 AA;  34243 MW;  BB6A077256F58022 CRC64;
     MTGVFDSLVA DMHSTQIAAS STYHQHQQPP SGGGAGPGGN SSSSSSLHKP QESPTLPVST
     ATDSSYYTNQ QHPAGGGGGG GSPYAHMGSY QYQASGLNNV PYSAKSSYDL GYTAAYTSYA
     PYGTSSSPAN NEPEKEDLEP EIRIVNGKPK KVRKPRTIYS SFQLAALQRR FQKTQYLALP
     ERAELAASLG LTQTQVKIWF QNRRSKFKKM WKSGEIPSEQ HPGASASPPC ASPPVSAPAS
     WDFGVPQRMA GGGGPGSGGS GAGSSGSSPS SAASAFLGNY PWYHQTSGSA SHLQATAPLL
     HPTQTPQPHH HHHHHGGGGA PVSAGTIF
//