THPO

Protein identityUniProt · HPA

UniProt accession

P40225

Gene

THPO

Ensembl

ENSG00000090534

Chromosome

3

Canonical length

353 aa

Protein class

Cancer-related genes, Disease related genes, Human disease related genes, Predicted membrane proteins, Predicted secreted proteins

Secretome location

Secreted to blood

OverviewNCBI Gene

Megakaryocytopoiesis is the cellular development process that leads to platelet production. The main functional protein encoded by this gene is a humoral growth factor that is necessary for megakaryocyte proliferation and maturation, as well as for thrombopoiesis. This protein is the ligand for MLP/C_MPL, the product of myeloproliferative leukemia virus oncogene. Mutations in this gene are the cause of thrombocythemia 1. Alternative promoter usage and differential splicing result in multiple transcript variants differing in the 5' UTR and/or coding region. Multiple AUG codons upstream of the main open reading frame (ORF) have been identified, and these upstream AUGs inhibit translation of the main ORF at different extent. [provided by RefSeq, Feb 2014]

Canonical amino-acid sequenceUniProt

353 residues, UniProt reviewed canonical sequence.

>P40225|THPO
     1  MELTELLLVV MLLLTARLTL SSPAPPACDL RVLSKLLRDS HVLHSRLSQC PEVHPLPTPV
    61  LLPAVDFSLG EWKTQMEETK AQDILGAVTL LLEGVMAARG QLGPTCLSSL LGQLSGQVRL
   121  LLGALQSLLG TQLPPQGRTT AHKDPNAIFL SFQHLLRGKV RFLMLVGGST LCVRRAPPTT
   181  AVPSRTSLVL TLNELPNRTS GLLETNFTAS ARTTGSGLLK WQQGFRAKIP GLLNQTSRSL
   241  DQIPGYLNRI HELLNGTRGL FPGPSRRTLG APDISSGTSD TGSLPPNLQP GYSPSPTHPP
   301  TGQYTLFPLP PTLPTPVVQL HPLLPDPSAP TPTPTSPLLN TSYTHSQNLS QEG

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against THPO can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.54

Highest tissue expression

34 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about THPO.

Disease | AllUniProt

Conditions THPO is implicated in, by any mechanism.

• Thrombocythemia 1 (THCYT1) MIM:187950
• Amegakaryocytic thrombocytopenia, congenital, 2 (CAMT2) MIM:620481
• Thrombocytopenia 9 (THC9) MIM:620478

Disease | GeneticClinVar

17 pathogenic / likely-pathogenic of 241 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Amegakaryocytic thrombocytopenia, congenital, 2
• Thrombocythemia 1
• Thrombocytopenia
• Thrombocytopenia 9
• Inborn genetic diseases

Disease | ImmuneIEDB

Conditions an epitope on THPO was assayed in.

• autoimmune thrombocytopenic purpura B cell
• thrombocytopenia B cell
• transplant-related disease and allo-reactivity T cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against THPO are reported. Each links to that disease's full target list.

• Purpura, Thrombocytopenic, Idiopathic 4

ReferencesPubMed · IEDB

Publications for THPO from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.7

gnomAD pLI

0.2

gnomAD missense Z

0.41

DepMap mean gene effect

-0.08

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cell population proliferation
• cell surface receptor signaling pathway via STAT
• megakaryocyte development
• megakaryocyte differentiation
• positive regulation of cell population proliferation
• positive regulation of ERK1 and ERK2 cascade
• positive regulation of hematopoietic stem cell proliferation
• positive regulation of MAPK cascade
• positive regulation of megakaryocyte differentiation
• positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
• positive regulation of protein phosphorylation
• thrombopoietin-mediated signaling pathway

Molecular functions

• cytokine activity
• growth factor activity
• hormone activity
• signaling receptor binding

Cellular components

• extracellular region
• extracellular space

Protein domainsUniProt · Pfam · InterPro

• Four-helical cytokine-like, core
• Erythropoietin/thrombopoietin
• Thrombopoietin
• Erythropoietin/thrombopoeitin, conserved site
• Erythropoietin/thrombopoietin

KeywordsUniProt

• Cytokine
• Disulfide bond
• Glycoprotein
• Hormone
• Secreted
• Signal

InteractionsUniProt · HPA

Protein binding partners of THPO in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• MPL