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Protein

Thrombopoietin receptor

Gene

Mpl

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

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.1 Publication
Isoform Mpl-tr: Acts as an inhibitor of thrombopoietin signaling by promoting protein down-regulation of full-length isoform Mpl-fl.1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionReceptor

Names & Taxonomyi

Protein namesi
Recommended name:
Thrombopoietin receptor
Short name:
TPO-R
Alternative name(s):
Myeloproliferative leukemia protein
Proto-oncogene c-Mpl
CD_antigen: CD110
Gene namesi
Name:Mpl
Synonyms:Tpor
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:97076 Mpl

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; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini26 – 482ExtracellularSequence analysisAdd BLAST457
Transmembranei483 – 504HelicalSequence analysisAdd BLAST22
Topological domaini505 – 625CytoplasmicSequence analysisAdd BLAST121

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL1075309

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
ChainiPRO_000001098826 – 625Thrombopoietin receptorAdd BLAST600

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi117N-linked (GlcNAc...) asparagineSequence analysis1
Cross-linki544Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki564Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity

Post-translational modificationi

Ubiquitination at Lys-544 and Lys-564 targets MPL for degradation by both the lysosomal and proteasomal pathways. The E3 ubiquitin-protein ligase CBL significantly contributes to this ubiquitination (By similarity).By similarity

Keywords - PTMi

Glycoprotein, Isopeptide bond, Ubl conjugation

Proteomic databases

MaxQBiQ08351
PaxDbiQ08351
PRIDEiQ08351

PTM databases

iPTMnetiQ08351
PhosphoSitePlusiQ08351

Expressioni

Inductioni

Expression in the bone marrow displays diurnal rhythmicity (a circadian rhythm that is synchronized with the day/night cycle).1 Publication

Gene expression databases

BgeeiENSMUSG00000006389 Expressed in 36 organ(s), highest expression level in blood
CleanExiMM_MPL
ExpressionAtlasiQ08351 baseline and differential
GenevisibleiQ08351 MM

Interactioni

Subunit structurei

Homodimer. Interacts with ATXN2L.By similarity

Protein-protein interaction databases

BioGridi201478, 2 interactors
IntActiQ08351, 1 interactor
STRINGi10090.ENSMUSP00000130167

Structurei

3D structure databases

ProteinModelPortaliQ08351
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini178 – 270Fibronectin type-III 1PROSITE-ProRule annotationAdd BLAST93
Domaini383 – 479Fibronectin type-III 2PROSITE-ProRule annotationAdd BLAST97

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi465 – 469WSXWS motif5
Motifi519 – 527Box 1 motif9

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi327 – 330Poly-Glu4

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.

Sequence similaritiesi

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IFK2 Eukaryota
ENOG410YM4I LUCA
GeneTreeiENSGT00920000149107
HOGENOMiHOG000138191
HOVERGENiHBG000085
InParanoidiQ08351
KOiK05082
TreeFamiTF336573

Family and domain databases

CDDicd00063 FN3, 1 hit
Gene3Di2.60.40.10, 2 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
SMARTiView protein in SMART
SM00060 FN3, 2 hits
SUPFAMiSSF49265 SSF49265, 3 hits
PROSITEiView protein in PROSITE
PS50853 FN3, 1 hit
PS01352 HEMATOPO_REC_L_F1, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 3 potential isoforms that are computationally mapped.Show allAlign All

Isoform Mpl-fl1 Publication (identifier: Q08351-1) [UniParc]FASTAAdd to basket
Also known as: Mpl-full-length1 Publication

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 SCLLLALPNQ AQVTSQDVFL LALGTEPLNC FSQTFEDLTC
60 70 80 90 100
FWDEEEAAPS GTYQLLYAYR GEKPRACPLY SQSVPTFGTR YVCQFPAQDE
110 120 130 140 150
VRLFFPLHLW VKNVSLNQTL IQRVLFVDSV GLPAPPRVIK ARGGSQPGEL
160 170 180 190 200
QIHWEAPAPE ISDFLRHELR YGPTDSSNAT APSVIQLLST ETCCPTLWMP
210 220 230 240 250
NPVPVLDQPP CVHPTASQPH GPAPFLTVKG GSCLVSGLQA GKSYWLQLRS
260 270 280 290 300
QPDGVSLRGS WGPWSFPVTV DLPGDAVTIG LQCFTLDLKM VTCQWQQQDR
310 320 330 340 350
TSSQGFFRHS RTRCCPTDRD PTWEKCEEEE PRPGSQPALV SRCHFKSRND
360 370 380 390 400
SVIHILVEVT TAQGAVHSYL GSPFWIHQAV LLPTPSLHWR EVSSGRLELE
410 420 430 440 450
WQHQSSWAAQ ETCYQLRYTG EGREDWKVLE PSLGARGGTL ELRPRARYSL
460 470 480 490 500
QLRARLNGPT YQGPWSAWSP PARVSTGSET AWITLVTALL LVLSLSALLG
510 520 530 540 550
LLLLKWQFPA HYRRLRHALW PSLPDLHRVL GQYLRDTAAL SPSKATVTDS
560 570 580 590 600
CEEVEPSLLE ILPKSSESTP LPLCPSQPQM DYRGLQPCLR TMPLSVCPPM
610 620
AETGSCCTTH IANHSYLPLS YWQQP
Length:625
Mass (Da):69,788
Last modified:July 27, 2011 - v2
Checksum:i87836E6EA4688ED7
GO
Isoform Mpl-tr1 Publication (identifier: Q08351-2) [UniParc]FASTAAdd to basket
Also known as: Mpl-truncated1 Publication

The sequence of this isoform differs from the canonical sequence as follows:
     428-457: VLEPSLGARGGTLELRPRARYSLQLRARLN → ETEACFVALASRPTPGPRPVPQRHCSPKSF
     458-625: Missing.

Note: Rbm15 regulates the production of isoform Mpl-tr.1 Publication
Show »
Length:457
Mass (Da):51,133
Checksum:iA35700F75220777B
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A2A9D4A2A9D4_MOUSE
Thrombopoietin receptor
Mpl
633Annotation score:
Q925F5Q925F5_MOUSE
C-mpl-II
Mpl
566Annotation score:
E9Q7U5E9Q7U5_MOUSE
Thrombopoietin receptor
Mpl
465Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1 – 7Missing in CAA52031 (PubMed:8397366).Curated7
Sequence conflicti99D → V in CAA52031 (PubMed:8397366).Curated1
Sequence conflicti222P → PVRTSPAGE in CAA52031 (PubMed:8397366).Curated1
Sequence conflicti241G → S in CAA80365 (PubMed:8334987).Curated1
Sequence conflicti241G → S in CAA52031 (PubMed:8397366).Curated1
Sequence conflicti241G → S in AAI46614 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_059621428 – 457VLEPS…RARLN → ETEACFVALASRPTPGPRPV PQRHCSPKSF in isoform Mpl-tr. Add BLAST30
Alternative sequenceiVSP_059622458 – 625Missing in isoform Mpl-tr. Add BLAST168

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z22649 mRNA Translation: CAA80365.1
Z22657 Genomic DNA Translation: CAA80372.1
X73677 mRNA Translation: CAA52031.1
AK041166 mRNA Translation: BAC30846.1
AL627212 Genomic DNA Translation: CAM15212.1
BC146613 mRNA Translation: AAI46614.1
CCDSiCCDS18552.1 [Q08351-1]
PIRiS35317
S37622
RefSeqiNP_001116421.1, NM_001122949.2
NP_001272425.1, NM_001285496.1
NP_001272426.1, NM_001285497.1
NP_034953.2, NM_010823.3 [Q08351-1]
UniGeneiMm.4864

Genome annotation databases

EnsembliENSMUST00000102671; ENSMUSP00000099732; ENSMUSG00000006389 [Q08351-1]
GeneIDi17480
KEGGimmu:17480
UCSCiuc008uke.3 mouse [Q08351-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z22649 mRNA Translation: CAA80365.1
Z22657 Genomic DNA Translation: CAA80372.1
X73677 mRNA Translation: CAA52031.1
AK041166 mRNA Translation: BAC30846.1
AL627212 Genomic DNA Translation: CAM15212.1
BC146613 mRNA Translation: AAI46614.1
CCDSiCCDS18552.1 [Q08351-1]
PIRiS35317
S37622
RefSeqiNP_001116421.1, NM_001122949.2
NP_001272425.1, NM_001285496.1
NP_001272426.1, NM_001285497.1
NP_034953.2, NM_010823.3 [Q08351-1]
UniGeneiMm.4864

3D structure databases

ProteinModelPortaliQ08351
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201478, 2 interactors
IntActiQ08351, 1 interactor
STRINGi10090.ENSMUSP00000130167

Chemistry databases

ChEMBLiCHEMBL1075309

PTM databases

iPTMnetiQ08351
PhosphoSitePlusiQ08351

Proteomic databases

MaxQBiQ08351
PaxDbiQ08351
PRIDEiQ08351

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000102671; ENSMUSP00000099732; ENSMUSG00000006389 [Q08351-1]
GeneIDi17480
KEGGimmu:17480
UCSCiuc008uke.3 mouse [Q08351-1]

Organism-specific databases

CTDi4352
MGIiMGI:97076 Mpl

Phylogenomic databases

eggNOGiENOG410IFK2 Eukaryota
ENOG410YM4I LUCA
GeneTreeiENSGT00920000149107
HOGENOMiHOG000138191
HOVERGENiHBG000085
InParanoidiQ08351
KOiK05082
TreeFamiTF336573

Miscellaneous databases

PROiPR:Q08351
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000006389 Expressed in 36 organ(s), highest expression level in blood
CleanExiMM_MPL
ExpressionAtlasiQ08351 baseline and differential
GenevisibleiQ08351 MM

Family and domain databases

CDDicd00063 FN3, 1 hit
Gene3Di2.60.40.10, 2 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
SMARTiView protein in SMART
SM00060 FN3, 2 hits
SUPFAMiSSF49265 SSF49265, 3 hits
PROSITEiView protein in PROSITE
PS50853 FN3, 1 hit
PS01352 HEMATOPO_REC_L_F1, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTPOR_MOUSE
AccessioniPrimary (citable) accession number: Q08351
Secondary accession number(s): A6H8H6, Q8BRX0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: July 27, 2011
Last modified: November 7, 2018
This is version 154 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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