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Protein

Thrombopoietin receptor

Gene

Mpl

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Receptor for thrombopoietin. May represent a regulatory molecule specific for TPO-R-dependent immune responses.

GO - Molecular functioni

GO - Biological processi

  • homeostasis of number of cells Source: MGI
  • regulation of chemokine production Source: MGI
  • thrombopoietin-mediated signaling pathway Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Enzyme and pathway databases

ReactomeiREACT_296516. Platelet Aggregation (Plug Formation).

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:97076. Mpl.

Subcellular locationi

  • Cell membrane; Single-pass type I membrane protein By similarity
  • Golgi apparatus By similarity
  • Cell surface By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini26 – 482457ExtracellularSequence AnalysisAdd
BLAST
Transmembranei483 – 50422HelicalSequence AnalysisAdd
BLAST
Topological domaini505 – 625121CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2525Sequence AnalysisAdd
BLAST
Chaini26 – 625600Thrombopoietin receptorPRO_0000010988Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi117 – 1171N-linked (GlcNAc...)Sequence Analysis
Cross-linki544 – 544Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Cross-linki564 – 564Glycyl 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

PRIDEiQ08351.

PTM databases

PhosphoSiteiQ08351.

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

BgeeiQ08351.
CleanExiMM_MPL.
ExpressionAtlasiQ08351. baseline and differential.
GenevisibleiQ08351. MM.

Interactioni

Subunit structurei

Homodimer. Interacts with ATXN2L.By similarity

Protein-protein interaction databases

BioGridi201478. 3 interactions.
IntActiQ08351. 1 interaction.
STRINGi10090.ENSMUSP00000130167.

Structurei

3D structure databases

ProteinModelPortaliQ08351.
SMRiQ08351. Positions 25-270.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini178 – 27093Fibronectin type-III 1PROSITE-ProRule annotationAdd
BLAST
Domaini383 – 47997Fibronectin type-III 2PROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi465 – 4695WSXWS motif
Motifi519 – 5279Box 1 motif

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi327 – 3304Poly-Glu

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

Contains 2 fibronectin type-III domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG39882.
GeneTreeiENSGT00730000111277.
HOGENOMiHOG000138191.
HOVERGENiHBG000085.
InParanoidiQ08351.
KOiK05082.
OrthoDBiEOG77126V.
TreeFamiTF336573.

Family and domain databases

Gene3Di2.60.40.10. 4 hits.
InterProiIPR003961. FN3_dom.
IPR015152. Growth/epo_recpt_lig-bind.
IPR013783. Ig-like_fold.
IPR003528. Long_hematopoietin_rcpt_CS.
[Graphical view]
PfamiPF09067. EpoR_lig-bind. 1 hit.
[Graphical view]
SMARTiSM00060. FN3. 2 hits.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 4 hits.
PROSITEiPS50853. FN3. 1 hit.
PS01352. HEMATOPO_REC_L_F1. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q08351-1 [UniParc]FASTAAdd to basket

« 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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1 – 77Missing in CAA52031 (PubMed:8397366).Curated
Sequence conflicti99 – 991D → V in CAA52031 (PubMed:8397366).Curated
Sequence conflicti222 – 2221P → PVRTSPAGE in CAA52031 (PubMed:8397366).Curated
Sequence conflicti241 – 2411G → S in CAA80365 (PubMed:8334987).Curated
Sequence conflicti241 – 2411G → S in CAA52031 (PubMed:8397366).Curated
Sequence conflicti241 – 2411G → S in AAI46614 (PubMed:15489334).Curated

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.
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.
UniGeneiMm.4864.

Genome annotation databases

EnsembliENSMUST00000102671; ENSMUSP00000099732; ENSMUSG00000006389.
GeneIDi17480.
KEGGimmu:17480.
UCSCiuc008uke.2. mouse.

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.
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.
UniGeneiMm.4864.

3D structure databases

ProteinModelPortaliQ08351.
SMRiQ08351. Positions 25-270.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201478. 3 interactions.
IntActiQ08351. 1 interaction.
STRINGi10090.ENSMUSP00000130167.

Chemistry

ChEMBLiCHEMBL1075309.

PTM databases

PhosphoSiteiQ08351.

Proteomic databases

PRIDEiQ08351.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000102671; ENSMUSP00000099732; ENSMUSG00000006389.
GeneIDi17480.
KEGGimmu:17480.
UCSCiuc008uke.2. mouse.

Organism-specific databases

CTDi4352.
MGIiMGI:97076. Mpl.

Phylogenomic databases

eggNOGiNOG39882.
GeneTreeiENSGT00730000111277.
HOGENOMiHOG000138191.
HOVERGENiHBG000085.
InParanoidiQ08351.
KOiK05082.
OrthoDBiEOG77126V.
TreeFamiTF336573.

Enzyme and pathway databases

ReactomeiREACT_296516. Platelet Aggregation (Plug Formation).

Miscellaneous databases

NextBioi292128.
PROiQ08351.
SOURCEiSearch...

Gene expression databases

BgeeiQ08351.
CleanExiMM_MPL.
ExpressionAtlasiQ08351. baseline and differential.
GenevisibleiQ08351. MM.

Family and domain databases

Gene3Di2.60.40.10. 4 hits.
InterProiIPR003961. FN3_dom.
IPR015152. Growth/epo_recpt_lig-bind.
IPR013783. Ig-like_fold.
IPR003528. Long_hematopoietin_rcpt_CS.
[Graphical view]
PfamiPF09067. EpoR_lig-bind. 1 hit.
[Graphical view]
SMARTiSM00060. FN3. 2 hits.
[Graphical view]
SUPFAMiSSF49265. SSF49265. 4 hits.
PROSITEiPS50853. FN3. 1 hit.
PS01352. HEMATOPO_REC_L_F1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Murine c-mpl: a member of the hematopoietic growth factor receptor superfamily that transduces a proliferative signal."
    Skoda R.C., Seldin D.C., Chiang M.K., Peichel C.L., Vogt T.F., Leder P.
    EMBO J. 12:2645-2653(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
  2. "Characterization of the murine Mpl proto-oncogene, a member of the hematopoietic cytokine receptor family: molecular cloning, chromosomal location and evidence for a function in cell growth."
    Vigon I., Florindo C., Fichelson S., Guenet J.-L., Mattei M.-G., Souyri M., Cosman D., Gisselbrecht S.
    Oncogene 8:2607-2615(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: ICFW.
    Tissue: Fetal liver.
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Aorta and Vein.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  6. "Diurnal expression of the thrombopoietin gene is regulated by CLOCK."
    Tracey C.J., Pan X., Catterson J.H., Harmar A.J., Hussain M.M., Hartley P.S.
    J. Thromb. Haemost. 10:662-669(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: INDUCTION.

Entry informationi

Entry nameiTPOR_MOUSE
AccessioniPrimary (citable) accession number: Q08351
Secondary accession number(s): A6H8H6, Q8BRX0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: July 27, 2011
Last modified: June 24, 2015
This is version 131 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.