DLX2_HUMAN
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 03-AUG-2022, entry version 180.
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. Plays a role in terminal
CC differentiation of interneurons, such as amacrine and bipolar cells in
CC the developing retina. Likely to play a regulatory role in the
CC development of the ventral forebrain. May play a role in craniofacial
CC patterning and morphogenesis. {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; 15.
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; Q07687; -.
DR PeptideAtlas; Q07687; -.
DR PRIDE; Q07687; -.
DR ProteomicsDB; 58526; -. [Q07687-1]
DR Antibodypedia; 19409; 360 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 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 PhylomeDB; Q07687; -.
DR TreeFam; TF350606; -.
DR PathwayCommons; Q07687; -.
DR SignaLink; Q07687; -.
DR SIGNOR; Q07687; -.
DR BioGRID-ORCS; 1746; 19 hits in 1106 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 buccal mucosa cell and 74 other tissues.
DR ExpressionAtlas; Q07687; baseline and differential.
DR Genevisible; Q07687; HS.
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: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: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; 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 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; 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; 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
