The testis-enhanced gene transcript (TEGT) family includes the testis-enhanced gene transcript proteins of mammals, which are expressed at high levels in the testis, the putative glutamate/aspartate binding proteins of plants and animals, the YccA protein of '' Escherichia coli'' and the YetJ protein of '' Bacillus subtilis''. These proteins are about 200-250 residues in length and exhibit 7 TMSs.

Homology

Homologues are found in a variety of Gram-negative and

Gram-positive bacteria In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...

, yeast, fungi, plants, animals and viruses. The ''E. coli'' genome encodes three paralogues, YbhL, YbhM and YccA. Distant homologues found in '' Drosophilia melanogaster'' and the rat are the N-methyl-D-aspartate receptor-associated protein (NMDARAI) and the N-methyl-D-aspartate receptor glutamate binding chain, respectively. Two others are the rat neural membrane protein 35 and the ''

Arabidopsis thaliana ''Arabidopsis thaliana'', the thale cress, mouse-ear cress or arabidopsis, is a small flowering plant native to Eurasia and Africa. ''A. thaliana'' is considered a weed; it is found along the shoulders of roads and in disturbed land. A winter a ...

'' Bax inhibitor-1 (BI-1) protein capable of suppressing Bax-induced cell death in yeast.

BI-1

One of these proteins, TEGT or the Bax Inhibitor-1
TC# 1.A.14.1.1
, has a C-terminal domain that forms a Ca²⁺-permeable channel. BI-1 is an ER-localized protein that protects against

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

and ER stress. BI-1 has been proposed to modulate ER Ca²⁺ homeostasis by acting as a Ca²⁺-leak channel. These proteins are distantly related to the ionotropic glutamate-binding protein of the N-methyl D-aspartate (NMDA) receptor of man. Homologues include a putative cold shock inducible protein and a SecY stabilizing protein.

Function

Based on experimental determination of the BI-1 topology, Bultynck et al. proposes that its C-terminal α-helical 20 amino acid peptide catalyzes Ca²⁺ flux both ''in vivo'' and ''in vitro''. The Ca²⁺-leak properties were conserved among animal, but not plant and yeast orthologs. By mutating one of the critical aspartate residues (D₂₁₃) in the proposed Ca²⁺-channel pore in full-length BI-1, D₂₁₃ proved to be essential for BI-1 dependent ER Ca²⁺-leak.

Structure

Chang ''et al.'' published crystal structures of a bacterial homolog, YetJ
TC# 1.A.14.2.3
at 1.9 Å resolution and characterized its calcium leak activity. Its seven-transmembrane-helix fold features two triple-helix sandwiches wrapped around a central C-terminal helix. Structures obtained in closed and open conformations are reversibly interconvertible by changes in the pH. A hydrogen-bonded perturbed pair of conserved aspartyl residues explains the pH dependence of this transition, and the pH regulates calcium influx in proteoliposomes. Homology models for human BI-1 provided insight into its cytoprotective activity.

Transport Reaction

The generalized reaction catalyzed by TEGT channels is: : cations (out) ⇌ cations (in)

References

{{CCBYSASource, sourcepath=http://tcdb.org/search/result.php?tc=1.A.14, sourcearticle=1.A.14 The Testis-Enhanced Gene Transfer (TEGT) Family, revision=699838558 Protein families Membrane proteins Transmembrane proteins Transmembrane transporters Transport proteins Integral membrane proteins