Table 2.

Defined T1SS substrates in Rickettsiales members.

Species	Protein	Locus ID/Accession	Function	Reference
Ehrlichia chaffeensis	TRP32	ECH_0170	Nucleomodulin that directly regulates expression of host genes governing differentiation and proliferation	(Wakeel et al., 2011; Farris et al., 2016)
	TRP47	ECH_0166	Nucleomodulin that enters the nucleus via a MYND-binding domain and plays a role in host cell reprogramming by regulation of transcription	(Wakeel et al., 2011; Kibler et al., 2018)
	TRP75	ECH_0558	Interacts with host cell targets involved in homeostasis, cytoskeleton organization, and apoptosis regulation to promote infection	(Luo et al., 2018)
	TRP120	ECH_0039	Moonlighting functions, including as molecular mimicry, nucleomodulin, DNA binding, a SUMO/HECT E3 ligase involved in self- and host ubiquitination to influence protein interactions and stability for intracellular survival	(Wakeel et al., 2011; Zhu et al., 2011; Dunphy et al., 2014; Zhu et al., 2017; Klema et al., 2018; Wang et al., 2020; Byerly et al., 2021; Rogan et al., 2021; Byerly et al., 2022; Patterson et al., 2022)
	Ank200	ECH_0684	Nucleomodulin that binds adenine-rich Alu elements in host promoter and intron regions	(Zhu et al., 2009; Wakeel et al., 2011)
Orientia tsutsugamushi	Ank1	OTT_0753	Modulates NF-κB p65 nuclear transport and inhibits NF-κB transcriptional activation	(VieBrock et al., 2015; Evans et al., 2018)
	Ank2	OTT_0049	NDa	(VieBrock et al., 2015)
	Ank3	OTT_1112	ND	(VieBrock et al., 2015)
	Ank4	OTT_0210	Modulates endoplasmic reticulum-associated degradation to benefit bacterial growth	(VieBrock et al., 2015; Rodino et al., 2018)
	Ank5	OTT_0214	ND	(VieBrock et al., 2015)
	Ank6	OTT_1149	Modulates NF-κB p65 nuclear transport and inhibits NF-κB transcriptional activation	(VieBrock et al., 2015; Evans et al., 2018)
	Ank7	OTT_1509	ND	(VieBrock et al., 2015)
	Ank8	OTT_0257	ND	(VieBrock et al., 2015)
	Ank9	OTT_0298	Utilizes a novel GRIP-like Golgi localization domain for Golgi-to-endoplasmic reticulum trafficking and interacts with host COPB2	(VieBrock et al., 2015; Beyer et al., 2017)
	Ank10	OTT_0398	ND	(VieBrock et al., 2015)
	Ank11	OTT_0459	ND	(VieBrock et al., 2015)
	Ank12	OTT_0602	ND	(VieBrock et al., 2015)
	Ank13	OTT_0852	Nucleomodulin that exploits the RaDAR nuclear import pathway to reprogram host cell transcription	(VieBrock et al., 2015; Adcox et al., 2021)
	Ank14	OTT_1019	ND	(VieBrock et al., 2015)
	Ank15	OTT_1232	ND	(VieBrock et al., 2015)
	Ank17	OTT_1478	ND	(VieBrock et al., 2015)
	Ank18	OTT_1518	ND	(VieBrock et al., 2015)
	Ank19	OTT_1519	ND	(VieBrock et al., 2015)
	Ank20	OTT_1575	ND	(VieBrock et al., 2015)

^aNot determined.