4.D.2 The Glycosyl Transferase 2 (GT2) Family The GT2 (COG0392) family has been implicated in several distinct functions including drug resistance and various enzymatic activities. Most members have about 8 - 10 TMSs plus a ~340aa C-terminal hydrophilic domain that may have catalytic activity. These proteins are implicated in glycosyl transfer with concomitant export across the membrane. They show very significant similarity to extra N-terminal domains in 3.A.3.4.3 and 4 as well as the C-terminal domain in 2.A.1.3.43 (unpublished results).
This family belongs to the Glycosyl Transferase/Transporter (GTT) Superfamily.
References:
Ardiccioni, C., O.B. Clarke, D. Tomasek, H.A. Issa, D.C. von Alpen, H.L. Pond, S. Banerjee, K.R. Rajashankar, Q. Liu, Z. Guan, C. Li, B. Kloss, R. Bruni, E. Kloppmann, B. Rost, M.C. Manzini, L. Shapiro, and F. Mancia. (2016). Structure of the polyisoprenyl-phosphate glycosyltransferase GtrB and insights into the mechanism of catalysis. Nat Commun 7: 10175.
Breazeale, S.D., A.A. Ribeiro, and C.R. Raetz. (2002). Oxidative decarboxylation of UDP-glucuronic acid in extracts of polymyxin-resistant Escherichia coli. Origin of lipid a species modified with 4-amino-4-deoxy-L-arabinose. J. Biol. Chem. 277: 2886-2896.
Tullius, M.V., C.A. Harmston, C.P. Owens, N. Chim, R.P. Morse, L.M. McMath, A. Iniguez, J.M. Kimmey, M.R. Sawaya, J.P. Whitelegge, M.A. Horwitz, and C.W. Goulding. (2011). Discovery and characterization of a unique mycobacterial heme acquisition system. Proc. Natl. Acad. Sci. USA 108: 5051-5056.
Examples:
TC#	Name	Organismal Type	Example
4.D.2.1.1	UPF0104 of 340 aas and 8 putative TMSs	Archaea	*UPF0104 of Methanococcoides burtonii* (Q12TG6)**

4.D.2.1.10	UPF0104 family protein of 345 aas and 9 or 10 TMSs, in a 5 or 6 + 4 TMS arrangement. Shows extensive similarity to the MFS domains of TC# 3.A.3.4.3 and 4.H.1.2.1.		UPF0104 protein of Chloroflexi bacterium

4.D.2.1.2	Nitrogenase molybdenum-iron (NMI) α and β chain-like protein of 347aas and 10 putative TMSs	Archaea	*NMI-like protein of Methanocorpusculum labreanum* Z (A2SSY9)**

4.D.2.1.3	Lysyl phosphatidyl glycerol synthetase	Archaea	*Lysyl-PG synthetase of Archaeoglobus veneficus* (F2KRG7)**

4.D.2.1.4	TerC of 326aas and 10 TMSs	Firmicutes	*TerC of Selenomonas* sp. oral taxon 149 (E0NY51)**

4.D.2.1.5	Putative ABC transporter (348 aas; 8 TMSs)	Bacteria	*Putative ABC transporter of Eubacterium yurii* (E0QJ98)**

4.D.2.1.6	Putative family 2 glycosyl transferase (538 aas; 8 putative TMSs), This protein is designated DPG synthase. Residues 1-220 are in the COGO392 or UPF0108 superfamily while residues 221-538 are in the lysyl phosphatidyl glycerol synthetase domain family). The N-terminal domain of 3.A.3.4.3 (e^-8) and an N-terminal domain of 4.D.1.1.3 (e^-5) are part of the MFS, but the common domain in TC family 4.D.2 is the lysyl phosphatidyl glycerol synthetase domain.	Archaea	*ORF of Archaeoglobus veneficus* (F2KQZ0)**

4.D.2.1.7	Putative transporter of 348 aas and 8 TMSs. Is encoded together with and probably functions with the ABC transporter TC# 3.A.1.147.6.	Firmicutes	Putaqtive transporter of Clostridium difficile

4.D.2.1.8	UPF0104 family protein of 387 aas and 7 TMSs.		UPF0104 protein of Ureaplasma parvum

4.D.2.1.9	Glycosyl transferase family 2 (GT2; N-terminal) - GtrA 4 TMS domain (C-terminal) protein of 384 aas and 4 - 7 TMSs.		*GT2-GtrA protein of Candidatus Zambryskibacteria* bacterium**

Examples:
TC#	Name	Organismal Type	Example
4.D.2.2.1	Uncharacterized protein of 344 aas with 1 N-terminal TMS and 3 C-terminal TMSs.	Archaea	*HP of Haloarcula marismotui* (Q5UXW9)**

4.D.2.2.2	Pych_15620 (330aas; 8 TMSs) (Most resembles 4.D.2.2.1 and 4.D.2.1.2).	Archaea	*Pych_15620 of Pyrococcus yayanosii* (F8AGU2)**

4.D.2.2.3	Uncharacterized protein of 331 aas and 8 TMSs.		UP of Bdellovibrio bacteriovorus

4.D.2.2.4	Uncharacterized protein of 335 aas and 8 probable TMSs in a 2 + 2 + 4 arrangement.		UP of Methanobacterium subterraneum

4.D.2.2.5	Uncharacterized flippase-like domain-containing protein of 243 aas and 8 TM		UP of Thermococcus sp. 4557

Examples:
TC#	Name	Organismal Type	Example
4.D.2.3.1	Sros_7630 (353aas; 8-9 TMSs) (UPF0164 Superfamily)	Actinobacteria	*Sros_7630 of Streptosporangium roseum* (D2ARG4)**

Examples:
TC#	Name	Organismal Type	Example
4.D.2.4.1	*Rv0204c (412aas; 8 putative TMSs). May be part of a heme iron acquisition system (Tullius et al.* 2011).**	Actinobacteria	*Rv0204c of Mycobacterium tuberculosis* (O53655)**

4.D.2.4.2	Varpa_1810 (335aas; 8 TMSs) (TMSs 1-7 resemble TMSs 1-7 of 2.A.1.3.47) (e^-10) and 2.A.1.3.44 (e^-9) of the MFS).	β-Proteobacteria	*Varpa_1810 of Variovorax paradoxus* (E6V6R4)**

4.D.2.4.3	YbhN of 318 aas and 8 TMSs	Proteobacteria	YbhN of E. coli

4.D.2.4.4	Uncharaterized protein of 377 aas and 8 TMSs.		UP of Acidithrix ferrooxidans

Examples:
TC#	Name	Organismal Type	Example
4.D.2.5.1	Cagg_0771 (348aas; 8 TMSs). Shows extensive sequence similarity to 3.A.3.4.3 (N-terminal 300aas; first ~8 TMSs before the ATPase domain) and 2.A.1.3.43 (C-terminal 300aas; last 8 TMSs).	Chloroflexi	*Cagg_0771 of Chloroflexus aggregans* (B8G562)**

4.D.2.5.2	Osct_1517 (341aas; 8 TMSs in a 5+3 arrangement like several of those cited above). (Resembles 4.D.2.1.3 and 6 in addition to 3.A.3.4.3 and 2.A.1.3.43)	Chloroflexi	*Osct_1517 of Oscillochloris trichoides* (E1IDW6)**

4.D.2.5.3	Flippase-like domain-containing protein of 370 aas and 8 TMSs in a 5 + 3 TMS arrangement.		Flippase of Anaerolinea thermophila