MEIS1_HUMAN
ID MEIS1_HUMAN Reviewed; 390 AA.
AC O00470; A8MV50;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 177.
DE RecName: Full=Homeobox protein Meis1;
GN Name=MEIS1;
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 [MRNA] (ISOFORM 1).
RX PubMed=9226379; DOI=10.1006/geno.1997.4766;
RA Smith J.E. Jr., Bollekens J.A., Inghirami G., Takeshita K.;
RT "Cloning and mapping of the MEIS1 gene, the human homolog of a murine
RT leukemogenic gene.";
RL Genomics 43:99-103(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
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=Uterus;
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 FUNCTION, AND INTERACTION WITH PBX1 AND PBX2.
RX PubMed=12609849; DOI=10.1182/blood-2002-02-0380;
RA Okada Y., Nagai R., Sato T., Matsuura E., Minami T., Morita I., Doi T.;
RT "Homeodomain proteins MEIS1 and PBXs regulate the lineage-specific
RT transcription of the platelet factor 4 gene.";
RL Blood 101:4748-4756(2003).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [7]
RP INTERACTION WITH PBX1.
RX PubMed=19799567; DOI=10.1042/bj20090694;
RA Mojsin M., Stevanovic M.;
RT "PBX1 and MEIS1 up-regulate SOX3 gene expression by direct interaction with
RT a consensus binding site within the basal promoter region.";
RL Biochem. J. 425:107-116(2009).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [9] {ECO:0007744|PDB:4XRS}
RP X-RAY CRYSTALLOGRAPHY (3.50 ANGSTROMS) OF 279-336 IN COMPLEX WITH DLX3 AND
RP DNA, SUBUNIT, AND DNA-BINDING.
RX PubMed=26550823; DOI=10.1038/nature15518;
RA Jolma A., Yin Y., Nitta K.R., Dave K., Popov A., Taipale M., Enge M.,
RA Kivioja T., Morgunova E., Taipale J.;
RT "DNA-dependent formation of transcription factor pairs alters their binding
RT specificity.";
RL Nature 527:384-388(2015).
RN [10] {ECO:0007744|PDB:5EGO}
RP X-RAY CRYSTALLOGRAPHY (2.54 ANGSTROMS) OF 279-333 IN COMPLEX WITH HOXB13
RP AND METHYLATED DNA, SUBUNIT, AND DNA-BINDING.
RX PubMed=28473536; DOI=10.1126/science.aaj2239;
RA Yin Y., Morgunova E., Jolma A., Kaasinen E., Sahu B., Khund-Sayeed S.,
RA Das P.K., Kivioja T., Dave K., Zhong F., Nitta K.R., Taipale M., Popov A.,
RA Ginno P.A., Domcke S., Yan J., Schubeler D., Vinson C., Taipale J.;
RT "Impact of cytosine methylation on DNA binding specificities of human
RT transcription factors.";
RL Science 356:0-0(2017).
RN [11]
RP VARIANT HIS-272, AND POSSIBLE INVOLVEMENT IN SUSCEPTIBILITY TO RESTLESS
RP LEGS SYNDROME TYPE 7.
RX PubMed=19620614; DOI=10.1212/wnl.0b013e3181ae7c79;
RA Vilarino-Guell C., Chai H., Keeling B.H., Young J.E., Rajput A., Lynch T.,
RA Aasly J.O., Uitti R.J., Wszolek Z.K., Farrer M.J., Lin S.-C.;
RT "MEIS1 p.R272H in familial restless legs syndrome.";
RL Neurology 73:243-245(2009).
CC -!- FUNCTION: Acts as a transcriptional regulator of PAX6. Acts as a
CC transcriptional activator of PF4 in complex with PBX1 or PBX2. Required
CC for hematopoiesis, megakaryocyte lineage development and vascular
CC patterning. May function as a cofactor for HOXA7 and HOXA9 in the
CC induction of myeloid leukemias. {ECO:0000269|PubMed:12609849}.
CC -!- SUBUNIT: Interacts with the N-terminal region of PBX1 to form a
CC heterodimer which binds DNA including a cAMP-responsive sequence in
CC CYP17. Also forms heterodimers with PBX2. Forms heterotrimers with PBX1
CC or PBX2 and a number of HOX proteins including HOXA9, HOXD4 and HOXD9
CC where it acts as a non-DNA-binding partner. Also forms heterotrimers
CC with PBX1 and HOX proteins including HOXD9 and HOXD10 where PBX1 is the
CC non-DNA-binding partner. Heterodimer with DLX3 (PubMed:26550823).
CC Heterodimer with HOXB13 (PubMed:28473536).
CC {ECO:0000269|PubMed:12609849, ECO:0000269|PubMed:19799567,
CC ECO:0000269|PubMed:26550823, ECO:0000269|PubMed:28473536}.
CC -!- INTERACTION:
CC O00470; P16220: CREB1; NbExp=9; IntAct=EBI-1210694, EBI-711855;
CC O00470; P14921: ETS1; NbExp=2; IntAct=EBI-1210694, EBI-913209;
CC O00470; P40424: PBX1; NbExp=3; IntAct=EBI-1210694, EBI-301611;
CC O00470; P31314: TLX1; NbExp=4; IntAct=EBI-1210694, EBI-2820655;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O00470-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O00470-2; Sequence=VSP_034957, VSP_034958;
CC -!- TISSUE SPECIFICITY: Expressed at low level in normal
CC immunohepatopoietic tissues, including the fetal liver. Expressed in a
CC subset of myeloid leukemia cell lines, with the highest expression seen
CC in those with a megakaryocytic-erythroid phenotype. Also expressed at
CC high levels in the cerebellum.
CC -!- DISEASE: Restless legs syndrome 7 (RLS7) [MIM:612853]: A neurologic
CC sleep/wake disorder characterized by uncomfortable and unpleasant
CC sensations in the legs that appear at rest, usually at night, inducing
CC an irresistible desire to move the legs. The disorder results in
CC nocturnal insomnia and chronic sleep deprivation. The majority of
CC patients also have periodic limb movements in sleep, which are
CC characterized by involuntary, highly stereotypical, regularly occurring
CC limb movements that occur during sleep. {ECO:0000305|PubMed:19620614}.
CC Note=Disease susceptibility may be associated with variants affecting
CC the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the TALE/MEIS homeobox family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MEIS1ID41331ch2p14.html";
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DR EMBL; U85707; AAC51642.1; -; mRNA.
DR EMBL; CR612956; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC007392; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC092669; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC093641; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC043503; AAH43503.1; -; mRNA.
DR CCDS; CCDS46309.1; -. [O00470-1]
DR RefSeq; NP_002389.1; NM_002398.2. [O00470-1]
DR PDB; 4XRS; X-ray; 3.50 A; A/B=279-336.
DR PDB; 5EGO; X-ray; 2.54 A; A=279-333.
DR PDBsum; 4XRS; -.
DR PDBsum; 5EGO; -.
DR AlphaFoldDB; O00470; -.
DR SMR; O00470; -.
DR BioGRID; 110375; 30.
DR IntAct; O00470; 25.
DR MINT; O00470; -.
DR STRING; 9606.ENSP00000272369; -.
DR GlyGen; O00470; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O00470; -.
DR PhosphoSitePlus; O00470; -.
DR BioMuta; MEIS1; -.
DR EPD; O00470; -.
DR jPOST; O00470; -.
DR MassIVE; O00470; -.
DR MaxQB; O00470; -.
DR PaxDb; O00470; -.
DR PeptideAtlas; O00470; -.
DR PRIDE; O00470; -.
DR ProteomicsDB; 47917; -. [O00470-1]
DR ProteomicsDB; 47918; -. [O00470-2]
DR Antibodypedia; 3157; 332 antibodies from 41 providers.
DR DNASU; 4211; -.
DR Ensembl; ENST00000272369.14; ENSP00000272369.8; ENSG00000143995.20. [O00470-1]
DR Ensembl; ENST00000398506.6; ENSP00000381518.2; ENSG00000143995.20. [O00470-2]
DR GeneID; 4211; -.
DR KEGG; hsa:4211; -.
DR MANE-Select; ENST00000272369.14; ENSP00000272369.8; NM_002398.3; NP_002389.1.
DR UCSC; uc002sdu.4; human. [O00470-1]
DR CTD; 4211; -.
DR DisGeNET; 4211; -.
DR GeneCards; MEIS1; -.
DR HGNC; HGNC:7000; MEIS1.
DR HPA; ENSG00000143995; Low tissue specificity.
DR MIM; 601739; gene.
DR MIM; 612853; phenotype.
DR neXtProt; NX_O00470; -.
DR OpenTargets; ENSG00000143995; -.
DR PharmGKB; PA30740; -.
DR VEuPathDB; HostDB:ENSG00000143995; -.
DR eggNOG; KOG0773; Eukaryota.
DR GeneTree; ENSGT00940000156327; -.
DR InParanoid; O00470; -.
DR OMA; PENNRAM; -.
DR OrthoDB; 1126341at2759; -.
DR PhylomeDB; O00470; -.
DR TreeFam; TF318093; -.
DR PathwayCommons; O00470; -.
DR Reactome; R-HSA-5617472; Activation of anterior HOX genes in hindbrain development during early embryogenesis.
DR SignaLink; O00470; -.
DR SIGNOR; O00470; -.
DR BioGRID-ORCS; 4211; 26 hits in 1105 CRISPR screens.
DR ChiTaRS; MEIS1; human.
DR GeneWiki; MEIS1; -.
DR GenomeRNAi; 4211; -.
DR Pharos; O00470; Tbio.
DR PRO; PR:O00470; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; O00470; protein.
DR Bgee; ENSG00000143995; Expressed in right uterine tube and 180 other tissues.
DR ExpressionAtlas; O00470; baseline and differential.
DR Genevisible; O00470; HS.
DR GO; GO:0000785; C:chromatin; ISA:NTNU_SB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005667; C:transcription regulator complex; IEA:Ensembl.
DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IBA:GO_Central.
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:0001525; P:angiogenesis; IBA:GO_Central.
DR GO; GO:0009887; P:animal organ morphogenesis; IBA:GO_Central.
DR GO; GO:0007420; P:brain development; IBA:GO_Central.
DR GO; GO:0060216; P:definitive hemopoiesis; IEA:Ensembl.
DR GO; GO:0009880; P:embryonic pattern specification; IBA:GO_Central.
DR GO; GO:0001654; P:eye development; IBA:GO_Central.
DR GO; GO:0030097; P:hemopoiesis; IBA:GO_Central.
DR GO; GO:0002089; P:lens morphogenesis in camera-type eye; IEA:Ensembl.
DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR GO; GO:0035855; P:megakaryocyte development; IEA:Ensembl.
DR GO; GO:0045638; P:negative regulation of myeloid cell differentiation; ISS:UniProtKB.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
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 3D-structure; Activator; Alternative splicing; Developmental protein;
KW DNA-binding; Homeobox; Nucleus; Reference proteome; Transcription.
FT CHAIN 1..390
FT /note="Homeobox protein Meis1"
FT /id="PRO_0000049105"
FT DOMAIN 108..192
FT /note="MEIS N-terminal"
FT /evidence="ECO:0000255"
FT DNA_BIND 272..334
FT /note="Homeobox; TALE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 190..279
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 299..329
FT /note="Interaction with DNA"
FT /evidence="ECO:0000305|PubMed:26550823,
FT ECO:0000305|PubMed:28473536"
FT REGION 335..390
FT /note="Required for transcriptional activation"
FT /evidence="ECO:0000250"
FT COMPBIAS 223..260
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..4
FT /note="MAQR -> MQ (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_034957"
FT VAR_SEQ 373..390
FT /note="PMSGMGMNMGMEGQWHYM -> LQSMPGEYVARGGPMGVSMGQPSYTQPQMP
FT PHPAQLRHGPPMHTYIPGHPHHPTVMMHGGPPHPGMPMSASSPTVLNTGDPTMSGQVMD
FT IHAQ (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_034958"
FT VARIANT 272
FT /note="R -> H (found in a patient with susceptibility to
FT restless legs syndrome; dbSNP:rs61752693)"
FT /evidence="ECO:0000269|PubMed:19620614"
FT /id="VAR_063166"
FT HELIX 281..293
FT /evidence="ECO:0007829|PDB:5EGO"
FT TURN 294..296
FT /evidence="ECO:0007829|PDB:5EGO"
FT HELIX 302..312
FT /evidence="ECO:0007829|PDB:5EGO"
FT HELIX 316..329
FT /evidence="ECO:0007829|PDB:5EGO"
FT TURN 330..333
FT /evidence="ECO:0007829|PDB:5EGO"
SQ SEQUENCE 390 AA; 43016 MW; 3B6A0ACCF0C39121 CRC64;
MAQRYDDLPH YGGMDGVGIP STMYGDPHAA RSMQPVHHLN HGPPLHSHQY PHTAHTNAMA
PSMGSSVNDA LKRDKDAIYG HPLFPLLALI FEKCELATCT PREPGVAGGD VCSSESFNED
IAVFAKQIRA EKPLFSSNPE LDNLMIQAIQ VLRFHLLELE KVHELCDNFC HRYISCLKGK
MPIDLVIDDR EGGSKSDSED ITRSANLTDQ PSWNRDHDDT ASTRSGGTPG PSSGGHTSHS
GDNSSEQGDG LDNSVASPST GDDDDPDKDK KRHKKRGIFP KVATNIMRAW LFQHLTHPYP
SEEQKKQLAQ DTGLTILQVN NWFINARRRI VQPMIDQSNR AVSQGTPYNP DGQPMGGFVM
DGQQHMGIRA PGPMSGMGMN MGMEGQWHYM
