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FLASH GENE

Symbol

MPL

contributors: mct - updated : 10-12-2015

HGNC name	myeloproliferative leukemia virus oncogene
HGNC id	7217

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	16.66 kb     12 Exon(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

text	three alternatively spliced isoforms

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed variant P - - 3700 isoform P - 365 hematopoietic cells 1992 1608974 variant K - splicing 1800 isoform K - 579 hematopoietic cells 1992 1608974 also called MPL-K last exon made of exon 10 and part of intron 10 variant S - splicing - isoform S - - secreted - also called MPL-S lacking exons 9, 10 NM_005373 12 - 3645 NP_005364 - 635 - 2000 10880227 also called isoform DEL

EXPRESSION

Type

constitutive of

expressed in	(based on citations)
organ(s)

cell lineage	hematopoietic cells
cell lines
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two intracellular cytokine receptor box motifs containing cysteine residues receptor, transducing exclusive signals in embryonic and fetal hematopoietic cells; within the Mpl-EC domain 1 (Mpl-EC-D1), AAs 102–251 were strongly involved in ligand binding (TPO and NUDC- binding to the AA region from 206 to 251)
	the WSXWS motif, participating in the interaction between MPL and NUDC, and may play a role in stabilizing the conformation of the receptor during cytokine binding
	two fibronectin type 3 domains

mono polymer

dimer

HOMOLOGY

intraspecies

homolog to virus myeloproliferative leukemia oncogene

Homologene

FAMILY	type I cytokine receptor family
	type 1 subfamily

CATEGORY

protooncogene , receptor membrane

SUBCELLULAR LOCALIZATION	plasma membrane
text	type 1 membrane protein

basic FUNCTION	may be a regulatory molecule specific for TPOR dependent immune responses
	playing a specific role in early embryonic or fetal hematopoietic progenitors and stem cells
	positive-selection marker for the isolation of cancer stem cells in some case of T-caute lymphoblastic leukemia (Yamazaki 2009)

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

protein constituent of transmembrane

INTERACTION

DNA

RNA

small molecule

protein	. regulated by RUNX1, both positively and negatively by changing the binding partner according to cell types
	receptor of thrombopoietin
	interacts with NUDC
	following commitment to megakaryocyte differentiation, the H3K27 demethylase KDM6B up-regulation influences both ITGA2B and MPL expression
	CLASP2-mediated stabilization of microtubules is required for proper attachment, homing, and maintenance of hematopoietic stem cells, and this is necessary to sustain MPL transcription
	association between ATP5F1D and the Aa98-113 domain of MPL (the dissociation of ATP5F1D from MPL after TPO stimulation suggests that ATP5F1D may be a new component of TPO signaling
	RBM15 which associates with HDAC3 and the histone methyltransferase, SETD1B, binds to both MPL RNA and chromatin and regulates H4 acetylation and H3K4me3 marks
	DLGAP1 is a novel, potent factor in MPL signaling, affecting megakaryocytic growth and differentiation

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

CAMT

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in polycythemia vera and idiopathic myelofibrosis tumoral     --over   in B precursor leukemia cells

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS