TYROBP
entrez
7305
canonical
uniprot
O43914
canonical
ensembl
ENSG00000011600
resolver
ensp
ENSP00000262629
resolver
ensp
ENSP00000402371
resolver
ensp
ENSP00000445332
resolver
ensp
ENSP00000468447
resolver
enst
ENST00000424586
resolver
genesymbol
TYROBP
resolver
genesymbol_syn
DAP12
resolver
genesymbol_syn
KARAP
resolver
hgnc
HGNC:12449
resolver
uniprot
A8K2X0
resolver
uniprot
F5H389
resolver
uniprot
Q6FGA5
resolver
uniprot
Q9UMT3
resolver
uniprot
X6RGC9
resolver
uniprot_entry
TYOBP_HUMAN
resolver
uniprot_entry
X6RGC9_HUMAN
resolver
uniprot_sec
A8K2X0
resolver
uniprot_sec
F5H389
resolver
uniprot_sec
Q6FGA5
resolver
uniprot_sec
Q9UMT3
resolver
amino_acid_sequence
MGGLEPCSRLLLLPLLLAVSGLRPVQAQAQSDCSCSTVSPGVLAGIVMGDLVLTVLIALAVYFLGRLVPRGRGAAEAATRKQRITETESPYQELQGQRSDVYSDLNTQRPYYK
uniprot
proteins
disease_involvement
DISEASE: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 (PLOSL1) [MIM:221770]: A recessively inherited disease characterized by presenile dementia along with large-scale destruction of cancellous bones. Initial symptoms, starting in the twenties, are pain and swelling resulting from cysts in the wrists and ankles. Extremity bone fractures could occur with minor trauma. At around 30 years of age, patients gradually develop neuropsychiatric symptoms, including epileptic seizures, agnosia, apraxia, speech disorder, memory disturbance, euphoria, and loss of social inhibitions. The disorder usually leads to death in the fifth decade of life. {ECO:0000269|PubMed:10888890, ECO:0000269|PubMed:12370476}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Adapter protein which non-covalently associates with activating receptors found on the surface of a variety of immune cells to mediate signaling and cell activation following ligand binding by the receptors (PubMed:10604985, PubMed:9490415, PubMed:9655483). TYROBP is tyrosine-phosphorylated in the ITAM domain following ligand binding by the associated receptors which leads to activation of additional tyrosine kinases and subsequent cell activation (PubMed:9490415). Also has an inhibitory role in some cells (PubMed:21727189). Non-covalently associates with activating receptors of the CD300 family to mediate cell activation (PubMed:15557162, PubMed:16920917, PubMed:17928527, PubMed:26221034). Also mediates cell activation through association with activating receptors of the CD200R family (By similarity). Required for neutrophil activation mediated by integrin (By similarity). Required for the activation of myeloid cells mediated by the CLEC5A/MDL1 receptor (PubMed:10449773). Associates with natural killer (NK) cell receptors such as KIR2DS2 and the KLRD1/KLRC2 heterodimer to mediate NK cell activation (PubMed:23715743, PubMed:9490415, PubMed:9655483). Also enhances trafficking and cell surface expression of NK cell receptors KIR2DS1, KIR2DS2 and KIR2DS4 and ensures their stability at the cell surface (PubMed:23715743). Associates with SIRPB1 to mediate activation of myeloid cells such as monocytes and dendritic cells (PubMed:10604985). Associates with TREM1 to mediate activation of neutrophils and monocytes (PubMed:10799849). Associates with TREM2 on monocyte-derived dendritic cells to mediate up-regulation of chemokine receptor CCR7 and dendritic cell maturation and survival (PubMed:11602640). Association with TREM2 mediates cytokine-induced formation of multinucleated giant cells which are formed by the fusion of macrophages (PubMed:18957693). Stabilizes the TREM2 C-terminal fragment (TREM2-CTF) produced by TREM2 ectodomain shedding which suppresses the release of pro-inflammatory cytokines (PubMed:25957402). In microglia, required with TREM2 for phagocytosis of apoptotic neurons (By similarity). Required with ITGAM/CD11B in microglia to control production of microglial superoxide ions which promote the neuronal apoptosis that occurs during brain development (By similarity). Promotes pro-inflammatory responses in microglia following nerve injury which accelerates degeneration of injured neurons (By similarity). Positively regulates the expression of the IRAK3/IRAK-M kinase and IL10 production by liver dendritic cells and inhibits their T cell allostimulatory ability (By similarity). Negatively regulates B cell proliferation (PubMed:21727189). Required for CSF1-mediated osteoclast cytoskeletal organization (By similarity). Positively regulates multinucleation during osteoclast development (By similarity). {ECO:0000250|UniProtKB:O54885, ECO:0000269|PubMed:10449773, ECO:0000269|PubMed:10604985, ECO:0000269|PubMed:10799849, ECO:0000269|PubMed:11602640, ECO:0000269|PubMed:15557162, ECO:0000269|PubMed:16920917, ECO:0000269|PubMed:17928527, ECO:0000269|PubMed:18957693, ECO:0000269|PubMed:21727189, ECO:0000269|PubMed:23715743, ECO:0000269|PubMed:25957402, ECO:0000269|PubMed:26221034, ECO:0000269|PubMed:9490415, ECO:0000269|PubMed:9655483}.
uniprot
proteins
mass_dalton
12179
uniprot
proteins
mutagenesis
MUTAGEN 41; /note="G->L: Does not significantly alter the formation of homotrimers or homotetramers; when associated with L-45 and L-49."; /evidence="ECO:0000269|PubMed:25981043"; MUTAGEN 45; /note="G->L: Does not significantly alter the formation of homotrimers or homotetramers; when associated with L-41 and L-49."; /evidence="ECO:0000269|PubMed:25981043"; MUTAGEN 49; /note="G->L: Does not significantly alter the formation of homotrimers or homotetramers; when associated with L-41 and L-45."; /evidence="ECO:0000269|PubMed:25981043"; MUTAGEN 50; /note="D->A: Reduced cell surface expression of KIR2DS1. Severely impairs formation of homotrimers and homotetramers. Abolishes interaction with TREM2 and stabilization of TREM2-CTF. Impairs the expression of KLRD1-KLRC2 on the cell surface."; /evidence="ECO:0000269|PubMed:23715743, ECO:0000269|PubMed:25957402, ECO:0000269|PubMed:25981043, ECO:0000269|PubMed:9655483"; MUTAGEN 50; /note="D->E,Q: Severely impairs formation of homotrimers and homotetramers."; /evidence="ECO:0000269|PubMed:25981043"; MUTAGEN 50; /note="D->N: Reduces formation of homotrimers and homotetramers."; /evidence="ECO:0000269|PubMed:25981043"; MUTAGEN 54; /note="T->A: Reduced interaction with KLRC2 and KIR2DS3. Reduces homotrimer formation and increases homotetramer formation."; /evidence="ECO:0000269|PubMed:20890284, ECO:0000269|PubMed:25981043
uniprot
proteins
post_translational_modification
PTM: Following ligand binding by associated receptors, tyrosine phosphorylated in the ITAM domain which leads to activation of additional tyrosine kinases and subsequent cell activation. {ECO:0000269|PubMed:9490415}.
uniprot
proteins
protein_family
TYROBP family
uniprot
proteins
pubmed
10449773
uniprot
proteins
pubmed
10604985
uniprot
proteins
pubmed
10799849
uniprot
proteins
pubmed
10888890
uniprot
proteins
pubmed
11602640
uniprot
proteins
pubmed
11922939
uniprot
proteins
pubmed
12370476
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15057824
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15557162
uniprot
proteins
pubmed
15940674
uniprot
proteins
pubmed
16344560
uniprot
proteins
pubmed
16920917
uniprot
proteins
pubmed
17012248
uniprot
proteins
pubmed
17928527
uniprot
proteins
pubmed
18624290
uniprot
proteins
pubmed
18957693
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
20890284
uniprot
proteins
pubmed
21727189
uniprot
proteins
pubmed
23715743
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
25957402
uniprot
proteins
pubmed
25981043
uniprot
proteins
pubmed
26221034
uniprot
proteins
pubmed
26358190
uniprot
proteins
pubmed
27658901
uniprot
proteins
pubmed
28716534
uniprot
proteins
pubmed
9490415
uniprot
proteins
pubmed
9655483
uniprot
proteins
sequence_length
113
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:9655483}; Single-pass type I membrane protein {ECO:0000255}.
uniprot
proteins
transmembrane_region
TRANSMEM 41..61; /note="Helical"; /evidence="ECO:0000269|PubMed:25981043
uniprot
proteins