P19235 (EPOR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Erythropoietin receptor
Short name=EPO-R

Gene names

Name:

EPOR

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	508 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Defects in EPOR are the cause of familial erythrocytosis type 1 (ECYT1) [MIM:133100]. ECYT1 is 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. 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.

Ontologies

Keywords
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Congenital erythrocytosis Disease mutation
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Disulfide bond Glycoprotein Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	erythropoietin receptor activity Inferred from direct assay Ref.2. Source: UniProtKB identical protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-617321,EBI-617321
Cish	Q62225	4	EBI-617321,EBI-617489	From a different organism.
EPO	P01588	2	EBI-617321,EBI-1027362
PLCG2	P16885	3	EBI-617321,EBI-617403
SOCS2	O14508	3	EBI-617321,EBI-617737

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 24

24

Chain

25 – 508

484

Erythropoietin receptor

PRO_0000010868

Regions

Topological domain

25 – 250

226

Extracellular Potential

Transmembrane

251 – 273

23

Helical; Potential

Topological domain

274 – 508

235

Cytoplasmic Potential

Domain

144 – 240

97

Fibronectin type-III

Region

454 – 456

3

Required for high-affinity SOCS3 binding

Motif

233 – 237

5

WSXWS motif

Motif

282 – 290

9

Box 1 motif

Motif

452 – 457

6

ITIM motif

Sites

Site

117

1

Required for ligand binding

Site

368

1

Interaction with APS and STAT5, and activation By similarity

Site

426

1

Required for STAT5/PTPN11/SOCS3 binding By similarity

Site

454

1

Interaction with PTPN6 By similarity

Site

456

1

Required for STAT1/STAT3 activation

Site

485

1

Required for CrkL binding By similarity

Amino acid modifications

Modified residue

368

1

Phosphotyrosine; by JAK2 By similarity

Modified residue

426

1

Phosphotyrosine; by JAK2 By similarity

Modified residue

454

1

Phosphotyrosine; by JAK2 By similarity

Modified residue

456

1

Phosphotyrosine; by JAK2 By similarity

Modified residue

468

1

Phosphotyrosine; by JAK2 By similarity

Modified residue

485

1

Phosphotyrosine; by JAK2 By similarity

Modified residue

489

1

Phosphotyrosine; by JAK2 By similarity

Modified residue

504

1

Phosphotyrosine; by JAK2 By similarity

Glycosylation

76

1

N-linked (GlcNAc...) Potential

Disulfide bond

52 ↔ 62

Disulfide bond

91 ↔ 107

Cross-link

281

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Cross-link

453

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Natural variations

Alternative sequence

196 – 241

46

VEILE…SEPVS → GTVFLSPDWLSSTRARPHVI YFCLLRVPRPDSAPRWRSWR AAPSVC in isoform EPOR-S.

VSP_009508

Alternative sequence

242 – 508

267

Missing in isoform EPOR-S.

VSP_009509

Alternative sequence

306 – 328

23

LWLYQ…TEDPP → VGGLVVPSVPGLPCFLQPNC RPL in isoform EPOR-T.

VSP_009510

Alternative sequence

329 – 508

180

Missing in isoform EPOR-T.

VSP_009511

Natural variant

380

1

P → A.
Corresponds to variant rs35423344 [ dbSNP | Ensembl ].

VAR_033919

Natural variant

487

1

N → S in ECYT1 and erythroleukemia. Ref.27

VAR_027372

Natural variant

488

1

P → S in ECYT1. Ref.26

VAR_027373

Experimental info

Mutagenesis

114

1

T → A: Little effect on EPO binding. Ref.14

Mutagenesis

115

1

S → A: Little effect on EPO binding. Ref.14

Mutagenesis

116

1

S → A: 10-fold reduction in EPO binding. Ref.14

Mutagenesis

117

1

F → A or L: Greatly reduced EPO binding. Ref.14

Mutagenesis

117

1

F → W: 60-fold reduction in EPO binding. Ref.14

Mutagenesis

117

1

F → Y: 8-fold reduction in EPO binding. Ref.14

Mutagenesis

118

1

V → A: 16-fold reduction in EPO binding. Ref.14

Mutagenesis

120

1

L → A: Some reduction in EPO binding. Ref.14

Mutagenesis

121

1

E → A: Little effect on EPO binding. Ref.14

Mutagenesis

165

1

R → A: Little effect on EPO binding. Ref.14

Mutagenesis

174

1

M → A: Little effect on EPO binding. Ref.14

Mutagenesis

176

1

S → A: 16-fold reduction in EPO binding. Ref.14

Mutagenesis

177

1

H → A: Little effect on EPO binding. Ref.14

Mutagenesis

179

1

R → A: Little effect on EPO binding. Ref.14

Mutagenesis

454

1

Y → F: Some loss of SOCS3 binding. Ref.16

Mutagenesis

456

1

Y → F: Inhibition of STAT1/STAT3 activity. No effect on STAT5 activity. Some loss of SOCS3 binding. Ref.12 Ref.16

Mutagenesis

468

1

Y → F: No effect on STAT1/STAT3 nor STAT5 activity. Ref.12

Sequence conflict

102

1

A → R no nucleotide entry Ref.1

Sequence conflict

189 – 190

2

GA → RP no nucleotide entry Ref.1

Sequence conflict

244

1

T → E no nucleotide entry Ref.1

Secondary structure

1

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508

Helix Strand Turn

Details...

Helix

33 – 45

13

Beta strand

51 – 58

8

Beta strand

61 – 67

7

Beta strand

76 – 83

8

Beta strand

89 – 91

3

Beta strand

93 – 98

6

Turn

99 – 101

3

Beta strand

102 – 108

7

Helix

111 – 113

3

Beta strand

116 – 118

3

Beta strand

120 – 126

7

Beta strand

131 – 137

7

Helix

139 – 141

3

Beta strand

142 – 144

3

Beta strand

149 – 155

7

Beta strand

162 – 167

6

Helix

175 – 177

3

Beta strand

178 – 185

8

Beta strand

188 – 190

3

Beta strand

195 – 198

4

Beta strand

204 – 207

4

Beta strand

212 – 224

13

Turn

226 – 228

3

Beta strand

240 – 244

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform EPOR-F (Full-length form) [UniParc]. Last modified November 1, 1990. Version 1. Checksum: F9F326E162E9512A	FASTA	508	55,065
	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
	Isoform EPOR-S (Soluble form) [UniParc]. Checksum: 0E74BF60CCFB694D	FASTA	241	26,456
	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 GSVQRGTVFL SPDWLSSTRA RPHVIYFCLL RVPRPDSAPR WRSWRAAPSV C
	Isoform EPOR-T (Truncated form) [UniParc]. Checksum: 7A22EFEBA11A430F	FASTA	328	35,809
	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 KGNFQVGGLV VPSVPGLPCF LQPNCRPL

References

	« Hide 'large scale' referencesShow '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: 2163695] [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: 2163696] [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: 1668606] [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: 1654273] [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: 1324524] [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. , 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: 14702039] [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. , 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: 15489334] [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: 1668607] [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: 1664413] [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: 1657727] [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: 11756159] [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: 7534299] [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: 8662939] [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: 11722595] [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: 12027890] [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: 12746455] [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: 10374881] [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: 11784712] [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: 8662530] [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: 9808045] [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: 9774108] [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: 10388848] [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: 9974392] [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: 8506290] [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: 8174675] [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: 8608241] [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.

IPI

IPI00017476.
IPI00401740.
IPI00401741.

PIR

ZUHUR. A43799.
I38208.

RefSeq

NP_000112.1. NM_000121.3.

UniGene

Hs.631624.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1CN4	X-ray	2.80	A/B	25-249	[»]
1EBA	X-ray	2.70	A/B	34-248	[»]
1EBP	X-ray	2.80	A/B	34-244	[»]
1EER	X-ray	1.90	B/C	31-250	[»]
1ERN	X-ray	2.40	A/B	34-246	[»]
2JIX	X-ray	3.20	B/C/E	25-249	[»]

ProteinModelPortal

P19235.

SMR

P19235. Positions 32-247.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-5732N.

IntAct

P19235. 16 interactions.

MINT

MINT-273225.

STRING

P19235.

PTM databases

PhosphoSite

P19235.

Polymorphism databases

DMDM

119524.

Proteomic databases

PRIDE

P19235.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000222139; ENSP00000222139; ENSG00000187266.

GeneID

2057.

KEGG

hsa:2057.

UCSC

uc002mrj.1. human.

Organism-specific databases

CTD

2057.

GeneCards

GC19M011489.

H-InvDB

HIX0014768.
HIX0080119.

HGNC

HGNC:3416. EPOR.

MIM

133100. phenotype.
133171. gene.

neXtProt

NX_P19235.

Orphanet

90042. Primary familial polycythemia.

PharmGKB

PA27834.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04483.

GeneTree

ENSGT00530000063864.

HOGENOM

HBG127165.

HOVERGEN

HBG005595.

InParanoid

P19235.

OMA

SERCWGV.

OrthoDB

EOG46HG9M.

Enzyme and pathway databases

Pathway_Interaction_DB

epopathway. EPO signaling pathway.
a4b1_paxindep_pathway. Paxillin-independent events mediated by a4b1 and a4b7.
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).

Gene expression databases

ArrayExpress

P19235.

Bgee

P19235.

CleanEx

HS_EPOR.

Genevestigator

P19235.

GermOnline

ENSG00000187266. Homo sapiens.

Family and domain databases

InterPro

IPR009167. Erythropoietin_rcpt.
IPR003961. Fibronectin_type3.
IPR015152. Growth/epo_recpt_lig-bind.
IPR013783. Ig-like_fold.
IPR003528. Long_hematopoietin_rcpt_CS.
[Graphical view]

Gene3D

G3DSA:2.60.40.10. Ig-like_fold. 2 hits.

KO

K05079.

PANTHER

PTHR23037:SF10. PTHR23037:SF10. 1 hit.

Pfam

PF09067. EpoR_lig-bind. 1 hit.
PF00041. fn3. 1 hit.
[Graphical view]

PIRSF

PIRSF001959. EPO_receptor. 1 hit.

SMART

SM00060. FN3. 1 hit.
[Graphical view]

SUPFAM

SSF49265. FN_III-like. 2 hits.

PROSITE

PS50853. FN3. 1 hit.
PS01352. HEMATOPO_REC_L_F1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00012. Darbepoetin alfa.
DB00016. Epoetin alfa.

NextBio

8365.

SOURCE

Search...

Entry information

Entry name

EPOR_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 151 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.