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 - 210 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 is 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). Homologues, CMTM2A and 2B, (TC# 1.A.64.5.6 and 5.7, respectively) are required for male fertility (Fujihara et al. 2018).
The transport reaction that occurs with plasmolipin in artificial membranes is:
Ions (in) Ions (out)
Plasmolipin, PllP, or MARVEL domain-containing protein of 173 aas and 4 TMSs.
PllP of Taeniopygia guttata (Zebra finch) (Poephila guttata)
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). It has 4 TMSs that align with those of plasmolipin.
MAL/VIP17 of Canis familiaris (Q28296)
Myelin and lymphocyte protein, MAL, of 153 aas and 4 TMSs. This human ortholog is 88% identical to the dog protein, TC# 1.A.64.2.1. It may be a component in vesicular trafficking cycling between the Golgi complex and the apical plasma membrane, and could be involved in myelin biogenesis and/or myelin function. It (1) has lipid-like properties that qualify it as a member of the group of proteolipid proteins. (2) it partitions selectively into detergent-insoluble membranes, consistent with MAL being distributed in highly ordered membranes in the cell. The structure, expression and biochemical characteristics of MAL, the association of MAL with raft membranes and the function of MAL in polarized epithelial cells have been discussed (Rubio-Ramos et al. 2021).
MAL of Homo sapiens
T-cell differentiation protein A, MAL, of 163 aas and 4 TMSs.
MAL of Tetraodon nigroviridis (Spotted green pufferfish) (Chelonodon nigroviridis)
Myeloid-associated differentiation marker, MyADM (322 aas; 8 TMSs)
MyADM of Homo sapiens (Q96S97)
Uncharacterized protein of 299 aas and 8 TMSs.
UP of Ovis aries (Sheep)
4 TMS MARVEL superfamily member
4TMS homologue of Caenorhabditis elegans (P83387)
Uncharacterized MARVEL domain-containing protein of 174 aas and 3 TMSs.
UP of Tetranychus urticae (Two-spotted spider mite)
MARVEL domain-containing protein of 192 aas and 4 TMSs.
MARVEL protein of Strigamia maritima (European centipede) (Geophilus maritimus)
CKLF-like MARVEL transmembrane domain-containing protein 4, CMTM4, of 234 aas and 4 TMSs. It acts as a backup for CMTM6 to regulate plasma membrane expression of PD-L1/CD274, an immune inhibitory ligand critical for immune tolerance to self and antitumor immunity (Mezzadra et al. 2017).
CMTM4 of Homo sapiens
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, or chemokine-like factor superfamily member 1, of 169 aas and 4 TMSs. It is not required for mouse fertility although CMTM2A (TC# 1.A.64.5.6) and CMTM2B (TC#1.A.64.5.7 are required (Fujihara et al. 2018).
CMTM1 of Homo sapiens
CKIF-like MARVEL transmembrane domain containing protein, CMTM2A of 169 aas and 4 TMSs, also called chemokine-like factor superfamily member 2A. It and CMTM2B (TC#1.A.64.5.7) are required for mouse fertility although CMTM1 (TC# 1.A.64.5.5) is not required (Fujihara et al. 2018).
CMTM2A of Mus musculus
CKIF-like MARVEL transmembrane domain containing protein, CMTM2B of 210 aas and 4 TMSs, also called chemokine-like factor superfamily member 2B. It and CMTM2A (TC#1.A.64.5.6) are required for mouse fertility although CMTM1 (TC# 1.A.64.5.5) is not required (Fujihara et al. 2018).
CMTM2B of Mus musculus
CKLF-Like MARVEL Transmembrane Member 5, CMTM5, or Chemokine-like factor superfamily member 5, of 223 aas and 4 or 5 TMSs. CMTM5 associates with pathways in MARVEL domains, chemotaxis, cytokines, transmembrane structures, and integral component of membrane (Zhou et al. 2019).
CMTM5 of Homo sapiens
Marvel D3 tight junction-associated occludin of 401 aas and 4 TMSs; a determinant of paracellular permeability (Steed et al. 2009).
MarvelD3 of Homo sapiens
MARVEL domain containing 3, MARVELD3, of 314 aas and 4 TMSs, within the C-terminal half of the protein.
MARVELD3 of Myotis lucifugus (Little brown bat)