MPL

Protein identityUniProt · HPA

UniProt accession

P40238

Gene

MPL

Ensembl

ENSG00000117400

Chromosome

1

Canonical length

635 aa

Protein class

Cancer-related genes, CD markers, Disease related genes, FDA approved drug targets, Human disease related genes, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Nuclear membrane,Plasma membrane

Quaternary structure

Homodimer

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

635 residues, UniProt reviewed canonical sequence.

>P40238|MPL
     1  MPSWALFMVT SCLLLAPQNL AQVSSQDVSL LASDSEPLKC FSRTFEDLTC FWDEEEAAPS
    61  GTYQLLYAYP REKPRACPLS SQSMPHFGTR YVCQFPDQEE VRLFFPLHLW VKNVFLNQTR
   121  TQRVLFVDSV GLPAPPSIIK AMGGSQPGEL QISWEEPAPE ISDFLRYELR YGPRDPKNST
   181  GPTVIQLIAT ETCCPALQRP HSASALDQSP CAQPTMPWQD GPKQTSPSRE ASALTAEGGS
   241  CLISGLQPGN SYWLQLRSEP DGISLGGSWG SWSLPVTVDL PGDAVALGLQ CFTLDLKNVT
   301  CQWQQQDHAS SQGFFYHSRA RCCPRDRYPI WENCEEEEKT NPGLQTPQFS RCHFKSRNDS
   361  IIHILVEVTT APGTVHSYLG SPFWIHQAVR LPTPNLHWRE ISSGHLELEW QHPSSWAAQE
   421  TCYQLRYTGE GHQDWKVLEP PLGARGGTLE LRPRSRYRLQ LRARLNGPTY QGPWSSWSDP
   481  TRVETATETA WISLVTALHL VLGLSAVLGL LLLRWQFPAH YRRLRHALWP SLPDLHRVLG
   541  QYLRDTAALS PPKATVSDTC EEVEPSLLEI LPKSSERTPL PLCSSQAQMD YRRLQPSCLG
   601  TMPLSVCPPM AESGSCCTTH IANHSYLPLS YWQQP

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MPL 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

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.42

Highest tissue expression

1.9 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MPL.

Disease | AllUniProt

Conditions MPL is implicated in, by any mechanism.

• Amegakaryocytic thrombocytopenia, congenital, 1 (CAMT1) MIM:604498
• Thrombocythemia 2 (THCYT2) MIM:601977
• Myelofibrosis with myeloid metaplasia (MMM) MIM:254450

Disease | GeneticClinVar

210 pathogenic / likely-pathogenic of 944 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Congenital amegakaryocytic thrombocytopenia
• Essential thrombocythemia
• Congenital amegakaryocytic thrombocytopenia 1
• Thrombocythemia 2
• Primary myelofibrosis

Disease | AutoantibodyPubMed

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

• Thrombocytopenia 3

ReferencesPubMed · IEDB

Publications for MPL 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)

0.76

gnomAD pLI

0

gnomAD missense Z

0.39

DepMap mean gene effect

-0.09

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular response to hypoxia
• eosinophil homeostasis
• monocyte homeostasis
• neutrophil homeostasis
• platelet formation
• positive regulation of lymphocyte proliferation
• positive regulation of platelet formation
• thrombopoietin-mediated signaling pathway
• basophil homeostasis

Molecular functions

• thrombopoietin receptor activity

Cellular components

• cell surface
• external side of plasma membrane
• Golgi apparatus
• neuronal cell body
• nuclear membrane
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Long hematopoietin receptor, single chain, conserved site
• Fibronectin type III
• Immunoglobulin-like fold
• Growth hormone/erythropoietin receptor, ligand binding
• Fibronectin type III superfamily
• Erythropoietin receptor, ligand binding

KeywordsUniProt

• Cell membrane
• Disulfide bond
• Glycoprotein
• Golgi apparatus
• Isopeptide bond
• Membrane
• Phosphoprotein
• Receptor
• Repeat
• Signal
• Transmembrane
• Transmembrane helix
• Ubl conjugation

InteractionsUniProt · HPA

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

• ATXN2L
• BTK
• JAK2
• SYK
• THPO
• TYK2