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Homeobox protein Meis2 (Meis1-related protein 1)

 MEIS2_MOUSE             Reviewed;         477 AA.
P97367; O35676; O35677; P97403; P97404;
15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
15-DEC-1998, sequence version 2.
18-JUL-2018, entry version 146.
RecName: Full=Homeobox protein Meis2;
AltName: Full=Meis1-related protein 1;
Name=Meis2; Synonyms=Mrg1, Stra10;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM MEIS2A).
STRAIN=Swiss Webster;
PubMed=8950991;
Nakamura T., Jenkins N.A., Copeland N.G.;
"Identification of a new family of Pbx-related homeobox genes.";
Oncogene 13:2235-2242(1996).
[2]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS MEIS2A; MEIS2B; MEIS2C AND
MEIS2D).
PubMed=9337137;
DOI=10.1002/(SICI)1097-0177(199710)210:2<173::AID-AJA9>3.0.CO;2-D;
Oulad-Abdelghani M., Chazaud C., Bouillet P., Sapin V., Chambon P.,
Dolle P.;
"Meis2, a novel mouse Pbx-related homeobox gene induced by retinoic
acid during differentiation of P19 embryonal carcinoma cells.";
Dev. Dyn. 210:173-183(1997).
[3]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS MEIS2B AND MEIS2D).
PubMed=9049632; DOI=10.1101/gr.7.2.142;
Steelman S., Moskow J.J., Muzynski K., North C., Druck T.,
Montgomery J.C., Huebner K., Daar I.O., Buchberg A.M.;
"Identification of a conserved family of Meis1-related homeobox
genes.";
Genome Res. 7:142-156(1997).
[4]
SUBCELLULAR LOCATION, AND IDENTIFICATION IN A COMPLEX WITH PDX1 AND
PBX1.
PubMed=9710595; DOI=10.1128/MCB.18.9.5109;
Swift G.H., Liu Y., Rose S.D., Bischof L.J., Steelman S.,
Buchberg A.M., Wright C.V., MacDonald R.J.;
"An endocrine-exocrine switch in the activity of the pancreatic
homeodomain protein PDX1 through formation of a trimeric complex with
PBX1b and MRG1 (MEIS2).";
Mol. Cell. Biol. 18:5109-5120(1998).
[5]
DEVELOPMENTAL STAGE.
PubMed=10842069; DOI=10.1016/S0925-4773(00)00324-5;
Toresson H., Parmar M., Campbell K.;
"Expression of Meis and Pbx genes and their protein products in the
developing telencephalon: implications for regional differentiation.";
Mech. Dev. 94:183-187(2000).
[6]
FUNCTION, AND SUBUNIT.
PubMed=11438208; DOI=10.1016/S0301-472X(01)00655-5;
Fujino T., Yamazaki Y., Largaespada D.A., Jenkins N.A., Copeland N.G.,
Hirokawa K., Nakamura T.;
"Inhibition of myeloid differentiation by Hoxa9, Hoxb8, and Meis
homeobox genes.";
Exp. Hematol. 29:856-863(2001).
[7]
FUNCTION, INTERACTION WITH PBX1, AND IDENTIFICATION IN A COMPLEX WITH
PDX1 AND PBX1.
PubMed=11279116; DOI=10.1074/jbc.M100678200;
Liu Y., MacDonald R.J., Swift G.H.;
"DNA binding and transcriptional activation by a PDX1.PBX1b.MEIS2b
trimer and cooperation with a pancreas-specific basic helix-loop-helix
complex.";
J. Biol. Chem. 276:17985-17993(2001).
[8]
INTERACTION WITH HOXA13.
PubMed=15617687; DOI=10.1016/j.ydbio.2004.10.004;
Williams T.M., Williams M.E., Innis J.W.;
"Range of HOX/TALE superclass associations and protein domain
requirements for HOXA13:MEIS interaction.";
Dev. Biol. 277:457-471(2005).
[9]
FUNCTION, AND DNA-BINDING.
PubMed=17178831; DOI=10.1128/MCB.01429-06;
Shim S., Kim Y., Shin J., Kim J., Park S.;
"Regulation of EphA8 gene expression by TALE homeobox transcription
factors during development of the mesencephalon.";
Mol. Cell. Biol. 27:1614-1630(2007).
[10]
SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
PubMed=21059917; DOI=10.1073/pnas.1007001107;
Liu J., Wang Y., Birnbaum M.J., Stoffers D.A.;
"Three-amino-acid-loop-extension homeodomain factor Meis3 regulates
cell survival via PDK1.";
Proc. Natl. Acad. Sci. U.S.A. 107:20494-20499(2010).
-!- FUNCTION: Involved in transcriptional regulation. Binds to HOX or
PBX proteins to form dimers, or to a DNA-bound dimer of PBX and
HOX proteins and thought to have a role in stabilization of the
homeoprotein-DNA complex. Isoform Meis2B is required for the
activity of a PDX1:PBX1b:MEIS2b complex in pancreatic acinar cells
involved in the transcriptional activation of the ELA1 enhancer;
the complex binds to the enhancer B element and cooperates with
the transcription factor 1 complex (PTF1) bound to the enhancer A
element; MEIS2 is not involved in complex DNA-binding. Probably in
complex with PBX1, is involved in transcriptional regulation by
KLF4. Isoforms Meis2B and Meis2D can bind to a EPHA8 promoter
sequence containing the DNA motif 5'-CGGTCA-3'; in cooperation
with a PBX protein (such as PBX2) is proposed to be involved in
the transcriptional activation of EPHA8 in the developing
midbrain. May be involved in regulation of myeloid
differentiation. Can bind to the DNA sequence 5'-TGACAG-3'in the
activator ACT sequence of the D(1A) dopamine receptor (DRD1)
promoter and activate DRD1 transcription.
{ECO:0000269|PubMed:11279116, ECO:0000269|PubMed:11438208,
ECO:0000269|PubMed:17178831}.
-!- SUBUNIT: Monomer and homodimer. Heterodimer with HOXB13 (By
similarity). Isoform Meis2A interacts with TLX1. Isoform Meis2B
interacts with HOXA13 and PBX1 isoform PBX1b. Isoform Meis2D
interacts with SP1, SP3 and KLF4. Isoform Meis2D interacts with
PBX1 isoform PBX1a; the interaction partially relieves MEIS2
autoinhibition. Isoform Meis2B is part of a PDX1:PBX1b:MEIS2b
complex; Meis2B is recruited by PBX1b and can be replaced by
isoform Meis2D in a small fraction of complexes. Can form trimeric
complexes including HOXB8 and PBX2 or PBX3.
{ECO:0000250|UniProtKB:O14770, ECO:0000269|PubMed:11279116,
ECO:0000269|PubMed:11438208, ECO:0000269|PubMed:15617687,
ECO:0000269|PubMed:9710595}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-
ProRule:PRU00108, ECO:0000269|PubMed:9710595}. Cytoplasm,
perinuclear region {ECO:0000269|PubMed:21059917}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=4;
Comment=Additional isoforms seem to exist.;
Name=Meis2C;
IsoId=P97367-1; Sequence=Displayed;
Name=Meis2A;
IsoId=P97367-2; Sequence=VSP_002248, VSP_002249;
Name=Meis2B; Synonyms=Mrg1A;
IsoId=P97367-3; Sequence=VSP_002247, VSP_002248, VSP_002249;
Name=Meis2D; Synonyms=Mrg1B;
IsoId=P97367-4; Sequence=VSP_002247;
-!- TISSUE SPECIFICITY: Displays spatially restricted expression
patterns in the developing nervous system, limbs, face, and in
various viscera. In adult, it is mainly expressed in the brain and
female genital tract, with a different distribution of the
alternative splice forms in these organs. Lower expression in lung
and only basal level in heart, liver, kidney, spleen, and testis.
Expressed in pancreatic islets (beta-cells only)
(PubMed:21059917). {ECO:0000269|PubMed:21059917}.
-!- DEVELOPMENTAL STAGE: Expressed at high levels in all stages of
embryonic development analyzed (7 days to 17 days). First detected
around E10.5 in the developing ventrolateral telencephalon. Is
found at moderate levels throughout the ventricle zone (VZ) of the
entire telencephalon with the exception of the ventro- and dorso-
medial regions. The highest expression is detected in the
subventricular zone (SVZ) of the lateral ganglionic eminence (LGE)
and developing striatum. By E16.5, also found in the cortical
plate. Also expressed at high levels in the caudal ganglionic
eminence (CGE) and amygdala. Expression in the telencephalon
remains unchanged at birth and into adulthood.
{ECO:0000269|PubMed:10842069}.
-!- INDUCTION: By retinoic acid.
-!- SIMILARITY: Belongs to the TALE/MEIS homeobox family.
{ECO:0000305}.
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EMBL; U57343; AAC52948.1; -; mRNA.
EMBL; AJ000504; CAA04138.1; -; mRNA.
EMBL; AJ000505; CAA04139.1; -; mRNA.
EMBL; AJ000506; CAA04140.1; -; mRNA.
EMBL; AJ000507; CAA04141.1; -; mRNA.
EMBL; U68383; AAB19193.1; -; mRNA.
EMBL; U68384; AAB19194.1; -; mRNA.
CCDS; CCDS16568.1; -. [P97367-4]
CCDS; CCDS50666.1; -. [P97367-3]
CCDS; CCDS50667.1; -. [P97367-1]
CCDS; CCDS50668.1; -. [P97367-2]
RefSeq; NP_001129544.1; NM_001136072.2. [P97367-3]
RefSeq; NP_001153039.1; NM_001159567.1. [P97367-2]
RefSeq; NP_001153040.1; NM_001159568.1. [P97367-1]
RefSeq; NP_034955.1; NM_010825.3. [P97367-4]
UniGene; Mm.247566; -.
UniGene; Mm.261124; -.
UniGene; Mm.471935; -.
ProteinModelPortal; P97367; -.
SMR; P97367; -.
BioGrid; 201487; 8.
CORUM; P97367; -.
IntAct; P97367; 1.
STRING; 10090.ENSMUSP00000028639; -.
iPTMnet; P97367; -.
PhosphoSitePlus; P97367; -.
MaxQB; P97367; -.
PaxDb; P97367; -.
PRIDE; P97367; -.
Ensembl; ENSMUST00000028639; ENSMUSP00000028639; ENSMUSG00000027210. [P97367-1]
Ensembl; ENSMUST00000102538; ENSMUSP00000099597; ENSMUSG00000027210. [P97367-4]
Ensembl; ENSMUST00000110907; ENSMUSP00000106532; ENSMUSG00000027210. [P97367-2]
Ensembl; ENSMUST00000110908; ENSMUSP00000106533; ENSMUSG00000027210. [P97367-3]
GeneID; 17536; -.
KEGG; mmu:17536; -.
UCSC; uc008lqw.2; mouse. [P97367-2]
UCSC; uc008lqy.2; mouse. [P97367-1]
CTD; 4212; -.
MGI; MGI:108564; Meis2.
eggNOG; KOG0773; Eukaryota.
eggNOG; ENOG410XPMQ; LUCA.
GeneTree; ENSGT00550000074260; -.
HOGENOM; HOG000253923; -.
HOVERGEN; HBG055193; -.
InParanoid; P97367; -.
KO; K16670; -.
OMA; PGEYVPQ; -.
OrthoDB; EOG091G0KDP; -.
PhylomeDB; P97367; -.
TreeFam; TF318093; -.
ChiTaRS; Meis2; mouse.
PRO; PR:P97367; -.
Proteomes; UP000000589; Chromosome 2.
Bgee; ENSMUSG00000027210; -.
CleanEx; MM_MEIS2; -.
ExpressionAtlas; P97367; baseline and differential.
Genevisible; P97367; MM.
GO; GO:0005634; C:nucleus; IDA:MGI.
GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
GO; GO:0003677; F:DNA binding; IDA:MGI.
GO; GO:0000978; F:RNA polymerase II proximal promoter sequence-specific DNA binding; ISO:MGI.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
GO; GO:0003712; F:transcription coregulator activity; IDA:UniProtKB.
GO; GO:0008134; F:transcription factor binding; IDA:UniProtKB.
GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding; ISO:MGI.
GO; GO:0001654; P:eye development; IGI:MGI.
GO; GO:0045638; P:negative regulation of myeloid cell differentiation; IDA:UniProtKB.
GO; GO:0031016; P:pancreas development; IEA:Ensembl.
GO; GO:0110024; P:positive regulation of cardiac muscle myoblast proliferation; ISO:MGI.
GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISO:MGI.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
GO; GO:0070848; P:response to growth factor; IEA:Ensembl.
GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl.
GO; GO:0008542; P:visual learning; IMP:MGI.
CDD; cd00086; homeodomain; 1.
InterPro; IPR009057; Homeobox-like_sf.
InterPro; IPR001356; Homeobox_dom.
InterPro; IPR008422; Homeobox_KN_domain.
InterPro; IPR032453; PKNOX/Meis_N.
Pfam; PF05920; Homeobox_KN; 1.
Pfam; PF16493; Meis_PKNOX_N; 1.
SMART; SM00389; HOX; 1.
SUPFAM; SSF46689; SSF46689; 1.
PROSITE; PS50071; HOMEOBOX_2; 1.
1: Evidence at protein level;
Activator; Alternative splicing; Complete proteome; Cytoplasm;
Developmental protein; DNA-binding; Homeobox; Nucleus;
Reference proteome; Transcription; Transcription regulation.
CHAIN 1 477 Homeobox protein Meis2.
/FTId=PRO_0000049109.
DNA_BIND 276 338 Homeobox; TALE-type.
{ECO:0000255|PROSITE-ProRule:PRU00108}.
REGION 71 191 Required for interaction with PBX1.
{ECO:0000269|PubMed:11279116}.
REGION 299 333 Interaction with DNA.
{ECO:0000250|UniProtKB:O14770}.
REGION 340 477 Transcriptional activation domain.
{ECO:0000250}.
COMPBIAS 195 244 Ser/Thr-rich.
COMPBIAS 246 273 Asp/Glu-rich (acidic).
COMPBIAS 266 273 Poly-Asp.
VAR_SEQ 346 352 Missing (in isoform Meis2B and isoform
Meis2D). {ECO:0000303|PubMed:9049632,
ECO:0000303|PubMed:9337137}.
/FTId=VSP_002247.
VAR_SEQ 384 401 LQSMPGDYVSQGGPMGMG -> PMSGMGMNMGMDGQWHYM
(in isoform Meis2A and isoform Meis2B).
{ECO:0000303|PubMed:8950991,
ECO:0000303|PubMed:9049632,
ECO:0000303|PubMed:9337137}.
/FTId=VSP_002248.
VAR_SEQ 402 477 Missing (in isoform Meis2A and isoform
Meis2B). {ECO:0000303|PubMed:8950991,
ECO:0000303|PubMed:9049632,
ECO:0000303|PubMed:9337137}.
/FTId=VSP_002249.
CONFLICT 2 2 A -> E (in Ref. 1; AAC52948).
{ECO:0000305}.
CONFLICT 316 316 T -> A (in Ref. 1; AAC52948).
{ECO:0000305}.
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


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