HVEM (Fc-Fusion)

HVEM, a member of the TNF receptor family, contains two perfect and two imperfect TNFR-like cysteine-rich domains (CRDs) and a short cytoplasmic tail with some similarity to 4-1BB and CD40.

Interacting protein(s): LT-a (P7006M), LIGHT, BTLA
Related products: TNF-Receptor Superfamily

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Quick Specs

Description

HVEM, a member of the TNF receptor superfamily, contains two perfect and two imperfect TNFR-like cysteine-rich domains (CRDs) and a short cytoplasmic tail with some similarity to 4-1BB and CD40. HVEM was initially identified as the cell surface molecule mediating the entry of herpesvisu (HSV) into T lymphocytes. HVEM interacts with three proteins, LIGHT, LT-α (lymphotoxin-α), and BTLA (B and T lymphocyte attenuator).

Importantly, in contrast to LIGHT and LT-α (both are members of TNF superfamily), BTLA belongs to Ig superfamily and is structurally related to the CD28 protein family. Hence, the connection between BTLA and HVEM was not expected. HVEM was described as a co-stimulator triggered by LIGHT and LT-α. However, studies of HVEM-deficient mice and interaction between BTLA and HVEM revealed that HVEM also plays a co-inhibitory role.

In addition to binding BTLA, LIGHT and LT-α, HVEM also interacts with the herpes simplex virus I glycoprotein D (gD) which facilitates virus entry. HVEM mutations have been associated to cases of diffuse large B-cell lymphoma.

Amino Acid Sequence.

References

1. Wojciechowicz K, Spodzieja M, Lisowska KA, Wardowska A. The role of the BTLA-HVEM complex in the pathogenesis of autoimmune diseases. Cell Immunol. 2022;376:104532. Epub 20220505. doi: 10.1016/j.cellimm.2022.104532. PubMed PMID: 35537322.

2. Herpes simplex virus-1 entry into cells mediated by a novel member of the TNF/NGF receptor family. Montgomery R.I., Warner M.S., Lum B.J., Spear P.G. Cell 87:427-436 (1996)

3. A newly identified member of the tumor necrosis factor receptor superfamily with a wide tissue distribution and involvement in lymphocyte activation. Kwon B.S., Tan K.B., Ni J., Oh K.-O., Lee Z.H., Kim K.K., Kim Y.-J., Wang S., Gentz R., Yu G.-L., Harrop J., Lyn S.D., Silverman C., Porter T.G., Truneh A., Young P.R. J. Biol. Chem. 272:14272-14276 (1997) 

4. Herpes simplex virus glycoprotein D can bind to poliovirus receptor-related protein 1 or herpesvirus entry mediator, two structurally unrelated mediators of virus entry. Krummenacher C., Nicola A.V., Whitbeck J.C., Lou H., Hou W., Lambris J.D., Geraghty R.J., Spear P.G., Cohen G.H., Eisenberg R.J. J. Virol. 72:7064-7074 (1998)

5. Attenuating lymphocyte activity: the crystal structure of the BTLA-HVEM complex. Compaan D.M., Gonzalez L.C., Tom I., Loyet K.M., Eaton D., Hymowitz S.G. J. Biol. Chem. 280:39553-3956 (2005)