8.A.144.  The Nicalin (Nicalin) Family

McGilvray et al. 2020 described a ~ 360 kDa ribosome-associated complex comprising the core Sec61 channel (TC# 3.A.5.9.1) and five accessory factors: TMCO1 (TC# 1.A.106.1.1), CCDC47 (TC# 8.A.142.1.1) and the Nicalin (TC# 8.A.144.1.1)-TMEM147 (TC# 8.A.145.1.1)-NOMO2 (8.A.146.1.1) complex. Cryo-EM revealed a large assembly at the ribosome exit tunnel organized around a central membrane cavity. Similar to protein-conducting channels that facilitate movement of TMSs, cytosolic and luminal funnels in TMCO1 and TMEM147, respectively, suggested routes into the central membrane cavity. High-throughput mRNA sequencing showed selective translocon engagement with hundreds of different multi-pass membrane proteins. Consistent with a role in multi-pass membrane protein biogenesis, cells lacking different accessory components showed reduced levels of one such client, the glutamate transporter EAAT1 (TC# 2.A.23.2.6). These results identified a human translocon complex and provided a molecular framework for understanding its role in multi-pass membrane protein biogenesis (McGilvray et al. 2020).


 

References:

McGilvray, P.T., S.A. Anghel, A. Sundaram, F. Zhong, M.J. Trnka, J.R. Fuller, H. Hu, A.L. Burlingame, and R.J. Keenan. (2020). An ER translocon for multi-pass membrane protein biogenesis. Elife 9:.

Examples:

TC#NameOrganismal TypeExample
8.A.144.1.1

Nicalin, NCLN, of 563 aas and 2 TMSs, N- and C-terminal.  The protein forms a complex with Sec61 (TC# 3.A.5.9.1) together with several other accessory proteins (see family description) (McGilvray et al. 2020).

NCLN of Homo sapiens

 
8.A.144.1.2

Nicolin-1 of 586 aas and probably 2 TMSs, N- and C-terminal.

Nicolin-1 of Eimeria brunetti

 
8.A.144.1.3

Uncharacterized protein of 549 aas and 2 TMSs, N- and C-terminal.

UP of Leishmania donovani

 
8.A.144.1.4

Uncharacterized protein of 541 aas and 2 TMSs, N- and C-terminal, but possibly as many as two TMSs in the central region.

UP of Halteria grandinella

 
8.A.144.1.5

M28 family peptidase of 301 aas and 1 N-terminal TM

Peptidase of Cecembia rubra

 
Examples:

TC#NameOrganismal TypeExample
8.A.144.2.1

M20/M25/M40 family metallo-hydrolase of 302 aas and no TMSs.

Protease of Fibrisoma limi