ID MEIS2_MOUSE Reviewed; 477 AA. AC P97367; O35676; O35677; P97403; P97404; DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot. DT 15-DEC-1998, sequence version 2. DT 24-JAN-2024, entry version 175. DE RecName: Full=Homeobox protein Meis2; DE AltName: Full=Meis1-related protein 1; GN Name=Meis2; Synonyms=Mrg1, Stra10; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MEIS2A). RC STRAIN=Swiss Webster; RX PubMed=8950991; RA Nakamura T., Jenkins N.A., Copeland N.G.; RT "Identification of a new family of Pbx-related homeobox genes."; RL Oncogene 13:2235-2242(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS MEIS2A; MEIS2B; MEIS2C AND MEIS2D). RX PubMed=9337137; RX DOI=10.1002/(sici)1097-0177(199710)210:2<173::aid-aja9>3.0.co;2-d; RA Oulad-Abdelghani M., Chazaud C., Bouillet P., Sapin V., Chambon P., RA Dolle P.; RT "Meis2, a novel mouse Pbx-related homeobox gene induced by retinoic acid RT during differentiation of P19 embryonal carcinoma cells."; RL Dev. Dyn. 210:173-183(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS MEIS2B AND MEIS2D). RX PubMed=9049632; DOI=10.1101/gr.7.2.142; RA Steelman S., Moskow J.J., Muzynski K., North C., Druck T., Montgomery J.C., RA Huebner K., Daar I.O., Buchberg A.M.; RT "Identification of a conserved family of Meis1-related homeobox genes."; RL Genome Res. 7:142-156(1997). RN [4] RP SUBCELLULAR LOCATION, AND IDENTIFICATION IN A COMPLEX WITH PDX1 AND PBX1. RX PubMed=9710595; DOI=10.1128/mcb.18.9.5109; RA Swift G.H., Liu Y., Rose S.D., Bischof L.J., Steelman S., Buchberg A.M., RA Wright C.V., MacDonald R.J.; RT "An endocrine-exocrine switch in the activity of the pancreatic homeodomain RT protein PDX1 through formation of a trimeric complex with PBX1b and MRG1 RT (MEIS2)."; RL Mol. Cell. Biol. 18:5109-5120(1998). RN [5] RP DEVELOPMENTAL STAGE. RX PubMed=10842069; DOI=10.1016/s0925-4773(00)00324-5; RA Toresson H., Parmar M., Campbell K.; RT "Expression of Meis and Pbx genes and their protein products in the RT developing telencephalon: implications for regional differentiation."; RL Mech. Dev. 94:183-187(2000). RN [6] RP FUNCTION, AND SUBUNIT. RX PubMed=11438208; DOI=10.1016/s0301-472x(01)00655-5; RA Fujino T., Yamazaki Y., Largaespada D.A., Jenkins N.A., Copeland N.G., RA Hirokawa K., Nakamura T.; RT "Inhibition of myeloid differentiation by Hoxa9, Hoxb8, and Meis homeobox RT genes."; RL Exp. Hematol. 29:856-863(2001). RN [7] RP FUNCTION, INTERACTION WITH PBX1, AND IDENTIFICATION IN A COMPLEX WITH PDX1 RP AND PBX1. RX PubMed=11279116; DOI=10.1074/jbc.m100678200; RA Liu Y., MacDonald R.J., Swift G.H.; RT "DNA binding and transcriptional activation by a PDX1.PBX1b.MEIS2b trimer RT and cooperation with a pancreas-specific basic helix-loop-helix complex."; RL J. Biol. Chem. 276:17985-17993(2001). RN [8] RP INTERACTION WITH HOXA13. RX PubMed=15617687; DOI=10.1016/j.ydbio.2004.10.004; RA Williams T.M., Williams M.E., Innis J.W.; RT "Range of HOX/TALE superclass associations and protein domain requirements RT for HOXA13:MEIS interaction."; RL Dev. Biol. 277:457-471(2005). RN [9] RP FUNCTION, AND DNA-BINDING. RX PubMed=17178831; DOI=10.1128/mcb.01429-06; RA Shim S., Kim Y., Shin J., Kim J., Park S.; RT "Regulation of EphA8 gene expression by TALE homeobox transcription factors RT during development of the mesencephalon."; RL Mol. Cell. Biol. 27:1614-1630(2007). RN [10] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=21059917; DOI=10.1073/pnas.1007001107; RA Liu J., Wang Y., Birnbaum M.J., Stoffers D.A.; RT "Three-amino-acid-loop-extension homeodomain factor Meis3 regulates cell RT survival via PDK1."; RL Proc. Natl. Acad. Sci. U.S.A. 107:20494-20499(2010). CC -!- FUNCTION: Involved in transcriptional regulation. Binds to HOX or PBX CC proteins to form dimers, or to a DNA-bound dimer of PBX and HOX CC proteins and thought to have a role in stabilization of the CC homeoprotein-DNA complex. Isoform Meis2B is required for the activity CC of a PDX1:PBX1b:MEIS2b complex in pancreatic acinar cells involved in CC the transcriptional activation of the ELA1 enhancer; the complex binds CC to the enhancer B element and cooperates with the transcription factor CC 1 complex (PTF1) bound to the enhancer A element; MEIS2 is not involved CC in complex DNA-binding. Probably in complex with PBX1, is involved in CC transcriptional regulation by KLF4. Isoforms Meis2B and Meis2D can bind CC to a EPHA8 promoter sequence containing the DNA motif 5'-CGGTCA-3'; in CC cooperation with a PBX protein (such as PBX2) is proposed to be CC involved in the transcriptional activation of EPHA8 in the developing CC midbrain. May be involved in regulation of myeloid differentiation. Can CC bind to the DNA sequence 5'-TGACAG-3'in the activator ACT sequence of CC the D(1A) dopamine receptor (DRD1) promoter and activate DRD1 CC transcription. {ECO:0000269|PubMed:11279116, CC ECO:0000269|PubMed:11438208, ECO:0000269|PubMed:17178831}. CC -!- SUBUNIT: Monomer and homodimer. Heterodimer with HOXB13 (By CC similarity). Isoform Meis2A interacts with TLX1. Isoform Meis2B CC interacts with HOXA13 and PBX1 isoform PBX1b. Isoform Meis2D interacts CC with SP1, SP3 and KLF4. Isoform Meis2D interacts with PBX1 isoform CC PBX1a; the interaction partially relieves MEIS2 autoinhibition. Isoform CC Meis2B is part of a PDX1:PBX1b:MEIS2b complex; Meis2B is recruited by CC PBX1b and can be replaced by isoform Meis2D in a small fraction of CC complexes. Can form trimeric complexes including HOXB8 and PBX2 or CC PBX3. {ECO:0000250|UniProtKB:O14770, ECO:0000269|PubMed:11279116, CC ECO:0000269|PubMed:11438208, ECO:0000269|PubMed:15617687, CC ECO:0000269|PubMed:9710595}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108, CC ECO:0000269|PubMed:9710595}. Cytoplasm, perinuclear region CC {ECO:0000269|PubMed:21059917}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Comment=Additional isoforms seem to exist.; CC Name=Meis2C; CC IsoId=P97367-1; Sequence=Displayed; CC Name=Meis2A; CC IsoId=P97367-2; Sequence=VSP_002248, VSP_002249; CC Name=Meis2B; Synonyms=Mrg1A; CC IsoId=P97367-3; Sequence=VSP_002247, VSP_002248, VSP_002249; CC Name=Meis2D; Synonyms=Mrg1B; CC IsoId=P97367-4; Sequence=VSP_002247; CC -!- TISSUE SPECIFICITY: Displays spatially restricted expression patterns CC in the developing nervous system, limbs, face, and in various viscera. CC In adult, it is mainly expressed in the brain and female genital tract, CC with a different distribution of the alternative splice forms in these CC organs. Lower expression in lung and only basal level in heart, liver, CC kidney, spleen, and testis. Expressed in pancreatic islets (beta-cells CC only) (PubMed:21059917). {ECO:0000269|PubMed:21059917}. CC -!- DEVELOPMENTAL STAGE: Expressed at high levels in all stages of CC embryonic development analyzed (7 days to 17 days). First detected CC around 10.5 dpc in the developing ventrolateral telencephalon. Is found CC at moderate levels throughout the ventricle zone (VZ) of the entire CC telencephalon with the exception of the ventro- and dorso-medial CC regions. The highest expression is detected in the subventricular zone CC (SVZ) of the lateral ganglionic eminence (LGE) and developing striatum. CC By 16.5 dpc, also found in the cortical plate. Also expressed at high CC levels in the caudal ganglionic eminence (CGE) and amygdala. Expression CC in the telencephalon remains unchanged at birth and into adulthood. CC {ECO:0000269|PubMed:10842069}. CC -!- INDUCTION: By retinoic acid. CC -!- SIMILARITY: Belongs to the TALE/MEIS 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; U57343; AAC52948.1; -; mRNA. DR EMBL; AJ000504; CAA04138.1; -; mRNA. DR EMBL; AJ000505; CAA04139.1; -; mRNA. DR EMBL; AJ000506; CAA04140.1; -; mRNA. DR EMBL; AJ000507; CAA04141.1; -; mRNA. DR EMBL; U68383; AAB19193.1; -; mRNA. DR EMBL; U68384; AAB19194.1; -; mRNA. DR CCDS; CCDS16568.1; -. [P97367-4] DR CCDS; CCDS50666.1; -. [P97367-3] DR CCDS; CCDS50667.1; -. [P97367-1] DR CCDS; CCDS50668.1; -. [P97367-2] DR RefSeq; NP_001129544.1; NM_001136072.2. [P97367-3] DR RefSeq; NP_001153039.1; NM_001159567.1. [P97367-2] DR RefSeq; NP_001153040.1; NM_001159568.1. [P97367-1] DR RefSeq; NP_034955.1; NM_010825.3. [P97367-4] DR AlphaFoldDB; P97367; -. DR SMR; P97367; -. DR BioGRID; 201487; 8. DR CORUM; P97367; -. DR IntAct; P97367; 7. DR STRING; 10090.ENSMUSP00000028639; -. DR iPTMnet; P97367; -. DR PhosphoSitePlus; P97367; -. DR MaxQB; P97367; -. DR PaxDb; 10090-ENSMUSP00000028639; -. DR ProteomicsDB; 295879; -. [P97367-1] DR ProteomicsDB; 295880; -. [P97367-2] DR ProteomicsDB; 295881; -. [P97367-3] DR ProteomicsDB; 295882; -. [P97367-4] DR Pumba; P97367; -. DR Antibodypedia; 918; 332 antibodies from 36 providers. DR DNASU; 17536; -. DR Ensembl; ENSMUST00000028639.13; ENSMUSP00000028639.7; ENSMUSG00000027210.21. [P97367-1] DR Ensembl; ENSMUST00000102538.11; ENSMUSP00000099597.4; ENSMUSG00000027210.21. [P97367-4] DR Ensembl; ENSMUST00000110907.8; ENSMUSP00000106532.2; ENSMUSG00000027210.21. [P97367-2] DR Ensembl; ENSMUST00000110908.9; ENSMUSP00000106533.3; ENSMUSG00000027210.21. [P97367-3] DR GeneID; 17536; -. DR KEGG; mmu:17536; -. DR UCSC; uc008lqw.2; mouse. [P97367-2] DR UCSC; uc008lqy.2; mouse. [P97367-1] DR AGR; MGI:108564; -. DR CTD; 4212; -. DR MGI; MGI:108564; Meis2. DR VEuPathDB; HostDB:ENSMUSG00000027210; -. DR eggNOG; KOG0773; Eukaryota. DR GeneTree; ENSGT00940000155643; -. DR HOGENOM; CLU_023139_1_1_1; -. DR InParanoid; P97367; -. DR OMA; FNDDIAC; -. DR OrthoDB; 3180467at2759; -. DR PhylomeDB; P97367; -. DR TreeFam; TF318093; -. DR BioGRID-ORCS; 17536; 2 hits in 78 CRISPR screens. DR ChiTaRS; Meis2; mouse. DR PRO; PR:P97367; -. DR Proteomes; UP000000589; Chromosome 2. DR RNAct; P97367; Protein. DR Bgee; ENSMUSG00000027210; Expressed in rostral migratory stream and 282 other cell types or tissues. DR ExpressionAtlas; P97367; baseline and differential. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0003677; F:DNA binding; IDA:MGI. DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:GO_Central. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:MGI. DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI. DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI. DR GO; GO:0008134; F:transcription factor binding; IDA:UniProtKB. DR GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central. DR GO; GO:0007420; P:brain development; IBA:GO_Central. DR GO; GO:0009880; P:embryonic pattern specification; IBA:GO_Central. DR GO; GO:0001654; P:eye development; IGI:MGI. DR GO; GO:0045638; P:negative regulation of myeloid cell differentiation; IDA:UniProtKB. DR GO; GO:0031016; P:pancreas development; IEA:Ensembl. DR GO; GO:0110024; P:positive regulation of cardiac muscle myoblast proliferation; ISO:MGI. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central. DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISO:MGI. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI. DR GO; GO:0070848; P:response to growth factor; IEA:Ensembl. DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl. DR GO; GO:0008542; P:visual learning; IMP:MGI. DR CDD; cd00086; homeodomain; 1. DR Gene3D; 1.10.10.60; Homeodomain-like; 1. DR InterPro; IPR009057; Homeobox-like_sf. DR InterPro; IPR001356; Homeobox_dom. DR InterPro; IPR008422; Homeobox_KN_domain. DR InterPro; IPR032453; PKNOX/Meis_N. DR PANTHER; PTHR11850:SF47; HOMEOBOX PROTEIN MEIS2; 1. DR PANTHER; PTHR11850; HOMEOBOX PROTEIN TRANSCRIPTION FACTORS; 1. DR Pfam; PF05920; Homeobox_KN; 1. DR Pfam; PF16493; Meis_PKNOX_N; 1. DR SMART; SM00389; HOX; 1. DR SUPFAM; SSF46689; Homeodomain-like; 1. DR PROSITE; PS50071; HOMEOBOX_2; 1. DR Genevisible; P97367; MM. PE 1: Evidence at protein level; KW Activator; Alternative splicing; Cytoplasm; Developmental protein; KW DNA-binding; Homeobox; Nucleus; Reference proteome; Transcription; KW Transcription regulation. FT CHAIN 1..477 FT /note="Homeobox protein Meis2" FT /id="PRO_0000049109" FT DOMAIN 110..193 FT /note="MEIS N-terminal" FT /evidence="ECO:0000255" FT DNA_BIND 276..338 FT /note="Homeobox; TALE-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108" FT REGION 71..191 FT /note="Required for interaction with PBX1" FT /evidence="ECO:0000269|PubMed:11279116" FT REGION 193..283 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 299..333 FT /note="Interaction with DNA" FT /evidence="ECO:0000250|UniProtKB:O14770" FT REGION 340..477 FT /note="Transcriptional activation domain" FT /evidence="ECO:0000250" FT COMPBIAS 227..258 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VAR_SEQ 346..352 FT /note="Missing (in isoform Meis2B and isoform Meis2D)" FT /evidence="ECO:0000303|PubMed:9049632, FT ECO:0000303|PubMed:9337137" FT /id="VSP_002247" FT VAR_SEQ 384..401 FT /note="LQSMPGDYVSQGGPMGMG -> PMSGMGMNMGMDGQWHYM (in isoform FT Meis2A and isoform Meis2B)" FT /evidence="ECO:0000303|PubMed:8950991, FT ECO:0000303|PubMed:9049632, ECO:0000303|PubMed:9337137" FT /id="VSP_002248" FT VAR_SEQ 402..477 FT /note="Missing (in isoform Meis2A and isoform Meis2B)" FT /evidence="ECO:0000303|PubMed:8950991, FT ECO:0000303|PubMed:9049632, ECO:0000303|PubMed:9337137" FT /id="VSP_002249" FT CONFLICT 2 FT /note="A -> E (in Ref. 1; AAC52948)" FT /evidence="ECO:0000305" FT CONFLICT 316 FT /note="T -> A (in Ref. 1; AAC52948)" FT /evidence="ECO:0000305" SQ SEQUENCE 477 AA; 51728 MW; 923610800B647A21 CRC64; MAQRYDELPH YGGMDGVGVP ASMYGDPHAP RPIPPVHHLN HGPPLHATQH YGAHAPHPNV MPASMGSAVN DALKRDKDAI YGHPLFPLLA LVFEKCELAT CTPREPGVAG GDVCSSDSFN EDIAVFAKQV RAEKPLFSSN PELDNLMIQA IQVLRFHLLE LEKVHELCDN FCHRYISCLK GKMPIDLVID ERDGSSKSDH EELSGSSTNL ADHNPSSWRD HDDATSTHSA GTPGPSSGGH ASQSGDNSSE QGDGLDNSVA SPGTGDDDDP DKDKKRQKKR GIFPKVATNI MRAWLFQHLT HPYPSEEQKK QLAQDTGLTI LQVNNWFINA RRRIVQPMID QSNRAGFLLD PSVSQGAAYS PEGQPMGSFV LDGQQHMGIR PAGLQSMPGD YVSQGGPMGM GMAQPSYTPP QMTPHPTQLR HGPPMHSYLP SHPHHPAMVM HGGPPTHPGM TMSAQSPTML NSVDPNVGGQ VMDIHAQ //