EPOR_HUMAN » Erythropoietin receptor

EPOR_HUMAN » Erythropoietin receptor
Magnify EPOR_HUMAN » Erythropoietin receptorEnlarged view of image
3D view in GLMol or JMol

gray dot

Download Coordinates

gray dot

Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
EPOR_HUMAN » Erythropoietin receptor » EPO-R;
Hydrophobic Thickness 34.8 ± 2.0 Å
Tilt Angle 0 ± 0°
ΔGtransfer -44.1 kcal/mol
ΔGfold -27.2 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC
Topology Out
TM Segments 250-275 (250-278)
Pathways

Cytokine-cytokine receptor interaction (KEGG)

Hematopoietic cell lineage (KEGG)

Jak-STAT signaling pathway (KEGG)

PI3K-Akt signaling pathway (KEGG)

PDB 2mv6 (237-284), 1cn4 (A/B=25-249), 1ebp (A/B=34-244), 1ern (A/B=34-246), 1eba (A/B=34-248), 2jix (B/C/E=25-249), 1eer (B/C=27-250)
OPM 2mv6
Complexes

EPOR:EPOR_HUMAN

Interactions

EPOR, Complex: Homodimer of erythropoietin receptor, PDBID: 1ERN

IL3RA, Complex: IL3RA:TEC:VAV:EPOR, PubMed

IL3RB, Complex: IL3RB:EPOR, PubMed

KIT, Complex: EPOR:KIT, PubMed

PTPRB, Complex: EPOR:PTPRB

PTPRC, Complex: EPOR:PTPRC

PTPRG, Complex: EPOR:PTPRG

PTPRJ, Complex: EPOR:PTPRJ

PTPRO, Complex: EPOR:PTPRO

RON, Complex: EPOR:RON, PubMed

SCF, Complex: SCF:EPOR, PubMed

Domains

AA: 37-140, PDBID: 1CN4, Subunit B, Seq Identity:100%, Erythropoietin receptor, ligand binding

AA: 146-232, PDBID: 1CN4, Subunit B, Seq Identity:100%, Fibronectin type III domain

UniProt annotation for EPOR_HUMAN » Erythropoietin receptor
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.

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

SUBUNIT: 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.

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.

DOMAIN: The box 1 motif is required for JAK interaction and/or activation.

DOMAIN: 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.

DISEASE: Erythrocytosis, familial, 1 (ECYT1) OMIM: 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. disease is caused by mutations affecting the gene represented in this entry.

UniProt features for EPOR_HUMAN » Erythropoietin receptor
SIGNAL 1 24
CHAIN 25 508 Erythropoietin receptor.
DOMAIN 144 240 Fibronectin type-III.
REGION 454 456 Required for high-affinity SOCS3 binding.
MOTIF 233 237 WSXWS motif.
MOTIF 282 290 Box 1 motif.
MOTIF 452 457 ITIM motif.
SITE 117 117 Required for ligand binding.
SITE 368 368 Interaction with APS and STAT5, and activation (By similarity).
SITE 426 426 Required for STAT5/PTPN11/SOCS3 binding (By similarity).
SITE 454 454 Interaction with PTPN6 (By similarity).
SITE 456 456 Required for STAT1/STAT3 activation.
SITE 485 485 Required for CrkL binding (By similarity).
DISULFID 52 62
DISULFID 91 107
CROSSLNK 281 281 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) (By similarity).
CROSSLNK 453 453 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) (By similarity).
Amino Acid Sequence for EPOR_HUMAN » Erythropoietin receptor
MDHLGASLWP QVGSLCLLLA GAAWAPPPNL PDPKFESKAA LLAARGPEEL LCFTERLEDL VCFWEEAASA GVGPGNYSFS YQLEDEPWKL CRLHQAPTAR GAVRFWCSLP TADTSSFVPL ELRVTAASGA PRYHRVIHIN EVVLLDAPVG LVARLADESG HVVLRWLPPP ETPMTSHIRY EVDVSAGNGA GSVQRVEILE GRTECVLSNL RGRTRYTFAV RARMAEPSFG GFWSAWSEPV SLLTPSDLDP LILTLSLILV VILVLLTVLA LLSHRRALKQ KIWPGIPSPE SEFEGLFTTH KGNFQLWLYQ NDGCLWWSPC TPFTEDPPAS LEVLSERCWG TMQAVEPGTD DEGPLLEPVG SEHAQDTYLV LDKWLLPRNP PSEDLPGPGG SVDIVAMDEG SEASSCSSAL ASKPSPEGAS AASFEYTILD PSSQLLRPWT LCPELPPTPP HLKYLYLVVS DSGISTDYSS GDSQGAQGGL SDGPYSNPYE NSLIPAAEPL PPSYVACS