8.A.74 The TM9 or Phg1 Targeting Receptor (Ppg1) Family 

TM9 family proteins (also named Phg1 proteins) control cell adhesion by determining the cell surface localization of adhesion proteins such as the Dictyostelium SibA protein. Perrin et al. 2015 showed that the glycine-rich transmembrane segments (TMSs) of SibA is sufficient to confer Phg1A-dependent surface targeting to a reporter protein. In Dictyostelium phg1A- knockout (KO) cells, proteins with glycine-rich TMSs were less efficiently transported out of the endoplasmic reticulum (ER) and to the cell surface. Phg1A, as well as its human ortholog TM9SF4 specifically associated with glycine-rich TMSs. In human cells, genetic inactivation of TM9SF4 resulted in an increased retention of glycine-rich TMSs in the endoplasmic reticulum, whereas TM9SF4 overexpression enhanced their surface localization. The bulk of the TM9SF4 protein was localized in the Golgi complex, and a proximity-ligation assay suggested that it might interact with glycine-rich TMSs. It thus appears that one of the main roles of TM9 proteins is to serve as intramembrane cargo receptors controlling exocytosis and surface localization of a subset of membrane proteins.

This family belongs to the .



Lee, S.J., T. Uemura, T. Yoshida, and M. Mishina. (2012). GluRĪ“2 assembles four neurexins into trans-synaptic triad to trigger synapse formation. J. Neurosci. 32: 4688-4701.

Matsuda, K. (2016). Synapse organization and modulation via C1q family proteins and their receptors in the central nervous system. Neurosci Res. [Epub: Ahead of Print]

Perrin, J., M. Le Coadic, A. Vernay, M. Dias, N. Gopaldass, H. Ouertatani-Sakouhi, and P. Cosson. (2015). TM9 family proteins control surface targeting of glycine-rich transmembrane domains. J Cell Sci 128: 2269-2277.


TC#NameOrganismal TypeExample

Integrin β-like protein A of 1927 aas and 2 TMSs, N- and C-terminal, Sib1 of the TM9 (Phg1) family. Serves as an intramembrane cargo receptor controlling exocytosis and surface localization of a subset of membrane proteins (Perrin et al. 2015).

Sib1 of Dictyostelium discoideum (Slime mold)


Neurexin-1 (NRX1) of 1477 aas and 2 TMSs, one N-terminal and one C-terminal.  It is a cell surface protein involved in cell-cell-interactions, exocytosis of secretory granules and regulation of signal transmission including several transport systems. Neurexin function is isoform-specific. It is found in trans-synaptic tripartite complexes which consist of one unit of the cerebellin-1 (Cbln1) hexamer,  four monomeric neurexins containing a splice site 4 insertion at presynaptic terminals and the postsynaptic GluD2 dimers (Matsuda 2016). The trans-synaptic interaction of postsynaptic glutamate receptor δ2 (GluRδ2, an orthologue of TC#1.A.10.1.8) and presynaptic neurexins through cerebellin precursor protein 1 (Cbln1) mediates synapse formation in vivo in the cerebellum (Lee et al. 2012). Members of the neurexin family appear to be homologous to domains in some members of TC family 9.B.87.

Neurexin-1 of Homo sapiens