9.B.199 The 4 TMS PF05225 (PF0225) Family

The PF05225 family consists of uncharacterized 4 TMS proteins containing the conserved Pfam domain UPF0220 (Attwood et al. 2016).  Some members of the family appear to be involved in vacuolar protein trafficking in yeast (Schluter et al. 2008). Additionally, targeted degradation of integral membrane proteins is ensured by a complex network of proteins, among which the endosomal sorting complex required for transport (ESCRT) plays a central role (Isono and Kalinowska 2017) (see 9.B.199.1.7).

This family belongs to the .



Attwood, M.M., A. Krishnan, V. Pivotti, S. Yazdi, M.S. Almén, and H.B. Schiöth. (2016). Topology based identification and comprehensive classification of four-transmembrane helix containing proteins (4TMs) in the human genome. BMC Genomics 17: 268.

Isono, E. and K. Kalinowska. (2017). ESCRT-dependent degradation of ubiquitylated plasma membrane proteins in plants. Curr. Opin. Plant Biol. 40: 49-55. [Epub: Ahead of Print]

Künzl, F., S. Früholz, F. Fäßler, B. Li, and P. Pimpl. (2016). Receptor-mediated sorting of soluble vacuolar proteins ends at the trans-Golgi network/early endosome. Nat Plants 2: 16017.

Schluter, C., K.K. Lam, J. Brumm, B.W. Wu, M. Saunders, T.H. Stevens, J. Bryan, and E. Conibear. (2008). Global analysis of yeast endosomal transport identifies the vps55/68 sorting complex. Mol. Biol. Cell 19: 1282-1294.


TC#NameOrganismal TypeExample

Uncharacterized TMEM50A protein of 157 aas and 4 TM

TMEM50A of Homo sapiens


The TMEM50B or TM255B protein of 158 aas and 4 TMSs.

TMEM50B of Homo sapiens


Transmembrane protein 50A, TMEM50A of 135 aas and 4 TMSs

TMEM50A of Medicago truncatula (Barrel medic) (Medicago tribuloides)


Transmembrane protein with UPF0220 domain of 173 aas and 4 TMSs.

UPF0220 domain-containing protein of Aspergillus clavatus


Vacuolar sorting protein, Vps68 of 170 aas and 4 TMSs (Künzl et al. 2016).

Vps68 of Schizosaccharomyces pombe (Fission yeast)


Uncharacterized protein of 141 aas and 4 TMSs

UP of Leishmania braziliensis


Vacuolar protein sorting-associated protein 68, Vps68, of 184 aas and 4 TMSs.  Vps55p and Vps68p form a complex that acts with or downstream of ESCRT function to regulate endosomal trafficking. Loss of Vps68p disrupts recycling to the trans-Golgi network (TGN) as well as onward trafficking to the vacuole without preventing the formation of lumenal vesicles (Schluter et al. 2008).

Vps68 of Saccharomyces cerevisiae (Baker's yeast)


Uncharacterized protein of 218 aas and 4 TMSs.

UP of Guillardia theta