MPL myeloproliferative leukemia virus oncogene [Homo sapiens (human)] - Gene

Summary

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Official Symbol: MPLprovided by HGNC
Official Full Name: myeloproliferative leukemia virus oncogeneprovided by HGNC
Primary source: HGNC:7217
Locus tag: RP1-92O14.1
See related: HPRD:01161; MIM:159530
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: MPLV; TPOR; C-MPL; CD110; THCYT2
Summary: In 1990 an oncogene, v-mpl, was identified from the murine myeloproliferative leukemia virus that was capable of immortalizing bone marrow hematopoietic cells from different lineages. In 1992 the human homologue, named, c-mpl, was cloned. Sequence data revealed that c-mpl encoded a protein that was homologous with members of the hematopoietic receptor superfamily. Presence of anti-sense oligodeoxynucleotides of c-mpl inhibited megakaryocyte colony formation. The ligand for c-mpl, thrombopoietin, was cloned in 1994. Thrombopoietin was shown to be the major regulator of megakaryocytopoiesis and platelet formation. The protein encoded by the c-mpl gene, CD110, is a 635 amino acid transmembrane domain, with two extracellular cytokine receptor domains and two intracellular cytokine receptor box motifs . TPO-R deficient mice were severely thrombocytopenic, emphasizing the important role of CD110 and thrombopoietin in megakaryocyte and platelet formation. Upon binding of thrombopoietin CD110 is dimerized and the JAK family of non-receptor tyrosine kinases, as well as the STAT family, the MAPK family, the adaptor protein Shc and the receptors themselves become tyrosine phosphorylated. [provided by RefSeq, Jul 2008]

Genomic context

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Location :: 1p34

Sequence :: Chromosome: 1; NC_000001.10 (43803475..43820135)

See MPL in Epigenomics, MapViewer

Chromosome 1 - NC_000001.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

MPL Baltimore mutation is associated with thrombocytosis.
Title: MPL Baltimore mutation and thrombocytosis: case report and literature review.
Tryptophan at the transmembrane-cytosolic junction modulates thrombopoietin receptor dimerization and activation.
Title: Tryptophan at the transmembrane-cytosolic junction modulates thrombopoietin receptor dimerization and activation.
Up-regulation of wild-type MPL levels promotes leukemia development and maintenance through activation of the PI3K/AKT axis.
Title: Thrombopoietin/MPL participates in initiating and maintaining RUNX1-ETO acute myeloid leukemia via PI3K/AKT signaling.
High MPL expression is associated with leukemia.
Title: The thrombopoietin/MPL/Bcl-xL pathway is essential for survival and self-renewal in human preleukemia induced by AML1-ETO.
genetic association studies in Italian population: Data suggest that JAK2 GGCC haplotype is associated with JAK2 mutation (V617F) but is not associated with MPL mutation in exon 10 in myeloproliferative neoplasm subjects. [meta-analysis included]
Title: JAK2 GGCC haplotype in MPL mutated myeloproliferative neoplasms.
This study shows for the first time a link between homozygous MPL mutations and familial aplastic anemia. It also highlights the important role of MPL in trilineage hematopoiesis.
Title: Exome sequencing identifies MPL as a causative gene in familial aplastic anemia.
Ligand-inducible dimerization of intracellular Mpl in human myeloerythroid progenitors induces progenitor expansion and erythropoiesis.
Title: Novel pathways to erythropoiesis induced by dimerization of intracellular C-Mpl in human hematopoietic progenitors.
Selection against TpoR antiproliferative signaling occurs by TpoR down-modulation and that restoration of down-modulated TpoR levels could become a biomarker for the treatment of myeloproliferative neoplasms.
Title: Thrombopoietin receptor down-modulation by JAK2 V617F: restoration of receptor levels by inhibitors of pathologic JAK2 signaling and of proteasomes.
The expression of EPOR and TPOR on CD34+ CD59+ bone marrow cells are significantly higher than those on CD34+ CD59- cells of paroxysmal nocturnal hemoglobinuria patients.
Title: [EPOR and TPOR expressions on CD34+ CD59- and CD34+ CD59+ bone marrow cells from patients with paroxysmal nocturnal hemoglobinuria].
Thrombopoietin receptor agonist therapy in primary immune thrombocytopenia is associated with bone marrow hypercellularity and mild reticulin fibrosis but not other stromal abnormalities.
Title: Thrombopoietin receptor agonist therapy in primary immune thrombocytopenia is associated with bone marrow hypercellularity and mild reticulin fibrosis but not other stromal abnormalities.

Submit: New GeneRIF Correction See all (110)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Congenital amegakaryocytic thrombocytopenia

MIM: 604498

Genetic Testing Registry

Thrombocytosis, benign familial microcytic

MIM: 601977

Genetic Testing Registry

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
P40238	Q8WWM7	ATXN2L	HPRD	PubMed
P40238	Q9Y4H2	IRS2	HPRD	PubMed
P40238	O60674	JAK2	HPRD	PubMed
P40238	Q06124	PTPN11	HPRD	PubMed
P40238	P29353	SHC1	HPRD	PubMed
P40238	O15524	SOCS1	HPRD	PubMed
P40238	P40225	THPO	HPRD	PubMed
BioGRID:110492	BioGRID:121758	ANKRA2	BioGRID	PubMed	Protein-peptide
BioGRID:110492	BioGRID:116429	ATXN2L	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:110492	BioGRID:114203	SOCS1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110492	BioGRID:116168	YWHAQ	BioGRID	PubMed	Protein-peptide

Pathways from BioSystems

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Cytokine-cytokine receptor interaction, organism-specific biosystem (from KEGG)
Cytokine-cytokine receptor interaction, organism-specific biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
Cytokine-cytokine receptor interaction, conserved biosystem (from KEGG)
Cytokine-cytokine receptor interaction, conserved biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
Hemostasis, organism-specific biosystem (from REACTOME)
Hemostasis, organism-specific biosystemHemostasis is a physiological response that culminates in the arrest of bleeding from an injured vessel. Under normal conditions the vascular endothelium supports vasodilation, inhibits platelet adhe...
Jak-STAT signaling pathway, organism-specific biosystem (from KEGG)
Jak-STAT signaling pathway, organism-specific biosystemThe Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeost...
Jak-STAT signaling pathway, conserved biosystem (from KEGG)
Jak-STAT signaling pathway, conserved biosystemThe Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway is one of a handful of pleiotropic cascades used to transduce a multitude of signals for development and homeost...
Platelet Aggregation (Plug Formation), organism-specific biosystem (from REACTOME)
Platelet Aggregation (Plug Formation), organism-specific biosystemThe tethering of platelets to the site of vascular injury is the first step in the formation of a platelet thrombus. Firm adhesion of these tethered platelets, as well as the additional recruitment o...
Platelet activation, signaling and aggregation, organism-specific biosystem (from REACTOME)
Platelet activation, signaling and aggregation, organism-specific biosystemPlatelet activation begins with the initial binding of adhesive ligands and of the excitatory platelet agonists (released or generated at the sites of vascular trauma) to cognate receptors on the pla...

General gene information

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Markers

MARC_4067-4068:996679330:1 (e-PCR)
- UniSTS:269316

RH80231 (e-PCR)
- UniSTS:87088

PMC15907P1 (e-PCR)
- UniSTS:271440

PMC15907P2 (e-PCR)
- UniSTS:271441

PMC15907P3 (e-PCR)
- UniSTS:271442

PMC15907P4 (e-PCR)
- UniSTS:271443

PMC15907P5 (e-PCR)
- UniSTS:271444

D13S1553 (e-PCR)
- UniSTS:473482

SHGC-74727 (e-PCR)
- UniSTS:50836

Genotypes

See MPL SNP Geneview Report
See MPL SNP Genotype Report
See MPL SNP Variation Viewer Report

Homology

Homologs of the MPL gene: The MPL gene is conserved in Rhesus monkey, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
cytokine receptor activity	IEA Inferred from Electronic Annotation more info
transmembrane signaling receptor activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
blood coagulation	TAS Traceable Author Statement more info
cell proliferation	TAS Traceable Author Statement more info	PubMed
cell surface receptor signaling pathway	TAS Traceable Author Statement more info	PubMed
homeostasis of number of cells	IEA Inferred from Electronic Annotation more info
platelet activation	TAS Traceable Author Statement more info
regulation of chemokine production	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
integral to plasma membrane	TAS Traceable Author Statement more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info
plasma membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: thrombopoietin receptor

Names: thrombopoietin receptor; TPO-R; proto-oncogene c-Mpl; myeloproliferative leukemia protein

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007525.1 RefSeqGene

Range

5001..21661

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_005373.2 → NP_005364.1 thrombopoietin receptor precursor

Status: REVIEWED

Source sequence(s)

AL139289, M90102

Consensus CDS

CCDS483.1

UniProtKB/Swiss-Prot

P40238

Conserved Domains (2) summary

cd00063
Location:392 – 485
Blast Score: 121

FN3; Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all ...

pfam09067
Location:25 – 128
Blast Score: 354

EpoR_lig-bind; Erythropoietin receptor, ligand binding

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000001.10 Reference GRCh37.p10 Primary Assembly

Range

43803475..43820135

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000133.1 Alternate HuRef

Range

41923380..41939975

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018912.1 Alternate CHM1_1.0

Range

43882055..43898713

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01050957.1 (889..11907)	None
genomic	ABBA01050958.1	None
genomic	AL139289.6 (18734..35394)	None
genomic	AMYH01000557.1 (183535..200193)	None
genomic	CH471059.2	EAX07103.1
		EAX07104.1
		EAX07105.1
genomic	U68159.1	AAB08424.1
genomic	U68160.1	AAB08424.1
genomic	U68161.1	AAB08424.1
genomic	U68162.1	AAB08424.1
		AAB08425.1
mRNA	DQ234353.1	ABB29982.1
mRNA	M90102.1	AAA69971.1
mRNA	M90103.1	AAA69972.1
other-genetic	BC140298.1	AAI40299.1
other-genetic	BC153092.1	AAI53093.1