Protein
Tegument protein UL46
Organism
Human herpesvirus 1 (strain 17)
Function
Plays a role in the activation of the host PI3K/AKT pathway to promote cell survival. Interacts with and activates host LCK and thereby recruits downstream partners SHC1, GRB2 and PI3KR1 in order to activate the PI3K pathway by phosphorylating host AKT on its activating residues. This mechanism is inhibited by the viral protein US3 that instead promotes incorporation of UL46 into virions. Plays a role in the inhibition of TMEM173/STING-mediated type I interferon production (PubMed:28592536). Interacts with host DOK2 and induces its degradation. This immune evasion mechanism to inactivate T-cells may play an important role during pathogenesis (PubMed:28841444).
Similarity
Belongs to the herpesviridae HHV-1 VP11/12 protein family.
Sequence
MQRRTRGASSLRLARCLTPANLIRGDNAGVPERRIFGGCLLPTPEGLLSAAVGALRQRSDDAQPAFLTCTDRSVRLAARQHNTVPESLIVDGLASDPHYEYIRHYASAATQALGEVELPGGQLSRAILTQYWKYLQTVVPSGLDVPEDPVGDCDPSLHVLLRPTLAPKLLARTPFKSGAVAAKYAATVAGLRDALHRIQQYMFFMRPADPSRPSTDTALRLNELLAYVSVLYRWASWMLWTTDKHVCHRLSPSNRRFLPLGGSPEAPAETFARHLDRGPSGTTGSMQCMALRAAVSDVLGHLTRLANLWQTGKRSGGTYGTVDTVVSTVEVLSIVHHHAQYIINATLTGYGVWATDSLNNEYLRAAVDSQERFCRTTAPLFPTMTAPSWARMELSIKAWFGAALAADLLRNGAPSLHYESILRLVASRRTTWSAGPPPDDMASGPGGHRAGGGTCREKIQRARRDNEPPPLPRPRLHSTPASTRRFRRRRADGAGPPLPDANDPVAEPPAAATQPATYYTHMGEVPPRLPARNVAGPDRRPPAATCPLLVRRASLGSLDRPRVWGPAPEGEPDQMEATYLTADDDDDDARRKATHAASARERHAPYEDDESIYETVSEDGGRVYEEIPWMRVYENVCVNTANAAPASPYIEAENPLYDWGGSALFSPPGRTGPPPPPLSPSPVLARHRANALTNDGPTNVAALSALLTKLKREGRRSR