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Entry version 191 (08 May 2019)
Sequence version 1 (01 Feb 1995)
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Protein

Thrombopoietin receptor

Gene

MPL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Receptor for thrombopoietin that acts as a primary regulator of megakaryopoiesis and platelet production. May represent a regulatory molecule specific for TPO-R-dependent immune responses.By similarity

Caution

It is uncertain whether Met-1 or Met-8 is the initiator.Curated

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionReceptor

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

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Reactomei
R-HSA-76009 Platelet Aggregation (Plug Formation)

SignaLink: a signaling pathway resource with multi-layered regulatory networks

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SignaLinki
P40238

SIGNOR Signaling Network Open Resource

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SIGNORi
P40238

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Thrombopoietin receptor
Short name:
TPO-R
Alternative name(s):
Myeloproliferative leukemia protein
Proto-oncogene c-Mpl
CD_antigen: CD110
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:MPL
Synonyms:TPOR
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 1

Organism-specific databases

Human Gene Nomenclature Database

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HGNCi
HGNC:7217 MPL

Online Mendelian Inheritance in Man (OMIM)

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MIMi
159530 gene

neXtProt; the human protein knowledge platform

More...
neXtProti
NX_P40238

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini26 – 491ExtracellularSequence analysisAdd BLAST466
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei492 – 513HelicalSequence analysisAdd BLAST22
Topological domaini514 – 635CytoplasmicSequence analysisAdd BLAST122

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Congenital amegakaryocytic thrombocytopenia (CAMT)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionDisease characterized by isolated thrombocytopenia and megakaryocytopenia with no physical anomalies.
See also OMIM:604498
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_073030102R → C in CAMT. 1 PublicationCorresponds to variant dbSNP:rs763568293Ensembl.1
Natural variantiVAR_073031102R → P in CAMT; loss of function; loss of membrane localization, impaired glycosylation. 2 PublicationsCorresponds to variant dbSNP:rs28928907EnsemblClinVar.1
Natural variantiVAR_073032104F → S in CAMT; loss of function. 2 PublicationsCorresponds to variant dbSNP:rs1196161699Ensembl.1
Natural variantiVAR_073034136P → L in CAMT. 1 PublicationCorresponds to variant dbSNP:rs764904424Ensembl.1
Natural variantiVAR_073035154W → R in CAMT. 1 PublicationCorresponds to variant dbSNP:rs758428763Ensembl.1
Natural variantiVAR_073036257R → L in CAMT. 1 Publication1
Natural variantiVAR_073037275P → T in CAMT. 1 PublicationCorresponds to variant dbSNP:rs28928908EnsemblClinVar.1
Natural variantiVAR_073038435W → C in CAMT. 1 PublicationCorresponds to variant dbSNP:rs1006158872Ensembl.1
Natural variantiVAR_073039594L → W in CAMT. 1 PublicationCorresponds to variant dbSNP:rs1448812001EnsemblClinVar.1
Thrombocythemia 2 (THCYT2)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA myeloproliferative disorder characterized by excessive platelet production, resulting in increased numbers of circulating platelets. It can be associated with spontaneous hemorrhages and thrombotic episodes.
See also OMIM:601977
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073033106P → L in THCYT2; gain of function; loss of membrane localization, impaired glycosylation. 1 PublicationCorresponds to variant dbSNP:rs750046020EnsemblClinVar.1
Natural variantiVAR_067559505S → N in THCYT2; activating mutation; induces MPL autonomous dimerization and signal activation in the absence of the ligand. 2 PublicationsCorresponds to variant dbSNP:rs121913614EnsemblClinVar.1
Natural variantiVAR_067561515W → L in THCYT2 and MMM; somatic mutation in myelofibrosis with myeloid metaplasia; results in cytokine-independent growth and thrombopoietin hypersensitivity; results in constitutive activation of JAK-STAT signaling pathway. 2 PublicationsCorresponds to variant dbSNP:rs121913615EnsemblClinVar.1
Myelofibrosis with myeloid metaplasia (MMM)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA chronic myeloproliferative disorder characterized by replacement of the bone marrow by fibrous tissue, extramedullary hematopoiesis, anemia, leukoerythroblastosis and hepatosplenomegaly.
See also OMIM:254450
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_067560515W → K in MMM; somatic mutation; requires 2 nucleotide substitutions. 1 PublicationCorresponds to variant dbSNP:rs121913616EnsemblClinVar.1
Natural variantiVAR_067561515W → L in THCYT2 and MMM; somatic mutation in myelofibrosis with myeloid metaplasia; results in cytokine-independent growth and thrombopoietin hypersensitivity; results in constitutive activation of JAK-STAT signaling pathway. 2 PublicationsCorresponds to variant dbSNP:rs121913615EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNET

More...
DisGeNETi
4352

MalaCards human disease database

More...
MalaCardsi
MPL
MIMi254450 phenotype
601977 phenotype
604498 phenotype

Open Targets

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OpenTargetsi
ENSG00000117400

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...
Orphaneti
3319 Congenital amegakaryocytic thrombocytopenia
3318 Essential thrombocythemia
71493 Familial thrombocytosis
397692 Hereditary isolated aplastic anemia
729 Polycythemia vera
824 Primary myelofibrosis

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...
PharmGKBi
PA30923

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

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ChEMBLi
CHEMBL1864

Drug and drug target database

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DrugBanki
DB06210 Eltrombopag
DB05332 Romiplostim
DB05930 SB-559448

IUPHAR/BPS Guide to PHARMACOLOGY

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GuidetoPHARMACOLOGYi
1722

Polymorphism and mutation databases

BioMuta curated single-nucleotide variation and disease association database

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BioMutai
MPL

Domain mapping of disease mutations (DMDM)

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DMDMi
730980

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 25Sequence analysisAdd BLAST25
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000001098726 – 635Thrombopoietin receptorAdd BLAST610

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi40 ↔ 50By similarity
Disulfide bondi77 ↔ 93By similarity
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi117N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi178N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi291 ↔ 301By similarity
Glycosylationi298N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi323 ↔ 334By similarity
Glycosylationi358N-linked (GlcNAc...) asparagineSequence analysis1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki553Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Cross-linki573Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Ubiquitination at Lys-553 and Lys-573 targets MPL for degradation by both the lysosomal and proteasomal pathways. The E3 ubiquitin-protein ligase CBL significantly contributes to this ubiquitination.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Isopeptide bond, Ubl conjugation

Proteomic databases

jPOST - Japan Proteome Standard Repository/Database

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jPOSTi
P40238

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
P40238

PeptideAtlas

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PeptideAtlasi
P40238

PRoteomics IDEntifications database

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PRIDEi
P40238

ProteomicsDB human proteome resource

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ProteomicsDBi
55354
55355 [P40238-2]

PTM databases

GlyConnect protein glycosylation platform

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GlyConnecti
1803

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
P40238

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
P40238

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Expressed at a low level in a large number of cells of hematopoietic origin. Isoform 1 and isoform 2 are always found to be coexpressed.

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...
Bgeei
ENSG00000117400 Expressed in 65 organ(s), highest expression level in dorsolateral prefrontal cortex

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
P40238 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
P40238 HS

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer (PubMed:25538044). Interacts with ATXN2L.1 Publication1 Publication

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

WithEntry#Exp.IntActNotes
JAK2O606746EBI-6511486,EBI-518647

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
110492, 5 interactors

Database of interacting proteins

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DIPi
DIP-5730N

The Eukaryotic Linear Motif resource for Functional Sites in Proteins

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ELMi
P40238

Protein interaction database and analysis system

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IntActi
P40238, 2 interactors

STRING: functional protein association networks

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STRINGi
9606.ENSP00000361548

Chemistry databases

BindingDB database of measured binding affinities

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BindingDBi
P40238

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family_and_domains_section">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini172 – 281Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST110
Domaini392 – 486Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST95

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi474 – 478WSXWS motif5
Motifi528 – 536Box 1 motif9

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes the position of regions of compositional bias within the protein and the particular amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi335 – 338Poly-Glu4
Compositional biasi508 – 513Poly-Leu6

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The WSXWS motif appears to be necessary for proper protein folding and thereby efficient intracellular transport and cell-surface receptor binding.
The box 1 motif is required for JAK interaction and/or activation.

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
ENOG410IFK2 Eukaryota
ENOG410YM4I LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00940000161225

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

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HOGENOMi
HOG000138191

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
P40238

KEGG Orthology (KO)

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KOi
K05082

Identification of Orthologs from Complete Genome Data

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OMAi
PTETCCP

Database of Orthologous Groups

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OrthoDBi
704215at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
P40238

TreeFam database of animal gene trees

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TreeFami
TF336573

Family and domain databases

Conserved Domains Database

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CDDi
cd00063 FN3, 2 hits

Gene3D Structural and Functional Annotation of Protein Families

More...
Gene3Di
2.60.40.10, 3 hits

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR015152 Growth/epo_recpt_lig-bind
IPR013783 Ig-like_fold
IPR003528 Long_hematopoietin_rcpt_CS

Pfam protein domain database

More...
Pfami
View protein in Pfam
PF09067 EpoR_lig-bind, 1 hit
PF00041 fn3, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

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SMARTi
View protein in SMART
SM00060 FN3, 2 hits

Superfamily database of structural and functional annotation

More...
SUPFAMi
SSF49265 SSF49265, 3 hits

PROSITE; a protein domain and family database

More...
PROSITEi
View protein in PROSITE
PS50853 FN3, 2 hits
PS01352 HEMATOPO_REC_L_F1, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P40238-1) [UniParc]FASTAAdd to basket
Also known as: C-mpl-P

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MPSWALFMVT SCLLLAPQNL AQVSSQDVSL LASDSEPLKC FSRTFEDLTC
60 70 80 90 100
FWDEEEAAPS GTYQLLYAYP REKPRACPLS SQSMPHFGTR YVCQFPDQEE
110 120 130 140 150
VRLFFPLHLW VKNVFLNQTR TQRVLFVDSV GLPAPPSIIK AMGGSQPGEL
160 170 180 190 200
QISWEEPAPE ISDFLRYELR YGPRDPKNST GPTVIQLIAT ETCCPALQRP
210 220 230 240 250
HSASALDQSP CAQPTMPWQD GPKQTSPSRE ASALTAEGGS CLISGLQPGN
260 270 280 290 300
SYWLQLRSEP DGISLGGSWG SWSLPVTVDL PGDAVALGLQ CFTLDLKNVT
310 320 330 340 350
CQWQQQDHAS SQGFFYHSRA RCCPRDRYPI WENCEEEEKT NPGLQTPQFS
360 370 380 390 400
RCHFKSRNDS IIHILVEVTT APGTVHSYLG SPFWIHQAVR LPTPNLHWRE
410 420 430 440 450
ISSGHLELEW QHPSSWAAQE TCYQLRYTGE GHQDWKVLEP PLGARGGTLE
460 470 480 490 500
LRPRSRYRLQ LRARLNGPTY QGPWSSWSDP TRVETATETA WISLVTALHL
510 520 530 540 550
VLGLSAVLGL LLLRWQFPAH YRRLRHALWP SLPDLHRVLG QYLRDTAALS
560 570 580 590 600
PPKATVSDTC EEVEPSLLEI LPKSSERTPL PLCSSQAQMD YRRLQPSCLG
610 620 630
TMPLSVCPPM AESGSCCTTH IANHSYLPLS YWQQP
Length:635
Mass (Da):71,245
Last modified:February 1, 1995 - v1
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iD25D8D8959359DDC
GO
Isoform 2 (identifier: P40238-2) [UniParc]FASTAAdd to basket
Also known as: C-mpl-K

The sequence of this isoform differs from the canonical sequence as follows:
     523-579: RLRHALWPSL...ILPKSSERTP → YRPRQAGDWR...LWDSPRLLTL
     580-635: Missing.

Show »
Length:579
Mass (Da):65,521
Checksum:i7A1431E9F64E21D4
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5JUY5Q5JUY5_HUMAN
Thrombopoietin receptor
MPL
628Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
A0A2R8YE13A0A2R8YE13_HUMAN
Thrombopoietin receptor
MPL
177Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04917339K → N Functional polymorphism associated with thrombocytosis; results in altered MPL expression. 1 PublicationCorresponds to variant dbSNP:rs17292650EnsemblClinVar.1
Natural variantiVAR_01198858A → V1 PublicationCorresponds to variant dbSNP:rs6087EnsemblClinVar.1
Natural variantiVAR_073030102R → C in CAMT. 1 PublicationCorresponds to variant dbSNP:rs763568293Ensembl.1
Natural variantiVAR_073031102R → P in CAMT; loss of function; loss of membrane localization, impaired glycosylation. 2 PublicationsCorresponds to variant dbSNP:rs28928907EnsemblClinVar.1
Natural variantiVAR_073032104F → S in CAMT; loss of function. 2 PublicationsCorresponds to variant dbSNP:rs1196161699Ensembl.1
Natural variantiVAR_073033106P → L in THCYT2; gain of function; loss of membrane localization, impaired glycosylation. 1 PublicationCorresponds to variant dbSNP:rs750046020EnsemblClinVar.1
Natural variantiVAR_049174114V → M. Corresponds to variant dbSNP:rs12731981EnsemblClinVar.1
Natural variantiVAR_073034136P → L in CAMT. 1 PublicationCorresponds to variant dbSNP:rs764904424Ensembl.1
Natural variantiVAR_073035154W → R in CAMT. 1 PublicationCorresponds to variant dbSNP:rs758428763Ensembl.1
Natural variantiVAR_011989168E → K1 PublicationCorresponds to variant dbSNP:rs6088Ensembl.1
Natural variantiVAR_073036257R → L in CAMT. 1 Publication1
Natural variantiVAR_073037275P → T in CAMT. 1 PublicationCorresponds to variant dbSNP:rs28928908EnsemblClinVar.1
Natural variantiVAR_073038435W → C in CAMT. 1 PublicationCorresponds to variant dbSNP:rs1006158872Ensembl.1
Natural variantiVAR_067559505S → N in THCYT2; activating mutation; induces MPL autonomous dimerization and signal activation in the absence of the ligand. 2 PublicationsCorresponds to variant dbSNP:rs121913614EnsemblClinVar.1
Natural variantiVAR_067560515W → K in MMM; somatic mutation; requires 2 nucleotide substitutions. 1 PublicationCorresponds to variant dbSNP:rs121913616EnsemblClinVar.1
Natural variantiVAR_067561515W → L in THCYT2 and MMM; somatic mutation in myelofibrosis with myeloid metaplasia; results in cytokine-independent growth and thrombopoietin hypersensitivity; results in constitutive activation of JAK-STAT signaling pathway. 2 PublicationsCorresponds to variant dbSNP:rs121913615EnsemblClinVar.1
Natural variantiVAR_073039594L → W in CAMT. 1 PublicationCorresponds to variant dbSNP:rs1448812001EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_001734523 – 579RLRHA…SERTP → YRPRQAGDWRWTRWSRTCKQ AFLVRSVTPDLRPPPVRTYG FALPARHLWDSPRLLTL in isoform 2. 1 PublicationAdd BLAST57
Alternative sequenceiVSP_001735580 – 635Missing in isoform 2. 1 PublicationAdd BLAST56

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...
EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...
DDBJi
Links Updated
M90102 mRNA Translation: AAA69971.1
M90103 mRNA Translation: AAA69972.1
U68162
, U68159, U68160, U68161 Genomic DNA Translation: AAB08424.1
U68162
, U68159, U68160, U68161 Genomic DNA Translation: AAB08425.1
AL139289 Genomic DNA No translation available.
CH471059 Genomic DNA Translation: EAX07103.1

The Consensus CDS (CCDS) project

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CCDSi
CCDS483.1 [P40238-1]

Protein sequence database of the Protein Information Resource

More...
PIRi
A45266
B45266

NCBI Reference Sequences

More...
RefSeqi
NP_005364.1, NM_005373.2 [P40238-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...
Ensembli
ENST00000372470; ENSP00000361548; ENSG00000117400 [P40238-1]

Database of genes from NCBI RefSeq genomes

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GeneIDi
4352

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
hsa:4352

UCSC genome browser

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UCSCi
uc001ciw.4 human [P40238-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M90102 mRNA Translation: AAA69971.1
M90103 mRNA Translation: AAA69972.1
U68162
, U68159, U68160, U68161 Genomic DNA Translation: AAB08424.1
U68162
, U68159, U68160, U68161 Genomic DNA Translation: AAB08425.1
AL139289 Genomic DNA No translation available.
CH471059 Genomic DNA Translation: EAX07103.1
CCDSiCCDS483.1 [P40238-1]
PIRiA45266
B45266
RefSeqiNP_005364.1, NM_005373.2 [P40238-1]

3D structure databases

Database of comparative protein structure models

More...
ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

More...
MobiDBi
Search...

SWISS-MODEL Interactive Workspace

More...
SWISS-MODEL-Workspacei
Submit a new modelling project...

Protein-protein interaction databases

BioGridi110492, 5 interactors
DIPiDIP-5730N
ELMiP40238
IntActiP40238, 2 interactors
STRINGi9606.ENSP00000361548

Chemistry databases

BindingDBiP40238
ChEMBLiCHEMBL1864
DrugBankiDB06210 Eltrombopag
DB05332 Romiplostim
DB05930 SB-559448
GuidetoPHARMACOLOGYi1722

PTM databases

GlyConnecti1803
iPTMnetiP40238
PhosphoSitePlusiP40238

Polymorphism and mutation databases

BioMutaiMPL
DMDMi730980

Proteomic databases

jPOSTiP40238
PaxDbiP40238
PeptideAtlasiP40238
PRIDEiP40238
ProteomicsDBi55354
55355 [P40238-2]

Protocols and materials databases

The DNASU plasmid repository

More...
DNASUi
4352
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000372470; ENSP00000361548; ENSG00000117400 [P40238-1]
GeneIDi4352
KEGGihsa:4352
UCSCiuc001ciw.4 human [P40238-1]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
4352
DisGeNETi4352

GeneCards: human genes, protein and diseases

More...
GeneCardsi
MPL
HGNCiHGNC:7217 MPL
MalaCardsiMPL
MIMi159530 gene
254450 phenotype
601977 phenotype
604498 phenotype
neXtProtiNX_P40238
OpenTargetsiENSG00000117400
Orphaneti3319 Congenital amegakaryocytic thrombocytopenia
3318 Essential thrombocythemia
71493 Familial thrombocytosis
397692 Hereditary isolated aplastic anemia
729 Polycythemia vera
824 Primary myelofibrosis
PharmGKBiPA30923

GenAtlas: human gene database

More...
GenAtlasi
Search...

Phylogenomic databases

eggNOGiENOG410IFK2 Eukaryota
ENOG410YM4I LUCA
GeneTreeiENSGT00940000161225
HOGENOMiHOG000138191
InParanoidiP40238
KOiK05082
OMAiPTETCCP
OrthoDBi704215at2759
PhylomeDBiP40238
TreeFamiTF336573

Enzyme and pathway databases

ReactomeiR-HSA-76009 Platelet Aggregation (Plug Formation)
SignaLinkiP40238
SIGNORiP40238

Miscellaneous databases

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...
ChiTaRSi
MPL human

The Gene Wiki collection of pages on human genes and proteins

More...
GeneWikii
Thrombopoietin_receptor

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...
GenomeRNAii
4352

Protein Ontology

More...
PROi
PR:P40238

The Stanford Online Universal Resource for Clones and ESTs

More...
SOURCEi
Search...

Gene expression databases

BgeeiENSG00000117400 Expressed in 65 organ(s), highest expression level in dorsolateral prefrontal cortex
ExpressionAtlasiP40238 baseline and differential
GenevisibleiP40238 HS

Family and domain databases

CDDicd00063 FN3, 2 hits
Gene3Di2.60.40.10, 3 hits
InterProiView protein in InterPro
IPR003961 FN3_dom
IPR036116 FN3_sf
IPR015152 Growth/epo_recpt_lig-bind
IPR013783 Ig-like_fold
IPR003528 Long_hematopoietin_rcpt_CS
PfamiView protein in Pfam
PF09067 EpoR_lig-bind, 1 hit
PF00041 fn3, 1 hit
SMARTiView protein in SMART
SM00060 FN3, 2 hits
SUPFAMiSSF49265 SSF49265, 3 hits
PROSITEiView protein in PROSITE
PS50853 FN3, 2 hits
PS01352 HEMATOPO_REC_L_F1, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiTPOR_HUMAN
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P40238
Secondary accession number(s): Q5JUZ0
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: February 1, 1995
Last modified: May 8, 2019
This is version 191 of the entry and version 1 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  6. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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