TYOBP_RAT
ID TYOBP_RAT Reviewed; 114 AA.
AC Q6X9T7;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 114.
DE RecName: Full=TYRO protein tyrosine kinase-binding protein {ECO:0000312|RGD:1303081};
DE AltName: Full=DNAX-activation protein 12 {ECO:0000250|UniProtKB:O43914};
DE Flags: Precursor;
GN Name=Tyrobp {ECO:0000312|RGD:1303081};
GN Synonyms=Dap12 {ECO:0000250|UniProtKB:O43914};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Fischer 344;
RA Wittmann M.E., Bryceson Y.T., Dissen E.;
RT "Molecular cloning of rat DAP10 and DAP12.";
RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Adapter protein which non-covalently associates with
CC activating receptors found on the surface of a variety of immune cells
CC to mediate signaling and cell activation following ligand binding by
CC the receptors (By similarity). TYROBP is tyrosine-phosphorylated in the
CC ITAM domain following ligand binding by the associated receptors which
CC leads to activation of additional tyrosine kinases and subsequent cell
CC activation (By similarity). Also has an inhibitory role in some cells
CC (By similarity). Non-covalently associates with activating receptors of
CC the CD300 family to mediate cell activation (By similarity). Also
CC mediates cell activation through association with activating receptors
CC of the CD200R family (By similarity). Required for neutrophil
CC activation mediated by integrin (By similarity). Required for the
CC activation of myeloid cells mediated by the CLEC5A/MDL1 receptor (By
CC similarity). Associates with natural killer (NK) cell receptors such as
CC the KLRD1/KLRC2 heterodimer to mediate NK cell activation (By
CC similarity). Associates with TREM1 to mediate activation of neutrophils
CC and monocytes (By similarity). Associates with TREM2 on monocyte-
CC derived dendritic cells to mediate up-regulation of chemokine receptor
CC CCR7 and dendritic cell maturation and survival (By similarity).
CC PAssociation with TREM2 mediates cytokine-induced formation of
CC multinucleated giant cells which are formed by the fusion of
CC macrophages (By similarity). Stabilizes the TREM2 C-terminal fragment
CC (TREM2-CTF) produced by TREM2 ectodomain shedding which suppresses the
CC release of pro-inflammatory cytokines (By similarity). In microglia,
CC required with TREM2 for phagocytosis of apoptotic neurons (By
CC similarity). Required with ITGAM/CD11B in microglia to control
CC production of microglial superoxide ions which promote the neuronal
CC apoptosis that occurs during brain development (By similarity).
CC Promotes pro-inflammatory responses in microglia following nerve injury
CC which accelerates degeneration of injured neurons (By similarity).
CC ositively regulates the expression of the IRAK3/IRAK-M kinase and IL10
CC production by liver dendritic cells and inhibits their T cell
CC allosimulatory ability (By similarity). Negatively regulates B cell
CC proliferation (By similarity). Required for CSF1-mediated osteoclast
CC cytoskeletal organization (By similarity). Positively regulates
CC multinucleation during osteoclast development (By similarity).
CC {ECO:0000250|UniProtKB:O43914, ECO:0000250|UniProtKB:O54885}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Homotrimer;
CC disulfide-linked (By similarity). Homotetramer; disulfide-linked (By
CC similarity). Homotrimers and homotetramers form when low levels of
CC partner receptors are available and is competitive with assembly with
CC interacting receptors (By similarity). They may represent alternative
CC oligomerization states or may be intermediates in the receptor assembly
CC process (By similarity). Binding of a metal cation aids in
CC homooligomerization through coordination of the metal ion by the
CC subunits of the oligomer (By similarity). Interacts with TREM1 (By
CC similarity). Interacts with TREM2 (By similarity). Interacts with
CC CLECSF5 (By similarity). Interacts with CD300LB and CD300C2 (By
CC similarity). Interacts with CD300E (By similarity). Interacts (via ITAM
CC domain) with SYK (via SH2 domains); activates SYK mediating neutrophils
CC and macrophages integrin-mediated activation (By similarity). Interacts
CC with KLRC2 (By similarity). Interacts with CD300H (By similarity).
CC Interacts with KLRD1 (By similarity). {ECO:0000250|UniProtKB:O43914,
CC ECO:0000250|UniProtKB:O54885}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O43914};
CC Single-pass type I membrane protein {ECO:0000255}.
CC -!- PTM: Following ligand binding by associated receptors, tyrosine
CC phosphorylated in the ITAM domain which leads to activation of
CC additional tyrosine kinases and subsequent cell activation.
CC {ECO:0000250|UniProtKB:O43914}.
CC -!- SIMILARITY: Belongs to the TYROBP family. {ECO:0000305}.
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DR EMBL; AY247021; AAP79987.1; -; mRNA.
DR RefSeq; NP_997690.1; NM_212525.1.
DR AlphaFoldDB; Q6X9T7; -.
DR SMR; Q6X9T7; -.
DR STRING; 10116.ENSRNOP00000028284; -.
DR PaxDb; Q6X9T7; -.
DR Ensembl; ENSRNOT00000028284; ENSRNOP00000028284; ENSRNOG00000020845.
DR GeneID; 361537; -.
DR KEGG; rno:361537; -.
DR UCSC; RGD:1303081; rat.
DR CTD; 7305; -.
DR RGD; 1303081; Tyrobp.
DR eggNOG; ENOG502SCVI; Eukaryota.
DR GeneTree; ENSGT00390000016786; -.
DR HOGENOM; CLU_141718_0_0_1; -.
DR InParanoid; Q6X9T7; -.
DR OMA; VFCFATH; -.
DR OrthoDB; 1508977at2759; -.
DR PhylomeDB; Q6X9T7; -.
DR TreeFam; TF336898; -.
DR Reactome; R-RNO-2172127; DAP12 interactions.
DR Reactome; R-RNO-2424491; DAP12 signaling.
DR Reactome; R-RNO-391160; Signal regulatory protein family interactions.
DR Reactome; R-RNO-416700; Other semaphorin interactions.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR PRO; PR:Q6X9T7; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000020845; Expressed in spleen and 20 other tissues.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; ISO:RGD.
DR GO; GO:0030036; P:actin cytoskeleton organization; ISO:RGD.
DR GO; GO:0043277; P:apoptotic cell clearance; ISS:UniProtKB.
DR GO; GO:0097190; P:apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0030900; P:forebrain development; ISO:RGD.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; ISO:RGD.
DR GO; GO:0002281; P:macrophage activation involved in immune response; ISO:RGD.
DR GO; GO:0002282; P:microglial cell activation involved in immune response; ISO:RGD.
DR GO; GO:0002274; P:myeloid leukocyte activation; ISO:RGD.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; ISO:RGD.
DR GO; GO:0032693; P:negative regulation of interleukin-10 production; ISO:RGD.
DR GO; GO:1900272; P:negative regulation of long-term synaptic potentiation; ISO:RGD.
DR GO; GO:0032911; P:negative regulation of transforming growth factor beta1 production; ISO:RGD.
DR GO; GO:0002283; P:neutrophil activation involved in immune response; ISO:RGD.
DR GO; GO:0030316; P:osteoclast differentiation; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0110090; P:positive regulation of hippocampal neuron apoptotic process; ISO:RGD.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; ISO:RGD.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:RGD.
DR GO; GO:0034241; P:positive regulation of macrophage fusion; ISO:RGD.
DR GO; GO:1904151; P:positive regulation of microglial cell mediated cytotoxicity; ISO:RGD.
DR GO; GO:0032816; P:positive regulation of natural killer cell activation; ISO:RGD.
DR GO; GO:1901216; P:positive regulation of neuron death; ISO:RGD.
DR GO; GO:2001206; P:positive regulation of osteoclast development; ISO:RGD.
DR GO; GO:2000010; P:positive regulation of protein localization to cell surface; ISO:RGD.
DR GO; GO:1902685; P:positive regulation of receptor localization to synapse; ISO:RGD.
DR GO; GO:0032930; P:positive regulation of superoxide anion generation; ISO:RGD.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISO:RGD.
DR GO; GO:0050821; P:protein stabilization; ISO:RGD.
DR GO; GO:2001204; P:regulation of osteoclast development; ISO:RGD.
DR GO; GO:0048678; P:response to axon injury; ISO:RGD.
DR GO; GO:0002223; P:stimulatory C-type lectin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0002222; P:stimulatory killer cell immunoglobulin-like receptor signaling pathway; ISS:UniProtKB.
DR InterPro; IPR026200; Tyrobp.
DR PANTHER; PTHR17554; PTHR17554; 1.
PE 3: Inferred from homology;
KW Calcium; Cell membrane; Disulfide bond; Immunity; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..27
FT /evidence="ECO:0000255"
FT CHAIN 28..114
FT /note="TYRO protein tyrosine kinase-binding protein"
FT /id="PRO_0000022607"
FT TOPO_DOM 28..42
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O43914"
FT TRANSMEM 43..63
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O43914"
FT TOPO_DOM 64..114
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O43914"
FT DOMAIN 81..109
FT /note="ITAM"
FT REGION 72..114
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 89..114
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 52
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_note="ligand shared between two neighboring
FT subunits in homooligomer"
FT /evidence="ECO:0000250|UniProtKB:O43914"
FT SITE 56
FT /note="Important for interaction with transmembrane
FT receptors"
FT /evidence="ECO:0000250|UniProtKB:O43914"
FT MOD_RES 92
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O54885"
FT MOD_RES 103
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O54885"
FT DISULFID 37
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:O43914"
SQ SEQUENCE 114 AA; 12361 MW; B551352F4FA2760A CRC64;
MGAPEPSWCF LFLPVLLTVG GLSPVQAQSD NYPGCECSSV SPGVLAGIVL GDLVLTLLIA
LAVYSLGRLV SRGRGTADGT RKQHMAETES PYQELQGQRP EVYSDLNTQR QYYR
