MEIS2_MOUSE
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 03-AUG-2022, entry version 167.
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}.
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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; P97367; -.
DR PRIDE; P97367; -.
DR ProteomicsDB; 295879; -. [P97367-1]
DR ProteomicsDB; 295880; -. [P97367-2]
DR ProteomicsDB; 295881; -. [P97367-3]
DR ProteomicsDB; 295882; -. [P97367-4]
DR Antibodypedia; 918; 306 antibodies from 36 providers.
DR DNASU; 17536; -.
DR Ensembl; ENSMUST00000028639; ENSMUSP00000028639; ENSMUSG00000027210. [P97367-1]
DR Ensembl; ENSMUST00000102538; ENSMUSP00000099597; ENSMUSG00000027210. [P97367-4]
DR Ensembl; ENSMUST00000110907; ENSMUSP00000106532; ENSMUSG00000027210. [P97367-2]
DR Ensembl; ENSMUST00000110908; ENSMUSP00000106533; ENSMUSG00000027210. [P97367-3]
DR GeneID; 17536; -.
DR KEGG; mmu:17536; -.
DR UCSC; uc008lqw.2; mouse. [P97367-2]
DR UCSC; uc008lqy.2; mouse. [P97367-1]
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; QIMDIHA; -.
DR OrthoDB; 1126341at2759; -.
DR PhylomeDB; P97367; -.
DR TreeFam; TF318093; -.
DR BioGRID-ORCS; 17536; 2 hits in 73 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 278 other tissues.
DR ExpressionAtlas; P97367; baseline and differential.
DR Genevisible; P97367; MM.
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:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA: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:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
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 InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR008422; Homeobox_KN_domain.
DR InterPro; IPR032453; PKNOX/Meis_N.
DR Pfam; PF05920; Homeobox_KN; 1.
DR Pfam; PF16493; Meis_PKNOX_N; 1.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
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
