Erythrocytosis-associated HIF-2α Mutations Demonstrate a Critical Role for Residues C-terminal to the Hydroxylacceptor Proline
Open accessAbstract
A classic physiologic response to hypoxia in humans is the up-regulation of the ERYTHROPOIETIN (EPO) gene, which is the central regulator of red blood cell mass. The EPO gene, in turn, is activated by hypoxia inducible factor (HIF). HIF is a transcription factor consisting of an alpha subunit (HIF-alpha) and a beta subunit (HIF-beta). Under normoxic conditions, prolyl hydroxylase domain protein (PHD, also known as HIF prolyl hydroxylase and egg laying-defective nine protein) site specifically hydroxylates HIF-alpha in a conserved LXXLAP motif (where underlining indicates the hydroxylacceptor proline). This provides a recognition motif for the von Hippel Lindau protein, a component of an E3 ubiquitin ligase complex that targets hydroxylated HIF-alpha for degradation. Under hypoxic conditions, this inherently oxygen-dependent modification is arrested, thereby stabilizing HIF-alpha and allowing it to activate the EPO gene. We previously identified and characterized an erythrocytosis-associated HIF2A mutation, G537W. More recently, we reported two additional erythrocytosis-associated HIF2A mutations, G537R and M535V. Here, we describe the functional characterization of these two mutants as well as a third novel erythrocytosis-associated mutation, P534L. These mutations affect residues C-terminal to the LXXLAP motif. We find that all result in impaired degradation and thus aberrant stabilization of HIF-2alpha. However, each exhibits a distinct profile with respect to their effects on PHD2 binding and von Hippel Lindau interaction. These findings reinforce the importance of HIF-2alpha in human EPO regulation, demonstrate heterogeneity of functional defects arising from these mutations, and point to a critical role for residues C-terminal to the LXXLAP motif in HIF-alpha.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Smith, D. B., & Johnson, K. S. (1988) · Gene · doi:10.1016/0378-1119(88)90005-4 · Cited by 5,974 · see citing works
Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535 · see citing works
Ivan, M., Kondo, K., Yang, H., Kim, W., Valiando, J., Ohh, M., Salic, A., Asara, J. M., Lane, W. S., & Kaelin Jr., W. G. (2001) · Science · doi:10.1126/science.1059817 · Cited by 4,735 · see citing works
Oxygen sensing by HIF hydroxylases
Schofield, C. J., & Ratcliffe, P. J. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1366 · Cited by 2,068 · see citing works
Regulation of Mammalian O <sub>2</sub> Homeostasis by Hypoxia-Inducible Factor 1
Semenza, G. L. (1999) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.15.1.551 · Cited by 1,914 · see citing works
Differential Roles of Hypoxia-Inducible Factor 1α (HIF-1α) and HIF-2α in Hypoxic Gene Regulation
Hu, C.-J., Wang, L.-Y., Chodosh, L. A., Keith, B., & Simon, M. C. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.24.9361-9374.2003 · Cited by 1,386 · see citing works
HIF-1α binding to VHL is regulated by stimulus-sensitive proline hydroxylation
Yu, F., White, S. B., Zhao, Q., & Lee, F. S. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.181341498 · Cited by 796 · see citing works
Structure of an HIF-1α-pVHL Complex: Hydroxyproline Recognition in Signaling
Min, J.-H., Yang, H., Ivan, M., Gertler, F., Kaelin, W. G., & Pavletich, N. P. (2002) · Science · doi:10.1126/science.1073440 · Cited by 765 · see citing works
Structural basis for the recognition of hydroxyproline in HIF-1α by pVHL
Hon, W.-C., Wilson, M. I., Harlos, K., Claridge, T. D. W., Schofield, C. J., Pugh, C. W., Maxwell, P. H., Ratcliffe, P. J., Stuart, D. I., & Jones, E. Y. (2002) · Nature · doi:10.1038/nature00767 · Cited by 751 · see citing works
Semenza, G. L. (2007) · Science · doi:10.1126/science.1147949 · Cited by 706 · see citing works
Disruption of oxygen homeostasis underlies congenital Chuvash polycythemia
Ang, S. O., Chen, H., Hirota, K., Gordeuk, V. R., Jelinek, J., Guan, Y., Liu, E., Sergueeva, A. I., Miasnikova, G. Y., Mole, D., et al. (2002) · Nature Genetics · doi:10.1038/ng1019 · Cited by 510 · see citing works
Hypoxia-inducible factors: central regulators of the tumor phenotype
Gordan, J. D., & Simon, M. C. (2007) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2006.12.006 · Cited by 450 · see citing works
[10] Posttranslational enzymes in the biosynthesis of collagen: Intracellular enzymes
Kivirikko, K. I., & Myllylä, R. (1982) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(82)82067-3 · Cited by 411 · see citing works
Erythropoietin after a century of research: younger than ever
JELKMANN, W. E. B. (2007) · European Journal Of Haematology · doi:10.1111/j.1600-0609.2007.00818.x · Cited by 365 · see citing works
Kaelin, W. G. (2006) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev.pathol.2.010506.092049 · Cited by 335 · see citing works
Percy, M. J., Zhao, Q., Flores, A., Harrison, C., Lappin, T. R. J., Maxwell, P. H., McMullin, M. F., & Lee, F. S. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508423103 · Cited by 330 · see citing works
Self-citationA Gain-of-Function Mutation in the <i>HIF2A</i> Gene in Familial Erythrocytosis
Percy, M. J., Furlow, P. W., Lucas, G. S., Li, X., Lappin, T. R. J., McMullin, M. F., & Lee, F. S. (2008) · New England Journal of Medicine · doi:10.1056/nejmoa073123 · Cited by 314 · see citing works
Huang, J., Zhao, Q., Mooney, S. M., & Lee, F. S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206955200 · Cited by 307 · see citing works
Gale, D. P., Harten, S. K., Reid, C. D. L., Tuddenham, E. G. D., & Maxwell, P. H. (2008) · Blood · doi:10.1182/blood-2008-04-153718 · Cited by 157 · see citing works
A novel erythrocytosis-associated PHD2 mutation suggests the location of a HIF binding groove
Percy, M. J., Furlow, P. W., Beer, P. A., Lappin, T. R. J., McMullin, M. F., & Lee, F. S. (2007) · Blood · doi:10.1182/blood-2007-04-084434 · Cited by 155 · see citing works
HYPOXIA‐INDUCED ERYTHROPOIETIN PRODUCTION: A PARADIGM FOR OXYGEN‐REGULATED GENE EXPRESSION
Stockmann, C., & Fandrey, J. (2006) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2006.04474.x · Cited by 154 · see citing works
Novel exon 12 mutations in the HIF2A gene associated with erythrocytosis
Percy, M. J., Beer, P. A., Campbell, G., Dekker, A. W., Green, A. R., Oscier, D., Rainey, M. G., van Wijk, R., Wood, M., Lappin, T. R. J., et al. (2008) · Blood · doi:10.1182/blood-2008-02-137703 · Cited by 127 · see citing works
Self-citationThe human oxygen sensing machinery and its manipulation
Chowdhury, R., Hardy, A., & Schofield, C. J. (2008) · Chemical Society Reviews · doi:10.1039/b701676j · Cited by 109 · see citing works
Mutations of von Hippel-Lindau tumor-suppressor gene and congenital polycythemia
Pastore, Y., Jedlickova, K., Guan, Y., Liu, E., Fahner, J., Hasle, H., Prchal, J. F., & Prchal, J. T. (2003) · The American Journal of Human Genetics · doi:10.1086/377108 · Cited by 106 · see citing works
Congenital polycythemias/erythrocytoses.
Gordeuk, V. R., Stockton, D. W., & Prchal, J. T. (2005) · PubMed · Cited by 104 · see citing works
Perrotta, S., Nobili, B., Ferraro, M., Migliaccio, C., Borriello, A., Cucciolla, V., Martinelli, V., Rossi, F., Punzo, F., Cirillo, P., et al. (2006) · Blood · doi:10.1182/blood-2005-06-2422 · Cited by 93 · see citing works
Chuvash-type congenital polycythemia in 4 families of Asian and Western European ancestry
Percy, M. J., McMullin, M. F., Jowitt, S. N., Potter, M., Treacy, M., Watson, W. H., & Lappin, T. R. J. (2003) · Blood · doi:10.1182/blood-2002-10-3246 · Cited by 90 · see citing works
Yu, F., White, S. B., Zhao, Q., & Lee, F. S. (2001) · PubMed · Cited by 87 · see citing works
(2005) · PubMed · Cited by 72 · see citing works
Al-Sheikh, M., Moradkhani, K., Lopez, M., Wajcman, H., & Préhu, C. (2008) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2007.07.017 · Cited by 50 · see citing works
IOP1, a novel hydrogenase-like protein that modulates hypoxia-inducible factor-1α activity
Huang, J., Song, D., Flores, A. G., Zhao, Q., Mooney, S. M., Shaw, L. M., & Lee, F. S. (2006) · Biochemical Journal · doi:10.1042/bj20060635 · Cited by 44 · see citing works
Genetic causes of erythrocytosis and the oxygen-sensing pathway
Lee, F. S. (2008) · Blood Reviews · doi:10.1016/j.blre.2008.04.003 · Cited by 42 · see citing works
Linke, S., Hampton‐Smith, R. J., & Peet, D. J. (2007) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(07)35004-0 · Cited by 29 · see citing works
(2008) · PubMed · Cited by 26 · see citing works
Familial erythrocytosis: molecular links to red blood cell control
Percy, M. J., & Lee, F. S. (2008) · Haematologica · doi:10.3324/haematol.13250 · Cited by 23 · see citing works
Oxygen Sensing: Recent Insights from Idiopathic Erythrocytosis
Lee, F. S., Percy, M. J., & McMulli, M. F. (2006) · Cell Cycle · doi:10.4161/cc.5.9.2723 · Cited by 15 · see citing works
The HIF2A gene in familial erythrocytosis.
Prchal, J. T., & Gordeuk, V. R. (2008) · PubMed · Cited by 13 · see citing works
Percy, M. J., Furlow, P. W., Beer, P. A., Campbell, G., Dekker, A. W., Green, A. R., Li, X., Sutherland, S., Oscier, D. G., Rainey, M., et al. (2008) · Blood · doi:10.1182/blood.v112.11.481.481 · Cited by 3 · see citing works
Flagged first, then by citations
Research works printed but not linked: 2
- Percy, M. J., Zhao, Q., Flores, A., Harrison, C., Lappin, T. R., Maxwell, P. H., McMullin, M. F., and Lee, F. S. (2006) Proc. Natl. Acad. Sci. U. S. A. 103, 654 -659
- Yu, F., White, S. B., Zhao, Q., and Lee, F. S. (2001) Proc. Natl. Acad. Sci.
Cited by
Sorted by citations
Hypoxia-inducible factors and the response to hypoxic stress
Majmundar, A. J., Wong, W. J., & Simon, M. C. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.022 · Cited by 2,380 · see citing works
Regulation of erythropoiesis by hypoxia-inducible factors
Haase, V. H. (2013) · Blood Reviews · doi:10.1016/j.blre.2012.12.003 · Cited by 787 · see citing works
Roey, K. V., Uyar, B., Weatheritt, R. J., Dinkel, H., Seiler, M., Budd, A., Gibson, T. J., & Davey, N. E. (2014) · Chemical Reviews · doi:10.1021/cr400585q · Cited by 496 · see citing works
Human high-altitude adaptation: forward genetics meets the HIF pathwayPreprint
Bigham, A. W., & Lee, F. S. (2014) · Genes & Development · doi:10.1101/gad.250167.114 · Cited by 350 · see citing works
ErythropoietinPreprint
Bunn, H. F. (2013) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a011619 · Cited by 247 · see citing works
The HIF pathway and erythrocytosis
Lee, F. S., & Percy, M. J. (2011) · Annual Review of Pathology Mechanisms of Disease · doi:10.1146/annurev-pathol-011110-130321 · Cited by 177 · see citing works
Rabinowitz, M. H. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400386j · Cited by 165 · see citing works
Genetic determinants of Tibetan high-altitude adaptation
Simonson, T. S., McClain, D. A., Jorde, L. B., & Prchal, J. T. (2011) · Human Genetics · doi:10.1007/s00439-011-1109-3 · Cited by 137 · see citing works
Genetic Basis of Congenital Erythrocytosis: Mutation Update and Online Databases
Bento, C., Percy, M. J., Gardie, B., Maia, T. M., van Wijk, R., Perrotta, S., Ragione, F. D., Almeida, H., Rossi, C., Girodon, F., et al. (2013) · Human Mutation · doi:10.1002/humu.22448 · Cited by 123 · see citing works
Regulated oxygen sensing by protein hydroxylation in renal erythropoietin-producing cells
Wenger, R. H., & Hoogewijs, D. (2010) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00736.2009 · Cited by 116 · see citing works
Cross-Species Insights Into Genomic Adaptations to Hypoxia
Pamenter, M. E., Hall, J. E., Tanabe, Y., & Simonson, T. S. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00743 · Cited by 118 · see citing works
Erythrocytosis and Pulmonary Hypertension in a Mouse Model of Human HIF2A Gain of Function Mutation
Tan, Q., Kerestes, H., Percy, M. J., Pietrofesa, R. A., Chen, L., Khurana, T. S., Christofidou‐Solomidou, M., Lappin, T. R. J., & Lee, F. S. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.444059 · Cited by 104 · see citing works
Hypoxia-Inducible Factor and Its Role in the Management of Anemia in Chronic Kidney Disease
Kaplan, J., Sharma, N., & Dikdan, S. J. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19020389 · Cited by 104 · see citing works
Yan, L. Y., Colandrea, V. J., & Hale, J. J. (2010) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543776.2010.510836 · Cited by 86 · see citing works
Novel insights into the polycythemia–paraganglioma–somatostatinoma syndrome
Därr, R., Nambuba, J., Rivero, J. D., Janssen, I., Merino, M. J., Todorović, M., Balint, B., Jochmanová, I., Prchal, J. T., Lechan, R. M., et al. (2016) · Endocrine Related Cancer · doi:10.1530/erc-16-0231 · Cited by 84 · see citing works
HIF prolyl hydroxylase inhibitors for anemia
Muchnik, E., & Kaplan, J. (2011) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2011.566861 · Cited by 76 · see citing works
HIF2AMutations in Paraganglioma with Polycythemia
Favier, J., Buffet, A., & Gimenez‐Roqueplo, A. (2012) · New England Journal of Medicine · doi:10.1056/nejmc1211953 · Cited by 65 · see citing works
Jasiecki, J., Targońska, M., & Wasąg, B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22042033 · Cited by 64 · see citing works
Mima, A. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.174583 · Cited by 63 · see citing works
Erythrocytosis associated with a novel missense mutation in the BPGM gene
Petousi, N., Copley, R. R., Lappin, T. R. J., Haggan, S. E., Bento, C., Cario, H., Percy, M. J., Ratcliffe, P. J., Robbins, P. A., McMullin, M. F., et al. (2014) · Haematologica · doi:10.3324/haematol.2014.109306 · Cited by 59 · see citing works
Idiopathic erythrocytosis: a disappearing entity
McMullin, M. F. (2009) · Hematology · doi:10.1182/asheducation-2009.1.629 · Cited by 56 · see citing works
Inherited predisposition to myeloproliferative neoplasms
Jones, A. V., & Cross, N. C. P. (2013) · Therapeutic Advances in Hematology · doi:10.1177/2040620713489144 · Cited by 53 · see citing works
The role of PHD2 mutations in the pathogenesis of erythrocytosis
Gardie, B., Percy, M. J., Hoogewijs, D., Chowdhury, R., Bento, C., McMullin, M. F., Schofield, C. J., Lee, F. S., Richard, S., Arsenault, P. R., et al. (2014) · Hypoxia · doi:10.2147/hp.s54455 · Cited by 51 · see citing works
Wenger, R. H., & Kurtz, A. (2011) · Comprehensive physiology · doi:10.1002/cphy.c100075 · Cited by 53 · see citing works
HIF-2α-pVHL complex reveals broad genotype-phenotype correlations in HIF-2α-driven disease
Tarade, D., Robinson, C. M., Lee, J. E., & Ohh, M. (2018) · Nature Communications · doi:10.1038/s41467-018-05554-1 · Cited by 44 · see citing works
Roles of HIF and 2-Oxoglutarate-Dependent Dioxygenases in Controlling Gene Expression in Hypoxia
Frost, J., Frost, M. G., Batie, M., Jiang, H., & Rocha, S. (2021) · Cancers · doi:10.3390/cancers13020350 · Cited by 47 · see citing works
Wang, H., Tang, C., Dang, Z., Yong, A., Liu, L., Wang, S., & Zhao, M. (2022) · Kidney International · doi:10.1016/j.kint.2022.03.027 · Cited by 41 · see citing works
Two new mutations in the <i>HIF2A</i> gene associated with erythrocytosis
Percy, M. J., Chung, Y. J., Harrison, C., Mercieca, J., Hoffbrand, A. V., Dinardo, C. L., Santos, P. C. J. L., Fonseca, G. H. H., Gualandro, S. F. M., Pereira, A. C., et al. (2012) · American Journal of Hematology · doi:10.1002/ajh.23123 · Cited by 37 · see citing works
Chan, X. Y., Volkova, E., Eoh, J. H., Black, R. M., Fang, L., Gorashi, R. M., Song, J., Wang, J., Elliott, M. B., Barreto-Ortiz, S. F., et al. (2021) · iScience · doi:10.1016/j.isci.2021.102246 · Cited by 36 · see citing works
Oxygen-dependent Regulation of Erythropoietin Receptor Turnover and Signaling
Heir, P., Srikumar, T., Bikopoulos, G. J., Bunda, S., Poon, B., Lee, J. E., Raught, B., & Ohh, M. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.694562 · Cited by 36 · see citing works
Current views on cell metabolism in SDHx-related pheochromocytoma and paraganglioma
Vícha, A., Taïeb, D., & Pacák, K. (2014) · Endocrine Related Cancer · doi:10.1530/erc-13-0398 · Cited by 35 · see citing works
Su, J., Li, Z., Cui, S., Ji, L., Geng, H., Chai, K.-X., Ma, X., Bai, Z., Yang, Y., Wuren, T., et al. (2015) · High Altitude Medicine & Biology · doi:10.1089/ham.2015.0015 · Cited by 31 · see citing works
Polycythemia and Paraganglioma With a Novel Somatic HIF2A Mutation in a Male
Toyoda, H., Hirayama, J., Sugimoto, Y., Uchida, K., Ohishi, K., Hirayama, M., & Komada, Y. (2014) · PEDIATRICS · doi:10.1542/peds.2013-2419 · Cited by 29 · see citing works
Perrotta, S., Stiehl, D. P., Punzo, F., Scianguetta, S., Borriello, A., Bencivenga, D., Casale, M., Nobili, B., Fasoli, S., Balduzzi, A., et al. (2013) · Haematologica · doi:10.3324/haematol.2013.088369 · Cited by 28 · see citing works
HIF pathway mutations and erythrocytosis
McMullin, M. F. (2010) · Expert Review of Hematology · doi:10.1586/ehm.09.68 · Cited by 25 · see citing works
Hypoxia-Inducible Factor Stabilizers: a New Avenue for Reducing BP While Helping Hemoglobin?
Yousaf, F., & Spinowitz, B. (2016) · Current Hypertension Reports · doi:10.1007/s11906-016-0629-6 · Cited by 23 · see citing works
Erythrocytosis and polycythemia
van der Walt, J. D. (2011) · Elsevier eBooks · doi:10.1016/b978-0-7020-3147-2.00022-5 · Cited by 23 · see citing works
Hereditary erythrocytosis, thrombocytosis and neutrophilia
Hong, W., & Gotlib, J. R. (2014) · Best Practice & Research Clinical Haematology · doi:10.1016/j.beha.2014.07.002 · Cited by 22 · see citing works
Integration and Visualization of Regulatory Elements and Variations of the EPAS1 Gene in Human
Kristan, A., Debeljak, N., & Kunej, T. (2021) · Genes · doi:10.3390/genes12111793 · Cited by 19 · see citing works
Hypoxia‐Inducible Factor‐2α Signaling in the Skeletal System
Mendoza, S. V., Genetos, D. C., & Yellowley, C. E. (2023) · JBMR Plus · doi:10.1002/jbm4.10733 · Cited by 22 · see citing works
Song, D., Bigham, A. W., & Lee, F. S. (2021) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2021.100461 · Cited by 19 · see citing works
Human Cytomegalovirus Inhibits Erythropoietin Production
Butler, L. M., Džabić, M., Bakker, F., Davoudi, B., Jeffery, H. C., Religa, P., Bojakowski, K., Yaiw, K.-C., Rahbar, A., & Söderberg‐Nauclér, C. (2014) · Journal of the American Society of Nephrology · doi:10.1681/asn.2013101125 · Cited by 16 · see citing works
Kristan, A., Debeljak, N., & Kunej, T. (2019) · European Journal Of Haematology · doi:10.1111/ejh.13304 · Cited by 14 · see citing works
Figg, W. D., Fiorini, G., Chowdhury, R., Nakashima, Y., Tumber, A., McDonough, M. A., & Schofield, C. J. (2023) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.26541 · Cited by 14 · see citing works
Hypoxia stabilizes SETDB1 to maintain genome stability
Park, S., Cho, J. H., Kim, J.-H., Park, S., (18229615), S. P., Kim, S., Kim, S., Kim, K., Park, B. C., Park, B. C., et al. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad796 · Cited by 12 · see citing works
Deficiency in PHD2-mediated hydroxylation of HIF2α underlies Pacak-Zhuang syndrome
Ferens, F. G., Taber, C. C., Stuart, S. E., Hubert, M., Tarade, D., Lee, J. E., & Ohh, M. (2024) · Communications Biology · doi:10.1038/s42003-024-05904-4 · Cited by 13 · see citing works
Kristan, A., Pajič, T., Maver, A., Režen, T., Kunej, T., Količ, R., Vuga, A., Fink, M., Žula, Š., Podgornik, H., et al. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.689868 · Cited by 11 · see citing works
Functional Significance of Erythrocytes
JELKMANN, W. E. B. (2012) · IMPERIAL COLLEGE PRESS eBooks · doi:10.1142/9781848166219_0001 · Cited by 10 · see citing works
HIF2 and endocrine neoplasia: an evolving story
Maher, E. R. (2013) · Endocrine Related Cancer · doi:10.1530/erc-13-0146 · Cited by 8 · see citing works
Wenger, R. H., & Kurtz, A. (2011) · Comprehensive physiology · doi:10.1002/j.2040-4603.2011.tb00381.x · Cited by 5 · see citing works
Kurtz, A., Wenger, R. H., & Eckardt, K. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-381462-3.00092-6 · Cited by 2 · see citing works
Dual control: the HIF-2 regulator
Lappin, T. (2010) · Blood · doi:10.1182/blood-2010-08-297606 · Cited by 1 · see citing works
Management of Renal Anemia in Children with Chronic Kidney Disease
Yorgin, P. D., & Zaritsky, J. J. (2011) · Springer eBooks · doi:10.1007/978-1-4614-0721-8_27 · Cited by 1 · see citing works
Kilambi, K. P., Xu, Q., Gururaj, G. K., Li, K., Artavanis‐Tsakonas, S., Dunbrack, R. L., & Lehmann, A. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.03.14.992149 · Cited by 1 · see citing works
家族性赤血球増加症における低酸素誘導因子(HIF)およびHIF制御分子異常
則夫, 小. (2009) · 臨床血液 · doi:10.11406/rinketsu.50.1589
Weiss, M. J. (2020) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.732587239.793577754
Gregor, T., Karakaya, S., Zethraeus, A., Ostenberg, S., Fredlund, E., Hammarlund, E. U., Hansson, J., Rosenblum, J., & Mohlin, S. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.05.04.722697
- Authors
- Furlow, P. W., Percy, M. J., Sutherland, S., Bierl, C., McMullin, M. F., Master, S. R., Lappin, T. R. J., & Lee, F. S.
- Affiliations
- University of Pennsylvania (US)
- Belfast City Hospital (GB)
- Queen's University Belfast (GB)
- Corresponding author
- Lee, Frank S.
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 284
- Issue
- 14
- Pages
- 9050-9058
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC2666553
- OpenAlex
- W2023382136
- Cited by
- 58
- References
- 38
- Citations by year
- 2026: 1 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 7 · 2020: 3 · 2019: 1 · 2018: 2 · 2016: 3 · 2015: 1 · 2014: 8 · 2013: 8 · 2012: 4
- FWCI
- 4.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (Queen's University Belfast) (submittedVersion)
- Funders
- University of Pennsylvania
- National Institutes of Health
- National Cancer Institute (R01CA090261)
- Topics
- Health Sciences › Medicine › Hematology › Erythropoietin and Anemia Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Genetics › Hemoglobinopathies and Related Disorders
- Keywords
- HIF-2α, erythrocytosis, prolyl hydroxylase 2, PHD2, von Hippel-Lindau protein, hypoxia, protein stability
- MeSH terms
- Endothelial PAS Domain-Containing Protein 1, Amino Acid Sequence, Cell Line, Humans, Hydroxylation, Molecular Sequence Data, Mutation, Polycythemia, Proline, Procollagen-Proline Dioxygenase, Protein Binding, Sequence Alignment, Basic Helix-Loop-Helix Proteins, Basic Helix-Loop-Helix Transcription Factors, Von Hippel-Lindau Tumor Suppressor Protein, Biocatalysis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
