Q13094 · LCP2_HUMAN
- ProteinLymphocyte cytosolic protein 2
- GeneLCP2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids533 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Adapter protein primarily involved in signaling pathways within T-cells, as well as other immune cells such as platelets, mast cells, and natural killer (NK) cells (PubMed:11313406, PubMed:33159816).
Plays a crucial role for transducing signal from the T-cell receptor (TCR) after antigen recognition leading to T-cell activation. Mechanistically, once phosphorylated by the kinase ZAP70, mediates interactions with the guanine-nucleotide exchange factor VAV1, the adapter protein NCK and the kinase ITK (PubMed:8702662, PubMed:8673706).
In turn, stimulates the activation of PKC-theta/PRKCQ and NF-kappa-B transcriptional activity in response to CD3 and CD28 costimulation (PubMed:11313406).
Plays also an essential role in AGER-induced signaling pathways including p38 MAPK and ERK1/2 activation leading to cytokine release and pro-inflammatory responses (PubMed:33436632).
Plays a crucial role for transducing signal from the T-cell receptor (TCR) after antigen recognition leading to T-cell activation. Mechanistically, once phosphorylated by the kinase ZAP70, mediates interactions with the guanine-nucleotide exchange factor VAV1, the adapter protein NCK and the kinase ITK (PubMed:8702662, PubMed:8673706).
In turn, stimulates the activation of PKC-theta/PRKCQ and NF-kappa-B transcriptional activity in response to CD3 and CD28 costimulation (PubMed:11313406).
Plays also an essential role in AGER-induced signaling pathways including p38 MAPK and ERK1/2 activation leading to cytokine release and pro-inflammatory responses (PubMed:33436632).
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 | |||
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Aspect | Term | |
---|---|---|
Cellular Component | cell-cell junction | |
Cellular Component | cytosol | |
Cellular Component | plasma membrane raft | |
Cellular Component | TCR signalosome | |
Biological Process | cell surface receptor protein tyrosine kinase signaling pathway | |
Biological Process | immune response | |
Biological Process | intracellular signal transduction | |
Biological Process | mast cell activation | |
Biological Process | positive regulation of protein kinase activity | |
Biological Process | T cell receptor signaling pathway |
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameLymphocyte cytosolic protein 2
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ13094
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Immunodeficiency 81 (IMD81)
- Note
- DescriptionAn autosomal recessive disorder characterized by recurrent infections, including fungal infections, associated with T cell, neutrophil, and NK cell dysfunction. B cells may also show maturation abnormalities. Other features include autoimmune hemolytic anemia and abnormal platelet aggregation.
- See alsoMIM:619374
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_070803 | 410 | in dbSNP:rs34192428 | |||
Sequence: S → C |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 624 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000084368 | 1-533 | UniProt | Lymphocyte cytosolic protein 2 | |||
Sequence: MALRNVPFRSEVLGWDPDSLADYFKKLNYKDCEKAVKKYHIDGARFLNLTENDIQKFPKLRVPILSKLSQEINKNEERRSIFTRKPQVPRFPEETESHEEDNGGWSSFEEDDYESPNDDQDGEDDGDYESPNEEEEAPVEDDADYEPPPSNDEEALQNSILPAKPFPNSNSMYIDRPPSGKTPQQPPVPPQRPMAALPPPPAGRNHSPLPPPQTNHEEPSRSRNHKTAKLPAPSIDRSTKPPLDRSLAPFDREPFTLGKKPPFSDKPSIPAGRSLGEHLPKIQKPPLPPTTERHERSSPLPGKKPPVPKHGWGPDRRENDEDDVHQRPLPQPALLPMSSNTFPSRSTKPSPMNPLPSSHMPGAFSESNSSFPQSASLPPYFSQGPSNRPPIRAEGRNFPLPLPNKPRPPSPAEEENSLNEEWYVSYITRPEAEAALRKINQDGTFLVRDSSKKTTTNPYVLMVLYKDKVYNIQIRYQKESQVYLLGTGLRGKEDFLSVSDIIDYFRKMPLLLIDGKNRGSRYQCTLTHAAGYP | |||||||
Modified residue | 23 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 207 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 207 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 297 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 298 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 341 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 376 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 376 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 410 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 410 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 417 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylated after T-cell receptor activation by ZAP70, ITK and TXK, which leads to the up-regulation of Th1 preferred cytokine IL-2. SYK-dependent phosphorylation is required for recruitment of PI3K signaling components.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Highly expressed in spleen, thymus and peripheral blood leukocytes. Highly expressed also in T-cell and monocytic cell lines, expressed at lower level in B-cell lines. Not detected in fibroblast or neuroblastoma cell lines.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with SLA. Interacts with CBLB (By similarity).
Interacts with GRB2 (PubMed:7706237).
Interacts with SHB (PubMed:12084069).
Interacts with PRAM1 (PubMed:11301322).
Interacts (via SH2 domain) with CD6 (via tyrosine phosphorylated C-terminus) (PubMed:16914752, PubMed:24584089).
Interacts with FYB1 and the phosphorylated form of FYB2 (PubMed:27335501).
Interacts with 14-3-3 adapter/YWHAZ; this phosphorylation leads to YWHAZ proteolytic degradation (PubMed:33159816).
Interacts with VAV1; this interaction plays a role in TCR-mediated cytokine production (PubMed:15144186).
Interacts with AGER; this interaction plays an important role in AGER-mediated pro-inflammatory responses and cytokine release (PubMed:33436632).
Interacts with GRB2 (PubMed:7706237).
Interacts with SHB (PubMed:12084069).
Interacts with PRAM1 (PubMed:11301322).
Interacts (via SH2 domain) with CD6 (via tyrosine phosphorylated C-terminus) (PubMed:16914752, PubMed:24584089).
Interacts with FYB1 and the phosphorylated form of FYB2 (PubMed:27335501).
Interacts with 14-3-3 adapter/YWHAZ; this phosphorylation leads to YWHAZ proteolytic degradation (PubMed:33159816).
Interacts with VAV1; this interaction plays a role in TCR-mediated cytokine production (PubMed:15144186).
Interacts with AGER; this interaction plays an important role in AGER-mediated pro-inflammatory responses and cytokine release (PubMed:33436632).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 15-81 | SAM | ||||
Sequence: WDPDSLADYFKKLNYKDCEKAVKKYHIDGARFLNLTENDIQKFPKLRVPILSKLSQEINKNEERRSI | ||||||
Compositional bias | 78-104 | Basic and acidic residues | ||||
Sequence: RRSIFTRKPQVPRFPEETESHEEDNGG | ||||||
Region | 78-417 | Disordered | ||||
Sequence: RRSIFTRKPQVPRFPEETESHEEDNGGWSSFEEDDYESPNDDQDGEDDGDYESPNEEEEAPVEDDADYEPPPSNDEEALQNSILPAKPFPNSNSMYIDRPPSGKTPQQPPVPPQRPMAALPPPPAGRNHSPLPPPQTNHEEPSRSRNHKTAKLPAPSIDRSTKPPLDRSLAPFDREPFTLGKKPPFSDKPSIPAGRSLGEHLPKIQKPPLPPTTERHERSSPLPGKKPPVPKHGWGPDRRENDEDDVHQRPLPQPALLPMSSNTFPSRSTKPSPMNPLPSSHMPGAFSESNSSFPQSASLPPYFSQGPSNRPPIRAEGRNFPLPLPNKPRPPSPAEEENS | ||||||
Compositional bias | 105-149 | Acidic residues | ||||
Sequence: WSSFEEDDYESPNDDQDGEDDGDYESPNEEEEAPVEDDADYEPPP | ||||||
Compositional bias | 152-178 | Polar residues | ||||
Sequence: DEEALQNSILPAKPFPNSNSMYIDRPP | ||||||
Compositional bias | 180-215 | Pro residues | ||||
Sequence: GKTPQQPPVPPQRPMAALPPPPAGRNHSPLPPPQTN | ||||||
Compositional bias | 309-327 | Basic and acidic residues | ||||
Sequence: KHGWGPDRRENDEDDVHQR | ||||||
Compositional bias | 333-353 | Polar residues | ||||
Sequence: ALLPMSSNTFPSRSTKPSPMN | ||||||
Compositional bias | 360-382 | Polar residues | ||||
Sequence: MPGAFSESNSSFPQSASLPPYFS | ||||||
Domain | 422-530 | SH2 | ||||
Sequence: WYVSYITRPEAEAALRKINQDGTFLVRDSSKKTTTNPYVLMVLYKDKVYNIQIRYQKESQVYLLGTGLRGKEDFLSVSDIIDYFRKMPLLLIDGKNRGSRYQCTLTHAA |
Domain
The SH2 domain mediates interaction with phosphorylated CD6 (PubMed:16914752).
The SH2 domain mediates interaction with SHB (PubMed:12084069).
The SH2 domain mediates interaction with SHB (PubMed:12084069).
Possesses an N-terminal acidic domain containing three tyrosine phosphorylation motifs, a central proline-rich region, and a C-terminal SH2 domain.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length533
- Mass (Da)60,188
- Last updated1996-11-01 v1
- ChecksumC5D22F31D36200C8
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Features
Showing features for sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 19 | in Ref. 3; BAF85579 | ||||
Sequence: S → G | ||||||
Compositional bias | 78-104 | Basic and acidic residues | ||||
Sequence: RRSIFTRKPQVPRFPEETESHEEDNGG | ||||||
Compositional bias | 105-149 | Acidic residues | ||||
Sequence: WSSFEEDDYESPNDDQDGEDDGDYESPNEEEEAPVEDDADYEPPP | ||||||
Compositional bias | 152-178 | Polar residues | ||||
Sequence: DEEALQNSILPAKPFPNSNSMYIDRPP | ||||||
Compositional bias | 180-215 | Pro residues | ||||
Sequence: GKTPQQPPVPPQRPMAALPPPPAGRNHSPLPPPQTN | ||||||
Compositional bias | 309-327 | Basic and acidic residues | ||||
Sequence: KHGWGPDRRENDEDDVHQR | ||||||
Compositional bias | 333-353 | Polar residues | ||||
Sequence: ALLPMSSNTFPSRSTKPSPMN | ||||||
Compositional bias | 360-382 | Polar residues | ||||
Sequence: MPGAFSESNSSFPQSASLPPYFS |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U20158 EMBL· GenBank· DDBJ | AAC50135.1 EMBL· GenBank· DDBJ | mRNA | ||
BT007273 EMBL· GenBank· DDBJ | AAP35937.1 EMBL· GenBank· DDBJ | mRNA | ||
AK292890 EMBL· GenBank· DDBJ | BAF85579.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471062 EMBL· GenBank· DDBJ | EAW61479.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC016618 EMBL· GenBank· DDBJ | AAH16618.1 EMBL· GenBank· DDBJ | mRNA |