TCDB is operated by the Saier Lab Bioinformatics Group
TCIDNameDomainKingdom/PhylumProtein(s)
*3.A.19.1.1









The ATP hydrolysis-dependent TRC receptor TRC40 (Asna-1) (Stefanovic and Hegde, 2007). (TRC40 is homologous to the ArsA ATPase of E. coli (TC# 3.A.4.1.1) and the GET3 ATPase of yeast (TC# 8.A.26.1.1)) Loss yields embryonic lethality. Tryptophan-rich basic protein (WRB) is the tail-anchored (TA) protein insertion receptor. Also called congenital heart disease protein-5 (CHD5). Related to the yeast Get1 protein in 3.A.21.1.1. Calcium-modulating cyclophilin ligand (CAML) is a mammal-specific receptor for TRC40, an ATPase targeting newly synthesized TA proteins.  CAML mediates membrane insertion of TA proteins.  TRC40 (Asna1) has been shown to mediate membrane insertion of two proteins, RAMP4 and Sec61beta, without the participation of other cytosolic proteins by a mechanism that depends on the presence of ATP or ADP and a protease-sensitive receptor in the ER membrane (Favaloro et al. 2010).  TRC40 is required for release of Herpes simplex virus 1 (HSV1) virions (Ott et al. 2016). The functions and reciprocal interactions of the two subunits of the heteromeric TRC40 recpeptor, WBR and CAML (CAMLG), have revealed mutual dependencies for stability; CAML seems to normally be present in 5-fold excess over WBR (Colombo et al. 2016). CAMLG interacts with Classical Swine Fever Virus (CSFV) p7 and mediates calcium permeability in the ER (Gladue et al. 2018).

Eukaryota
Metazoa
The TRC complex of Homo sapiens
TRC40 (O43681)
WRB (CHO5) (O00258)
CAML (P49069)
*3.A.19.1.2









GET1 protein homologue

Eukaryota
Fungi
GET1 of Aspergillus niger (A2QHQ3)
*3.A.19.1.3









Get3 ATPase homologue of 349 aas and 0 TMSs that drives the insertion of tail anchored (TA) proteins into the endoplasmic reticulum membrane.  The 3-d structure of the tetramer has been solved (Suloway et al. 2012). The tetramer generates a hydrophobic chamber that probably binds the single C-terminal TMS of the TA protein.

Archaea
Euryarchaeota
Get3 ATPase of Methanocaldococcus jannaschii (Methanococcus jannaschii)
*3.A.19.1.4









ArsA1 of 777 aas.  ATPase required for the post-translational delivery of tail-anchored (TA) proteins to the chloroplast. It is required for the accumulation of TOC34, an essential component of the outer chloroplast membrane translocon (TOC) complex (Formighieri et al. 2013, Maestre-Reyna et al. 2017). ArsA1 recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. This complex then targets the protein to the chloroplast, where the tail-anchored protein is released for insertion. This process is regulated by ATP binding and hydrolysis (Maestre-Reyna et al. 2017). Both ArsA proteins exhibit oxyanion-independent ATPase activity, but co-expression of ArsA proteins with TA-transmembrane regions showed not only that the former interact with the latter, but that ArsA1 does not share the same ligand specificity as ArsA2. ArsA1 mainly carries TA-proteins to the chloroplast, while ArsA2 carries them to the endoplasmic reticulum (Maestre-Reyna et al. 2017).

Eukaryota
Viridiplantae
ArsA1 of Chlamydomonas reinhardtii (Chlamydomonas smithii)
*3.A.19.1.5









ArsA2 of 362 aas (see description for ArsA1 (TC# 3.A.19.1.4) which has a similar function, but instead of targetting the chloroplast, ArsA2 targets the ER.  It recognizes and selectively binds the transmembrane domain of TA proteins in the cytosol. This complex then targets to the endoplasmic reticulum by membrane-bound receptors, where the tail-anchored protein is released for insertion. This process is regulated by ATP binding and hydrolysis (Maestre-Reyna et al. 2017). ATP binding drives the homodimer towards the closed dimer state, facilitating recognition of newly synthesized TA membrane proteins. ATP hydrolysis is required for insertion. Subsequently, the homodimer reverts towards the open dimer state, lowering its affinity for the membrane-bound receptor, and returning it to the cytosol to initiate a new round of targeting.

Eukaryota
Viridiplantae
ArsA2 of Chlamydomonas reinhardtii (Chlamydomonas smithii)
*3.A.19.2.1









CHD5 homologue

Eukaryota
Viridiplantae
GET1 homologue of Glycine max (I1L4Q8)
*3.A.19.2.2









CHD5 homologue

Eukaryota
Viridiplantae
GET homologue of Arabdiopsis thaliana (Q1H5D2)