8.A.115. The Transmembrane Protein 223 (TMEM223) Family

TMEM223 regulates the activity of Ca_V2.2 (Mallmann et al. 2019). It lowers the average current density, accelerates the kinetics of cumulative current inactivation and slows the kinetics of recovery from inactivation. TMEM223 interacts directly with Ca_v2.2 and negatively modulate Ca²⁺ entry via this channel protein, and this interaction is required for proper transmitter release and/or for dendritic plasticity under physiological conditions (Mallmann et al. 2019). Pain-causing stinging nettle toxins target TMEM233, and this interaction modulates Na_V1.7 function (Jami et al. 2023). Excelsatoxin A (ExTxA), a pain-causing knottin peptide from the Australian stinging tree Dendrocnide excelsa, is the first reported plant-derived Na(V) channel modulating peptide toxin. Jami et al. 2023 showed that TMEM233, a member of the dispanin family of transmembrane proteins expressed in sensory neurons, is essential for the pharmacological activity of ExTxA at Na_V channels, and that co-expression of TMEM233 modulates the gating properties of Na_V1.7. This family may be distantly related to TC family 8.A.58.

References:

Jami, S., J.R. Deuis, T. Klasfauseweh, X. Cheng, S. Kurdyukov, F. Chung, A.L. Okorokov, S. Li, J. Zhang, B. Cristofori-Armstrong, M.R. Israel, R.J. Ju, S.D. Robinson, P. Zhao, L. Ragnarsson, &.#.1.9.7.;. Andersson, P. Tran, V. Schendel, K.L. McMahon, H.N.T. Tran, Y.K. Chin, Y. Zhu, J. Liu, T. Crawford, S. Purushothamvasan, A.M. Habib, D.A. Andersson, L.D. Rash, J.N. Wood, J. Zhao, S.J. Stehbens, M. Mobli, A. Leffler, D. Jiang, J.J. Cox, S.G. Waxman, S.D. Dib-Hajj, G. Gregory Neely, T. Durek, and I. Vetter. (2023). Pain-causing stinging nettle toxins target TMEM233 to modulate Na1.7 function. Nat Commun 14: 2442.

Mallmann, R., K. Ondacova, L. Moravcikova, B. Jurkovicova-Tarabova, M. Pavlovicova, L. Lichvarova, V. Kominkova, N. Klugbauer, and L. Lacinova. (2019). Four novel interaction partners demonstrate diverse modulatory effects on voltage-gated Ca2.2 Ca channels. Pflugers Arch. [Epub: Ahead of Print]

Examples:

TC#

Name

Organismal Type

Example

8.A.115.1.1

TMEM223 protein of 202 aas and 2 TMSs. It negatively regulates the activity of the calcium channel, Ca_v2.2 (Mallmann et al. 2019).

TMEM223 of Homo sapiens

8.A.115.1.2

Uncharacterized protein of 228 aas and 2 TMSs.

UP of Coemansia pectinata

8.A.115.1.3

TMEM homologue of 273 aas and 2 TMSs.

TMEM223 homologue of Batrachochytrium salamandrivorans

8.A.115.1.4

Uncharacterized TMEM223 protein of 227 aas and 2 TMSs.

UP of Lichtheimia corymbifera

8.A.115.1.5

Uncharacterized homologue of TMEM223 protein of 239 aas and 2 TMSs.

UP of Polistes canadensis

8.A.115.1.6

Transmembrane protein 223, TMEM223 of 246 aas and 2 TMSs

TMEM223 of Bactrocera oleae

8.A.115.1.7

Uncharacterized TMEM223 homologue of 263 aas and 2 TMSs/

UP of Diaphorina citri

8.A.115.1.8

Uncharacterized membrane protein of 235 aas and 2 TMSs.

UP of Brachionus plicatilis

Examples:

TC#

Name

Organismal Type

Example

8.A.115.2.1

Uncharacterized protein of 384 aas and 2 TMSs.

UP of Dallia pectoralis

8.A.115.2.2

Uncharacterized protein of 243 aas and 2 TMSs.

UP of Tribonema minus

8.A.115.2.3

Uncharacterized protein of 251 aas with 2 or 3 TMSs in a 1 + 2 TMS arrangement

UP of Guillardia theta

Examples:

TC#

Name

Organismal Type

Example

8.A.115.3.1

Uncharacterized protein of 231 aas and 4 TMSs in a 2 + 2 arrangement.

UP of Gracilibacillus lacisalsi

Examples:

TC#

Name

Organismal Type

Example

8.A.115.4.1

TMEM223 of 388 aas and 2 TMSs

T223 of Candida boidinii

Examples:

TC#

Name

Organismal Type

Example

8.A.115.5.1

Uncharacterized protein of 247 aas and 2 TMSs

UP of Phlyctochytrium arcticum

8.A.115.5.2

Uncharacterized protein of 288 aas and 3 TMSs in a 2 + 1 TMS arrangement.

UP of Gorgonomyces haynaldii

Examples:

TC#

Name

Organismal Type

Example

8.A.115.6.1

Uncharacterized protein of 224 aas and 2 TMSs.

UP of Cyanidioschyzon merolae strain 10D

8.A.115.6.2

Uncharacterized protein of 217 aas and 2 TMSs

UP of Cyanidiococcus yangmingshanensis

8.A.115.6.3

Uncharacterized protein of 258 aas and 2 TMSs

UP of Monosiga brevicollis MX1

Examples:

TC#

Name

Organismal Type

Example

8.A.115.7.1

Uncharacterized protein on 211 aas and 2 TMSs.

UP of Synchytrium endobioticum

Examples:

TC#

Name

Organismal Type

Example

8.A.115.8.1

Mitochondrial membrane protein, TMEM186-like protein, implicated in respiratory complex assembly, of 276 aas and 2 TMSs.

TMEM186 of Schizosaccharomyces osmophilus