Reactome | UniProt:O43914 TYROBP

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UniProt:O43914 TYROBP Show undefined attributes

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.
crossReference	[DatabaseIdentifier:11490539] ENSEMBL:ENSG00000011600 [DatabaseIdentifier:12409369] RefSeq:NP_937758.1 [DatabaseIdentifier:12409367] RefSeq:NP_001166985.1 [DatabaseIdentifier:12409368] RefSeq:NP_003323.1 [DatabaseIdentifier:12284229] Pharos - Targets:O43914 [DatabaseIdentifier:12243503] PRO:O43914 [DatabaseIdentifier:12170431] PDB:7Q5W [DatabaseIdentifier:12170215] PDB:2L35 [DatabaseIdentifier:12170432] PDB:4WOL [DatabaseIdentifier:12170434] PDB:4WO1 [DatabaseIdentifier:12170433] PDB:2L34 [DatabaseIdentifier:12135103] Orphanet:TYROBP [DatabaseIdentifier:12123910] OpenTargets:ENSG00000011600 [DatabaseIdentifier:11596984] ENSEMBL:ENSP00000468447 [DatabaseIdentifier:11596983] ENSEMBL:ENSP00000262629 [DatabaseIdentifier:11596982] ENSEMBL:ENSP00000445332 [DatabaseIdentifier:11719682] ENSEMBL:ENST00000262629 [DatabaseIdentifier:11719683] ENSEMBL:ENST00000544690 [DatabaseIdentifier:11719681] ENSEMBL:ENST00000589517 [DatabaseIdentifier:11786313] GeneCards:TYROBP [DatabaseIdentifier:11839390] HPA:ENSG00000011600-TYROBP
databaseName	UniProt
dbId	66631
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
displayName	UniProt:O43914 TYROBP
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:9926675] Weiser, Joel, 2024-11-03
moleculeType	Protein
name	TYROBP
otherIdentifier	11723287_at 11757635_a_at 16871546 204122_PM_at 204122_at 38363_at 3860138 3860139 3860140 3860142 3860143 3860144 3860145 3860146 3860147 3860148 3860149 3860150 3860151 3860153 3860154 7305 8036224 A_23_P27994 A_33_P3409062 GE54154 GO:0001818 GO:0002222 GO:0002223 GO:0002228 GO:0002252 GO:0002274 GO:0002281 GO:0002282 GO:0002283 GO:0002291 GO:0002376 GO:0002684 GO:0005102 GO:0005515 GO:0005886 GO:0006952 GO:0006955 GO:0006968 GO:0007165 GO:0007166 GO:0007229 GO:0009986 GO:0010628 GO:0016020 GO:0016192 GO:0030036 GO:0030154 GO:0030316 GO:0030667 GO:0030674 GO:0030889 GO:0030900 GO:0032480 GO:0032481 GO:0032693 GO:0032731 GO:0032755 GO:0032760 GO:0032816 GO:0032911 GO:0032930 GO:0034241 GO:0035556 GO:0042802 GO:0042803 GO:0043277 GO:0046872 GO:0048678 GO:0048856 GO:0050821 GO:0060090 GO:0065008 GO:0071526 GO:0097242 GO:0098542 GO:1900272 GO:1902685 GO:1904151 GO:1904646 GO:2000010 GO:2001204 GO:2001206 HMNXSV003043808 ILMN_1778977 PH_hs_0028753 TC19001458.hg TC19002463.hg g4507754_3p_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-210010] p-Y91,Y102-TYROBP [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-198087] TYROBP [plasma membrane] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-6804800] TYROBP [secretory granule membrane] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:12109378] OMIM:604142 TYROBP [ReferenceDNASequence:12749110] UCSC:O43914 TYROBP [ReferenceDNASequence:ensembl:ENSG00000011600] ENSEMBL:ENSG00000011600 TYROBP [ReferenceDNASequence:11355822] BioGPS Gene:7305 TYROBP [ReferenceDNASequence:11401468] COSMIC - genes:TYROBP TYROBP [ReferenceDNASequence:11411291] CTD Gene:7305 TYROBP [ReferenceDNASequence:11438800] dbSNP Gene:7305 TYROBP [ReferenceDNASequence:11817944] HGNC:12449 TYROBP [ReferenceDNASequence:11895274] KEGG:hsa:7305 TYROBP [ReferenceDNASequence:11985611] Monarch:7305 TYROBP [ReferenceDNASequence:12069704] NCBI Gene:7305 TYROBP
referenceTranscript	[ReferenceRNASequence:12591070] RefSeq:NM_001173514.2 TYROBP [ReferenceRNASequence:12591072] RefSeq:NM_003332.4 TYROBP [ReferenceRNASequence:12591071] RefSeq:NM_198125.3 TYROBP
schemaClass	ReferenceGeneProduct
secondaryIdentifier	TYOBP_HUMAN A8K2X0 F5H389 Q6FGA5 Q9UMT3
sequenceLength	113
species	[Species:48887] Homo sapiens
stId	uniprot:O43914
url	http://purl.uniprot.org/uniprot/O43914

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-210010] p-Y91,Y102-TYROBP [plasma membrane] [EntityWithAccessionedSequence:R-HSA-198087] TYROBP [plasma membrane] [EntityWithAccessionedSequence:R-HSA-6804800] TYROBP [secretory granule membrane]
(referenceSequence)	[ModifiedResidue:210021] O4'-phospho-L-tyrosine at 102 [ModifiedResidue:210009] O4'-phospho-L-tyrosine at 91
(interactor)	[UndirectedInteraction:11153091] UniProt:O95944 <-> UniProt:O43914 (IntAct) [UndirectedInteraction:11153153] UniProt:O43914 <-> UniProt:Q9NZC2 (IntAct) [UndirectedInteraction:11153155] UniProt:O43914 <-> UniProt:Q14953 (IntAct) [UndirectedInteraction:11153157] UniProt:O43914 <-> UniProt:O43914 (IntAct) [UndirectedInteraction:11153157] UniProt:O43914 <-> UniProt:O43914 (IntAct) [UndirectedInteraction:11153161] UniProt:O43914 <-> UniProt:Q8N2M4 (IntAct) [UndirectedInteraction:11153163] UniProt:O43914 <-> UniProt:Q969S0 (IntAct) [UndirectedInteraction:11153165] UniProt:O43914 <-> UniProt:Q8IWT6 (IntAct) [UndirectedInteraction:11153167] UniProt:O43914 <-> UniProt:Q92538 (IntAct) [UndirectedInteraction:11153169] UniProt:O43914 <-> UniProt:Q96RD7 (IntAct) [UndirectedInteraction:11153171] UniProt:O43914 <-> UniProt:P26012 (IntAct) [UndirectedInteraction:11153173] UniProt:O43914 <-> UniProt:Q86VR2 (IntAct) [UndirectedInteraction:11153175] UniProt:O43914 <-> UniProt:Q96D05 (IntAct) [UndirectedInteraction:11153177] UniProt:O43914 <-> UniProt:Q2TAA5 (IntAct) [UndirectedInteraction:11153179] UniProt:O43914 <-> UniProt:Q86U38 (IntAct) [UndirectedInteraction:11153183] UniProt:O43914 <-> UniProt:Q9H1E5 (IntAct) [UndirectedInteraction:11153185] UniProt:O43914 <-> UniProt:Q08722 (IntAct) [UndirectedInteraction:11153187] UniProt:O43914 <-> UniProt:Q9H3N1 (IntAct) [UndirectedInteraction:11153189] UniProt:O43914 <-> UniProt:Q4ZIN3 (IntAct) [UndirectedInteraction:11153193] UniProt:O43914 <-> UniProt:Q7Z2K6 (IntAct) [UndirectedInteraction:11153197] UniProt:O43914 <-> UniProt:Q99442 (IntAct) [UndirectedInteraction:11153199] UniProt:O43914 <-> UniProt:Q5SWX8 (IntAct) [UndirectedInteraction:11153201] UniProt:O43914 <-> UniProt:Q460N5 (IntAct) [UndirectedInteraction:11153203] UniProt:O43914 <-> UniProt:O00241 (IntAct)

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