2.A.113 The Nickel/cobalt Transporter (NicO) Family Homologues of the NicO family have differing predicted topologies: 6, 7 and 8 TMSs. One such homologue, RcnA (YohM) of E. coli (274 aas) has 6 putative TMSs in a 3+3 arrangement with a large hydrophilic loop between putative TMSs 3 and 4. This protein is believed to catalyze Co²⁺ and Ni²⁺ efflux (Marrero et al. 2007). Several homologues of RcnA (e.g., from Ralstonia solanacearum; CAD17703) have 7 putative TMSs (4+3). Still another homologue, UreH of Methanocaldococcus janaschii (TC# 2.A.113.1.4) has 6 putative TMSs in a more characteristic 3 + 3 TMS arrangement . The repeat unit of this family (within the LysE superfamily) may have a common orign with that in the NiCoT family (TC# 2.A.52) (within the TOG superfamily), having lost TMSs 1 and 4 in the 8 TMS TOG superfamily topology to give rise to a 3 TMS repeat unit. Thus, these two superfamilies may be related but different at the repeat unit level (M. Saier, unpublished observations). The overall reaction catalyzed by proteins of the NicO family is probably: [Ni²⁺ or Co²⁺] (in) [Ni²⁺ or Co²⁺] (out)
This family belongs to the LysE Superfamily.
References:
Marrero, J., G. Auling, O. Coto, and D.H. Nies. (2007). High-level resistance to cobalt and nickel but probably no transenvelope efflux: Metal resistance in the Cuban Serratia marcescens strain C-1. Microb Ecol 53: 123-133.
Protchenko, O., R. Rodriguez-Suarez, R. Androphy, H. Bussey, and C.C. Philpott. (2006). A screen for genes of heme uptake identifies the FLC family required for import of FAD into the endoplasmic reticulum. J. Biol. Chem. 281: 21445-21457.
Examples:
TC#	Name	Organismal Type	Example
2.A.113.1.1	*Ni²⁺/Co²⁺ exporter, RcnA/RcnB (Rodrigue et al., 2005; Iwig et al., 2006). RcnB, a small 1 or 2 TMS protein of the DUF3315 or PF11776 family, regulates the activity of RcnA.*	Bacteria	RcnAB of E. coli RcnA (P76425) RcnB (P64534)

2.A.113.1.10	Nickel/Cobalt uptake porter, NcrC of 231 aas (Marrero et al. 2007). This sequence is proably a partial sequence lacking the C-terminal 3-TMS domain as exists in it's closest homologues such as 2.A.113.1.2.	Proteobacteria	NcrC of Serratia marcescens

2.A.113.1.11	NicO homologue of 236 aas and 6 TMSs.	Firmicutes	NicO homologue of Geobacillus thermoleovorans

2.A.113.1.12	NicO homologue of 218 aas and 6 TMSs.	Euryarchaea	NicO of Haloferax mediterrainei

2.A.113.1.13	NicO homologue of 284 aas and 6 TMSs.	Chloroflexi	NicO of Sphaerobacter thermophilus

2.A.113.1.14	Putative high affinity nickel transporter	Spirochaetes	Putative Ni²⁺transporter of Treponema denticola

2.A.113.1.2	Ni²⁺ resistance protein, like NcrC	Bacteria	*NcrC homologue of Enterobacter cloaecae* (D5CKG5)**

2.A.113.1.3	RcnA homologue	Bacteria	*RcnA homologue of Ralstonia solanacearum* (CAD17703)**

2.A.113.1.4	Urease accessory protein, UreH	Archaea	*UreH of Methanocaldococcus jannaschii* (Q58492)**

2.A.113.1.5	NiCoT homologue of 6 TMSs with two putative 3 TMS repeats corresponding to TMSs 2-4 and 6-8 in the 8 TMS homologues (B Tsu and DC Yee, unpublished)	Acidobacteria	NiCoT homologue of Solibacter usitatus

2.A.113.1.6	NicO homologue of 6 TMSs with TMSs 1-3 corresponding to TMSs 2-4 in the 8 TMS homologues, and TMSs 6-8 corresponding to TMSs 6-8 in the 8 TMS homologues (B Tsu and DC Yee, unpublished).	Planctomycetes	NicO homologue of Rhodopirellula baltica

2.A.113.1.7	Putative high affinity Ni²⁺ transporter of 320 aas and 7 TMSs in a 1 3 3 arrangement.	Proteobacteria	Nickel transporter of Starkeya novella

2.A.113.1.8	Uncharacterized protein of 244 aas and 6 TMSs.	Fusobacteria	UP of Fusobacterium nucleatum

2.A.113.1.9	Uncharacterized protein of 232 aas and 6 TMSs	Proteobacteria	UP of Oligotropha carboxidovorans

Examples:
TC#	Name	Organismal Type	Example
2.A.113.2.1	High affinity Nickel transporter of 556 aas and 8 or 9 TMSs in a 1 + 4 +3 or 4 TMS arrangement. TMS 1 is N-terminal. distant from the others. Then there are 4 TMSs followed by a hydrophilic regiion with one peak of very weak hydrophobicity. This is followed by 3 clear TMSs.	Actinobacteria	NicO family member of Streptomyces griseus

2.A.113.2.2	Putative Nickel transporter of 597 aas and 7 TMSs in a 1 (N-terminal) + 3 + 3 arrangement.	Actinobacteria	NicO family member in Streptomyces ipomoeae

2.A.113.2.3	Uncharacterized protein of 488 aas and 7 TMSs in a clear 1 + 3 + 3 arrangement.	Cyanobacteria	UP of Nostoc punctiforme