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Database: UniProt
Entry: TPO_HUMAN
LinkDB: TPO_HUMAN
Original site: TPO_HUMAN 
ID   TPO_HUMAN               Reviewed;         353 AA.
AC   P40225; A1L3Y0; B7ZLR8; B9EGA8; Q13020; Q15790; Q15791; Q15792;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1995, sequence version 1.
DT   29-OCT-2014, entry version 145.
DE   RecName: Full=Thrombopoietin;
DE   AltName: Full=C-mpl ligand;
DE            Short=ML;
DE   AltName: Full=Megakaryocyte colony-stimulating factor;
DE   AltName: Full=Megakaryocyte growth and development factor;
DE            Short=MGDF;
DE   AltName: Full=Myeloproliferative leukemia virus oncogene ligand;
DE   Flags: Precursor;
GN   Name=THPO; Synonyms=MGDF;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Fetal liver;
RX   PubMed=8202154; DOI=10.1038/369533a0;
RA   de Sauvage F.J., Hass P.E., Spencer S.D., Malloy B.E., Gurney A.L.,
RA   Spencer S.A., Darbonne W.C., Henzel W.J., Wong S.C., Kuang W.-J.,
RA   Oles K.J., Hultgren B., Solberg L.A. Jr., Goeddel D.V., Eaton D.L.;
RT   "Stimulation of megakaryocytopoiesis and thrombopoiesis by the c-Mpl
RT   ligand.";
RL   Nature 369:533-538(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Fetal liver;
RX   PubMed=8020099; DOI=10.1016/0092-8674(94)90450-2;
RA   Bartley T.D., Bogenberger J., Hunt P., Li Y.-S., Lu H.S., Martin F.,
RA   Chang M.-S., Samal B.B., Nichol J.L., Swift S., Johnson M.J.,
RA   Hsu R.-Y., Parker V.P., Suggs S., Skrine J.D., Merewether L.A.,
RA   Clogson C., Hsu E., Hokom M.M., Hornkohl A., Choi E., Pangelinan M.,
RA   Sun Y., Mar V., McNich J., Simonet L., Jacobsen F., Xie C.,
RA   Shutter J., Chute H., Basu R., Selander L., Trollinger D., Sieu L.,
RA   Padilla D., Trail G., Elliott G., Izumi R., Covey T., Crouse J.,
RA   Garcia A., Xu W., del Castillo J., Biron J., Cole S., Hu M.C.-T.,
RA   Pacifici R., Ponting I., Saris C., Wen D., Yung Y.P., Lin H.,
RA   Bosselman R.A.;
RT   "Identification and cloning of a megakaryocyte growth and development
RT   factor that is a ligand for the cytokine receptor Mpl.";
RL   Cell 77:1117-1124(1994).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RX   PubMed=7809166; DOI=10.1073/pnas.91.26.13023;
RA   Foster D.C., Sprecher C.A., Grant F.J., Kramer J.M., Kuijper J.L.,
RA   Holly R.D., Whitmore T.E., Heipel M.D., Bell L.A.N., Ching A.F.,
RA   McGrane V., Hart C., O'Hara P.J., Lok S.;
RT   "Human thrombopoietin: gene structure, cDNA sequence, expression, and
RT   chromosomal localization.";
RL   Proc. Natl. Acad. Sci. U.S.A. 91:13023-13027(1994).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RX   PubMed=7926023; DOI=10.1016/0014-5793(94)01008-0;
RA   Sohma Y., Akahori H., Seki N., Hori T.-A., Ogami K., Kawamura K.,
RA   Miyazaki H.;
RT   "Molecular cloning and chromosomal localization of the human
RT   thrombopoietin gene.";
RL   FEBS Lett. 353:57-61(1994).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2).
RX   PubMed=7849319;
RA   Gurney A.L., Kuang W.-J., Xie M.-H., Malloy B.E., Eaton D.L.,
RA   de Sauvage F.J.;
RT   "Genomic structure, chromosomal localization, and conserved
RT   alternative splice forms of thrombopoietin.";
RL   Blood 85:981-988(1995).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC   TISSUE=Liver;
RX   PubMed=8537317;
RA   Kato T., Ogami K., Shimada Y., Iwamatsu A., Sohma Y., Akahori H.,
RA   Horie K., Kokubo A., Kudo Y., Maeda E., Kobayashi K., Ohashi H.,
RA   Ozawa T., Inoue H., Kawamura K., Miyazaki H.;
RT   "Purification and characterization of thrombopoietin.";
RL   J. Biochem. 118:229-236(1995).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RC   TISSUE=Placenta;
RX   PubMed=7822271; DOI=10.1074/jbc.270.2.685;
RA   Chang M., McNinch J., Basu R., Shutter J., Hsu R., Perkins C., Mar V.,
RA   Suggs S., Welcher A., Li L., Lu H., Bartley T., Hunt P., Martin F.,
RA   Samal B., Bogenberger J.;
RT   "Cloning and characterization of the human megakaryocyte growth and
RT   development factor (MGDF) gene.";
RL   J. Biol. Chem. 270:511-514(1995).
RN   [8]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 3).
RA   Im S.H., Lee W.S., Chung K.H.;
RT   "Cloning and sequencing of human thrombopoietin.";
RL   Submitted (MAY-1996) to the EMBL/GenBank/DDBJ databases.
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Brain, and Testis;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [10]
RP   DISEASE.
RX   PubMed=9425899; DOI=10.1038/ng0198-49;
RA   Wiestner A., Schlemper R.J., van der Maas A.P.C., Skoda R.C.;
RT   "An activating splice donor mutation in the thrombopoietin gene causes
RT   hereditary thrombocythaemia.";
RL   Nat. Genet. 18:49-52(1998).
RN   [11]
RP   DISULFIDE BONDS, AND GLYCOSYLATION AT SER-22; THR-58; THR-131;
RP   THR-179; THR-180; SER-184; ASN-197; ASN-206; THR-213; ASN-234; ASN-255
RP   AND SER-265.
RX   PubMed=8942648; DOI=10.1021/bi961075b;
RA   Hoffman R.C., Andersen H., Walker K., Krakover J.D., Patel S.,
RA   Stamm M.R., Osborn S.G.;
RT   "Peptide, disulfide, and glycosylation mapping of recombinant human
RT   thrombopoietin from ser1 to Arg246.";
RL   Biochemistry 35:14849-14861(1996).
RN   [12]
RP   X-RAY CRYSTALLOGRAPHY (2.51 ANGSTROMS) OF 22-184 IN COMPLEX WITH
RP   ANTIBODY, AND DISULFIDE BONDS.
RX   PubMed=14769915; DOI=10.1073/pnas.0308530100;
RA   Feese M.D., Tamada T., Kato Y., Maeda Y., Hirose M., Matsukura Y.,
RA   Shigematsu H., Muto T., Matsumoto A., Watarai H., Ogami K., Tahara T.,
RA   Kato T., Miyazaki H., Kuroki R.;
RT   "Structure of the receptor-binding domain of human thrombopoietin
RT   determined by complexation with a neutralizing antibody fragment.";
RL   Proc. Natl. Acad. Sci. U.S.A. 101:1816-1821(2004).
CC   -!- FUNCTION: Lineage-specific cytokine affecting the proliferation
CC       and maturation of megakaryocytes from their committed progenitor
CC       cells. It acts at a late stage of megakaryocyte development. It
CC       may be the major physiological regulator of circulating platelets.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=P40225-1; Sequence=Displayed;
CC       Name=2; Synonyms=TPO-2;
CC         IsoId=P40225-2; Sequence=VSP_001450;
CC       Name=3; Synonyms=Truncated;
CC         IsoId=P40225-3; Sequence=VSP_001451;
CC   -!- DOMAIN: Two-domain structure with an erythropoietin-like N-
CC       terminal and a Ser/Pro/Thr-rich C-terminal.
CC   -!- DISEASE: Thrombocythemia 1 (THCYT1) [MIM:187950]: A
CC       myeloproliferative disorder characterized by excessive platelet
CC       production, resulting in increased numbers of circulating
CC       platelets. It can be associated with spontaneous hemorrhages and
CC       thrombotic episodes. Note=The disease is caused by mutations
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the EPO/TPO family. {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=R&D Systems' cytokine source book:
CC       Thrombopoietin;
CC       URL="http://www.rndsystems.com/molecule_detail.aspx?m=2168";
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DR   EMBL; L33410; AAA59857.1; -; mRNA.
DR   EMBL; U11025; AAA50553.1; -; mRNA.
DR   EMBL; L36051; AAC37568.1; -; Genomic_DNA.
DR   EMBL; L36052; AAC37566.1; -; mRNA.
DR   EMBL; D32046; BAA06807.1; -; Genomic_DNA.
DR   EMBL; S76771; AAB33390.1; -; Genomic_DNA.
DR   EMBL; D32047; BAA21930.1; -; mRNA.
DR   EMBL; U59493; AAB03392.1; -; mRNA.
DR   EMBL; U59494; AAB03393.1; -; mRNA.
DR   EMBL; U59495; AAB03394.1; -; mRNA.
DR   EMBL; U17071; AAA74083.1; -; Genomic_DNA.
DR   EMBL; BC130322; AAI30323.1; -; mRNA.
DR   EMBL; BC136338; AAI36339.1; -; mRNA.
DR   EMBL; BC143982; AAI43983.1; -; mRNA.
DR   CCDS; CCDS3265.1; -. [P40225-1]
DR   CCDS; CCDS54693.1; -. [P40225-2]
DR   PIR; G02729; G02729.
DR   PIR; I59281; I80105.
DR   RefSeq; NP_000451.1; NM_000460.3. [P40225-1]
DR   RefSeq; NP_001171068.1; NM_001177597.2. [P40225-2]
DR   RefSeq; NP_001171069.1; NM_001177598.2.
DR   RefSeq; NP_001276926.1; NM_001289997.1.
DR   RefSeq; NP_001276927.1; NM_001289998.1. [P40225-1]
DR   RefSeq; NP_001276932.1; NM_001290003.1.
DR   RefSeq; NP_001276951.1; NM_001290022.1. [P40225-2]
DR   RefSeq; NP_001276955.1; NM_001290026.1.
DR   RefSeq; NP_001276956.1; NM_001290027.1.
DR   RefSeq; NP_001276957.1; NM_001290028.1. [P40225-1]
DR   UniGene; Hs.1166; -.
DR   UniGene; Hs.734657; -.
DR   PDB; 1V7M; X-ray; 2.51 A; V/X=22-184.
DR   PDB; 1V7N; X-ray; 3.30 A; V/X/Y/Z=22-184.
DR   PDBsum; 1V7M; -.
DR   PDBsum; 1V7N; -.
DR   ProteinModelPortal; P40225; -.
DR   SMR; P40225; 28-172.
DR   BioGrid; 112922; 3.
DR   DIP; DIP-5729N; -.
DR   IntAct; P40225; 3.
DR   STRING; 9606.ENSP00000204615; -.
DR   ChEMBL; CHEMBL1293256; -.
DR   PhosphoSite; P40225; -.
DR   DMDM; 730982; -.
DR   PaxDb; P40225; -.
DR   PRIDE; P40225; -.
DR   DNASU; 7066; -.
DR   Ensembl; ENST00000204615; ENSP00000204615; ENSG00000090534. [P40225-1]
DR   Ensembl; ENST00000445696; ENSP00000410763; ENSG00000090534. [P40225-2]
DR   GeneID; 7066; -.
DR   KEGG; hsa:7066; -.
DR   UCSC; uc003fol.1; human. [P40225-1]
DR   UCSC; uc003fom.2; human. [P40225-2]
DR   CTD; 7066; -.
DR   GeneCards; GC03M184089; -.
DR   HGNC; HGNC:11795; THPO.
DR   MIM; 187950; phenotype.
DR   MIM; 600044; gene.
DR   neXtProt; NX_P40225; -.
DR   Orphanet; 71493; Familial thrombocytosis.
DR   Orphanet; 397692; Hereditary aplastic anemia.
DR   Orphanet; 329319; Hereditary thrombocytosis with transverse limb defect.
DR   PharmGKB; PA36506; -.
DR   eggNOG; NOG84342; -.
DR   GeneTree; ENSGT00390000006294; -.
DR   HOVERGEN; HBG002468; -.
DR   InParanoid; P40225; -.
DR   KO; K06854; -.
DR   OMA; EQSKAQD; -.
DR   OrthoDB; EOG7PVWPW; -.
DR   PhylomeDB; P40225; -.
DR   TreeFam; TF338084; -.
DR   Reactome; REACT_278; Platelet Aggregation (Plug Formation).
DR   SignaLink; P40225; -.
DR   EvolutionaryTrace; P40225; -.
DR   GeneWiki; Thrombopoietin; -.
DR   GenomeRNAi; 7066; -.
DR   NextBio; 27627; -.
DR   PMAP-CutDB; P40225; -.
DR   PRO; PR:P40225; -.
DR   Bgee; P40225; -.
DR   CleanEx; HS_THPO; -.
DR   ExpressionAtlas; P40225; baseline and differential.
DR   Genevestigator; P40225; -.
DR   GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW.
DR   GO; GO:0008083; F:growth factor activity; TAS:ProtInc.
DR   GO; GO:0007596; P:blood coagulation; TAS:Reactome.
DR   GO; GO:0008283; P:cell proliferation; TAS:ProtInc.
DR   GO; GO:0007275; P:multicellular organismal development; TAS:ProtInc.
DR   GO; GO:0030099; P:myeloid cell differentiation; IEA:Ensembl.
DR   GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR   GO; GO:0045654; P:positive regulation of megakaryocyte differentiation; ISS:UniProtKB.
DR   GO; GO:0051897; P:positive regulation of protein kinase B signaling; ISS:UniProtKB.
DR   GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR   GO; GO:0038163; P:thrombopoietin-mediated signaling pathway; ISS:UniProtKB.
DR   Gene3D; 1.20.1250.10; -; 1.
DR   InterPro; IPR009079; 4_helix_cytokine-like_core.
DR   InterPro; IPR012351; 4_helix_cytokine_core.
DR   InterPro; IPR019767; EPO/TPO_CS.
DR   InterPro; IPR001323; EPO_TPO.
DR   InterPro; IPR003978; Thrombopoeitin.
DR   PANTHER; PTHR10560; PTHR10560; 1.
DR   Pfam; PF00758; EPO_TPO; 1.
DR   PRINTS; PR01485; THROMBOPTN.
DR   SUPFAM; SSF47266; SSF47266; 1.
DR   PROSITE; PS00817; EPO_TPO; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Complete proteome; Cytokine;
KW   Disulfide bond; Glycoprotein; Hormone; Polymorphism;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL        1     21
FT   CHAIN        22    353       Thrombopoietin.
FT                                /FTId=PRO_0000008411.
FT   COMPBIAS    285    337       Pro-rich.
FT   CARBOHYD     22     22       O-linked (GalNAc...).
FT                                {ECO:0000269|PubMed:8942648}.
FT   CARBOHYD     58     58       O-linked (GalNAc...).
FT                                {ECO:0000269|PubMed:8942648}.
FT   CARBOHYD    131    131       O-linked (GalNAc...).
FT                                {ECO:0000269|PubMed:8942648}.
FT   CARBOHYD    179    179       O-linked (GalNAc...).
FT                                {ECO:0000269|PubMed:8942648}.
FT   CARBOHYD    180    180       O-linked (GalNAc...).
FT                                {ECO:0000269|PubMed:8942648}.
FT   CARBOHYD    184    184       O-linked (GalNAc...).
FT                                {ECO:0000269|PubMed:8942648}.
FT   CARBOHYD    197    197       N-linked (GlcNAc...) (complex).
FT                                {ECO:0000269|PubMed:8942648}.
FT   CARBOHYD    206    206       N-linked (GlcNAc...) (complex).
FT                                {ECO:0000269|PubMed:8942648}.
FT   CARBOHYD    213    213       O-linked (GalNAc...).
FT                                {ECO:0000269|PubMed:8942648}.
FT   CARBOHYD    234    234       N-linked (GlcNAc...) (complex).
FT                                {ECO:0000269|PubMed:8942648}.
FT   CARBOHYD    255    255       N-linked (GlcNAc...) (complex).
FT                                {ECO:0000269|PubMed:8942648}.
FT   CARBOHYD    265    265       O-linked (GalNAc...).
FT                                {ECO:0000269|PubMed:8942648}.
FT   CARBOHYD    340    340       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD    348    348       N-linked (GlcNAc...). {ECO:0000255}.
FT   DISULFID     28    172
FT   DISULFID     50    106
FT   VAR_SEQ     133    136       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:15489334}.
FT                                /FTId=VSP_001450.
FT   VAR_SEQ     160    198       Missing (in isoform 3). {ECO:0000305}.
FT                                /FTId=VSP_001451.
FT   VARIANT      14     14       L -> P (in dbSNP:rs1042346).
FT                                /FTId=VAR_011795.
FT   VARIANT     116    116       G -> E (in dbSNP:rs1126665).
FT                                /FTId=VAR_011796.
FT   CONFLICT     46     46       R -> K (in Ref. 8; AAB03392/AAB03393/
FT                                AAB03394). {ECO:0000305}.
FT   CONFLICT     76     76       M -> MSQ (in Ref. 7; AAA74083).
FT                                {ECO:0000305}.
FT   CONFLICT    113    113       Q -> E (in Ref. 2; AAA50553).
FT                                {ECO:0000305}.
FT   CONFLICT    131    131       T -> P (in Ref. 7; AAA74083).
FT                                {ECO:0000305}.
FT   CONFLICT    277    277       G -> E (in Ref. 8; AAB03393/AAB03394).
FT                                {ECO:0000305}.
FT   CONFLICT    346    346       S -> C (in Ref. 8; AAB03393/AAB03394).
FT                                {ECO:0000305}.
FT   HELIX        32     45
FT   HELIX        46     48
FT   STRAND       49     52
FT   STRAND       60     63
FT   HELIX        70     74
FT   HELIX        77     98
FT   TURN         99    101
FT   STRAND      104    106
FT   HELIX       107    110
FT   HELIX       113    129
FT   STRAND      139    143
FT   HELIX       145    147
FT   HELIX       148    157
FT   TURN        158    160
FT   HELIX       161    163
FT   STRAND      165    167
SQ   SEQUENCE   353 AA;  37823 MW;  F0AB5449B72E5526 CRC64;
     MELTELLLVV MLLLTARLTL SSPAPPACDL RVLSKLLRDS HVLHSRLSQC PEVHPLPTPV
     LLPAVDFSLG EWKTQMEETK AQDILGAVTL LLEGVMAARG QLGPTCLSSL LGQLSGQVRL
     LLGALQSLLG TQLPPQGRTT AHKDPNAIFL SFQHLLRGKV RFLMLVGGST LCVRRAPPTT
     AVPSRTSLVL TLNELPNRTS GLLETNFTAS ARTTGSGLLK WQQGFRAKIP GLLNQTSRSL
     DQIPGYLNRI HELLNGTRGL FPGPSRRTLG APDISSGTSD TGSLPPNLQP GYSPSPTHPP
     TGQYTLFPLP PTLPTPVVQL HPLLPDPSAP TPTPTSPLLN TSYTHSQNLS QEG
//
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