ID   TYOBP_BOVIN             Reviewed;         108 AA.
AC   Q95J79; A0JNM8;
DT   01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, 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   Bos taurus (Bovine).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC   Bovinae; Bos.
OX   NCBI_TaxID=9913;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Friesian; TISSUE=Peripheral blood;
RA   Ellis S.A., Staines K.A.;
RT   "Immunoreceptor DAP12: alternative splicing generates 2 transcripts in
RT   cattle, pig and human.";
RL   Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Hereford; TISSUE=Fetal medulla;
RG   NIH - Mammalian Gene Collection (MGC) project;
RL   Submitted (OCT-2006) 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; AJ419227; CAD11669.1; -; mRNA.
DR   EMBL; BC126797; AAI26798.1; -; mRNA.
DR   RefSeq; XP_005218963.1; XM_005218906.3.
DR   AlphaFoldDB; Q95J79; -.
DR   SMR; Q95J79; -.
DR   STRING; 9913.ENSBTAP00000009652; -.
DR   PaxDb; Q95J79; -.
DR   PeptideAtlas; Q95J79; -.
DR   GeneID; 282390; -.
DR   CTD; 7305; -.
DR   eggNOG; ENOG502SCVI; Eukaryota.
DR   HOGENOM; CLU_141718_0_0_1; -.
DR   InParanoid; Q95J79; -.
DR   Proteomes; UP000009136; 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:0005102; F:signaling receptor binding; IBA:GO_Central.
DR   GO; GO:0043277; P:apoptotic cell clearance; ISS:UniProtKB.
DR   GO; GO:0002282; P:microglial cell activation involved in immune response; IBA:GO_Central.
DR   GO; GO:0030889; P:negative regulation of B cell proliferation; IBA:GO_Central.
DR   GO; GO:0032911; P:negative regulation of transforming growth factor beta1 production; IBA:GO_Central.
DR   GO; GO:0002283; P:neutrophil activation involved in immune response; IBA:GO_Central.
DR   GO; GO:0034241; P:positive regulation of macrophage fusion; IBA:GO_Central.
DR   GO; GO:1904151; P:positive regulation of microglial cell mediated cytotoxicity; IBA:GO_Central.
DR   GO; GO:0032816; P:positive regulation of natural killer cell activation; IBA:GO_Central.
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..25
FT                   /evidence="ECO:0000255"
FT   CHAIN           26..108
FT                   /note="TYRO protein tyrosine kinase-binding protein"
FT                   /id="PRO_0000022602"
FT   TOPO_DOM        26..36
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000250|UniProtKB:O43914"
FT   TRANSMEM        37..57
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:O43914"
FT   TOPO_DOM        58..108
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000250|UniProtKB:O43914"
FT   DOMAIN          75..103
FT                   /note="ITAM"
FT   REGION          71..108
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        83..108
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         46
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            50
FT                   /note="Important for interaction with transmembrane
FT                   receptors"
FT                   /evidence="ECO:0000250|UniProtKB:O43914"
FT   MOD_RES         86
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:O54885"
FT   MOD_RES         97
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250|UniProtKB:O54885"
FT   DISULFID        31
FT                   /note="Interchain"
FT                   /evidence="ECO:0000250|UniProtKB:O43914"
SQ   SEQUENCE   108 AA;  11836 MW;  A26EE49E87F4D6DA CRC64;
     MEGLRPSDRL LSLLLTVGGL SLVLAQSECN CSSVSPGVLA GIVLGDLMLT LLIALAVYYL
     GRLVPRGRGA TEVTRKQHIP ETESPYQELQ GQRTDVYSDL NTQRPYYK