Thpo thrombopoietin [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Thpoprovided by MGI
Official Full Name: thrombopoietinprovided by MGI
Primary source: MGI:MGI:101875
See related: Ensembl:ENSMUSG00000022847 AllianceGenome:MGI:101875
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Ml; Tpo; Mgdf; Mpllg
Summary: This gene encodes a humoral growth factor necessary for megakaryocyte proliferation and maturation, as well as for thrombopoiesis. The encoded protein is a ligand for the product of the myeloproliferative leukemia virus oncogene. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]
Expression: Ubiquitous expression in liver adult (RPKM 4.4), cortex adult (RPKM 4.1) and 24 other tissues See more
Orthologs: human all
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Genomic context

Location:: 16 B1; 16 12.51 cM

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	16	NC_000082.7 (20543204..20553261, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	16	NC_000082.6 (20724454..20734511, complement)

Chromosome 16 - NC_000082.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

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?

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.
Megakaryocyte/platelet-derived TGF-beta1 inhibits megakaryopoiesis in bone marrow by regulating thrombopoietin production in liver.
Title: Megakaryocyte/platelet-derived TGF-β1 inhibits megakaryopoiesis in bone marrow by regulating thrombopoietin production in liver.
Hematopoietic stem cells temporally transition to thrombopoietin dependence in the fetal liver.
Title: Hematopoietic stem cells temporally transition to thrombopoietin dependence in the fetal liver.
Prolonged maintenance of hematopoietic stem cells that escape from thrombopoietin deprivation.
Title: Prolonged maintenance of hematopoietic stem cells that escape from thrombopoietin deprivation.
Erythropoietin is a major regulator of thrombopoiesis in thrombopoietin-dependent and -independent contexts.
Title: Erythropoietin is a major regulator of thrombopoiesis in thrombopoietin-dependent and -independent contexts.
Thpo-regulated mitochondrial activity associated with mitochondrial translocation of STAT3 phosphorylated at serine 727.
Title: Thrombopoietin Metabolically Primes Hematopoietic Stem Cells to Megakaryocyte-Lineage Differentiation.
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.
Study of hepatocarcinogenesis induced by diethylnitrosamine in B6C3F1 mice, the BrafV637E mutation, corresponding to the human BRAFV600E mutation, suggested that the TPO-mediated macroenvironmental changes involving the liver and bone marrow may promote proliferation of the BRAFV600E-mutated hepatocytes, but cause hematological, renal, and pulmonary disorders that lead to death.
Title: Overproduction of thrombopoietin by BRAFV600E-mutated mouse hepatocytes and contribution of thrombopoietin to hepatocarcinogenesis.
The number of lung metastases was significantly lower in Tpo(-/-) mice compared to Tpo(+/+) mice. The same was true for the bone-tropic 4T1.2 derivative.
Title: Platelet deficiency in Tpo(-/-) mice can both promote and suppress the metastasis of experimental breast tumors in an organ-specific manner.

Submit: New GeneRIF Correction See all GeneRIFs (43)

Variation

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Alleles

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

Targeted (5) 1 citation
Endonuclease-mediated (2) 1 citation

General gene information

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Markers

L34169 (e-PCR)
- UniSTS:160548

Chrd (e-PCR), detects polymorphism
- UniSTS:234037

Thpo (e-PCR), detects polymorphism
- UniSTS:516664

Thpo (e-PCR), detects polymorphism
- UniSTS:265431

Thpo (e-PCR), detects polymorphism
- UniSTS:265432

L34169 (e-PCR)
- UniSTS:124901

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables cytokine activity	IEA Inferred from Electronic Annotation more info
enables hormone activity	IEA Inferred from Electronic Annotation more info
enables signaling receptor binding	IBA Inferred from Biological aspect of Ancestor more info

Process	Evidence Code	Pubs
involved_in cell population proliferation	IEA Inferred from Electronic Annotation more info
involved_in cell surface receptor signaling pathway via STAT	ISO Inferred from Sequence Orthology more info
involved_in megakaryocyte development	ISO Inferred from Sequence Orthology more info
involved_in megakaryocyte differentiation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within myeloid cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of ERK1 and ERK2 cascade	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of ERK1 and ERK2 cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of MAPK cascade	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cell population proliferation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of hematopoietic stem cell proliferation	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within positive regulation of hematopoietic stem cell proliferation	ISO Inferred from Sequence Orthology more info	PubMed
involved_in positive regulation of megakaryocyte differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of protein phosphorylation	IDA Inferred from Direct Assay 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
involved_in thrombopoietin-mediated signaling pathway	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
is_active_in extracellular region	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: thrombopoietin

Names: C-mpl ligand; megakaryocyte colony-stimulating factor; megakaryocyte growth and development factor; myeloproliferative leukemia virus oncogene ligand

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_001173505.1 → NP_001166976.1 thrombopoietin isoform 1 precursor

See identical proteins and their annotated locations for NP_001166976.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) encodes the longest isoform (1, also known as Tpo1). Both variants 1 and 2 encode the same isoform 1.

Source sequence(s)

AI314551, AK047512, CT010490

Consensus CDS

CCDS37292.1

UniProtKB/Swiss-Prot

P40226

UniProtKB/TrEMBL

A0A338P6S5, Q543R9

Related

ENSMUSP00000075756.6, ENSMUST00000076422.13

Conserved Domains (1) summary

pfam00758
Location:25 → 175

EPO_TPO; Erythropoietin/thrombopoietin
NM_001289894.1 → NP_001276823.1 thrombopoietin isoform 2 precursor

See identical proteins and their annotated locations for NP_001276823.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) has an alternate splice site in the 3' coding region, compared to variant 2. The resulting isoform (2, also known as Tpo2) lacks an internal 4aa peptide, compared to isoform 1.

Source sequence(s)

CT010490

UniProtKB/TrEMBL

A0A338P6S5

Conserved Domains (1) summary

pfam00758
Location:25 → 171

EPO_TPO; Erythropoietin/thrombopoietin
NM_001289896.1 → NP_001276825.1 thrombopoietin isoform 3 precursor

See identical proteins and their annotated locations for NP_001276825.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) has an alternate splice site in the 3' coding region, which results in a reading frameshift, compared to variant 2. The resulting isoform (3, also known as Tpo4) has a shorter and distinct C-terminus, compared to isoform 1.

Source sequence(s)

CT010490

UniProtKB/TrEMBL

A0A338P6C8

Related

ENSMUSP00000155914.2, ENSMUST00000231826.2

Conserved Domains (1) summary

pfam00758
Location:25 → 119

EPO_TPO; Erythropoietin/thrombopoietin
NM_009379.3 → NP_033405.1 thrombopoietin isoform 1 precursor

See identical proteins and their annotated locations for NP_033405.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) differs in the 5' UTR, compared to variant 2. Both variants 1 and 2 encode the same isoform 1.

Source sequence(s)

AK047512

Consensus CDS

CCDS37292.1

UniProtKB/Swiss-Prot

P40226

UniProtKB/TrEMBL

A0A338P6S5, Q543R9

Related

ENSMUSP00000111097.3, ENSMUST00000115437.4

Conserved Domains (1) summary

pfam00758
Location:25 → 175

EPO_TPO; Erythropoietin/thrombopoietin

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_000082.7 Reference GRCm39 C57BL/6J

Range

20543204..20553261 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017316926.3 → XP_017172415.1 thrombopoietin isoform X2

Conserved Domains (2) summary

pfam05109
Location:409 → 528

Herpes_BLLF1; Herpes virus major outer envelope glycoprotein (BLLF1)

pfam00758
Location:208 → 354

EPO_TPO; Erythropoietin/thrombopoietin
XM_017316929.3 → XP_017172418.1 thrombopoietin isoform X1

Conserved Domains (2) summary

pfam05109
Location:413 → 532

Herpes_BLLF1; Herpes virus major outer envelope glycoprotein (BLLF1)

pfam00758
Location:208 → 358

EPO_TPO; Erythropoietin/thrombopoietin
XM_017316927.2 → XP_017172416.1 thrombopoietin isoform X3

Conserved Domains (2) summary

pfam05109
Location:396 → 515

Herpes_BLLF1; Herpes virus major outer envelope glycoprotein (BLLF1)

pfam00758
Location:191 → 341

EPO_TPO; Erythropoietin/thrombopoietin
XM_017316928.1 → XP_017172417.1 thrombopoietin isoform X4

Conserved Domains (2) summary

pfam05109
Location:392 → 511

Herpes_BLLF1; Herpes virus major outer envelope glycoprotein (BLLF1)

pfam00758
Location:191 → 337

EPO_TPO; Erythropoietin/thrombopoietin
XM_006521987.3 → XP_006522050.1 thrombopoietin isoform X7

UniProtKB/TrEMBL

A0A338P6S5

Conserved Domains (2) summary

pfam05109
Location:300 → 419

Herpes_BLLF1; Herpes virus major outer envelope glycoprotein (BLLF1)

pfam00758
Location:95 → 245

EPO_TPO; Erythropoietin/thrombopoietin
XM_017316930.3 → XP_017172419.1 thrombopoietin isoform X5

Conserved Domains (1) summary

pfam00758
Location:208 → 302

EPO_TPO; Erythropoietin/thrombopoietin
XM_017316932.3 → XP_017172421.1 thrombopoietin isoform X8

Conserved Domains (1) summary

pfam00758
Location:208 → 302

EPO_TPO; Erythropoietin/thrombopoietin
XM_017316931.1 → XP_017172420.1 thrombopoietin isoform X6

Conserved Domains (1) summary

pfam00758
Location:191 → 285

EPO_TPO; Erythropoietin/thrombopoietin
XM_017316933.2 → XP_017172422.1 thrombopoietin isoform X9

Conserved Domains (1) summary

pfam00758
Location:191 → 285

EPO_TPO; Erythropoietin/thrombopoietin
XM_036159871.1 → XP_036015764.1 thrombopoietin isoform X10