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Details on Person UniProt:P04413 US3

Class:IdReferenceGeneProduct:9715395
_chainChangeLogchain:1-481 for 9715395 added on Wed February 17 2021
_displayNameUniProt:P04413 US3
_timestamp2025-08-15 21:35:11
chainchain:1-481
checksum71838AB0483BE055
commentFUNCTION Multifunctional serine/threonine kinase that plays a role in several processes including egress of virus particles from the nucleus, modulation of the actin cytoskeleton and inhibition of host immune response (PubMed:25907557, PubMed:31249678, PubMed:34935440). Phosphorylates UL31 and UL34, two critical regulators of capsid budding from nucleus to endoplasmic reticulum, thereby facilitating virion egress (PubMed:15994828, PubMed:1656069). Modulates and redistributes host components of the nuclear envelope, including LMNA, emerin/EMD and the nuclear matrix protein MATR3 (PubMed:20962082). In turn, facilitates nuclear pore impairment and capsid release through impaired nuclear envelope (PubMed:31249678). Phosphorylates envelope glycoprotein B (gB), probably to direct it to the cell surface (PubMed:19846518). Promotes virus intracellular spread by restructuring host cell cytoskeleton. Blocks host apoptosis to extend cell survival and allow efficient viral replication. Promotes viral gene expression by phosphorylating host HDAC2 to reduce viral genome silencing (PubMed:20660201). Strongly inhibits TCR-activated signal transduction in T-cells by reducing the ubiquitination of LAT and TRAF6, leading to a suboptimal activation of LAT (PubMed:25907557). Subverts host antiviral innate immunity by inhibiting type I interferon production through hyperphosphorylation of beta-catenin/CTNNB1 (PubMed:31801859). In addition, phosphorylates the RNA sensor RIGI and the transcription factor IRF3 to prevent the RLR-mediated antiviral signaling pathway (PubMed:24049179, PubMed:34935440). Hyperphosphorylates host RELA and thereby dampens NF-kappa-B signaling (PubMed:24807716). Acts as an immunoevasin partly responsible for inhibition of MR1 expression and antigen presentation in response to bacterial infection.CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)SUBUNIT Interacts with host LAT; this interaction prevents LAT activation of TRAF6 (PubMed:25907557).SUBCELLULAR LOCATION Phosphorylated by UL13; this phosphorylation regulates subsequent phosphorylation of UL31 and UL34 by US3. Autophosphorylated.SIMILARITY Belongs to the protein kinase superfamily. Ser/Thr protein kinase family.
created[InstanceEdit:9715437] Shamovsky, Veronica, 2021-02-17
descriptionrecommendedName: Serine/threonine-protein kinase US3 ecNumber: 2.7.11.1
geneNameUS3
identifierP04413
isSequenceChangedFALSE
keywordATP-binding
Host cytoplasm
Host nucleus
Host-virus interaction
Kinase
Modulation of host cell apoptosis by virus
Modulation of host chromatin by virus
Nucleotide-binding
Phosphoprotein
Reference proteome
Serine/threonine-protein kinase
Transferase
modified[InstanceEdit:9715482] Weiser, JD
[InstanceEdit:9819394] Weiser, Joel
[InstanceEdit:9829221] Weiser, Joel
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
nameUS3
referenceDatabase[ReferenceDatabase:2] UniProt
secondaryIdentifierUS03_HHV11
sequenceLength481
species[Species:5689680] Human herpesvirus 1
(referenceEntity)[EntityWithAccessionedSequence:9715417] US3 [cytosol] [Human herpesvirus 1]
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