Mpl myeloproliferative leukemia virus oncogene [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Mplprovided by MGI
Official Full Name: myeloproliferative leukemia virus oncogeneprovided by MGI
Primary source: MGI:MGI:97076
See related: Ensembl:ENSMUSG00000006389 AllianceGenome:MGI:97076
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: CD110; TPO-R; c-mpl; hlb219
Summary: Predicted to enable thrombopoietin receptor activity. Involved in thrombopoietin-mediated signaling pathway. Acts upstream of or within several processes, including hemopoiesis; regulation of gene expression; and regulation of stem cell division. Predicted to be located in several cellular components, including Golgi apparatus; neuronal cell body; and nuclear membrane. Predicted to be active in external side of plasma membrane. Is expressed in several structures, including brain; hemolymphoid system; mesenchyme derived from splanchnopleure; spinal cord; and vestibulo-cochlear ganglion. Used to study congenital amegakaryocytic thrombocytopenia. Human ortholog(s) of this gene implicated in essential thrombocythemia; myelofibrosis; thrombocytopenia; and thrombocytosis. Orthologous to human MPL (MPL proto-oncogene, thrombopoietin receptor). [provided by Alliance of Genome Resources, Dec 2024]
Expression: Biased expression in spleen adult (RPKM 4.4), liver E14.5 (RPKM 3.8) and 7 other tissues See more
Orthologs: human all
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Genomic context

Location:: 4 D2.1; 4 54.61 cM

Exon count:: 12

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	4	NC_000070.7 (118299609..118314771, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	4	NC_000070.6 (118442412..118457688, complement)

Chromosome 4 - NC_000070.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Differential in vivo roles of Mpl cytoplasmic tyrosine residues in murine hematopoiesis and myeloproliferative disease.
Title: Differential in vivo roles of Mpl cytoplasmic tyrosine residues in murine hematopoiesis and myeloproliferative disease.
Spatiotemporal expression profiles of c-Mpl mRNA in the tooth germ: Comparative expression dynamics of vascularization-related genes.
Title: Spatiotemporal expression profiles of c-Mpl mRNA in the tooth germ: Comparative expression dynamics of vascularization-related genes.
Cryo-EM structure of the extracellular domain of murine Thrombopoietin Receptor in complex with Thrombopoietin.
Title: Cryo-EM structure of the extracellular domain of murine Thrombopoietin Receptor in complex with Thrombopoietin.
Structure of the thrombopoietin-MPL receptor complex is a blueprint for biasing hematopoiesis.
Title: Structure of the thrombopoietin-MPL receptor complex is a blueprint for biasing hematopoiesis.
C-Cbl regulates c-MPL receptor trafficking and its internalization.
Title: C-Cbl regulates c-MPL receptor trafficking and its internalization.
Signaling properties of murine MPL and MPL mutants after stimulation with thrombopoietin and romiplostim.
Title: Signaling properties of murine MPL and MPL mutants after stimulation with thrombopoietin and romiplostim.
Authors demonstrate that thrombopoietin and its receptor MPL are critical for the human JAK2V617F-bearing MK-induced myeloproliferation in mice, both by directly affecting the quantity and quality of MKs and by altering the MK-endothelial interaction and vascular niche function.
Title: JAK2V617F Megakaryocytes Promote Hematopoietic Stem/Progenitor Cell Expansion in Mice Through Thrombopoietin/MPL Signaling.
These results indicate that c-MPL is a candidate LSC surface marker that may serve as a therapeutic target for the elimination of LSCs.
Title: c-MPL Is a Candidate Surface Marker and Confers Self-Renewal, Quiescence, Chemotherapy Resistance, and Leukemia Initiation Potential in Leukemia Stem Cells.
these findings indicate that c-MPL deficiency is associated with abnormal maturation of neonatal megakaryocytes and developmental stage-specific defects in platelet function
Title: Developmental Stage-Specific Manifestations of Absent TPO/c-MPL Signalling in Newborn Mice.
these results demonstrate that MPL P106L is a receptor with an incomplete defect in trafficking.
Title: An incomplete trafficking defect to the cell-surface leads to paradoxical thrombocytosis for human and murine MPL P106L.

Submit: New GeneRIF Correction See all GeneRIFs (44)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Chemically induced (ENU) (1)
Endonuclease-mediated (5)
Targeted (5) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

Mpl (e-PCR), detects polymorphism
- UniSTS:516608

Mpl (e-PCR), detects polymorphism
- UniSTS:143904

Mpl (e-PCR), detects polymorphism
- UniSTS:259516

Mpl (e-PCR), detects polymorphism
- UniSTS:256445

Mpl (e-PCR), detects polymorphism
- UniSTS:265419

Mpl (e-PCR), detects polymorphism
- UniSTS:265420

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables thrombopoietin receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables thrombopoietin receptor activity	ISO Inferred from Sequence Orthology more info
enables thrombopoietin receptor activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in basophil homeostasis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within definitive hemopoiesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in eosinophil homeostasis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within homeostasis of number of cells	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in monocyte homeostasis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neutrophil homeostasis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within platelet formation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of lymphocyte proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of platelet formation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within regulation of chemokine production	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of stem cell division	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of stem cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in thrombopoietin-mediated signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in thrombopoietin-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi apparatus	ISO Inferred from Sequence Orthology more info
located_in Golgi apparatus	ISS Inferred from Sequence or Structural Similarity more info
located_in cell surface	ISO Inferred from Sequence Orthology more info
located_in cell surface	ISS Inferred from Sequence or Structural Similarity more info
is_active_in external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in neuronal cell body	ISO Inferred from Sequence Orthology more info
located_in nuclear membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: thrombopoietin receptor

Names: myeloproliferative leukemia protein; proto-oncogene c-Mpl

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.

mRNA and Protein(s)

NM_001122949.3 → NP_001116421.1 thrombopoietin receptor isoform 1 precursor

See identical proteins and their annotated locations for NP_001116421.1

Status: VALIDATED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1, also known as c-mpl-I).

Source sequence(s)

AL627212

Consensus CDS

CCDS51284.1

UniProtKB/TrEMBL

A2A9D4, Q3ZB68

Related

ENSMUSP00000006556.5, ENSMUST00000006556.11

Conserved Domains (2) summary

cd00063
Location:395 → 484

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

EpoR_lig-bind; Erythropoietin receptor, ligand binding
NM_001285496.2 → NP_001272425.1 thrombopoietin receptor isoform 3 precursor

Status: VALIDATED

Description

Transcript Variant: This variant (3) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1, resulting in an isoform (3, also known as c-mpl-II) that is shorter than isoform 1.

Source sequence(s)

AL627212

UniProtKB/TrEMBL

Q925F5

Related

ENSMUSP00000101983.2, ENSMUST00000106375.2

Conserved Domains (2) summary

cd00063
Location:335 → 424

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

EpoR_lig-bind; Erythropoietin receptor, ligand binding
NM_001285497.2 → NP_001272426.1 thrombopoietin receptor isoform 4 precursor

Status: VALIDATED

Description

Transcript Variant: This variant (4) lacks two alternate exons, which results in a frameshift in the 3' coding region, compared to variant 1. The encoded isoform (4) has a distinct C-terminus and is shorter than isoform 1.

Source sequence(s)

AL627212

UniProtKB/TrEMBL

E9Q7U5

Related

ENSMUSP00000130167.3, ENSMUST00000168404.9

Conserved Domains (1) summary

pfam09067
Location:25 → 128

EpoR_lig-bind; Erythropoietin receptor, ligand binding
NM_010823.4 → NP_034953.2 thrombopoietin receptor isoform 2 precursor

See identical proteins and their annotated locations for NP_034953.2

Status: VALIDATED

Description

Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region, compared to variant 1, resulting in an isoform (2) that is shorter than isoform 1.

Source sequence(s)

AL627212

Consensus CDS

CCDS18552.1

UniProtKB/Swiss-Prot

A6H8H6, Q08351, Q8BRX0

UniProtKB/TrEMBL

Q3ZB69

Related

ENSMUSP00000099732.4, ENSMUST00000102671.10

Conserved Domains (2) summary

cd00063
Location:387 → 476

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

EpoR_lig-bind; Erythropoietin receptor, ligand binding

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000070.7 Reference GRCm39 C57BL/6J

Range

118299609..118314771 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011240468.3 → XP_011238770.1 thrombopoietin receptor isoform X1

Conserved Domains (1) summary

cd00063
Location:114 → 203

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 ...