9.A.29 The Lantibiotic Immunity Protein/Serine Connector Protein (LIP/SIP) Family
LanG may or may not function with LanEF ( an ABC antibiotic exporter; TC 3.A.1.131.2) (Okuda et al., 2010).
HIV-1 Nef and the unrelated mouse leukaemia virus glycosylated Gag (glycoGag) proteins strongly enhance the infectivity of HIV-1 virions produced in certain cell types in a clathrin-dependent manner. Usami et al. 2015 showed that Nef and glycoGag prevent the incorporation of the multipass transmembrane proteins serine incorporator 3 (SERINC3; TC# 9.A.29.3.4) and SERINC5 into HIV-1 virions to an extent that correlates with infectivity enhancement. Silencing of both SERINC3 and SERINC5 precisely phenocopied the effects of Nef and glycoGag on HIV-1 infectivity. The infectivity of nef-deficient virions increased more than 100-fold when produced in double-knockout human CD4+ T cells that lacked both SERINC3 and SERINC5, and re-expression experiments confirmed that the absence of SERINC3 and SERINC5 accounted for the infectivity enhancement. Furthermore, SERINC3 and SERINC5 together restricted HIV-1 replication, and this restriction was evaded by Nef. SERINC3 and SERINC5 are highly expressed in primary human HIV-1 target cells, and inhibiting their downregulation by Nef is a potential strategy to combat HIV/AIDS (Usami et al. 2015).
LanG is a Lantibiotic immunity protein. It may or may not function with LanEF ( an ABC antibiotic exporter; TC 3.A.1.131.2) (Okuda et al., 2010). The 6 TMSs of LanG show sequence similarity with TMSs 6-10 of DME family proteins (see 2.A.7.3.17).
LanG of Bacillus licheniformis (A5A639)
Uncharacterized protein of 445 aas and 11 TMSs
UP of Bacteroides sp.
Uncharacterized protein of 441 aas and 11 TMSs.
UP of Schizosaccharomyces pombe (Fission yeast)
Uncharacterized protein of 528 aas and 8 TMSs in a 6 + 2 arrangement.
UP of Arabidopsis thaliana (Mouse-ear cress)
Serine incorporator of 708 aas and 7 - 9 TMSs.
Serine incorporator of Clonorchis sinensis (Chinese liver fluke)
Serine incorporator 3 of 473 aas and 11 TMSs. May exhibit L-serine transmembrane transport activity. Restriction factor required to restrict
infectivity of lentiviruses, such as HIV-1: acts by inhibiting an early
step of viral infection. Impairs the penetration of the viral particle
into the cytoplasm (Usami et al. 2015).
Serinc3 of Homo sapiens