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Erythrocyte stomatin (STOM; Band 7) (Similar to Mechanosensory protein Mec2, a stomatin-like subunit of the ASIC channel with TC# 1.A.6.2.2).  STOM is an inhibitor of ASIC3 (TC# 1.A.6.1.2), and is anchored to the ASIC3 channel via a site on the distal C-terminus of the channel. This interaction stabilizes the desensitized state  via an interaction with TMS1 in ASIC3 (Klipp et al. 2020).

Stomatin of Homo sapiens (P27105)

Podocin of 383 aas and 1 TMS.  Expressed exclusively in the slit-diaphragm of podocytes.  Mutations lead to steroid resistance followed by renal disease (Mulukala et al. 2016). Podocytes are crucial cells of the glomerular filtration unit that play a vital role at the interface of the blood-urine barrier. Podocyte slit-diaphragm is a modified tight junction that facilitates size and charge-dependent permselectivity. Several proteins including podocin, nephrin (TC# 8.a.23.1.33), CD2AP (8.A.34.1.5), and TRPC6 (1.A.4.1.5) form a macromolecular assembly that constitutes the slit-diaphragm that resembles tight junctions. Podocin is an integral membrane protein attached to the inner membrane of the podocyte via a short transmembrane region (101-125). The cytosolic N- and C-termini help podocin attain a hook-like structure. The protein forms a homooligomer, a 16-mer (Mulukala et al. 2020).

Podocin of Homo sapiens

Stomatin-like protein 3, STROML3 of 291 aas and 2 TMSs.  Functions in the regulation of ASIC channels in mobile vesicles in sensory neurons (Lapatsina et al. 2012).

STROML3 of Homo sapiens

Stomatin homologue. Cleavage of this protein by a protease encoded within the same operon as the stomatin has been reported to open an ion channel (Yokoyama and Matsui, 2005).

Stomatin homologue and its protease of Pyrococcus horikoshii
Stomatin homologue (O59180)
Protease (NP_143370)

QmcA protein (bacterial homologue) of 305 aas and 1 TMS (N-terminal).  May play a role in the quality control of integral membrane proteins. There is no evidence that it plays a role in transport.

QmcA of E. coli

Prohibitin, Wph or Phb, of273 aas and 1 N-terminal TMS.

Prohibitin of Triticum aestivum (Wheat)

Signal peptide peptidase of 325 aas and 4 or 5 TMSs, SppA1.

Peptidase of Bdellovibrio exovorus

Modulator of FtsH protease, HflK, of 266 aas and 1 strong N-terminal TMS as well as as many as 3 or 4 additional less hydrophobic peaks that could be TMSs. It shows strong similarity to recognized stomatin proteins and  may function with an uncharacterized protein of 231 aas and 6 TMSs in a 2 + 2 + 2 TMS arrangement encoded by the gene adjacent to the hflK gene. This latter uncharacterized protein exhibits weak similarity to the second half of the NfeD protease (TC# 8.A.21.2.1). The protease domain of NfeD is in the first half.

Candidatus Thorarchaeota
HflK/ORF of Candidatus Thorarchaeota archaeon AB_25

Membrane protease of 289 aas and 2 or 3 N-terminal TMSs of the stomatin/prohibitin family. The gene encoding this protein is adjacent to the two genes encoding an ABC exporter with TC# 3.A.1.143.4.

Protease of Thermobacillus composti KWC4

Signal peptide peptidase SppA (protease IV in the chromatophore of Paulinella chromatophora

of 276 aas.

SppA of Paulinella chromatophora

Prohibitin, Phb, of 272 aas and 1 N-terminal TMS. It plays a role in glucose homeostasis in adipose tissue. Expression of its structural gene is affected by emodin which also decreases body weight and blood lipids while increasing glucose tolerance and ceramides (Cheng et al. 2021). Together with PHB2, it forms large ring complexes (prohibitin complexes) in the inner mitochondrial membrane (IMM) and functions as a chaperone protein that stabilizes mitochondrial respiratory enzymes and maintains IMM mitochondrial integrity. It regulates mitochondrial respiratory activity, playing a role in cellular aging (Coates et al. 2001)

Phb of Homo sapiens

Hypersensitive induced response protein 3, HIR3, of 287 aas and 1 N-terminal TMS. It was isolated from wheat infected by stripe rust fungus. It contains the SPFH (Stomatins, Prohibitins, Flotillins and HflK/C) protein domain typical of stomatins which serve as a negative regulators of univalent cation permeability, especially for potassium (Yu et al. 2008).

HIR3 of Triticum aestivum (Wheat)

Flotillin-1 (FLOT1) or Reggie 2 (Reg2) of 423 aas and 1 N-terminal TMS. Flotillin upregulation is necessary and sufficient to promote epithelial and mesenchymal cancer cell invasion and ECM degradation by controlling  endocytosis and delivery of the transmembrane protease, MT1-MMP or MMP14 (TC# 8.B.14.2.3) to the endolysosomal recycling compartment  (Planchon et al. 2018). Flotillin-2, a  paralog of Flotillin-1 (48% identity) (see TC# 8.A.21.3.2), serves the same or an overlapping function. Flotillin-1 interacts with and sustains the surface levels of the TRPV2 channel (Hu et al. 2021).

Flotillin-1 of Homo sapiens

Flotillin-2 (Flot-2 or Flot2) or Reggie 1 (Reg-1 or Reg1), of 428 aas and 1 N-terminal TMS.  It may play a role in axon growth and regeneration as well as in epidermal cell adhesion and epidermal structure and function (Lang et al. 1998).

Flot-2 of Rattus norvegicus (Rat)