9.B.238. The Uncharacterized Bacterial 5 TMS Protein-2 (UBP1) Family This family consists of proteins with fairly uniform topologies with N-terminal transmembrane domains with 5 or 6 TMSs followed by C-terminal hydrophilic domains of variable sizes. Proteins from uncultured bacterial are much more similar to each other than to proteins from cultured bacteria. However, sensor histidine kinases with N-terminal integral membrane domains were found from cultured bacteria. The former were put into TC subfamily 9.B.238.1 with the latter being included in TC subfamily 9.B.238.2. The putative ABC transporters retrieved with low scores in the BLAST searches were included in ABC family 3.A.1.103, members 6, 7 and 8. Thus, some of the uncharacterized members of this family are probably sensor kinases, but some may be transporters. They are related to some members of TC family 9.B.259.2 which may also be histidine sensor kinases.
References:
Aguilar, P.S., A.M. Hernandez-Arriaga, L.E. Cybulski, A.C. Erazo, and D. de Mendoza. (2001). Molecular basis of thermosensing: a two-component signal transduction thermometer in Bacillus subtilis. EMBO. J. 20: 1681-1691.
Albanesi, D., M.C. Mansilla, and D. de Mendoza. (2004). The membrane fluidity sensor DesK of Bacillus subtilis controls the signal decay of its cognate response regulator. J. Bacteriol. 186: 2655-2663.
Almada, J.C., A. Bortolotti, J.M. Ruysschaert, D. de Mendoza, M.E. Inda, and L.E. Cybulski. (2021). Interhelical H-Bonds Modulate the Activity of a Polytopic Transmembrane Kinase. Biomolecules 11:.
Cybulski, L.E., D. Albanesi, M.C. Mansilla, S. Altabe, P.S. Aguilar, and D. de Mendoza. (2002). Mechanism of membrane fluidity optimization: isothermal control of the Bacillus subtilis acyl-lipid desaturase. Mol. Microbiol. 45: 1379-1388.
Hunger, K., C.L. Beckering, and M.A. Marahiel. (2004). Genetic evidence for the temperature-sensing ability of the membrane domain of the Bacillus subtilis histidine kinase DesK. FEMS Microbiol. Lett. 230: 41-46.
Leusenko, A.V., K.S. Mironov, and D.A. Los. (2023). Transmembrane and PAS domains of the histidine kinase Hik33 as regulators of cold and light responses in the cyanobacterium Synechocystis sp. PCC 6803. Biochimie. [Epub: Ahead of Print]
Examples:
TC#	Name	Organismal Type	Example
9.B.238.1.1	Uncharacterized protein of 244 aas and 5 N-terminal TMSs. This protein resembles (e^-8) the ABC membrane protein with TC# 2.A.1.103.7 and therefore may be an ABC membrane constituent.		UP of Candidatus Beckwithbacteria bacterium

9.B.238.1.2	Uncharacterized protein of 247 aas and 5 N-terminal TMSs.		UP of Candidatus Roizmanbacteria bacterium

9.B.238.1.3	Uncharacterized protein of 218 aas and 5 TMSs.		UP of Microgenomates bacterium

Examples:
TC#	Name	Organismal Type	Example
9.B.238.2.1	Histidine kinase of 399 aas and 5 TMSs.		*HK of Kordia* sp.**

9.B.238.2.2	Sensor histidine kinase of 402 aas and 5 N-terminal TMSs.		HK of Pricia antarctica

Examples:
TC#	Name	Organismal Type	Example
9.B.238.3.1	Hybrid sensor histidine kinase/response regulator of 568 aas and 6 TMSs.		HK of Balneola vulgaris

9.B.238.3.2	HAMP domain sensor kinase of 511 aas, with an N-terminal transmembrane domain with 6 TMSs.		*SK of Shinella* sp. HZN7**

9.B.238.3.3	HAMP domain-containing histidine kinase of 768 aas and 5 TMSs in a 1 (N-terminal) + 4 (central) TMS arrangement.		*Sensor Kinase of Anaerocolumna* sp.**

9.B.238.3.4	Uncharacterized protein of 435 aas and 7 N-terminal TMSs.		*UP of Enhydrobacter* sp.**

9.B.238.3.5	Integral membrane histidine sensor kinase, DesK or YocF, with 370 aas and 5 or 6 N-terminal TMSs plus a C-terminal kinase domain. It aligns with residues 20 - 420 of the histidine kinase with TC# 9.B.238.3.1. It is a member of the two-component regulatory system DesR/DesK (Albanesi et al. 2004), responsible for cold induction of the des gene coding for the Delta5 acyl-lipid desaturase (Aguilar et al. 2001). It acts as a sensor of membrane fluidity (Cybulski et al. 2002) and probably activates DesR by phosphorylation (Hunger et al. 2004). The transmembrane region triggers phosphorylation of the catalytic domain as soon as the membrane lipids rigidify. Interhelical H-bonds modulate its activity (Almada et al. 2021).		DesK of Bacillus subtilis

9.B.238.3.6	Drug sensory protein A, Dfr, Hik33, NblS, Syny4, a histidine kinase of 642 aas and 4 - 7 TMSs in a 2 + 2 or 3 + 3 + 1 TMS arrangement. It is a cell wall metabolism sensor histidine kinase, also called WalK. The transmembrane domains govern temperature responses, whereas the PAS domain may be involved in regulation of downstream gene expression in a light-dependent manner (Leusenko et al. 2023).		*Dfr of Synechocystis* sp. PCC 6714**

9.B.238.3.7	Arabidopsis histidine kinase 4, AtHK4; Cytokinin receptor; CYTOKININ RESPONSE PROTWIN 1; AtCRE1; Cytokinin receptor CRE1; Phosphoprotein phosphatase AHK4 of 1080 aas with 2 TMSs at about residues 130 and 430.		HK4 of Arabidopsis thaliana