TYROBP explained

TYRO protein tyrosine kinase-binding protein is an adapter protein that in humans is encoded by the TYROBP gene.^{[1] [2]}

Function

This gene encodes a transmembrane signaling polypeptide which contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain. The encoded protein may associate with the killer cell immunoglobulin-like receptor (KIR) family of membrane glycoproteins and may act as an activating signal transduction element. This protein may bind zeta-chain associated protein kinase 70 kDa (ZAP-70) and spleen tyrosine kinase (SYK) and play a role in signal transduction, bone modeling, brain myelination, and inflammation. Mutations within this gene have been associated with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), also known as Nasu-Hakola disease. Its putative receptor, triggering receptor expressed on myeloid cells 2 (TREM2), also causes PLOSL. Two alternative transcript variants encoding distinct isoforms have been identified for this gene. Other alternative splice variants have been described, but their full-length nature has not been determined.^[3]

Interactions

TYROBP has been shown to interact with SIRPB1.^{[4] [5]}

Clinical significance

Pathological mutations of the TYROBP gene cause polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1, a condition presenting as early-onset dementia.

External links

• GeneReviews/NIH/NCBI/UW entry on Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy (PLOSL)

Further reading

• Colonna M . DAP12 signaling: from immune cells to bone modeling and brain myelination . J. Clin. Invest. . 111 . 3 . 313–4 . 2003 . 12569153 . 151875 . 10.1172/JCI17745 .
• Takaki R, Watson SR, Lanier LL . DAP12: an adapter protein with dual functionality . Immunol. Rev. . 214 . 118–29 . 2007 . 17100880 . 10.1111/j.1600-065X.2006.00466.x . 12937527 .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Res. . 6 . 9 . 791–806 . 1997 . 8889548 . 10.1101/gr.6.9.791 . free .
• Pekkarinen P, Hovatta I, Hakola P, Järvi O, Kestilä M, Lenkkeri U, Adolfsson R, Holmgren G, Nylander PO, Tranebjaerg L, Terwilliger JD, Lönnqvist J, Peltonen L . Assignment of the locus for PLO-SL, a frontal-lobe dementia with bone cysts, to 19q13 . Am. J. Hum. Genet. . 62 . 2 . 362–72 . 1998 . 9463329 . 1376898 . 10.1086/301722 .
• Lanier LL, Corliss B, Wu J, Phillips JH . Association of DAP12 with activating CD94/NKG2C NK cell receptors . Immunity . 8 . 6 . 693–701 . 1998 . 9655483 . 10.1016/S1074-7613(00)80574-9 . free .
• Pekkarinen P, Kestilä M, Paloneva J, Terwillign J, Varilo T, Järvi O, Hakola P, Peltonen L . Fine-scale mapping of a novel dementia gene, PLOSL, by linkage disequilibrium . Genomics . 54 . 2 . 307–15 . 1999 . 9828133 . 10.1006/geno.1998.5591 . free .
• Cantoni C, Bottino C, Vitale M, Pessino A, Augugliaro R, Malaspina A, Parolini S, Moretta L, Moretta A, Biassoni R . NKp44, A Triggering Receptor Involved in Tumor Cell Lysis by Activated Human Natural Killer Cells, Is a Novel Member of the Immunoglobulin Superfamily . J. Exp. Med. . 189 . 5 . 787–96 . 1999 . 10049942 . 2192947 . 10.1084/jem.189.5.787 .
• Bellón T, Heredia AB, Llano M, Minguela A, Rodriguez A, López-Botet M, Aparicio P . Triggering of effector functions on a CD8+ T cell clone upon the aggregation of an activatory CD94/kp39 heterodimer . J. Immunol. . 162 . 7 . 3996–4002 . 1999 . 10.4049/jimmunol.162.7.3996 . 10201920 . free .
• Bakker AB, Baker E, Sutherland GR, Phillips JH, Lanier LL . Grant Robert Sutherland . Myeloid DAP12-associating lectin (MDL)-1 is a cell surface receptor involved in the activation of myeloid cells . Proc. Natl. Acad. Sci. U.S.A. . 96 . 17 . 9792–6 . 1999 . 10449773 . 22289 . 10.1073/pnas.96.17.9792 . 1999PNAS...96.9792B . free .
• Dietrich J, Cella M, Seiffert M, Bühring HJ, Colonna M . Cutting edge: signal-regulatory protein beta 1 is a DAP12-associated activating receptor expressed in myeloid cells . J. Immunol. . 164 . 1 . 9–12 . 2000 . 10604985 . 10.4049/jimmunol.164.1.9 . free .
• Bouchon A, Dietrich J, Colonna M . Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes . J. Immunol. . 164 . 10 . 4991–5 . 2000 . 10799849 . 10.4049/jimmunol.164.10.4991 . free .
• Tomasello E, Cant C, Bühring HJ, Vély F, André P, Seiffert M, Ullrich A, Vivier E . Association of signal-regulatory proteins beta with KARAP/DAP-12 . Eur. J. Immunol. . 30 . 8 . 2147–56 . 2000 . 10940905 . 10.1002/1521-4141(2000)30:8<2147::AID-IMMU2147>3.0.CO;2-1 . 84258013 .
• Bottino C, Falco M, Sivori S, Moretta L, Moretta A, Biassoni R . Identification and molecular characterization of a natural mutant of the p50.2/KIR2DS2 activating NK receptor that fails to mediate NK cell triggering . Eur. J. Immunol. . 30 . 12 . 3569–74 . 2001 . 11169398 . 10.1002/1521-4141(200012)30:12<3569::AID-IMMU3569>3.0.CO;2-E . free .
• Gingras MC, Lapillonne H, Margolin JF . TREM-1, MDL-1, and DAP12 expression is associated with a mature stage of myeloid development . Mol. Immunol. . 38 . 11 . 817–24 . 2002 . 11922939 . 10.1016/S0161-5890(02)00004-4 .
• Paloneva J, Manninen T, Christman G, Hovanes K, Mandelin J, Adolfsson R, Bianchin M, Bird T, Miranda R, Salmaggi A, Tranebjaerg L, Konttinen Y, Peltonen L . Mutations in Two Genes Encoding Different Subunits of a Receptor Signaling Complex Result in an Identical Disease Phenotype . Am. J. Hum. Genet. . 71 . 3 . 656–62 . 2002 . 12080485 . 379202 . 10.1086/342259 .
• Lucas M, Daniel L, Tomasello E, Guia S, Horschowski N, Aoki N, Figarella-Branger D, Gomez S, Vivier E . Massive inflammatory syndrome and lymphocytic immunodeficiency in KARAP/DAP12-transgenic mice . Eur. J. Immunol. . 32 . 9 . 2653–63 . 2002 . 12207350 . 10.1002/1521-4141(200209)32:9<2653::AID-IMMU2653>3.0.CO;2-V . free .
• Kondo T, Takahashi K, Kohara N, Takahashi Y, Hayashi S, Takahashi H, Matsuo H, Yamazaki M, Inoue K, Miyamoto K, Yamamura T . Heterogeneity of presenile dementia with bone cysts (Nasu-Hakola disease): three genetic forms . Neurology . 59 . 7 . 1105–7 . 2002 . 12370476 . 10.1212/wnl.59.7.1105 . 36364470 .
• Gilfillan S, Ho EL, Cella M, Yokoyama WM, Colonna M . NKG2D recruits two distinct adapters to trigger NK cell activation and costimulation . Nat. Immunol. . 3 . 12 . 1150–5 . 2002 . 12426564 . 10.1038/ni857 . 5859797 .

Notes and References

1. Lanier LL, Corliss BC, Wu J, Leong C, Phillips JH . Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells . Nature . 391 . 6668 . 703–7 . March 1998 . 9490415 . 10.1038/35642 . 1998Natur.391..703L . 4324672 .
2. Paloneva J, Kestilä M, Wu J, Salminen A, Böhling T, Ruotsalainen V, Hakola P, Bakker AB, Phillips JH, Pekkarinen P, Lanier LL, Timonen T, Peltonen L . Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts . Nat Genet . 25 . 3 . 357–61 . August 2000 . 10888890 . 10.1038/77153 . 9243117 .
3. Web site: Entrez Gene: TYROBP TYRO protein tyrosine kinase binding protein.
4. Dietrich J, Cella M, Seiffert M, Bühring HJ, Colonna M . Cutting edge: signal-regulatory protein beta 1 is a DAP12-associated activating receptor expressed in myeloid cells . J. Immunol. . 164 . 1 . 9–12 . January 2000 . 10604985 . 10.4049/jimmunol.164.1.9 . free .
5. Tomasello E, Cant C, Bühring HJ, Vély F, André P, Seiffert M, Ullrich A, Vivier E . Association of signal-regulatory proteins beta with KARAP/DAP-12 . Eur. J. Immunol. . 30 . 8 . 2147–56 . August 2000 . 10940905 . 10.1002/1521-4141(2000)30:8<2147::AID-IMMU2147>3.0.CO;2-1 . 84258013 .