Family 1.A.8 - The Major Intrinsic Protein Family
Family ID: 52598
The MIP family is large and diverse, possessing over 100 members
that all form transmembrane channels. These channel proteins function
in water, small carbohydrate (e.g., glycerol), urea, NH3, CO2
and possibly ion transport by an energy independent mechanism.
They are found ubiquitously in bacteria, archaea and eukaryotes.
Phylogenetic clustering of the proteins is largely according to
phylum of the organisms of origin, but one to three clusters are
observed for each phylogenetic kingdom (plants, animals, yeast,
bacteria and archaea). One of the plant clusters includes only
tonoplast (TIP) proteins, with another includes plasma membrane
(PIP) proteins.
The known aquaporins cluster loosely together
as do the known glycerol facilitators. MIP family proteins are
believed to form aqueous pores that selectively allow passive
transport of their solute(s) across the membrane with minimal
apparent recognition. Aquaporins selectively transport water (but
not glycerol) while glycerol facilitators selectively transport
glycerol but not water. Some aquaporins can transport NH3 and
CO2. Glycerol facilitators function as solute nonspecific channels,
and transport glycerol, dihydroxyacetone, propanediol, urea and
other small neutral molecules in physiologically important processes.
Some members of the family, including the yeast FPS protein (TC
#1.A.8.5.1) and tobacco NtTIPA may transport both water and small
solutes.
Several reports of MIP family proteins transporting
ions may or may not be physiologically significant. For example,
AQP6 of renal epithelia have been reported to transport anions
at low pH (Yasui et al., 1999). Moreover, demonstration of the
involvement of the cyanobacterial channel protein (TC #1.A.8.4.1)
in copper homeostasis suggests that it may transport Cu2+. The
physiological functions of many MIP family proteins are unknown.
They consist of homotetramers (GlpF of E. coli; TC #1.A.8.1.1);
(MIP of Bos taurus; TC #1.A.8.8.1). Each subunit spans the membrane
six times as putative a-helicies and arose from a 3-spanner-encoding
genetic element by a tandem, intragenic duplication event. The
two halves of the proteins are therefore of opposite orientation
in the membrane. However a well conserved region between TMSs
2 and 3 and TMSs 5 and 6 dip into the membrane, each loop forming
a half TMS.
