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P19235 (EPOR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 177. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Erythropoietin receptor

Short name=EPO-R
Gene names
Name:EPOR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length508 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor for erythropoietin. Mediates erythropoietin-induced erythroblast proliferation and differentiation. Upon EPO stimulation, EPOR dimerizes triggering the JAK2/STAT5 signaling cascade. In some cell types, can also activate STAT1 and STAT3. May also activate the LYN tyrosine kinase.

Isoform EPOR-T acts as a dominant-negative receptor of EPOR-mediated signaling.

Subunit structure

Forms homodimers on EPO stimulation. The tyrosine-phosphorylated form interacts with several SH2 domain-containing proteins including LYN By similarity, the adapter protein APS, PTPN6 By similarity, PTPN11, JAK2, PI3 kinases, STAT5A/B, SOCS3, CRKL By similarity. Interacts with INPP5D/SHIP1 By similarity. The N-terminal SH2 domain of PTPN6 binds Tyr-454 and inhibits signaling through dephosphorylation of JAK2 By similarity. APS binding also inhibits the JAK-STAT signaling. Binding to PTPN11, preferentially through the N-terminal SH2 domain, promotes mitogenesis and phosphorylation of PTPN11 By similarity. Binding of JAK2 (through its N-terminal) promotes cell-surface expression By similarity. Interaction with the ubiquitin ligase NOSIP mediates EPO-induced cell proliferation. Interacts with ATXN2L. Ref.13 Ref.16 Ref.17 Ref.18 Ref.19

Subcellular location

Cell membrane; Single-pass type I membrane protein Ref.15.

Isoform EPOR-S: Secreted. Note: Secreted and located to the cell surface. Ref.15

Tissue specificity

Erythroid cells and erythroid progenitor cells. Isoform EPOR-F is the most abundant form in EPO-dependent erythroleukemia cells and in late-stage erythroid progenitors. Isoform EPOR-S and isoform EPOR-T are the predominant forms in bone marrow. Isoform EPOR-T is the most abundant from in early-stage erythroid progenitor cells.

Domain

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.

Contains 1 copy of a cytoplasmic motif that is referred to as the immunoreceptor tyrosine-based inhibitor motif (ITIM). This motif is involved in modulation of cellular responses. The phosphorylated ITIM motif can bind the SH2 domain of several SH2-containing phosphatases.

Post-translational modification

On EPO stimulation, phosphorylated on C-terminal tyrosine residues by JAK2. The phosphotyrosine motifs are also recruitment sites for several SH2-containing proteins and adapter proteins which mediate cell proliferation. Phosphorylation on Tyr-454 is required for PTPN6 interaction, Tyr-426 for PTPN11. Tyr-426 is also required for SOCS3 binding, but Tyr-454/Tyr-456 motif is the preferred binding site. Ref.18

Ubiquitination at Lys-281 mediates receptor internalization, whereas ubiquitination at Lys-453 promotes trafficking of activated receptors to the lysosomes for degradation By similarity. Ubiquitinated by NOSIP; appears to be either multi-monoubiquitinated or polyubiquitinated. Ubiquitination mediates proliferation and survival of EPO-dependent cells.

Involvement in disease

Erythrocytosis, familial, 1 (ECYT1) [MIM:133100]: An autosomal dominant disorder characterized by increased serum red blood cell mass, elevated hemoglobin and hematocrit, hypersensitivity of erythroid progenitors to erythropoietin, erythropoietin low serum levels, and no increase in platelets nor leukocytes. It has a relatively benign course and does not progress to leukemia.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.25 Ref.26 Ref.27

Sequence similarities

Belongs to the type I cytokine receptor family. Type 1 subfamily.

Contains 1 fibronectin type-III domain.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform EPOR-F (identifier: P19235-1)

Also known as: Full-length form;

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.
Isoform EPOR-S (identifier: P19235-2)

Also known as: Soluble form;

The sequence of this isoform differs from the canonical sequence as follows:
     196-241: VEILEGRTEC...FWSAWSEPVS → GTVFLSPDWL...RSWRAAPSVC
     242-508: Missing.
Isoform EPOR-T (identifier: P19235-3)

Also known as: Truncated form;

The sequence of this isoform differs from the canonical sequence as follows:
     306-328: LWLYQNDGCLWWSPCTPFTEDPP → VGGLVVPSVPGLPCFLQPNCRPL
     329-508: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424
Chain25 – 508484Erythropoietin receptor
PRO_0000010868

Regions

Topological domain25 – 250226Extracellular Potential
Transmembrane251 – 27323Helical; Potential
Topological domain274 – 508235Cytoplasmic Potential
Domain147 – 247101Fibronectin type-III
Region454 – 4563Required for high-affinity SOCS3 binding
Motif233 – 2375WSXWS motif
Motif282 – 2909Box 1 motif
Motif452 – 4576ITIM motif

Sites

Site1171Required for ligand binding
Site3681Interaction with APS and STAT5, and activation By similarity
Site4261Required for STAT5/PTPN11/SOCS3 binding By similarity
Site4541Interaction with PTPN6 By similarity
Site4561Required for STAT1/STAT3 activation
Site4851Required for CrkL binding By similarity

Amino acid modifications

Modified residue3681Phosphotyrosine; by JAK2 By similarity
Modified residue4261Phosphotyrosine; by JAK2 By similarity
Modified residue4541Phosphotyrosine; by JAK2 By similarity
Modified residue4561Phosphotyrosine; by JAK2 By similarity
Modified residue4681Phosphotyrosine; by JAK2 By similarity
Modified residue4851Phosphotyrosine; by JAK2 By similarity
Modified residue4891Phosphotyrosine; by JAK2 By similarity
Modified residue5041Phosphotyrosine; by JAK2 By similarity
Glycosylation761N-linked (GlcNAc...) Potential
Disulfide bond52 ↔ 62
Disulfide bond91 ↔ 107
Cross-link281Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Cross-link453Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Natural variations

Alternative sequence196 – 24146VEILE…SEPVS → GTVFLSPDWLSSTRARPHVI YFCLLRVPRPDSAPRWRSWR AAPSVC in isoform EPOR-S.
VSP_009508
Alternative sequence242 – 508267Missing in isoform EPOR-S.
VSP_009509
Alternative sequence306 – 32823LWLYQ…TEDPP → VGGLVVPSVPGLPCFLQPNC RPL in isoform EPOR-T.
VSP_009510
Alternative sequence329 – 508180Missing in isoform EPOR-T.
VSP_009511
Natural variant3801P → A.
Corresponds to variant rs35423344 [ dbSNP | Ensembl ].
VAR_033919
Natural variant4871N → S in ECYT1 and erythroleukemia. Ref.27
Corresponds to variant rs62638745 [ dbSNP | Ensembl ].
VAR_027372
Natural variant4881P → S in ECYT1. Ref.26
Corresponds to variant rs142094773 [ dbSNP | Ensembl ].
VAR_027373

Experimental info

Mutagenesis1141T → A: Little effect on EPO binding. Ref.14
Mutagenesis1151S → A: Little effect on EPO binding. Ref.14
Mutagenesis1161S → A: 10-fold reduction in EPO binding. Ref.14
Mutagenesis1171F → A or L: Greatly reduced EPO binding. Ref.14
Mutagenesis1171F → W: 60-fold reduction in EPO binding. Ref.14
Mutagenesis1171F → Y: 8-fold reduction in EPO binding. Ref.14
Mutagenesis1181V → A: 16-fold reduction in EPO binding. Ref.14
Mutagenesis1201L → A: Some reduction in EPO binding. Ref.14
Mutagenesis1211E → A: Little effect on EPO binding. Ref.14
Mutagenesis1651R → A: Little effect on EPO binding. Ref.14
Mutagenesis1741M → A: Little effect on EPO binding. Ref.14
Mutagenesis1761S → A: 16-fold reduction in EPO binding. Ref.14
Mutagenesis1771H → A: Little effect on EPO binding. Ref.14
Mutagenesis1791R → A: Little effect on EPO binding. Ref.14
Mutagenesis4541Y → F: Some loss of SOCS3 binding. Ref.16
Mutagenesis4561Y → F: Inhibition of STAT1/STAT3 activity. No effect on STAT5 activity. Some loss of SOCS3 binding. Ref.12 Ref.16
Mutagenesis4681Y → F: No effect on STAT1/STAT3 nor STAT5 activity. Ref.12
Sequence conflict1021A → R no nucleotide entry Ref.1
Sequence conflict189 – 1902GA → RP no nucleotide entry Ref.1
Sequence conflict2441T → E no nucleotide entry Ref.1

Secondary structure

................................................... 508
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform EPOR-F (Full-length form) [UniParc].

Last modified November 1, 1990. Version 1.
Checksum: F9F326E162E9512A

FASTA50855,065
        10         20         30         40         50         60 
MDHLGASLWP QVGSLCLLLA GAAWAPPPNL PDPKFESKAA LLAARGPEEL LCFTERLEDL 

        70         80         90        100        110        120 
VCFWEEAASA GVGPGNYSFS YQLEDEPWKL CRLHQAPTAR GAVRFWCSLP TADTSSFVPL 

       130        140        150        160        170        180 
ELRVTAASGA PRYHRVIHIN EVVLLDAPVG LVARLADESG HVVLRWLPPP ETPMTSHIRY 

       190        200        210        220        230        240 
EVDVSAGNGA GSVQRVEILE GRTECVLSNL RGRTRYTFAV RARMAEPSFG GFWSAWSEPV 

       250        260        270        280        290        300 
SLLTPSDLDP LILTLSLILV VILVLLTVLA LLSHRRALKQ KIWPGIPSPE SEFEGLFTTH 

       310        320        330        340        350        360 
KGNFQLWLYQ NDGCLWWSPC TPFTEDPPAS LEVLSERCWG TMQAVEPGTD DEGPLLEPVG 

       370        380        390        400        410        420 
SEHAQDTYLV LDKWLLPRNP PSEDLPGPGG SVDIVAMDEG SEASSCSSAL ASKPSPEGAS 

       430        440        450        460        470        480 
AASFEYTILD PSSQLLRPWT LCPELPPTPP HLKYLYLVVS DSGISTDYSS GDSQGAQGGL 

       490        500 
SDGPYSNPYE NSLIPAAEPL PPSYVACS 

« Hide

Isoform EPOR-S (Soluble form) [UniParc].

Checksum: 0E74BF60CCFB694D
Show »

FASTA24126,456
Isoform EPOR-T (Truncated form) [UniParc].

Checksum: 7A22EFEBA11A430F
Show »

FASTA32835,809

References

« Hide 'large scale' references
[1]"The gene for the human erythropoietin receptor: analysis of the coding sequence and assignment to chromosome 19p."
Winkelmann J.C., Penny L.A., Deaven L.L., Forget B.G., Jenkins R.B.
Blood 76:24-30(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Human erythropoietin receptor: cloning, expression, and biologic characterization."
Jones S.S., D'Andrea A.D., Haines L.L., Wong G.G.
Blood 76:31-35(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM EPOR-F).
Tissue: Erythroleukemia and Fetal liver.
[3]"Cloning of the human erythropoietin receptor gene."
Noguchi C.T., Bae K.S., Chin K., Wada Y., Schechter A.N., Hankins W.D.
Blood 78:2548-2556(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Placenta.
[4]"The erythropoietin receptor gene: cloning and identification of multiple transcripts in an erythroid cell line OCIM1."
Ehrenman K., St John T.
Exp. Hematol. 19:973-977(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM EPOR-F).
Tissue: Erythroleukemia.
[5]"A truncated erythropoietin receptor that fails to prevent programmed cell death of erythroid cells."
Nakamura Y., Komatsu N., Nakauchi H.
Science 257:1138-1141(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS EPOR-F; EPOR-S AND EPOR-T).
Tissue: Bone marrow and Megakaryoblast.
[6]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM EPOR-F).
Tissue: Caudate nucleus.
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"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] (ISOFORM EPOR-F).
Tissue: Brain.
[9]"Cloning of the gene encoding the human erythropoietin receptor."
Maouche L., Tournamille C., Hattab C., Boffa G., Cartron J.-P., Chretien S.
Blood 78:2557-2563(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-96.
Tissue: Placenta.
[10]"Genomic organization of the human erythropoietin receptor gene."
Penny L.A., Forget B.G.
Genomics 11:974-980(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-17.
[11]"Isolation of a cDNA encoding a potential soluble receptor for human erythropoietin."
Todokoro K., Kuramochi S., Nagasawa T., Abe T., Ikawa Y.
Gene 106:283-284(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (EPOR-S).
Tissue: Erythroid cell.
[12]"Identification of the human erythropoietin receptor region required for Stat1 and Stat3 activation."
Kirito K., Nakajima K., Watanabe T., Uchida M., Tanaka M., Ozawa K., Komatsu N.
Blood 99:102-110(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: STAT1/STAT3 ACTIVATION, MUTAGENESIS OF TYR-456 AND TYR-468.
[13]"Involvement of SH2-containing phosphotyrosine phosphatase Syp in erythropoietin receptor signal transduction pathways."
Tauchi T., Feng G.-S., Shen R., Hoatlin M., Bagby G.C. Jr., Kabat D., Lu L., Broxmeyer H.E.
J. Biol. Chem. 270:5631-5635(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PTPN11.
[14]"Identification of a critical ligand binding determinant of the human erythropoietin receptor. Evidence for common ligand binding motifs in the cytokine receptor family."
Middleton S.A., Johnson D.L., Jin R., McMahon F.J., Collins A., Tullai J., Gruninger R.H., Jolliffe L.K., Mulcahy L.S.
J. Biol. Chem. 271:14045-14054(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: LIGAND-BINDING SITE, MUTAGENESIS OF THR-114; SER-115; SER-116; PHE-117; VAL-118; LEU-120; GLU-121; ARG-165; MET-174; SER-176; HIS-177 AND ARG-179.
[15]"Increased cell surface expression of C-terminal truncated erythropoietin receptors in polycythemia."
Motohashi T., Nakamura Y., Osawa M., Hiroyama T., Iwama A., Shibuya A., Nakauchi H.
Eur. J. Haematol. 67:88-93(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION (ISOFORM EPOR-S).
[16]"A new high affinity binding site for suppressor of cytokine signaling-3 on the erythropoietin receptor."
Hoertner M., Nielsch U., Mayr L.M., Heinrich P.C., Haan S.
Eur. J. Biochem. 269:2516-2526(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SOCS3, MUTAGENESIS OF TYR-454 AND TYR-456.
[17]"Erythropoietin receptors associate with a ubiquitin ligase, p33RUL, and require its activity for erythropoietin-induced proliferation."
Friedman A.D., Nimbalkar D., Quelle F.W.
J. Biol. Chem. 278:26851-26861(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NOSIP.
[18]"APS, an adaptor protein containing pleckstrin homology (PH) and Src homology-2 (SH2) domains inhibits the JAK-STAT pathway in collaboration with c-Cbl."
Wakioka T., Sasaki A., Mitsui K., Yokouchi M., Inoue A., Komiya S., Yoshimura A.
Leukemia 13:760-767(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, INTERACTION WITH APS.
[19]"Cloning and characterization of a family of proteins associated with Mpl."
Meunier C.F., Bordereaux D., Porteu F., Gisselbrecht S., Chretien S., Courtois G.
J. Biol. Chem. 277:9139-9147(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATXN2L.
[20]"Functional mimicry of a protein hormone by a peptide agonist: the EPO receptor complex at 2.8 A."
Livnah O., Stura E.A., Johnson D.L., Middleton S.A., Mulcahy L.S., Wrighton N.C., Dower W.J., Jolliffe L.K., Wilson I.A.
Science 273:464-471(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 34-244.
[21]"An antagonist peptide-EPO receptor complex suggests that receptor dimerization is not sufficient for activation."
Livnah O., Johnson D.L., Stura E.A., Farrell F.X., Barbone F.P., You Y., Liu K.D., Goldsmith M.A., He W., Krause C.D., Pestka S., Jolliffe L.K., Wilson I.A.
Nat. Struct. Biol. 5:993-1004(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 34-244.
[22]"Efficiency of signalling through cytokine receptors depends critically on receptor orientation."
Syed R.S., Reid S.W., Li C., Cheetham J.C., Aoki K.H., Liu B., Zhan H., Osslund T.D., Chirino A.J., Zhang J., Finer-Moore J., Elliott S., Sitney K., Katz B.A., Matthews D.J., Wendoloski J.J., Egrie J., Stroud R.M.
Nature 395:511-516(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 32-244 IN COMPLEX WITH EPO.
[23]"Engineering a soluble extracellular erythropoietin receptor (EPObp) in Pichia pastoris to eliminate microheterogeneity, and its complex with erythropoietin."
Zhan H., Liu B., Reid S.W., Aoki K.H., Li C., Syed R.S., Karkaria C., Koe G., Sitney K., Hayenga K., Mistry F., Savel L., Dreyer M., Katz B.A., Schreurs J., Matthews D.J., Cheetham J.C., Egrie J., Giebel L.B., Stroud R.M.
Protein Eng. 12:505-513(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 22-249 IN COMPLEX WITH EPO.
[24]"Crystallographic evidence for preformed dimers of erythropoietin receptor before ligand activation."
Livnah O., Stura E.A., Middleton S.A., Johnson D.L., Jolliffe L.K., Wilson I.A.
Science 283:987-990(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 34-246.
[25]"Truncated erythropoietin receptor causes dominantly inherited benign human erythrocytosis."
de la Chapelle A., Traskelin A.-L., Juvonen E.
Proc. Natl. Acad. Sci. U.S.A. 90:4495-4499(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN ECYT1.
[26]"Mutation in the negative regulatory element of the erythropoietin receptor gene in a case of sporadic primary polycythemia."
Sokol L., Prchal J.F., D'Andrea A., Rado T.A., Prchal J.T.
Exp. Hematol. 22:447-453(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ECYT1 SER-488.
[27]"Missense mutation of the erythropoietin receptor is a rare event in human erythroid malignancies."
Le Couedic J.-P., Mitjavila M.-T., Villeval J.-L., Feger F., Gobert S., Mayeux P., Casadevall N., Vainchenker W.
Blood 87:1502-1511(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT ECYT1 SER-487, VARIANT ERYTHROLEUKEMIA SER-487.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M60459 mRNA. Translation: AAA52403.1.
S45332 Genomic DNA. Translation: AAB23271.1.
M34986 mRNA. Translation: AAA52401.1.
AK315097 mRNA. Translation: BAG37561.1.
CH471106 Genomic DNA. Translation: EAW84205.1.
BC112153 mRNA. Translation: AAI12154.1.
M76595 Genomic DNA. Translation: AAA52393.1.
M77244 Genomic DNA. Translation: AAA52392.1.
X57282 mRNA. Translation: CAA40550.1.
CCDSCCDS12260.1. [P19235-1]
PIRZUHUR. A43799.
I38208.
RefSeqNP_000112.1. NM_000121.3. [P19235-1]
UniGeneHs.631624.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1CN4X-ray2.80A/B25-249[»]
1EBAX-ray2.70A/B34-248[»]
1EBPX-ray2.80A/B34-244[»]
1EERX-ray1.90B/C27-250[»]
1ERNX-ray2.40A/B34-246[»]
2JIXX-ray3.20B/C/E25-249[»]
ProteinModelPortalP19235.
SMRP19235. Positions 32-247.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108371. 30 interactions.
DIPDIP-5732N.
IntActP19235. 21 interactions.
MINTMINT-273225.
STRING9606.ENSP00000222139.

Chemistry

BindingDBP19235.
ChEMBLCHEMBL1817.
DrugBankDB00012. Darbepoetin alfa.
DB00016. Epoetin alfa.
GuidetoPHARMACOLOGY1718.

PTM databases

PhosphoSiteP19235.

Polymorphism databases

DMDM119524.

Proteomic databases

PaxDbP19235.
PRIDEP19235.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000222139; ENSP00000222139; ENSG00000187266. [P19235-1]
ENST00000592375; ENSP00000467809; ENSG00000187266. [P19235-3]
GeneID2057.
KEGGhsa:2057.
UCSCuc002mrj.2. human. [P19235-1]

Organism-specific databases

CTD2057.
GeneCardsGC19M011489.
H-InvDBHIX0080119.
HGNCHGNC:3416. EPOR.
MIM133100. phenotype.
133171. gene.
neXtProtNX_P19235.
Orphanet90042. Primary familial polycythemia.
PharmGKBPA27834.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG46583.
HOGENOMHOG000059639.
HOVERGENHBG005595.
InParanoidP19235.
KOK05079.
OMAFMVRARM.
OrthoDBEOG74BJS6.
PhylomeDBP19235.
TreeFamTF336573.

Enzyme and pathway databases

SignaLinkP19235.

Gene expression databases

ArrayExpressP19235.
BgeeP19235.
CleanExHS_EPOR.
GenevestigatorP19235.

Family and domain databases

Gene3D2.60.40.10. 2 hits.
InterProIPR009167. Erythropoietin_rcpt.
IPR003961. Fibronectin_type3.
IPR015152. Growth/epo_recpt_lig-bind.
IPR013783. Ig-like_fold.
IPR003528. Long_hematopoietin_rcpt_CS.
[Graphical view]
PfamPF09067. EpoR_lig-bind. 1 hit.
PF00041. fn3. 1 hit.
[Graphical view]
PIRSFPIRSF001959. EPO_receptor. 1 hit.
SMARTSM00060. FN3. 1 hit.
[Graphical view]
SUPFAMSSF49265. SSF49265. 2 hits.
PROSITEPS50853. FN3. 1 hit.
PS01352. HEMATOPO_REC_L_F1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSEPOR. human.
EvolutionaryTraceP19235.
GeneWikiErythropoietin_receptor.
GenomeRNAi2057.
NextBio8365.
PROP19235.
SOURCESearch...

Entry information

Entry nameEPOR_HUMAN
AccessionPrimary (citable) accession number: P19235
Secondary accession number(s): B2RCG4, Q15443, Q2M205
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1990
Last sequence update: November 1, 1990
Last modified: July 9, 2014
This is version 177 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM