TYOBP_MOUSE
ID TYOBP_MOUSE Reviewed; 114 AA.
AC O54885; O88603;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=TYRO protein tyrosine kinase-binding protein {ECO:0000312|MGI:MGI:1277211};
DE AltName: Full=DNAX-activation protein 12 {ECO:0000303|PubMed:9490415};
DE AltName: Full=Killer-activating receptor-associated protein {ECO:0000303|PubMed:9852069};
DE Short=KAR-associated protein {ECO:0000303|PubMed:9852069};
DE Flags: Precursor;
GN Name=Tyrobp {ECO:0000312|MGI:MGI:1277211};
GN Synonyms=Dap12 {ECO:0000303|PubMed:9490415},
GN Karap {ECO:0000303|PubMed:9852069};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PHOSPHORYLATION.
RC STRAIN=C57BL/6J;
RX PubMed=9490415; DOI=10.1038/35642;
RA Lanier L.L., Corliss B.C., Wu J., Leong C., Phillips J.H.;
RT "Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved
RT in activating NK cells.";
RL Nature 391:703-707(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PHOSPHORYLATION.
RX PubMed=9852069; DOI=10.1074/jbc.273.51.34115;
RA Tomasello E., Olcese L., Vely F., Geourgeon C., Blery M., Moqrich A.,
RA Gautheret D., Djabali M., Mattei M.-G., Vivier E.;
RT "Gene structure, expression pattern, and biological activity of mouse
RT killer cell activating receptor-associated protein (KARAP)/DAP-12.";
RL J. Biol. Chem. 273:34115-34119(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP FUNCTION, INTERACTION WITH KLRA4 AND KLRA8, AND SUBCELLULAR LOCATION.
RX PubMed=9647200;
RA Smith K.M., Wu J., Bakker A.B., Phillips J.H., Lanier L.L.;
RT "Ly-49D and Ly-49H associate with mouse DAP12 and form activating
RT receptors.";
RL J. Immunol. 161:7-10(1998).
RN [5]
RP INTERACTION WITH CLECSF5.
RX PubMed=10449773; DOI=10.1073/pnas.96.17.9792;
RA Bakker A.B.H., Baker E., Sutherland G.R., Phillips J.H., Lanier L.L.;
RT "Myeloid DAP12-associating lectin (MDL)-1 is a cell surface receptor
RT involved in the activation of myeloid cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:9792-9796(1999).
RN [6]
RP INTERACTION WITH TREM3, AND PHOSPHORYLATION.
RX PubMed=11754004;
RX DOI=10.1002/1521-4141(200201)32:1<59::aid-immu59>3.0.co;2-u;
RA Chung D.H., Seaman W.E., Daws M.R.;
RT "Characterization of TREM-3, an activating receptor on mouse macrophages:
RT definition of a family of single Ig domain receptors on mouse chromosome
RT 17.";
RL Eur. J. Immunol. 32:59-66(2002).
RN [7]
RP INTERACTION WITH KLRK1, AND PHOSPHORYLATION.
RX PubMed=12426565; DOI=10.1038/ni858;
RA Diefenbach A., Tomasello E., Lucas M., Jamieson A.M., Hsia J.K., Vivier E.,
RA Raulet D.H.;
RT "Selective associations with signaling proteins determine stimulatory
RT versus costimulatory activity of NKG2D.";
RL Nat. Immunol. 3:1142-1149(2002).
RN [8]
RP INTERACTION WITH KLRK1.
RX PubMed=12426564; DOI=10.1038/ni857;
RA Gilfillan S., Ho E.L., Cella M., Yokoyama W.M., Colonna M.;
RT "NKG2D recruits two distinct adapters to trigger NK cell activation and
RT costimulation.";
RL Nat. Immunol. 3:1150-1155(2002).
RN [9]
RP INTERACTION WITH CD300C2.
RX PubMed=12893283; DOI=10.1016/s0006-291x(03)01245-2;
RA Kumagai H., Oki T., Tamitsu K., Feng S.-Z., Ono M., Nakajima H., Bao Y.-C.,
RA Kawakami Y., Nagayoshi K., Copeland N.G., Gilbert D.J., Jenkins N.A.,
RA Kawakami T., Kitamura T.;
RT "Identification and characterization of a new pair of immunoglobulin-like
RT receptors LMIR1 and 2 derived from murine bone marrow-derived mast cells.";
RL Biochem. Biophys. Res. Commun. 307:719-729(2003).
RN [10]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=12569157; DOI=10.1172/jci200316923;
RA Kaifu T., Nakahara J., Inui M., Mishima K., Momiyama T., Kaji M.,
RA Sugahara A., Koito H., Ujike-Asai A., Nakamura A., Kanazawa K.,
RA Tan-Takeuchi K., Iwasaki K., Yokoyama W.M., Kudo A., Fujiwara M., Asou H.,
RA Takai T.;
RT "Osteopetrosis and thalamic hypomyelinosis with synaptic degeneration in
RT DAP12-deficient mice.";
RL J. Clin. Invest. 111:323-332(2003).
RN [11]
RP INTERACTION WITH CD300C2.
RX PubMed=12874256; DOI=10.1084/jem.20021825;
RA Yotsumoto K., Okoshi Y., Shibuya K., Yamazaki S., Tahara-Hanaoka S.,
RA Honda S., Osawa M., Kuroiwa A., Matsuda Y., Tenen D.G., Iwama A.,
RA Nakauchi H., Shibuya A.;
RT "Paired activating and inhibitory immunoglobulin-like receptors, MAIR-I and
RT MAIR-II, regulate mast cell and macrophage activation.";
RL J. Exp. Med. 198:223-233(2003).
RN [12]
RP FUNCTION.
RX PubMed=15471863; DOI=10.1074/jbc.m406997200;
RA Voehringer D., Rosen D.B., Lanier L.L., Locksley R.M.;
RT "CD200 receptor family members represent novel DAP12-associated activating
RT receptors on basophils and mast cells.";
RL J. Biol. Chem. 279:54117-54123(2004).
RN [13]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=14969392; DOI=10.1359/jbmr.0301234;
RA Humphrey M.B., Ogasawara K., Yao W., Spusta S.C., Daws M.R., Lane N.E.,
RA Lanier L.L., Nakamura M.C.;
RT "The signaling adapter protein DAP12 regulates multinucleation during
RT osteoclast development.";
RL J. Bone Miner. Res. 19:224-234(2004).
RN [14]
RP INTERACTION WITH KLRK1.
RX PubMed=15294961; DOI=10.4049/jimmunol.173.4.2470;
RA Rosen D.B., Araki M., Hamerman J.A., Chen T., Yamamura T., Lanier L.L.;
RT "A Structural basis for the association of DAP12 with mouse, but not human,
RT NKG2D.";
RL J. Immunol. 173:2470-2478(2004).
RN [15]
RP FUNCTION IN INTEGRIN-MEDIATED NEUTROPHIL ACTIVATION, INTERACTION WITH SYK,
RP AND PHOSPHORYLATION.
RX PubMed=17086186; DOI=10.1038/ni1407;
RA Mocsai A., Abram C.L., Jakus Z., Hu Y., Lanier L.L., Lowell C.A.;
RT "Integrin signaling in neutrophils and macrophages uses adapters containing
RT immunoreceptor tyrosine-based activation motifs.";
RL Nat. Immunol. 7:1326-1333(2006).
RN [16]
RP FUNCTION, AND PHOSPHORYLATION.
RX PubMed=15728241; DOI=10.1084/jem.20041611;
RA Takahashi K., Rochford C.D., Neumann H.;
RT "Clearance of apoptotic neurons without inflammation by microglial
RT triggering receptor expressed on myeloid cells-2.";
RL J. Exp. Med. 201:647-657(2005).
RN [17]
RP INTERACTION WITH CD300C2.
RX PubMed=17202337; DOI=10.4049/jimmunol.178.2.765;
RA Nakahashi C., Tahara-Hanaoka S., Totsuka N., Okoshi Y., Takai T.,
RA Ohkohchi N., Honda S., Shibuya K., Shibuya A.;
RT "Dual assemblies of an activating immune receptor, MAIR-II, with ITAM-
RT bearing adapters DAP12 and FcRgamma chain on peritoneal macrophages.";
RL J. Immunol. 178:765-770(2007).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-92 AND TYR-103, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [19]
RP INTERACTION WITH CD300LB.
RX PubMed=17928527; DOI=10.1182/blood-2007-04-085787;
RA Yamanishi Y., Kitaura J., Izawa K., Matsuoka T., Oki T., Lu Y., Shibata F.,
RA Yamazaki S., Kumagai H., Nakajima H., Maeda-Yamamoto M., Tybulewicz V.L.J.,
RA Takai T., Kitamura T.;
RT "Analysis of mouse LMIR5/CLM-7 as an activating receptor: differential
RT regulation of LMIR5/CLM-7 in mouse versus human cells.";
RL Blood 111:688-698(2008).
RN [20]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=18685038; DOI=10.1523/jneurosci.1006-08.2008;
RA Wakselman S., Bechade C., Roumier A., Bernard D., Triller A., Bessis A.;
RT "Developmental neuronal death in hippocampus requires the microglial CD11b
RT integrin and DAP12 immunoreceptor.";
RL J. Neurosci. 28:8138-8143(2008).
RN [21]
RP FUNCTION, PHOSPHORYLATION AT TYR-92 AND TYR-103, DISRUPTION PHENOTYPE, AND
RP MUTAGENESIS OF ASP-52; TYR-92 AND TYR-103.
RX PubMed=18691974; DOI=10.1016/j.molcel.2008.06.023;
RA Zou W., Reeve J.L., Liu Y., Teitelbaum S.L., Ross F.P.;
RT "DAP12 couples c-Fms activation to the osteoclast cytoskeleton by
RT recruitment of Syk.";
RL Mol. Cell 31:422-431(2008).
RN [22]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18957693; DOI=10.1126/scisignal.1159665;
RA Helming L., Tomasello E., Kyriakides T.R., Martinez F.O., Takai T.,
RA Gordon S., Vivier E.;
RT "Essential role of DAP12 signaling in macrophage programming into a fusion-
RT competent state.";
RL Sci. Signal. 1:RA11-RA11(2008).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [24]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [25]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21727189; DOI=10.1084/jem.20101623;
RA Nakano-Yokomizo T., Tahara-Hanaoka S., Nakahashi-Oda C., Nabekura T.,
RA Tchao N.K., Kadosaki M., Totsuka N., Kurita N., Nakamagoe K., Tamaoka A.,
RA Takai T., Yasui T., Kikutani H., Honda S., Shibuya K., Lanier L.L.,
RA Shibuya A.;
RT "The immunoreceptor adapter protein DAP12 suppresses B lymphocyte-driven
RT adaptive immune responses.";
RL J. Exp. Med. 208:1661-1671(2011).
RN [26]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=21257958; DOI=10.4049/jimmunol.1000527;
RA Sumpter T.L., Packiam V., Turnquist H.R., Castellaneta A., Yoshida O.,
RA Thomson A.W.;
RT "DAP12 promotes IRAK-M expression and IL-10 production by liver myeloid
RT dendritic cells and restrains their T cell allostimulatory ability.";
RL J. Immunol. 186:1970-1980(2011).
RN [27]
RP PHOSPHORYLATION AT TYR-92 AND TYR-103, AND MUTAGENESIS OF TYR-92 AND
RP TYR-103.
RX PubMed=24078628; DOI=10.1074/jbc.m113.517540;
RA Wunderlich P., Glebov K., Kemmerling N., Tien N.T., Neumann H., Walter J.;
RT "Sequential proteolytic processing of the triggering receptor expressed on
RT myeloid cells-2 (TREM2) protein by ectodomain shedding and gamma-secretase-
RT dependent intramembranous cleavage.";
RL J. Biol. Chem. 288:33027-33036(2013).
RN [28]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25690660; DOI=10.1002/glia.22802;
RA Kobayashi M., Konishi H., Takai T., Kiyama H.;
RT "A DAP12-dependent signal promotes pro-inflammatory polarization in
RT microglia following nerve injury and exacerbates degeneration of injured
RT neurons.";
RL Glia 63:1073-1082(2015).
RN [29]
RP INTERACTION WITH TREM2.
RX PubMed=29518356; DOI=10.1016/j.neuron.2018.01.031;
RA Zhao Y., Wu X., Li X., Jiang L.L., Gui X., Liu Y., Sun Y., Zhu B.,
RA Pina-Crespo J.C., Zhang M., Zhang N., Chen X., Bu G., An Z., Huang T.Y.,
RA Xu H.;
RT "TREM2 Is a Receptor for beta-Amyloid that Mediates Microglial Function.";
RL Neuron 97:1023-1031(2018).
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 (PubMed:15471863, PubMed:9647200). TYROBP is tyrosine-
CC phosphorylated in the ITAM domain following ligand binding by the
CC associated receptors which leads to activation of additional tyrosine
CC kinases and subsequent cell activation (PubMed:15728241). Also has an
CC inhibitory role in some cells (PubMed:21727189). Non-covalently
CC associates with activating receptors of the CD300 family to mediate
CC cell activation (By similarity). Also mediates cell activation through
CC association with activating receptors of the CD200R family
CC (PubMed:15471863). Required for neutrophil activation mediated by
CC integrin (PubMed:17086186). Required for the activation of myeloid
CC cells mediated by the CLEC5A/MDL1 receptor (By similarity). Associates
CC with natural killer (NK) cell receptors such as the KLRD1/KLRC2
CC heterodimer to mediate NK cell activation (By similarity). Also
CC associates non-covalently with the NK cell receptors KLRA4/LY49D and
CC KLRA8/LY49H which leads to NK cell activation (PubMed:9647200).
CC Associates with TREM1 to mediate activation of neutrophils and
CC monocytes (By similarity). Associates with TREM2 on monocyte-derived
CC dendritic cells to mediate up-regulation of chemokine receptor CCR7 and
CC dendritic cell maturation and survival (By similarity). Association
CC with TREM2 mediates cytokine-induced formation of multinucleated giant
CC cells which are formed by the fusion of macrophages (PubMed:18957693).
CC Stabilizes the TREM2 C-terminal fragment (TREM2-CTF) which is produced
CC by TREM2 ectodomain shedding (By similarity). In microglia, required
CC with TREM2 for phagocytosis of apoptotic neurons (PubMed:15728241).
CC Required with ITGAM/CD11B in microglia to control production of
CC microglial superoxide ions which promote the neuronal apoptosis that
CC occurs during brain development (PubMed:18685038). Promotes pro-
CC inflammatory responses in microglia following nerve injury which
CC accelerates degeneration of injured neurons (PubMed:25690660).
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 allostimulatory ability (PubMed:21257958). Negatively regulates B cell
CC proliferation (PubMed:21727189). Required for CSF1-mediated osteoclast
CC cytoskeletal organization (PubMed:18691974). Positively regulates
CC multinucleation during osteoclast development (PubMed:12569157,
CC PubMed:14969392). {ECO:0000250|UniProtKB:O43914,
CC ECO:0000269|PubMed:12569157, ECO:0000269|PubMed:14969392,
CC ECO:0000269|PubMed:15471863, ECO:0000269|PubMed:15728241,
CC ECO:0000269|PubMed:17086186, ECO:0000269|PubMed:18685038,
CC ECO:0000269|PubMed:18691974, ECO:0000269|PubMed:18957693,
CC ECO:0000269|PubMed:21257958, ECO:0000269|PubMed:21727189,
CC ECO:0000269|PubMed:25690660, ECO:0000269|PubMed:9647200}.
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 are 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 (PubMed:29518356). Interacts with
CC TREM3 (PubMed:11754004). Interacts with CLECSF5 (PubMed:10449773).
CC Interacts with CD300LB and CD300C2 (PubMed:12874256, PubMed:12893283,
CC PubMed:17202337, PubMed:17928527). Interacts with CD300E (By
CC similarity). Interacts (via ITAM domain) with SYK (via SH2 domains);
CC activates SYK mediating neutrophil and macrophage integrin-mediated
CC activation (PubMed:17086186). Interacts (via transmembrane domain) with
CC KLRK1 isoform 2 (via transmembrane domain); the interaction is required
CC for KLRK1 NK cell surface expression and NK cell-mediated cytotoxicity
CC (PubMed:12426564, PubMed:12426565, PubMed:15294961). Interacts with
CC KLRC2 (By similarity). Interacts with CD300H (By similarity). Interacts
CC with KLRD1 (By similarity). Interacts with KLRA4 and KLRA8
CC (PubMed:9647200). {ECO:0000250|UniProtKB:O43914,
CC ECO:0000269|PubMed:10449773, ECO:0000269|PubMed:11754004,
CC ECO:0000269|PubMed:12426564, ECO:0000269|PubMed:12426565,
CC ECO:0000269|PubMed:12874256, ECO:0000269|PubMed:12893283,
CC ECO:0000269|PubMed:15294961, ECO:0000269|PubMed:17086186,
CC ECO:0000269|PubMed:17202337, ECO:0000269|PubMed:17928527,
CC ECO:0000269|PubMed:29518356, ECO:0000269|PubMed:9647200}.
CC -!- INTERACTION:
CC O54885; Q9R007: Clec5a; NbExp=3; IntAct=EBI-15687058, EBI-15761206;
CC O54885; Q9QUJ0: Hcst; NbExp=4; IntAct=EBI-15687058, EBI-15761243;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:9647200};
CC Single-pass type I membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Expressed on microglia (at protein level)
CC (PubMed:12569157, PubMed:18685038). Expressed on oligodendrocytes (at
CC protein level) (PubMed:12569157). Expressed on macrophages and
CC osteoclasts (PubMed:14969392). Expressed on dendritic cells in liver,
CC spleen, kidney and lung with highest levels in liver dendritic cells
CC (PubMed:21257958). {ECO:0000269|PubMed:12569157,
CC ECO:0000269|PubMed:14969392, ECO:0000269|PubMed:18685038,
CC ECO:0000269|PubMed:21257958}.
CC -!- INDUCTION: Induced in microglia following nerve injury (at protein
CC level) (PubMed:25690660). Induced in liver dendritic cells by
CC physiological concentrations of lipopolysaccharide (PubMed:21257958).
CC {ECO:0000269|PubMed:21257958, ECO:0000269|PubMed:25690660}.
CC -!- PTM: Tyrosine phosphorylated (PubMed:11754004, PubMed:12426565,
CC PubMed:15728241, PubMed:17086186, PubMed:18691974, PubMed:9490415,
CC PubMed:9852069). Following ligand binding by associated receptors,
CC tyrosine phosphorylated in the ITAM domain which leads to activation of
CC additional tyrosine kinases and subsequent cell activation (By
CC similarity). {ECO:0000250|UniProtKB:O43914,
CC ECO:0000269|PubMed:11754004, ECO:0000269|PubMed:12426565,
CC ECO:0000269|PubMed:17086186, ECO:0000269|PubMed:9490415,
CC ECO:0000269|PubMed:9852069}.
CC -!- DISRUPTION PHENOTYPE: Increased bone mass and failure to generate
CC multinuclear osteoclasts in vitro (PubMed:12569157, PubMed:14969392).
CC Thalamic hypomyelination, synaptic degeneration, reduced startle
CC response and aberrant electrophysiological profiles (PubMed:12569157).
CC Enhanced proliferation of B cells (PubMed:21727189). Reduced number of
CC microglia at sites of nerve injury and high rate of neuronal survival
CC (PubMed:25690660). Impaired macrophage fusion (PubMed:18957693).
CC Defective osteoclast cytoskeletal organization and function
CC (PubMed:18691974). {ECO:0000269|PubMed:12569157,
CC ECO:0000269|PubMed:14969392, ECO:0000269|PubMed:18691974,
CC ECO:0000269|PubMed:18957693, ECO:0000269|PubMed:21727189,
CC ECO:0000269|PubMed:25690660}.
CC -!- SIMILARITY: Belongs to the TYROBP family. {ECO:0000305}.
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DR EMBL; AF024637; AAD09438.1; -; mRNA.
DR EMBL; AF077829; AAC95529.1; -; mRNA.
DR EMBL; BC056450; AAH56450.1; -; mRNA.
DR CCDS; CCDS21089.1; -.
DR RefSeq; NP_035792.1; NM_011662.2.
DR AlphaFoldDB; O54885; -.
DR SMR; O54885; -.
DR BioGRID; 204396; 6.
DR CORUM; O54885; -.
DR DIP; DIP-29746N; -.
DR IntAct; O54885; 4.
DR STRING; 10090.ENSMUSP00000032800; -.
DR iPTMnet; O54885; -.
DR PhosphoSitePlus; O54885; -.
DR PaxDb; O54885; -.
DR PeptideAtlas; O54885; -.
DR PRIDE; O54885; -.
DR ProteomicsDB; 298443; -.
DR Antibodypedia; 4010; 298 antibodies from 38 providers.
DR DNASU; 22177; -.
DR Ensembl; ENSMUST00000032800; ENSMUSP00000032800; ENSMUSG00000030579.
DR GeneID; 22177; -.
DR KEGG; mmu:22177; -.
DR UCSC; uc009gef.1; mouse.
DR CTD; 7305; -.
DR MGI; MGI:1277211; Tyrobp.
DR VEuPathDB; HostDB:ENSMUSG00000030579; -.
DR eggNOG; ENOG502SCVI; Eukaryota.
DR GeneTree; ENSGT00390000016786; -.
DR HOGENOM; CLU_141718_0_0_1; -.
DR InParanoid; O54885; -.
DR OMA; VFCFATH; -.
DR OrthoDB; 1508977at2759; -.
DR PhylomeDB; O54885; -.
DR TreeFam; TF336898; -.
DR Reactome; R-MMU-2172127; DAP12 interactions.
DR Reactome; R-MMU-2424491; DAP12 signaling.
DR Reactome; R-MMU-391160; Signal regulatory protein family interactions.
DR Reactome; R-MMU-416700; Other semaphorin interactions.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 22177; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Tyrobp; mouse.
DR PRO; PR:O54885; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; O54885; protein.
DR Bgee; ENSMUSG00000030579; Expressed in granulocyte and 214 other tissues.
DR ExpressionAtlas; O54885; baseline and differential.
DR Genevisible; O54885; MM.
DR GO; GO:0009986; C:cell surface; IDA:UniProtKB.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
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; IPI:ARUK-UCL.
DR GO; GO:0030036; P:actin cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0043277; P:apoptotic cell clearance; IMP:UniProtKB.
DR GO; GO:0097190; P:apoptotic signaling pathway; IDA:ARUK-UCL.
DR GO; GO:0030900; P:forebrain development; IDA:ARUK-UCL.
DR GO; GO:0007229; P:integrin-mediated signaling pathway; IMP:UniProtKB.
DR GO; GO:0002281; P:macrophage activation involved in immune response; IMP:UniProtKB.
DR GO; GO:0002282; P:microglial cell activation involved in immune response; IMP:UniProtKB.
DR GO; GO:0002274; P:myeloid leukocyte activation; ISO:MGI.
DR GO; GO:0030889; P:negative regulation of B cell proliferation; IMP:UniProtKB.
DR GO; GO:0032693; P:negative regulation of interleukin-10 production; IMP:ARUK-UCL.
DR GO; GO:1900272; P:negative regulation of long-term synaptic potentiation; IMP:ARUK-UCL.
DR GO; GO:0032911; P:negative regulation of transforming growth factor beta1 production; IMP:ARUK-UCL.
DR GO; GO:0002283; P:neutrophil activation involved in immune response; IMP:UniProtKB.
DR GO; GO:0030316; P:osteoclast differentiation; IDA:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ARUK-UCL.
DR GO; GO:0110090; P:positive regulation of hippocampal neuron apoptotic process; IDA:ARUK-UCL.
DR GO; GO:0032731; P:positive regulation of interleukin-1 beta production; IMP:ARUK-UCL.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IMP:ARUK-UCL.
DR GO; GO:0034241; P:positive regulation of macrophage fusion; IMP:UniProtKB.
DR GO; GO:1904151; P:positive regulation of microglial cell mediated cytotoxicity; IMP:UniProtKB.
DR GO; GO:0032816; P:positive regulation of natural killer cell activation; IDA:UniProtKB.
DR GO; GO:1901216; P:positive regulation of neuron death; IMP:ARUK-UCL.
DR GO; GO:2001206; P:positive regulation of osteoclast development; IMP:UniProtKB.
DR GO; GO:2000010; P:positive regulation of protein localization to cell surface; ISO:MGI.
DR GO; GO:1902685; P:positive regulation of receptor localization to synapse; IMP:ARUK-UCL.
DR GO; GO:0032930; P:positive regulation of superoxide anion generation; IDA:ARUK-UCL.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:ARUK-UCL.
DR GO; GO:0050821; P:protein stabilization; ISS:UniProtKB.
DR GO; GO:2001204; P:regulation of osteoclast development; IGI:MGI.
DR GO; GO:0048678; P:response to axon injury; IMP:ARUK-UCL.
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 1: Evidence at protein level;
KW Calcium; Cell membrane; Disulfide bond; Immunity; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..114
FT /note="TYRO protein tyrosine kinase-binding protein"
FT /id="PRO_0000022605"
FT TOPO_DOM 22..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 74..107
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 89..107
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:0000269|PubMed:18691974,
FT ECO:0000269|PubMed:24078628, ECO:0007744|PubMed:17947660"
FT MOD_RES 103
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:18691974,
FT ECO:0000269|PubMed:24078628, ECO:0007744|PubMed:17947660"
FT DISULFID 37
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:O43914"
FT MUTAGEN 52
FT /note="D->A: Failure to rescue cytoskeletal defects when
FT introduced into TYROBP-deficient cells."
FT /evidence="ECO:0000269|PubMed:18691974"
FT MUTAGEN 92
FT /note="Y->F: Abolishes phosphorylation and ability to
FT regulate cytoskeletal organization; when associated with F-
FT 103."
FT /evidence="ECO:0000269|PubMed:18691974,
FT ECO:0000269|PubMed:24078628"
FT MUTAGEN 103
FT /note="Y->F: Abolishes phosphorylation and ability to
FT regulate cytoskeletal organization; when associated with F-
FT 92."
FT /evidence="ECO:0000269|PubMed:18691974,
FT ECO:0000269|PubMed:24078628"
FT CONFLICT 20
FT /note="G -> E (in Ref. 2; AAC95529)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 114 AA; 12367 MW; 6A530D52E51FED8F CRC64;
MGALEPSWCL LFLPVLLTVG GLSPVQAQSD TFPRCDCSSV SPGVLAGIVL GDLVLTLLIA
LAVYSLGRLV SRGQGTAEGT RKQHIAETES PYQELQGQRP EVYSDLNTQR QYYR
