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FLASH GENE
Symbol TYROBP contributors: mct/npt - updated : 03-05-2016
HGNC name TYRO protein tyrosine kinase binding protein
HGNC id 12449
Corresponding disease
PLOSL1 polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1
Location 19q13.12      Physical location : 36.395.305 - 36.399.211
Synonym name
  • DNAX-activating protein
  • killer activating receptor associated protein
  • DNAX-activation protein 12
  • KAR-associated protein
  • Synonym symbol(s) DAP12, KARAP, PLO-SL, PLOSL,
    DNA
    TYPE functioning gene
    STRUCTURE 3.91 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    motif repetitive sequence   ALU
    text structure Alu sequences in 5' utr and intron 4
    MAPPING cloned Y linked   status confirmed
    Map cen - D19S425 - GPI - TYROBP - COX6B1 - D19S208 - CAPNS1 ,D19S224 - qter
    Authors GeneMap (98)
    Physical map
    LOC388533 19 similar to KIPV467 ZD52F10 19q13.13 hypothetical gene ZD52F10 UNQ698 19q13.13 HLAR698 GAPDS 19q13.1 glyceraldehyde-3-phosphate dehydrogenase, testis-specific NIFIE14 19q13.1 seven transmembrane domain protein ATP4A 19q13.1 ATPase, H+/K+ exchanging, alpha polypeptide KIAA0841 19q13.13 KIAA0841 MGC10433 19q13.13 hypothetical protein MGC10433 LOC339321 19q13.13 hypothetical protein LOC339321 COX6B 19q13.1 cytochrome c oxidase subunit VIb UPK1A 19q12-q13.1 uroplakin 1A TZFP 19q13.1 uroplakin 1A MLL4 19q13.1 myeloid/lymphoid or mixed-lineage leukemia 4 FLJ22573 19q13.13 hypothetical protein FLJ22573 U2AF1L3 19q13.13 U2(RNU2) small nuclear RNA auxiliary factor 1-like 3 PEN2 19q13.13 presenilin enhancer 2 F25965 19q13.1 protein F25965 FLJ32389 19q13.13 hypothetical protein FLJ32389 LOC148137 19q13.13 hypothetical protein BC017947 SNX26 19q13.13 sorting nexin 26 PRODH2 19q13.1 proline dehydrogenase (oxidase) 2 NPHS1 19q13.1 nephrosis 1, congenital, Finnish type (nephrin) KIRREL2 19q13.13 kin of IRRE like 2 (Drosophila) APLP1 19q13.1-q13.2 amyloid beta (A4) precursor-like protein 1 TA-NFKBH 19q13.13 T-cell activation NFKB-like protein HCST 19q13.1 hematopoietic cell signal transducer TYROBP 19q13.1 TYRO protein tyrosine kinase binding protein MGC2656 FLJ36445 19q13.13 hypothetical protein FLJ36445 MGC15677 19q13.13 hypothetical protein MGC15677 CLIPR-59 19q13.13 CLIP-170-related protein THAP8 19q13.13 THAP domain containing 8 FLJ33298 19q13.13 hypothetical protein FLJ33298 DKFZP434J046 LOC390925 POLR2I 19q12 polymerase (RNA) II (DNA directed) polypeptide I, 14.5kDa CKAP1 19q13.11-q13.12 cytoskeleton-associated protein 1 CAPNS1 19q13.13 calpain, small subunit 1 COX7A1 19q13.1 cytochrome c oxidase subunit VIIa polypeptide 1 (muscle)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    5 - 608 12.18 113 - 2013 23715743
    5 - 605 12.1 112 - 2013 23715743
    4 - 572 - 101 - 2013 23715743
    3 - 575 11.04 102 - 2013 23715743
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivemouthtongue  predominantly
    Hearing/Equilibriumear   highly
    Nervousbrain     Homo sapiens
    Reproductivefemale systembreastmammary gland  
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
     bone marrow  highly
    Connectiveadipose  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte
    Blood/Hematopoieticmonocyte
    Lymphoid/Immunemacrophage
    Nervousglia Homo sapiens
    Nervousneuron
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a signal sequence
  • a short extracellular domain
  • a transmembrane domain
  • a cytoplasmic tail with the immunoreceptor tyrosine based activation motif (ITAM)
  • mono polymer homomer , dimer
    HOMOLOGY
    Homologene
    FAMILY
  • CD3 zeta family
  • TYROBP family
  • CATEGORY adaptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm
    text type I transmembrane protein
    basic FUNCTION
  • playing a role in signal transduction, bone modeling, brain myelination, and inflammation
  • general macrophage fusion regulator, involved in modulating the expression of several macrophage-associated genes, including those encoding known mediators of macrophage fusion, such as DCST1 and DCST2 and Cadherin 1
  • involved in programming of macrophages through the regulation of gene and protein expression to induce a fusion-competent state
  • HCST and TYROBP, can either activate or inhibit immune responses
  • trans-membrane adaptor molecule that transduces activating signals in NK and myeloid cells
  • CLEC5A associates with its adaptor protein TYROBP to activate a signaling cascade resulting in activation of downstream kinases in inflammatory responses
  • ITAM molecules, FCER1G, TREM2 and TYROBP play an important role in osteoclast development and activity
  • impacts trafficking and surface stability of killer immunoglobulin-like receptors on natural killer cells
  • is an immunoreceptor tyrosine-based activation motif (ITAM)-containing adaptor protein found in myeloid cells and natural killer cells
  • TREM2 and its signaling adaptor protein TYROBP/DAP12 play important roles in signal transduction in dendritic cells, osteoclasts, tissue macrophages, and microglia
  • role for TYROBP expression in tissue-resident alveolar macrophages in mediating acute noninfectious tissue injury through regulation of neutrophil trafficking
  • role of TYROBP in stabilizing TREM2-C-terminal fragment, thereby protecting against excessive pro-inflammatory responses
  • significant role in the initial inflammatory response, bone remodeling and regeneration
  • is an immunoadaptor protein with associated immunoreceptors on myeloid lineage cells, including osteoclasts
  • TREM2 and TYROBP—possess the ability to modulate critical cellular functions via crosstalk with diverse signaling pathways
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
  • SIGLEC15-TYROBP-SYK-signaling cascade plays a critical role in functional osteoclast formation
  • a component
  • a disulfide-bonded dimer
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • associate with the killer-cell inhibitory receptor (KIR) family of membrane glycoproteins
  • interacting with SIRPB1 and TREM1
  • interacts with CLECSF5
  • PLXNA1 associates with the triggering receptor expressed on myeloid cells-2 (TREM2), linking semaphorin-signalling to the immuno-receptor tyrosine-based activation motif (ITAM)-bearing adaptor protein, TYROBP
  • TYROBP and TREM2, with SYK are required for the cytokine-induced formation of giant cells
  • CLEC5A associates with both TYROBP and HCST in osteoclasts and bone marrow-derived macrophages, where HCST association depends almost entirely on TYROBP
  • interaction with HCST, a signaling adaptor molecule that play a key role in the TREM2- and TYROBP-dependent recruitment of PI3K to the signaling complex
  • TREM1 associated with TYROBP in hypoxic mature dendritic cells, and its engagement elicited TYROBP-linked signaling, resulting in MAPK3, AKT1, and NFKBIA phosphorylation
  • binding of dengue virus to CLEC5A triggers signaling through the associated adapter molecule TYROBP, stimulating proinflammatory cytokine release
  • SIGLEC15 is a TYROBP-associated receptor in osteoclasts
  • OSCAR and TREM2 are essential receptors that pair with adaptor molecules Fc receptor common gamma chain (FCR1G) and TYROBP respectively to induce calcium signalling
  • TYROBP/TREM2 activation plays an important role in activation and differentiation of osteoclasts, brain and bone homeostasis and inhibition of the toll-like receptor (TLR) signaling in macrophages and dendritic cells
  • SIGLEC15 interacts with the adapter protein TYROBP and can induce AKT1 activation when clustered on the osteoclast cell surface, which likely represents its normal signaling function
  • capable of associating with KLRD1 and TYROBP but the complex was retained intracellularly at the endoplasmic reticulum instead of being expressed on cell surfaces, and this localization was dependent on a sequence of hydrophobic AAs in the extracellular domain of KLRC3
  • immunoreceptor that regulates osteoclast development and bone resorption in association with an immunoreceptor tyrosine-based activation motif (ITAM) adaptor protein (TYROBP)
  • TREM2 is a TYROBP-associated receptor expressed in microglia, macrophages, and other myeloid-derived cells
  • cell & other
  • associating with natural killer cell receptors lacking ITIM sequence (see KIRDS1 to 5), resulting in cellular activation
  • associating with KLRD1, KLRC2, CLECSF5
  • REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) PLOSL1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    impairs fracture healing
    constitutional     --over  
    results in both increased osteoclastogenesis and impaired hematopoiesis underlining the relationship between bone homeostasis and hematopoiesis
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerhemopathy 
    inhibitors of HCST and TYROBP or other proteins involved in this signaling pathway will be attractive therapeutic targets for the treatment of large granular lymphocyte (LGL) leukemia
    immunologyautoimmune 
    inhibitors of HCST and TYROBP or other proteins involved in this signaling pathway will be attractive therapeutic targets for the treatment of autoimmune diseases and syndromes
    ANIMAL & CELL MODELS
    Dap12-deficient mice exhibit mild osteopetrosis