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).

This family belongs to the .



Okuda, K., S. Yanagihara, T. Sugayama, T. Zendo, J. Nakayama, and K. Sonomoto. (2010). Functional significance of the E loop, a novel motif conserved in the lantibiotic immunity ATP-binding cassette transport systems. J. Bacteriol. 192: 2801-2808.

Usami, Y., Y. Wu, and H.G. Göttlinger. (2015). SERINC3 and SERINC5 restrict HIV-1 infectivity and are counteracted by Nef. Nature 526: 218-223.


TC#NameOrganismal TypeExample

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)


TC#NameOrganismal TypeExample

Uncharacterized protein of 445 aas and 11 TMSs


UP of Bacteroides sp.


TC#NameOrganismal TypeExample

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