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Gene Review

PHC2  -  polyhomeotic homolog 2 (Drosophila)

Homo sapiens

Synonyms: EDR2, Early development regulatory protein 2, HPH2, PH2, Polyhomeotic-like protein 2, ...
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Disease relevance of PHC2

  • CONCLUSIONS: Risk of early neurological deterioration and of 3-month death was severely increased after PH2, indicating that large hematoma is the only type of hemorrhagic transformation that may alter the clinical course of ischemic stroke [1].
  • Stool specimens were examined for Oxalobacter formigenes in HyOx not related to PH type 1 or 2 (PH1, PH2) and in controls [2].
  • Two of the enzymes, HPH (HIF prolyl hydroxylase)-1 and HPH-2, are known to be inducible by hypoxia in a HIF-dependent manner [3].
  • By contrast, primary hyperoxaluria type 2 (PH2, McKusick 260000) is very rare indeed with only 22 patients recorded since the original description in 1968 [4].
  • PH2 is characterized by hyperoxaluria and L-glyceric aciduria and is caused by deficiency of D-glycerate dehydrogenase/glyoxylate reductase [4].

High impact information on PHC2

  • Hydrogen consumption varied directly with PH2, and methanogenic feces consumed H2 far more rapidly than did nonmethanogenic feces [5].
  • At low PH2, H2 production greatly exceeded consumption and there was negligible accumulation of the products of H2 catabolism, methane and sulfide [5].
  • By transient transfections in beta and non-beta cells, we show that mainly PH1 and PH2 preferentially confer beta-cell-specific activation on a heterologous promoter [6].
  • HPH1 and HPH2 coimmunoprecipitate and cofractionate with each other and with BMI1 [7].
  • HPH1 and HPH2 have little sequence homology with each other, except in two highly conserved domains, designated homology domains I and II [7].

Chemical compound and disease context of PHC2


Biological context of PHC2

  • The highest regeneration rate (>90%) and the largest number of shoot clumps per regenerating leaf (>4 shoot clumps/explant) were obtained with leaves of genotype PH2 cultured on MS basal medium supplemented with 17.76 microM BAP and 4.92 microM IBA [9].
  • We obtained here a monoclonal antibody named PH2 that inhibited macrophage phagocytosis of late apoptotic or necrotic cells, but not of early apoptotic cells [10].
  • These results suggest that the putative PH2 antigen is a novel phagocytosis marker that translocates to the cell surface at late stages of apoptosis, resulting in maximal recognition and engulfment by macrophages [10].
  • This study examines whether the course of adrenarche [rise of serum dehydroepiandrosterone sulfate (DHEAS)] and pubarche (Tanner stage PH2) is independent from ovarian function [11].
  • Rnf110 and Phc2 mutations impair development of PP anlagen by affecting proliferation of lymphoid lineage cells populated in PP anlagen in gene-dosage dependent manner [12].

Anatomical context of PHC2

  • HPH1, HPH2, and BMI1 show distinct, although overlapping expression patterns in different tissues and cell lines [7].
  • In this paper we outline diagnostic criteria for identification of PH2 in two patients, one with maintained renal function and one with ESRF on CPD, based on the use of a novel HPLC assay of L-glycerate in different body fluids [13].
  • Feces incubated at high and intermediate PH2 had a net H2 production of only 1/900 and 1/64 of absolute production [5].
  • Moreover, PH2 bound to apoptotic cells at late stages more efficiently than to those at early stages, and it did not bind to normal cells unless their plasma membrane was permeabilized [10].
  • Rnf110 and Phc2 are shown to be components of mammalian PcG multimeric complexes in HeLa cells [12].

Associations of PHC2 with chemical compounds

  • This comparison revealed three short conserved regions, designated PH1, PH2, and PH3 [14].
  • To elucidate this issue we have measured the bony content of oxalate on biopsies of the iliac crest taken from 32 uremic patients, 7 of them with ESRF associated with PH1 (6 cases) or PH2 (1 case) [15].
  • INTRODUCTION: The levels of urinary noradrenaline (NAd), adrenaline (Ad) and salivary cortisol (Cor) were determined in student and instructor pilots during Phase 1 (training with propeller engine; PH1), and Phase 2 (training with jet engine; PH2) flight training [16].
  • Neutral and especially dianionic 6- and 12-vertex closo ortho-carboranes (o-carboranes) 1,2-R2-1,2-C2BnHn (R = H, CH3, NH2, OH, F, SiH3, PH2, SH, Cl, as well as e-, CH2-, NH-, O-, SiH2-, PH-, and S- exhibit extremely large variations (over 1 A!) of the cage CC distances, from 1.626 to 2.638 A, at the B3LYP/6-31G//B3LYP/6-31G DFT level [17].
  • We previously isolated a monoclonal antibody named PH2 that inhibits phosphatidylserine-mediated phagocytosis of apoptotic cells by macrophages [18].

Physical interactions of PHC2

  • Two-hybrid analysis shows that homology domain II of HPH1 interacts with both homology domains I and II of HPH2 [7].

Other interactions of PHC2

  • These data demonstrate the involvement of homology domains I and II in protein-protein interactions and indicate that HPH1 and HPH2 are able to heterodimerize [7].
  • The interaction of MK2 with the 66 kDa isoform of ShcA, p66(ShcA), and HPH2 was confirmed using co-immunoprecipitation [19].
  • The mean age found for B2 was 10.30 +/- 0.28 years; for B3 was 11.01 +/- 0.16 years; for PH2 was 10.58 +/- 0.22 years; for PH3 was 11.39 +/- 0.11 years; and for menarche was 13.29 +/- 0.45 years [20].
  • While genetic analysis of PH2 is still at a relatively early stage, the AGXT gene defective in the Type 1 disorder is well characterized, and a number of mutations have been identified [21].

Analytical, diagnostic and therapeutic context of PHC2

  • Genomic DNA studies have identified those genetic defects of PH1 and PH2 that allow a precise early diagnosis [22].
  • However, there is little doubt of the value of genetic methods (mutation and linkage analysis) for diagnosing PH1 (and eventually PH2) in other family members and for prenatal diagnosis and carrier testing [21].
  • The performance of these detector arrays was evaluated against IMRT dose distributions created and calculated with Konrad and the results obtained were compared with film measurements performed with radiographic films (EDR2, Kodak) [23].
  • As a result, in the dose range that is commonly used for film dosimetry for IMRT and conventional external beam therapy, the sensitometric curves of EDR2 films cannot be approximated as a linear function, OD = c * D [24].
  • Intensity-modulated radiotherapy (IMRT) treatment plan verification is often done using Kodak EDR2 film and a Vidar Dosimetry PRO film digitizer [25].


  1. Hemorrhagic transformation within 36 hours of a cerebral infarct: relationships with early clinical deterioration and 3-month outcome in the European Cooperative Acute Stroke Study I (ECASS I) cohort. Fiorelli, M., Bastianello, S., von Kummer, R., del Zoppo, G.J., Larrue, V., Lesaffre, E., Ringleb, A.P., Lorenzano, S., Manelfe, C., Bozzao, L. Stroke (1999) [Pubmed]
  2. Urinary oxalate excretion in urolithiasis and nephrocalcinosis. Neuhaus, T.J., Belzer, T., Blau, N., Hoppe, B., Sidhu, H., Leumann, E. Arch. Dis. Child. (2000) [Pubmed]
  3. Endogenous 2-oxoacids differentially regulate expression of oxygen sensors. Dalgard, C.L., Lu, H., Mohyeldin, A., Verma, A. Biochem. J. (2004) [Pubmed]
  4. Primary hyperoxaluria type 2. Mansell, M.A. Nephrol. Dial. Transplant. (1995) [Pubmed]
  5. Factors affecting hydrogen production and consumption by human fecal flora. The critical roles of hydrogen tension and methanogenesis. Strocchi, A., Levitt, M.D. J. Clin. Invest. (1992) [Pubmed]
  6. Functional conservation of regulatory elements in the pdx-1 gene: PDX-1 and hepatocyte nuclear factor 3beta transcription factors mediate beta-cell-specific expression. Marshak, S., Benshushan, E., Shoshkes, M., Havin, L., Cerasi, E., Melloul, D. Mol. Cell. Biol. (2000) [Pubmed]
  7. Identification and characterization of interactions between the vertebrate polycomb-group protein BMI1 and human homologs of polyhomeotic. Gunster, M.J., Satijn, D.P., Hamer, K.M., den Blaauwen, J.L., de Bruijn, D., Alkema, M.J., van Lohuizen, M., van Driel, R., Otte, A.P. Mol. Cell. Biol. (1997) [Pubmed]
  8. Primary hyperoxaluria type 2 in children. Johnson, S.A., Rumsby, G., Cregeen, D., Hulton, S.A. Pediatr. Nephrol. (2002) [Pubmed]
  9. Adventitious shoot regeneration from in vitro cultured leaves of London plane tree (Platanus acerifolia Willd.). Liu, G., Bao, M. Plant Cell Rep. (2003) [Pubmed]
  10. Difference in the way of macrophage recognition of target cells depending on their apoptotic states. Fujii, C., Shiratsuchi, A., Manaka, J., Yonehara, S., Nakanishi, Y. Cell Death Differ. (2001) [Pubmed]
  11. The early dehydroepiandrosterone sulfate rise of adrenarche and the delay of pubarche indicate primary ovarian failure in Turner syndrome. Martin, D.D., Schweizer, R., Schwarze, C.P., Elmlinger, M.W., Ranke, M.B., Binder, G. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  12. Mammalian Polycomb complexes are required for Peyer's patch development by regulating lymphoid cell proliferation. Sato, T., Endoh, M., Yoshida, H., Yasuo, S., Katsuno, T., Saito, Y., Isono, K., Koseki, H. Gene (2006) [Pubmed]
  13. Detection of primary hyperoxaluria type 2 (L-glyceric aciduria) in patients with maintained renal function or end-stage renal failure. Marangella, M., Petrarulo, M., Cosseddu, D., Vitale, C., Cadario, A., Barbos, M.P., Gurioli, L., Linari, F. Nephrol. Dial. Transplant. (1995) [Pubmed]
  14. Regulatory elements involved in human pdx-1 gene expression. Marshak, S., Ben-Shushan, E., Shoshkes, M., Havin, L., Cerasi, E., Melloul, D. Diabetes (2001) [Pubmed]
  15. Bony content of oxalate in patients with primary hyperoxaluria or oxalosis-unrelated renal failure. Marangella, M., Vitale, C., Petrarulo, M., Tricerri, A., Cerelli, E., Cadario, A., Barbos, M.P., Linari, F. Kidney Int. (1995) [Pubmed]
  16. Hormonal responses of pilots to training flights: the effects of experience on apparent stress. Otsuka, Y., Onozawa, A., Miyamoto, Y. Aviation, space, and environmental medicine. (2006) [Pubmed]
  17. Strikingly long C...C distances in 1,2-disubstituted ortho-carboranes and their dianions. Oliva, J.M., Allan, N.L., Schleyer, P.V., Viñas, C., Teixidor, F. J. Am. Chem. Soc. (2005) [Pubmed]
  18. Externalization and recognition by macrophages of large subunit of eukaryotic translation initiation factor 3 in apoptotic cells. Nakai, Y., Shiratsuchi, A., Manaka, J., Nakayama, H., Takio, K., Zhang, J.T., Suganuma, T., Nakanishi, Y. Exp. Cell Res. (2005) [Pubmed]
  19. P66(ShcA) interacts with MAPKAP kinase 2 and regulates its activity. Yannoni, Y.M., Gaestel, M., Lin, L.L. FEBS Lett. (2004) [Pubmed]
  20. Sexual maturation of Jerusalem schoolgirls and its association with socio-economic factors and ethnic group. Belmaker, E. Ann. Hum. Biol. (1982) [Pubmed]
  21. Biochemical and genetic diagnosis of the primary hyperoxalurias: a review. Rumsby, G. Molecular urology. (2000) [Pubmed]
  22. Oxalate crystal deposition disease. Maldonado, I., Prasad, V., Reginato, A.J. Current rheumatology reports. (2002) [Pubmed]
  23. Dosimetric quality assurance for intensity-modulated radiotherapy feasibility study for a filmless approach. Wiezorek, T., Banz, N., Schwedas, M., Scheithauer, M., Salz, H., Georg, D., Wendt, T.G. Strahlentherapie und Onkologie : Organ der Deutschen Röntgengesellschaft ... [et al]. (2005) [Pubmed]
  24. Evaluation of Kodak EDR2 film for dose verification of intensity modulated radiation therapy delivered by a static multileaf collimator. Zhu, X.R., Jursinic, P.A., Grimm, D.F., Lopez, F., Rownd, J.J., Gillin, M.T. Medical physics. (2002) [Pubmed]
  25. Comparison of the epson expression 1680 flatbed and the vidar VXR-16 dosimetry PRO film scanners for use in IMRT dosimetry using gafchromic and radiographic film. Wilcox, E., Daskalov, G., Nedialkova, L. Medical physics (2007) [Pubmed]
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