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FLASH GENE

Symbol

MEIS1

contributors: mct - updated : 14-10-2015

HGNC name	Meis homeobox 1
HGNC id	7000

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	137.36 kb     13 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	Binding site
text structure	. promoter sequence revealed multiple GFI1B consensus binding motifs

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002398 13 - 3198 NP_002389 - 390 - 2009 19126776 variant 2 13 - - isoform 2 - 377 - 2009 19126776 exon 1b variant 3 11 - 2373 isoform 3 - 246 - 2009 19126776 lacks exons 1 and 2 variant 4 12 - - isoform 4 - 252 - 2009 19126776 skips exon 8 and prematurely truncates the protein to 252 amino acid by using a STOP codon located in exon 9 variant 5 14 - 4613 isoform 5 - 378 - 2009 19126776 includes the entire unspliced sequence from intron 11, and prematurely truncates the protein to 378 amino acid variant 6 13 - - isoform 6 - - - 2009 19126776 includes an additional 81 bp from the 5' end of intron 10, and is predicted to add a 27 amino acid in-frame segment near the C-terminus of the protein, with a putative PKG phosphorylation site

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous brain hindbrain cerebellum   highly Reproductive female system ovary     highly   female system uterus     highly Respiratory respiratory tract larynx     highly   respiratory tract trachea     highly

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune B cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, fetal

Text	mainly during embryonal development, liver

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	helix-turn-helix, DNA binding domain
	TALE (three AA loop extension between helices) subfamily

HOMOLOGY

interspecies

ortholog to murine Meis1 (myeloid ecotropic viral integration site 1)

Homologene

FAMILY	TALE/MEIS homeobox family
	three-amino-acid loop extension (TALE) class homeodomain proteins family

CATEGORY

DNA associated , transcription factor , protooncogene

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus
text	KAT6A localizes to the MEIS1 locus in pre-B-cells and maintains MEIS1 expression

basic FUNCTION	normal embryonic neuroblast development
	causative role in neuroblastoma pathogenesis
	playing an important role in megakaryocytic gene expression
	critical downstream effector within an essential homeoprotein network that serving a rate-limiting regulatory role in MLL leukemogenesis
	maintain retinal progenitor cells in a rapidly proliferating state and control the expression of some ocular-determination genes and components of the cell cycle machinery
	Hox cofactor known for its role in development and is strongly linked to normal and leukemic hematopoiesis
	up-regulating with PBX1 the expression of SOX3 gene (Mojsin 2010)
	potentially involved in regulation of genes acting in DNA replication and in cell-cycle entry (CDK2, CDK6, CDKN3, CDC7, cyclin D3, and others)
	works as a transcription factor for mitochondrial genes in pancreatic cancer cells
	regulated the expression of mitochondrial genes by direct binding to the H-strand mitochondrial promoter region
	involvement of PBX1, MEIS1, PKNOX1 during the early development in mammals

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

heterodimeric or heterotrimeric complex with PBX and HOX proteins to augment the affinity and specificity of DNA binding by HOX proteins

INTERACTION

DNA	binding cooperatively with the heterodimer E2A/myogenic transcription factors

RNA

small molecule

protein	HOXA7 and HOXA9, coactivating in acute myeloid leukemia
	PBX1, PBX2, PBX3 DNA-binding partner
	collaboration between IRF8 deficiency and MEIS1/MEIS3 in the acceleration of chronic myeloid leukemia-like disease
	co-operation between TLX1 and MEIS1, MEIS2 proteins may have a significant role in T-cell leukemogenesis
	binding of MEIS1 to the mitochondrial promoter region
	interaction with PKNOX1 (C-terminal domain of MEIS1 confers to PKNOX1 an ectopic transactivating function that promotes leukemogenesis by regulating expression of genes involved in chromatin accessibility and cell cycle progression)
	is a direct and prominent target of GFI1B (direct yet differential regulation of MEIS1 transcription by GFI1B in distinct hematopoietic lineages)
	MEIS1 regulates FOXN4 expression during retinal progenitor cell differentiation
	PKNOX1 posttranslationally controls the level of MEIS1, decreasing its stability by sequestering PBX1
	HOXA2 operates as a tissue-specific cofactor, enhancing MEIS1 binding to specific sites that provide the IIBA with its anatomical identity
	crucial role for RING1-dependent repression of MEIS2 and likely also MEIS1 for distal specification

cell & other

REGULATION

Other	positively regulated by HOXA9 through CREB1 targeting
	reulated by ETS transcription factor ELF1 which is an important positive regulator of MEIS1 expression

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral       gain of function coactivated by HOXA9 in myeloid leukemias, in infant acute lymphoblastic leukemia tumoral       gain of function in neuroblastoma cell lines and with HOXB3 in acute myeloid leukemia tumoral   amplification     or overexpressed in neuroblastoma, erythroleukemia or medulloblastoma tumoral     --over   represses myeloid-specific gene transcription, thereby contributing to differentiation block in leukemogenesis tumoral     --over   extensively expressed in ovarian carcinomas and may play a role in ovarian carcinogenesis constitutional       loss of function results in cardiac anomalies that resemble those caused by PBX mutations tumoral     --over   of HOXA9 and HOXA10 and their essential cofactor MEIS1 in cells with the t(4;11) chromosome translocation and MLL-AF4 in acute leukemia

Susceptibility

to restless legs (RLS)

Variant & Polymorphism other	Decreased expression possibly through intronic cis-regulatory element(s), predisposes to RLS

Candidate gene	combinatorial expression of Meis family proteins might be a candidate mechanism for the differential regulation of eye growth among vertebrate species
Marker
Therapy target

ANIMAL & CELL MODELS