TYOBP_MACMU
ID TYOBP_MACMU Reviewed; 113 AA.
AC Q8WNQ8;
DT 01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=TYRO protein tyrosine kinase-binding protein {ECO:0000250|UniProtKB:O43914};
DE AltName: Full=DNAX-activation protein 12 {ECO:0000250|UniProtKB:O43914};
DE Flags: Precursor;
GN Name=TYROBP {ECO:0000250|UniProtKB:O43914};
GN Synonyms=DAP12 {ECO:0000250|UniProtKB:O43914};
OS Macaca mulatta (Rhesus macaque).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9544;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA LaBonte M.L., Letvin N.L.;
RT "Identification of rhesus monkey DAP10 and DAP12.";
RL Submitted (NOV-2000) 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 Association 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 Positively 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; AF321611; AAL37224.1; -; mRNA.
DR RefSeq; NP_001028039.1; NM_001032867.1.
DR AlphaFoldDB; Q8WNQ8; -.
DR SMR; Q8WNQ8; -.
DR STRING; 9544.ENSMMUP00000010492; -.
DR GeneID; 574207; -.
DR KEGG; mcc:574207; -.
DR CTD; 7305; -.
DR eggNOG; ENOG502SCVI; Eukaryota.
DR HOGENOM; CLU_141718_0_0_1; -.
DR InParanoid; Q8WNQ8; -.
DR OMA; VFCFATH; -.
DR TreeFam; TF336898; -.
DR Proteomes; UP000006718; Unplaced.
DR GO; GO:0009986; C:cell surface; ISS:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0043277; P:apoptotic cell clearance; ISS:UniProtKB.
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..113
FT /note="TYRO protein tyrosine kinase-binding protein"
FT /id="PRO_0000022604"
FT TOPO_DOM 28..40
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:O43914"
FT TRANSMEM 41..61
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:O43914"
FT TOPO_DOM 62..113
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:O43914"
FT DOMAIN 80..108
FT /note="ITAM"
FT REGION 75..113
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 88..113
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 50
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 54
FT /note="Important for interaction with transmembrane
FT receptors"
FT /evidence="ECO:0000250|UniProtKB:O43914"
FT MOD_RES 91
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O54885"
FT MOD_RES 102
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:O54885"
FT DISULFID 35
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:O43914"
SQ SEQUENCE 113 AA; 12131 MW; 4BBCDC70B4CB6DE5 CRC64;
MGGLEPCSRL LLLPLLLAVG GLRPVQAQAQ SDCSCSTVSP GVLAGIVLGD LVLTVLIALA
VYFLGRLVPR GRGAAEAATR KQRITETESP YQELQGQRSD VYSDLNTQRP YYK
