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Protein

TYRO protein tyrosine kinase-binding protein

Gene

Tyrobp

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Non-covalently associates with activating receptors of the CD300 family. Cross-linking of CD300-TYROBP complexes results in cellular activation. Involved for instance in neutrophil activation mediated by integrin.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei56 – 561Important for interaction with transmembrane receptorsBy similarity

GO - Molecular functioni

GO - Biological processi

  • integrin-mediated signaling pathway Source: UniProtKB
  • macrophage activation involved in immune response Source: UniProtKB
  • neutrophil activation involved in immune response Source: UniProtKB
  • regulation of osteoclast development Source: MGI
Complete GO annotation...

Enzyme and pathway databases

ReactomeiR-MMU-2172127. DAP12 interactions.
R-MMU-2424491. DAP12 signaling.
R-MMU-391160. Signal regulatory protein (SIRP) family interactions.
R-MMU-416700. Other semaphorin interactions.

Names & Taxonomyi

Protein namesi
Recommended name:
TYRO protein tyrosine kinase-binding protein
Alternative name(s):
DNAX-activation protein 12
Killer-activating receptor-associated protein
Short name:
KAR-associated protein
Gene namesi
Name:Tyrobp
Synonyms:Dap12, Karap
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1277211. Tyrobp.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini22 – 4221ExtracellularSequence analysisAdd
BLAST
Transmembranei43 – 6321HelicalSequence analysisAdd
BLAST
Topological domaini64 – 11451CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence analysisAdd
BLAST
Chaini22 – 11493TYRO protein tyrosine kinase-binding proteinPRO_0000022605Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi37 – 37InterchainBy similarity
Modified residuei92 – 921PhosphotyrosineCombined sources
Modified residuei103 – 1031PhosphotyrosineCombined sources

Post-translational modificationi

Tyrosine phosphorylated.

Keywords - PTMi

Disulfide bond, Phosphoprotein

Proteomic databases

PaxDbiO54885.
PRIDEiO54885.

PTM databases

iPTMnetiO54885.
PhosphoSiteiO54885.

Expressioni

Gene expression databases

BgeeiO54885.
CleanExiMM_TYROBP.
ExpressionAtlasiO54885. baseline and differential.
GenevisibleiO54885. MM.

Interactioni

Subunit structurei

Homodimer; disulfide-linked. Interacts with SIRPB1 and TREM1. Interacts with SIGLEC14 (By similarity). Interacts with CLECSF5. Interacts with CD300LB and CD300D. Interacts with CD300E. Interacts with KLRC2 and KIR2DS3 (By similarity). Interacts (via ITAM domain) with SYK (via SH2 domains); activates SYK mediating neutrophils and macrophages integrin-mediated activation. Interacts (via transmembrane domain) with KLRK1 isoform 2 (via transmembrane domain); the interaction is required for KLRK1 NK cell surface expression and induce NK cell-mediated cytotoxicity.By similarity9 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204396. 5 interactions.
DIPiDIP-29746N.
STRINGi10090.ENSMUSP00000032800.

Structurei

3D structure databases

ProteinModelPortaliO54885.
SMRiO54885. Positions 40-69.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini81 – 10929ITAMAdd
BLAST

Sequence similaritiesi

Belongs to the TYROBP family.Curated
Contains 1 ITAM domain.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410J1XS. Eukaryota.
ENOG410Z4TN. LUCA.
HOGENOMiHOG000056440.
HOVERGENiHBG061468.
InParanoidiO54885.
KOiK07992.
OMAiNCSVVSP.
OrthoDBiEOG7NW6CH.
PhylomeDBiO54885.
TreeFamiTF336898.

Family and domain databases

InterProiIPR026200. Tyrobp.
[Graphical view]
PANTHERiPTHR17554. PTHR17554. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O54885-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGALEPSWCL LFLPVLLTVG GLSPVQAQSD TFPRCDCSSV SPGVLAGIVL
60 70 80 90 100
GDLVLTLLIA LAVYSLGRLV SRGQGTAEGT RKQHIAETES PYQELQGQRP
110
EVYSDLNTQR QYYR
Length:114
Mass (Da):12,367
Last modified:June 1, 1998 - v1
Checksum:i6A530D52E51FED8F
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti20 – 201G → E in AAC95529 (PubMed:9852069).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF024637 mRNA. Translation: AAD09438.1.
AF077829 mRNA. Translation: AAC95529.1.
BC056450 mRNA. Translation: AAH56450.1.
CCDSiCCDS21089.1.
RefSeqiNP_035792.1. NM_011662.2.
UniGeneiMm.46301.

Genome annotation databases

EnsembliENSMUST00000032800; ENSMUSP00000032800; ENSMUSG00000030579.
GeneIDi22177.
KEGGimmu:22177.
UCSCiuc009gef.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF024637 mRNA. Translation: AAD09438.1.
AF077829 mRNA. Translation: AAC95529.1.
BC056450 mRNA. Translation: AAH56450.1.
CCDSiCCDS21089.1.
RefSeqiNP_035792.1. NM_011662.2.
UniGeneiMm.46301.

3D structure databases

ProteinModelPortaliO54885.
SMRiO54885. Positions 40-69.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204396. 5 interactions.
DIPiDIP-29746N.
STRINGi10090.ENSMUSP00000032800.

PTM databases

iPTMnetiO54885.
PhosphoSiteiO54885.

Proteomic databases

PaxDbiO54885.
PRIDEiO54885.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000032800; ENSMUSP00000032800; ENSMUSG00000030579.
GeneIDi22177.
KEGGimmu:22177.
UCSCiuc009gef.1. mouse.

Organism-specific databases

CTDi7305.
MGIiMGI:1277211. Tyrobp.

Phylogenomic databases

eggNOGiENOG410J1XS. Eukaryota.
ENOG410Z4TN. LUCA.
HOGENOMiHOG000056440.
HOVERGENiHBG061468.
InParanoidiO54885.
KOiK07992.
OMAiNCSVVSP.
OrthoDBiEOG7NW6CH.
PhylomeDBiO54885.
TreeFamiTF336898.

Enzyme and pathway databases

ReactomeiR-MMU-2172127. DAP12 interactions.
R-MMU-2424491. DAP12 signaling.
R-MMU-391160. Signal regulatory protein (SIRP) family interactions.
R-MMU-416700. Other semaphorin interactions.

Miscellaneous databases

NextBioi302131.
PROiO54885.
SOURCEiSearch...

Gene expression databases

BgeeiO54885.
CleanExiMM_TYROBP.
ExpressionAtlasiO54885. baseline and differential.
GenevisibleiO54885. MM.

Family and domain databases

InterProiIPR026200. Tyrobp.
[Graphical view]
PANTHERiPTHR17554. PTHR17554. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells."
    Lanier L.L., Corliss B.C., Wu J., Leong C., Phillips J.H.
    Nature 391:703-707(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: C57BL/6J.
  2. "Gene structure, expression pattern, and biological activity of mouse killer cell activating receptor-associated protein (KARAP)/DAP-12."
    Tomasello E., Olcese L., Vely F., Geourgeon C., Blery M., Moqrich A., Gautheret D., Djabali M., Mattei M.-G., Vivier E.
    J. Biol. Chem. 273:34115-34119(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Brain.
  4. "Myeloid DAP12-associating lectin (MDL)-1 is a cell surface receptor involved in the activation of myeloid cells."
    Bakker A.B.H., Baker E., Sutherland G.R., Phillips J.H., Lanier L.L.
    Proc. Natl. Acad. Sci. U.S.A. 96:9792-9796(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CLECSF5.
  5. "Selective associations with signaling proteins determine stimulatory versus costimulatory activity of NKG2D."
    Diefenbach A., Tomasello E., Lucas M., Jamieson A.M., Hsia J.K., Vivier E., Raulet D.H.
    Nat. Immunol. 3:1142-1149(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH KLRK1.
  6. "NKG2D recruits two distinct adapters to trigger NK cell activation and costimulation."
    Gilfillan S., Ho E.L., Cella M., Yokoyama W.M., Colonna M.
    Nat. Immunol. 3:1150-1155(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH KLRK1.
  7. "Identification and characterization of a new pair of immunoglobulin-like receptors LMIR1 and 2 derived from murine bone marrow-derived mast cells."
    Kumagai H., Oki T., Tamitsu K., Feng S.-Z., Ono M., Nakajima H., Bao Y.-C., Kawakami Y., Nagayoshi K., Copeland N.G., Gilbert D.J., Jenkins N.A., Kawakami T., Kitamura T.
    Biochem. Biophys. Res. Commun. 307:719-729(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CD300D.
  8. "Paired activating and inhibitory immunoglobulin-like receptors, MAIR-I and MAIR-II, regulate mast cell and macrophage activation."
    Yotsumoto K., Okoshi Y., Shibuya K., Yamazaki S., Tahara-Hanaoka S., Honda S., Osawa M., Kuroiwa A., Matsuda Y., Tenen D.G., Iwama A., Nakauchi H., Shibuya A.
    J. Exp. Med. 198:223-233(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CD300D.
  9. "A Structural basis for the association of DAP12 with mouse, but not human, NKG2D."
    Rosen D.B., Araki M., Hamerman J.A., Chen T., Yamamura T., Lanier L.L.
    J. Immunol. 173:2470-2478(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH KLRK1.
  10. "Integrin signaling in neutrophils and macrophages uses adaptors containing immunoreceptor tyrosine-based activation motifs."
    Mocsai A., Abram C.L., Jakus Z., Hu Y., Lanier L.L., Lowell C.A.
    Nat. Immunol. 7:1326-1333(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN INTEGRIN-MEDIATED NEUTROPHIL ACTIVATION, INTERACTION WITH SYK.
  11. "Dual assemblies of an activating immune receptor, MAIR-II, with ITAM-bearing adapters DAP12 and FcRgamma chain on peritoneal macrophages."
    Nakahashi C., Tahara-Hanaoka S., Totsuka N., Okoshi Y., Takai T., Ohkohchi N., Honda S., Shibuya K., Shibuya A.
    J. Immunol. 178:765-770(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CD300D.
  12. "Quantitative time-resolved phosphoproteomic analysis of mast cell signaling."
    Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R.
    J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-92 AND TYR-103, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Mast cell.
  13. "Analysis of mouse LMIR5/CLM-7 as an activating receptor: differential regulation of LMIR5/CLM-7 in mouse versus human cells."
    Yamanishi Y., Kitaura J., Izawa K., Matsuoka T., Oki T., Lu Y., Shibata F., Yamazaki S., Kumagai H., Nakajima H., Maeda-Yamamoto M., Tybulewicz V.L.J., Takai T., Kitamura T.
    Blood 111:688-698(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CD300LB.
  14. "The phagosomal proteome in interferon-gamma-activated macrophages."
    Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
    Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  15. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Spleen.

Entry informationi

Entry nameiTYOBP_MOUSE
AccessioniPrimary (citable) accession number: O54885
Secondary accession number(s): O88603
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: June 1, 1998
Last modified: March 16, 2016
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.