P13285 · LMP2_EBVB9
- ProteinLatent membrane protein 2
- GeneLMP2
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids497 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Isoform LMP2A
Maintains EBV latent infection of B-lymphocyte, by preventing lytic reactivation of the virus in response to surface immunoglobulin (sIg) cross-linking. Acts like a dominant negative inhibitor of the sIg-associated protein tyrosine kinases, LYN and SYK. Also blocks translocation of the B-cell antigen receptor (BCR) into lipid rafts, preventing the subsequent signaling and accelerated internalization of the BCR upon BCR cross-linking. Serves as a molecular scaffold to recruit SYK, LYN and E3 protein-ubiquitin ligases, such as ITCH and NEDD4L, leading to ubiquitination and potential degradation of both tyrosines kinases. Possesses a constitutive signaling activity in non-transformed cells, inducing bypass of normal B lymphocyte developmental checkpoints allowing immunoglobulin-negative cells to colonize peripheral lymphoid organs (By similarity).
Isoform LMP2B
May be a negative regulator of isoform LMP2A.
Miscellaneous
In healthy individuals, EBV typically establishes a persistent latent infection in which the virus can be detected in resting, nonproliferating peripheral B-lymphocytes. These latently infected cells express only 2 virally encoded genes, LMP2A and EBNA1.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Aspect | Term | |
---|---|---|
Cellular Component | host cell endomembrane system | |
Cellular Component | host cell perinuclear region of cytoplasm | |
Cellular Component | host cell plasma membrane | |
Cellular Component | membrane | |
Biological Process | symbiont-mediated perturbation of host ubiquitin-like protein modification | |
Biological Process | viral latency |
Keywords
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameLatent membrane protein 2
- Alternative names
Gene names
Organism names
- Taxonomic lineageViruses > Duplodnaviria > Heunggongvirae > Peploviricota > Herviviricetes > Herpesvirales > Orthoherpesviridae > Gammaherpesvirinae > Lymphocryptovirus > Lymphocryptovirus humangamma4 > Epstein-Barr virus (strain GD1)
- Virus hosts
Accessions
- Primary accessionP13285
- Secondary accessions
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
Isoform LMP2A
Host cell membrane ; Multi-pass membrane protein
Note: Isoform LMP2A is localized in plasma membrane lipid rafts.
Isoform LMP2B
Host endomembrane system ; Multi-pass membrane protein
Note: Isoform LMP2B localizes to perinuclear regions.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-123 | Cytoplasmic | ||||
Sequence: MGSLEMVPMGAGPPSPGGDPDGYDGGNNSQYPSASGSSGNTPTPPNDEERESNEEPPPPYEDPYWGNGDRHSDYQPLGTQDQSLYLGLQHDGNDGLPPPPYSPRDDSSQHIYEEAGRGSMNPV | ||||||
Transmembrane | 124-144 | Helical | ||||
Sequence: CLPVIVAPYLFWLAAIAASCF | ||||||
Topological domain | 145-147 | Extracellular | ||||
Sequence: TAS | ||||||
Transmembrane | 148-168 | Helical | ||||
Sequence: VSTVVTATGLALSLLLLAAVA | ||||||
Topological domain | 169-177 | Cytoplasmic | ||||
Sequence: SSYAAAQRK | ||||||
Transmembrane | 178-198 | Helical | ||||
Sequence: LLTPVTVLTAVVTFFAICLTW | ||||||
Topological domain | 199-211 | Extracellular | ||||
Sequence: RIEDPPFNSLLFA | ||||||
Transmembrane | 212-232 | Helical | ||||
Sequence: LLAAAGGLQGIYVLVMLVLLI | ||||||
Topological domain | 233-241 | Cytoplasmic | ||||
Sequence: LAYRRRWRR | ||||||
Transmembrane | 242-262 | Helical | ||||
Sequence: LTVCGGIMFLACVLVLIVDAV | ||||||
Topological domain | 263-267 | Extracellular | ||||
Sequence: LQLSP | ||||||
Transmembrane | 268-288 | Helical | ||||
Sequence: LLGAVTVVSMTLLLLAFVLWL | ||||||
Topological domain | 289-296 | Cytoplasmic | ||||
Sequence: SSPGGLGT | ||||||
Transmembrane | 297-317 | Helical | ||||
Sequence: LGAALLTLAAALALLASLILG | ||||||
Topological domain | 318 | Extracellular | ||||
Sequence: T | ||||||
Transmembrane | 319-339 | Helical | ||||
Sequence: LNLTTMFLLMLLWTLVVLLIC | ||||||
Topological domain | 340-354 | Cytoplasmic | ||||
Sequence: SSCSSCPLSKILLAR | ||||||
Transmembrane | 355-375 | Helical | ||||
Sequence: LFLYALALLLLASALIAGGSI | ||||||
Topological domain | 376-388 | Extracellular | ||||
Sequence: LQTNFKSLSSTEF | ||||||
Transmembrane | 389-409 | Helical | ||||
Sequence: IPNLFCMLLLIVAGILFILAI | ||||||
Topological domain | 410-422 | Cytoplasmic | ||||
Sequence: LTEWGSGNRTYGP | ||||||
Transmembrane | 423-443 | Helical | ||||
Sequence: VFMCLGGLLTMVAGAVWLTVM | ||||||
Topological domain | 444-449 | Extracellular | ||||
Sequence: SNTLLS | ||||||
Transmembrane | 450-470 | Helical | ||||
Sequence: AWILTAGFLIFLIGFALFGVI | ||||||
Topological domain | 471-497 | Cytoplasmic | ||||
Sequence: RCCRYCCYYCLTLESEERPPTPYRNTV |
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 74 | Loss of interaction with human SYK. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 85 | Loss of interaction with human SYK. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 112 | Complete loss of phosphorylation. | ||||
Sequence: Y → F |
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000116280 | 1-497 | Latent membrane protein 2 | |||
Sequence: MGSLEMVPMGAGPPSPGGDPDGYDGGNNSQYPSASGSSGNTPTPPNDEERESNEEPPPPYEDPYWGNGDRHSDYQPLGTQDQSLYLGLQHDGNDGLPPPPYSPRDDSSQHIYEEAGRGSMNPVCLPVIVAPYLFWLAAIAASCFTASVSTVVTATGLALSLLLLAAVASSYAAAQRKLLTPVTVLTAVVTFFAICLTWRIEDPPFNSLLFALLAAAGGLQGIYVLVMLVLLILAYRRRWRRLTVCGGIMFLACVLVLIVDAVLQLSPLLGAVTVVSMTLLLLAFVLWLSSPGGLGTLGAALLTLAAALALLASLILGTLNLTTMFLLMLLWTLVVLLICSSCSSCPLSKILLARLFLYALALLLLASALIAGGSILQTNFKSLSSTEFIPNLFCMLLLIVAGILFILAILTEWGSGNRTYGPVFMCLGGLLTMVAGAVWLTVMSNTLLSAWILTAGFLIFLIGFALFGVIRCCRYCCYYCLTLESEERPPTPYRNTV | ||||||
Modified residue | 112 | Phosphotyrosine; by host | ||||
Sequence: Y |
Post-translational modification
Isoform LMP2A
Phosphorylated on cytoplasmic N-terminal tyrosine residues, possibly by human LYN.
Can be ubiquitinated by human ITCH and WWP2 on the N-terminus in a lysine-independent manner.
Keywords
- PTM
PTM databases
Interaction
Subunit
Isoform LMP2A
The cytoplasmic N-terminal domain interacts with human SRC family protein tyrosine kinases SYK and LYN. Binds human ITCH, WWP2 and NEDD4L.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
XENO | P13285 | ITCH Q96J02 | 3 | EBI-7181113, EBI-1564678 |
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, compositional bias, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-108 | Disordered | ||||
Sequence: MGSLEMVPMGAGPPSPGGDPDGYDGGNNSQYPSASGSSGNTPTPPNDEERESNEEPPPPYEDPYWGNGDRHSDYQPLGTQDQSLYLGLQHDGNDGLPPPPYSPRDDSS | ||||||
Compositional bias | 26-46 | Polar residues | ||||
Sequence: GNNSQYPSASGSSGNTPTPPN | ||||||
Compositional bias | 73-87 | Polar residues | ||||
Sequence: DYQPLGTQDQSLYLG | ||||||
Motif | 97-101 | PPxY motif | ||||
Sequence: PPPPY |
Sequence similarities
Belongs to the herpesviridae LMP-2 family.
Keywords
- Domain
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
P13285-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- NameLMP2A
- SynonymsTP1
- Length497
- Mass (Da)53,011
- Last updated1990-01-01 v1
- ChecksumF4DC9BB3C1FD83F1
P13285-2
- NameLMP2B
- SynonymsTP2
- Differences from canonical
- 1-119: Missing
Features
Showing features for alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_016139 | 1-119 | in isoform LMP2B | |||
Sequence: Missing | ||||||
Compositional bias | 26-46 | Polar residues | ||||
Sequence: GNNSQYPSASGSSGNTPTPPN | ||||||
Compositional bias | 73-87 | Polar residues | ||||
Sequence: DYQPLGTQDQSLYLG |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M24212 EMBL· GenBank· DDBJ | AAA45887.1 EMBL· GenBank· DDBJ | mRNA | ||
Y00835 EMBL· GenBank· DDBJ | CAA68762.1 EMBL· GenBank· DDBJ | mRNA | ||
V01555 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AJ507799 EMBL· GenBank· DDBJ | CAD53383.1 EMBL· GenBank· DDBJ | Genomic DNA | Sequence problems. | |
AJ507799 EMBL· GenBank· DDBJ | CAD53382.1 EMBL· GenBank· DDBJ | Genomic DNA | Sequence problems. |