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Details on Person UniProt:O43914 TYROBP

Class:Id	ReferenceGeneProduct:66631
_chainChangeLog	signal peptide:1-21 added on Sat February 7 2015;chain:22-113 added on Sat February 7 2015
_displayName	UniProt:O43914 TYROBP
_timestamp	2024-11-03 20:08:19
chain	signal peptide:1-21 chain:22-113
checksum	267CB1C1756F89F0
comment	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).SUBUNIT Homodimer; disulfide-linked (PubMed:20890284). Homotrimer; disulfide-linked (PubMed:25981043). Homotetramer; disulfide-linked (PubMed:25981043). Homotrimers and homotetramers form when low levels of partner receptors are available and are competitive with assembly with interacting receptors (PubMed:25981043). They may represent alternative oligomerization states or may be intermediates in the receptor assembly process (PubMed:25981043). Binding of a metal cation aids in homooligomerization through coordination of the metal ion by the subunits of the oligomer (PubMed:25981043). Interacts with TREM1 (PubMed:10799849). Interacts with TREM2 (PubMed:11602640, PubMed:25957402). Interacts with SIRPB1 (PubMed:10604985). Interacts with CLECSF5 (PubMed:10449773). Interacts with SIGLEC14 (PubMed:17012248). Interacts with CD300LB and CD300E (PubMed:15557162, PubMed:16920917, PubMed:17928527). Interacts with CD300C2 (By similarity). Interacts (via ITAM domain) with SYK (via SH2 domains); activates SYK mediating neutrophil and macrophage integrin-mediated activation (By similarity). Interacts with KLRC2, KIR2DS3 and KIR2DS5 (PubMed:18624290, PubMed:20890284). Interacts with CD300H (PubMed:26221034). Interacts with KIR2DS1 (PubMed:23715743). Interacts with KLRD1 (PubMed:15940674, PubMed:9655483). Interacts with SIGLEC1 (PubMed:26358190).INTERACTION Expressed at low levels in the early development of the hematopoietic system and in the promonocytic stage and at high levels in mature monocytes. Expressed in hematological cells and tissues such as peripheral blood leukocytes and spleen. Also found in bone marrow, lymph nodes, placenta, lung and liver. Expressed at lower levels in different parts of the brain especially in the basal ganglia and corpus callosum.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.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the TYROBP family.
description	recommendedName: fullName evidence="35"TYRO protein tyrosine kinase-binding protein alternativeName: fullName evidence="30"DNAX-activation protein 12 alternativeName: Killer-activating receptor-associated protein shortName: KAR-associated protein
geneName	TYROBP DAP12 KARAP
identifier	O43914
isSequenceChanged	FALSE
keyword	3D-structure Alternative splicing Calcium Cell membrane Disulfide bond Immunity Membrane Metal-binding Phosphoprotein Proteomics identification Reference proteome Signal Transmembrane Transmembrane helix
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03
name	TYROBP
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8997507] ENSEMBL:ENSG00000011600 TYROBP [Homo sapiens]
secondaryIdentifier	TYOBP_HUMAN A8K2X0 F5H389 Q6FGA5 Q9UMT3
sequenceLength	113
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:253226] UniProt:O43914-2 TYROBP [Homo sapiens] [ReferenceIsoform:401574] UniProt:O43914-1 TYROBP [Homo sapiens] [ReferenceIsoform:8977252] UniProt:O43914-3 TYROBP [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:198087] TYROBP [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:210010] p-Y91,Y102-TYROBP [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:6804800] TYROBP [secretory granule membrane] [Homo sapiens]
(referenceSequence)	[ModifiedResidue:210009] O4'-phospho-L-tyrosine at 91 [ModifiedResidue:210021] O4'-phospho-L-tyrosine at 102
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No pathways have been reviewed or authored by UniProt:O43914 TYROBP (66631)