1.A.64 The Plasmolipin (Plasmolipin) Family

Plasmolipin (PLLP) is an 18-kDa proteolipid or lipoprotein found in kidney and brain, where it is restricted to the apical surface of tubular epithelial cells and to mammalian myelinated tracts, respectively. This protein is made during sciatic nerve development and regeneration in the rat. It has 182 aas and 4 TMSs (Fischer and Sapirstein, 1994). Addition of plasmolipin to lipid bilayers induces the formation of ion channels, which are voltage-dependent and K+-selective (Tosteson and Sapirstein, 1981). PLLP functions in myelin biogenesis through organization of myelin liquid-ordered membranes in the Golgi complex (Yaffe et al. 2015).

Plasmolipin has many homologues. These are referred to as CKLF-like MARVEL transmembrane domain containing protein, chemokine-like factor and T-cell differentiation marker (Mitsugumin and Synaptogyrin). Most are about 180 residues, but several are about twice as large with 8 TMSs and an internal repeat (e.g., the myeloid-associated differentiation marker of humans (MAL or MYADM; Q96S97) or the rat (EAL84950). Synthesis of these proteins are induced by retinoic acid (Cui et al., 2001). 

Plasmolipin localizes to and recycles between the plasma membrane and the Golgi complex. In the Golgi complex, it forms oligomers which block Golgi to plasma membrane transport of the secretory  vesicular stomatitis virus G protein (VSVG) (Yaffe et al. 2015).

The transport reaction that occurs with plasmolipin in artificial membranes is:

Ions (in) Ions (out)

This family belongs to the Tetraspan Junctional Complex Protein (4JC) Superfamily.



Carmosino, M., F. Rizzo, G. Procino, D. Basco, G. Valenti, B. Forbush, N. Schaeren-Wiemers, M.J. Caplan, and M. Svelto. (2010). MAL/VIP17, a New Player in the Regulation of NKCC2 in the Kidney. Mol. Biol. Cell 21: 3985-3997.

Cui W., L. Yu, H. He, Y. Chu, J. Gao, B. Wan, L. Tang, S. Zhao. (2001). Cloning of human myeloid-associated differentiation marker (MYADM) gene whose expression was up-regulated in NB4 cells induced by all-trans retinoic acid. Mol Biol Rep. 28(3): 123-138.

Fischer I. and V.S. Sapirstein. (1994). Molecular cloning of plasmolipin. Characterization of a novel proteolipid restricted to brain and kidney. J. Biol. Chem. 269: 24912-24919.

Hartzell, H.C., Z. Qu, K. Yu, Q. Xiao, and L.T. Chien. (2008). Molecular physiology of bestrophins: multifunctional membrane proteins linked to best disease and other retinopathies. Physiol. Rev. 88: 639-672.

Li, D., C. Jin, C. Yin, Y. Zhang, B. Pang, L. Tian, W. Han, D. Ma, and Y. Wang. (2007). An alternative splice form of CMTM8 induces apoptosis. Int J Biochem. Cell Biol. 39: 2107-2119.

Miyazaki, A., S. Yogosawa, A. Murakami, and D. Kitamura. (2012). Identification of CMTM7 as a transmembrane linker of BLNK and the B-cell receptor. PLoS One 7: e31829.

Steed, E., N.T. Rodrigues, M.S. Balda, and K. Matter. (2009). Identification of MarvelD3 as a tight junction-associated transmembrane protein of the occludin family. BMC Cell Biol 10: 95.

Tosteson, M.T. and V.S. Sapirstein. (1981). Protein interactions with lipid bilayers: the channels of kidney plasma membrane proteolipids. J. Membr. Biol. 63: 77-84.

Yaffe, Y., I. Hugger, I.N. Yassaf, J. Shepshelovitch, E.H. Sklan, Y. Elkabetz, A. Yeheskel, M. Pasmanik-Chor, C. Benzing, A. Macmillan, K. Gaus, Y. Eshed-Eisenbach, E. Peles, and K. Hirschberg. (2015). The myelin proteolipid plasmolipin forms oligomers and induces liquid-ordered membranes in the Golgi complex. J Cell Sci 128: 2293-2302.


TC#NameOrganismal TypeExample
1.A.64.1.1Channel-forming Plasmolipin (Fischer and Sapirstein, 1994)AnimalsPlasmolipin of Rattus norvegicus (P47987)

TC#NameOrganismal TypeExample

Myelin and Lymphocyte Protein, MAL/VIP17 protein, a regulator of NKCC2 (2.A.30.1.1). It stabilizes kidney apical membranes, and facilitates sorting of proteins to these membranes (Carmosino et al., 2010). Like plasmolipin, it has 4 TMSs that align with those of plasmolipin.


MAL/VIP17 of Canis familiaris (Q28296)


TC#NameOrganismal TypeExample

Myeloid-associated differentiation marker, MyADM (322 aas; 8 TMSs) 


MyADM of Homo sapiens (Q96S97)


TC#NameOrganismal TypeExample

4 TMS MARVEL superfamily member


4TMS homologue of Caenorhabditis elegans (P83387)


TC#NameOrganismal TypeExample

CKLF-like MARVEL transmembrane domain-containing protein 7, CMTM7 (175aas; 4 TMSs; Miyazaki et al., 2012). CMTM7 functions to link sIgM and BLNK in the plasma membrane, to recruit BLNK to the vicinity of Syk, and to initiate BLNK-mediated signal transduction (Miyazaki et al., 2012). No transport function is known.


CMTM7 of Homo sapiens (Q96FZ5)


Proteolipid protein 2 (Differentiation-dependent protein A4) (Intestinal membrane A4 protein)



A4 protein of Homo sapiens


Uncharacterized protein of 208 aas


UP of Caenorhabditis elegans


CKLF-like MARVEL transmembrane domain-containing protein 8 of 343 aas and 4 TMSs, CMTM8. A short splice variant, CMTM8-v2, retains the ability to induce apoptosis via caspase-dependent and -independent pathways to inhibit cell growth and colony formation. CMTM8 and CMTM8-v2 display different expression profiles and distinct subcellular localization patterns, while operating via different mechanisms to induce apoptosis. CMTM8-v2 does not affect EGFR internalization, implying that the MARVEL domain and/or the cytosolic YXXPhi motifs are necessary for CMTM8 to accelerate ligand-induced EGFR internalization (Li et al. 2007).

CMTM8 of Anas platyrhynchos (Mallard) (Anas boschas)


CKIF-like MARVEL transmembrane domain containing protein 1 of 169 aas and 4 TMSs, CMTM1.

CMTM1 of Homo sapiens


TC#NameOrganismal TypeExample

Marvel D3 tight junctionh-associated occludin of 401 aas and 4 TMSs; a determinant of paracellular permeability (Steed et al. 2009).


MarvelD3 of Homo sapiens