HEMO protein
| HEMO | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | ERVMER34-1 | ||||||
| Alt. symbols | HEMO, ENVMER34 | ||||||
| NCBI gene | 100288413 | ||||||
| HGNC | 42970 | ||||||
| UniProt | Q9H9K5 | ||||||
| |||||||
HEMO (Human Endogenous MER34 ORF, or ERVMER34-1) is a human endogenous retroviral (HERV) envelope protein encoded by a proviral remnant of the MER34 retrovirus family on chromosome 4.[1] It was identified in 2017 at Institut Gustave Roussy.
Structure
The HEMO protein is 563 amino acids in length and retains several structural features of a retroviral envelope protein, including an N-terminal signal peptide, a CWLC motif in the surface (SU) subunit, and a transmembrane domain (TM).[1] Unlike other retroviral envelope proteins, HEMO is non-fusogenic: it has lost its furin cleavage site between the SU and TM subunits as well as its fusion peptide.[2] The gene is transcribed from a cellular CpG island promoter rather than a retroviral long terminal repeat (LTR).[1] A soluble shed form of the protein is released by metalloprotease cleavage upstream of the transmembrane domain, allowing detection in blood plasma.[1]
Overview
The endogenization even for the HEMO retroviral gene is estimated to have occurred more than 100 million years ago (Mya), prior to the divergence of Laurasiatheria and Euarchontoglire.[3]
HEMO is expressed at high levels in the placenta and in embryonic stem cells as well as induced pluripotent stem cells (iPSCs).[1] The shed soluble form is detectable in the blood of pregnant women.[2] In normal somatic tissues, the expression is low. A 2025 study identified BACE2 as a molecular partner of the HEMO protein.[2]
Clinical significance
HEMO has been proposed as a tumour biomarker and a potential immunotherapeutic target, given its preferential expression in tumour tissues relative to normal somatic cells and its presence at the cell surface and in blood.[1]
References
- 1 2 3 4 5 6 Heidmann, Odile; Vernochet, Christophe; Dupressoir, Anne; Heidmann, Thierry (2017). "HEMO, an ancestral endogenous retroviral envelope protein shed in the blood of pregnant women and expressed in pluripotent stem cells and tumors". Proceedings of the National Academy of Sciences. 114 (32): E6642–E6651. doi:10.1073/pnas.1702204114. PMC 5559007. PMID 28739914.
- 1 2 3 Béguin, Anthony; Chasseriaud, Marianne; Hollaender, Guillaume; Jacob, Yves; Mousseau, Guillaume; Heidmann, Thierry; Heidmann, Odile (2025). "The human endogenous retroviral envelope HEMO protein interacts with BACE2: Novel partnership acquired in the primate lineage". Proceedings of the National Academy of Sciences. 122 (49) e2515527122. doi:10.1073/pnas.2515527122. PMID 41329733.
- ↑ Kasperek, Emeline; Carpentier, Rodolphe; Béguin, Anthony; Guilbert, Thibault; Foulongne, Vincent; Pivert, Alexis; Vauléon, Élodie; Heidmann, Thierry; Heidmann, Odile (2022). "Therapeutic potential of the human endogenous retroviral envelope protein HEMO: a pan-cancer analysis". Molecular Oncology. 16: 1451–1473. doi:10.1002/1878-0261.13069. PMC 8978518. PMID 34741395.