Hemogen (HEMGN)
The protein contains 484 amino acids for an estimated molecular weight of 55341 Da.
Regulates the proliferation and differentiation of hematopoietic cells. Overexpression block the TPA-induced megakaryocytic differentiation in the K562 cell model. May also prevent cell apoptosis through the activation of the nuclear factor-kappa B (NF-kB). (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Cell differentiation
Multicellular organism development
Regulation of osteoblast differentiation
Molecular Function
The reference OMIM entry for this protein is 610715
Hemogen; hemgn
Erythroid differentiation-associated gene; edag
CLONING
Yang et al. (2001) cloned mouse Hemgn and, by database analysis and RT-PCR of a K562 myelogenous leukemia cell line cDNA library, they cloned human HEMGN, or EDAG. The deduced mouse and human proteins contain 503 and 484 amino acids, respectively, and share 43% identity. A coiled-coil region and bipartite nuclear localization signal are conserved in the N termini of both proteins. Northern blot analysis detected a major 2.4-kb transcript and a minor 1.8-kb transcript in adult human bone marrow and fetal liver. RT-PCR detected high HEMGN expression in untreated and mitogen-treated K562 cells, adult bone marrow, and CD34 (142230)-positive progenitor cells. Lower expression was detected in a child thymus and in a histiocyte lymphoma cell line, but no expression was detected in cultured T cells, monocytes, and nonhematopoietic cell lines examined. Northern blot analysis of adult mice detected Hemgn expression in bone marrow and spleen, but not in thymus and nonhematopoietic tissues. In situ hybridization of adult spleen revealed Hemgn in red, but not white, pulp. In situ hybridization of day-8.5 mouse embryos showed Hemgn in blood islands of the yolk sac and in circulating primitive blood cells. Hemgn was expressed in developing hepatic primordia at day 10.5 and, from day 11.5, it was expressed exclusively in fetal liver. FACS analysis showed Hemgn in hematopoietic precursors of adult mice, but not in mature blood cells. Transfected COS-7 cells expressed mouse Hemgn in nuclei, but not in nucleoli or cytoplasm. By database analysis, Yang et al. (2003) identified a testis-specific HEMGN splice variant that they called HEMGN-t. HEMGN-t and the hematopoietic variant, HEMGN-h, differ in their 5-prime and 3-prime UTRs, but they have the same coding region. Northern blot analysis detected a 1.9-kb HEMGN-t transcript in mouse and human testis. In situ hybridization of adult mouse testis revealed Hemgn only in round spermatids. Northern blot analysis showed that Hemgn expression in prepubertal mouse testis correlated with the appearance of postmeiotic cells, and Hemgn expression was weak in testis of mice lacking postmeiotic germ cells.GENE FUNCTION
Li et al. (2004) found that downregulation of EDAG in K562 cells resulted in inhibition of growth and colony formation, as well as enhancement of sensitivity to erythroid differentiation induced by hemin. Overexpression of EDAG in a human myeloid leukemia cell line significantly blocked expression of the monocyte/macrophage differentiation marker CD11b (ITGAM; 120980) after mitogen exposure. Moreover, overexpression of EDAG in a mouse pro-B cell line prolonged survival and increased expression of Myc (190080), Bcl2 (151430), and Bclxl (600039) in the absence of interleukin-3 (IL3; 147740). EDAG enhanced the transcriptional activity of NF-kappa-B (NFKB; see 164011), and high DNA-binding activity of Nfkb was sustained in EDAG-expressing pre-B cells after IL3 withdrawal. In these cells, inhibition of Nfkb activity promoted cell death. Li et al. (2004) concluded that EDAG regulates proliferation and differentiation of hematopoietic cells and resists cell death through activation of NFKB. By examining expression of a mouse Hemgn promoter-reporter plasmid in transgenic mice, Yang et al. (2006) showed that the promoter was transcriptionally active in embryonic yolk sac, fetal liver, and adult spleen, bone marrow, brain, thymus, lung, and testis. Mutagenesis analysis showed that 2 ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 610715 was added.