Protein-coding gene in the species Homo sapiens
TYRO protein tyrosine kinase -binding protein is an adapter protein that in humans is encoded by the TYROBP gene .[ 5] [ 6]
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.[ 7]
Interactions
TYROBP has been shown to interact with SIRPB1 .[ 8] [ 9]
Clinical significance
Pathological mutations of the TYROBP gene cause polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 1 , a condition presenting as early-onset dementia .
References
^ a b c GRCh38: Ensembl release 89: ENSG00000011600 – Ensembl , May 2017^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030579 – Ensembl , May 2017^ "Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .^ Lanier LL, Corliss BC, Wu J, Leong C, Phillips JH (March 1998). "Immunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells". Nature . 391 (6668): 703– 7. Bibcode :1998Natur.391..703L . doi :10.1038/35642 . PMID 9490415 . S2CID 4324672 . ^ 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 (August 2000). "Loss-of-function mutations in TYROBP (DAP12) result in a presenile dementia with bone cysts". Nat Genet . 25 (3): 357– 61. doi :10.1038/77153 . PMID 10888890 . S2CID 9243117 . ^ "Entrez Gene: TYROBP TYRO protein tyrosine kinase binding protein" .^ Dietrich J, Cella M, Seiffert M, Bühring HJ, Colonna M (January 2000). "Cutting edge: signal-regulatory protein beta 1 is a DAP12-associated activating receptor expressed in myeloid cells" . J. Immunol . 164 (1): 9– 12. doi :10.4049/jimmunol.164.1.9 PMID 10604985 . ^ Tomasello E, Cant C, Bühring HJ, Vély F, André P, Seiffert M, Ullrich A, Vivier E (August 2000). "Association of signal-regulatory proteins beta with KARAP/DAP-12". Eur. J. Immunol . 30 (8): 2147– 56. doi :10.1002/1521-4141(2000)30:8<2147::AID-IMMU2147>3.0.CO;2-1 . PMID 10940905 . S2CID 84258013 .
External links
Further reading
Colonna M (2003). "DAP12 signaling: from immune cells to bone modeling and brain myelination" . J. Clin. Invest . 111 (3): 313– 4. doi :10.1172/JCI17745 . PMC 151875 PMID 12569153 . Takaki R, Watson SR, Lanier LL (2007). "DAP12: an adapter protein with dual functionality". Immunol. Rev . 214 : 118– 29. doi :10.1111/j.1600-065X.2006.00466.x . PMID 17100880 . S2CID 12937527 . Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery" . Genome Res . 6 (9): 791– 806. doi :10.1101/gr.6.9.791 PMID 8889548 . 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 (1998). "Assignment of the locus for PLO-SL, a frontal-lobe dementia with bone cysts, to 19q13" . Am. J. Hum. Genet . 62 (2): 362– 72. doi :10.1086/301722 . PMC 1376898 PMID 9463329 . Lanier LL, Corliss B, Wu J, Phillips JH (1998). "Association of DAP12 with activating CD94/NKG2C NK cell receptors" . Immunity . 8 (6): 693– 701. doi :10.1016/S1074-7613(00)80574-9 PMID 9655483 . Pekkarinen P, Kestilä M, Paloneva J, Terwillign J, Varilo T, Järvi O, Hakola P, Peltonen L (1999). "Fine-scale mapping of a novel dementia gene, PLOSL, by linkage disequilibrium" . Genomics . 54 (2): 307– 15. doi :10.1006/geno.1998.5591 PMID 9828133 . Cantoni C, Bottino C, Vitale M, Pessino A, Augugliaro R, Malaspina A, Parolini S, Moretta L, Moretta A, Biassoni R (1999). "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. doi :10.1084/jem.189.5.787 . PMC 2192947 PMID 10049942 . Bellón T, Heredia AB, Llano M, Minguela A, Rodriguez A, López-Botet M, Aparicio P (1999). "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. doi :10.4049/jimmunol.162.7.3996 PMID 10201920 . Bakker AB, Baker E, Sutherland GR , Phillips JH, Lanier LL (1999). "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. Bibcode :1999PNAS...96.9792B . doi :10.1073/pnas.96.17.9792 PMC 22289 PMID 10449773 . Dietrich J, Cella M, Seiffert M, Bühring HJ, Colonna M (2000). "Cutting edge: signal-regulatory protein beta 1 is a DAP12-associated activating receptor expressed in myeloid cells" . J. Immunol . 164 (1): 9– 12. doi :10.4049/jimmunol.164.1.9 PMID 10604985 . Bouchon A, Dietrich J, Colonna M (2000). "Cutting edge: inflammatory responses can be triggered by TREM-1, a novel receptor expressed on neutrophils and monocytes" . J. Immunol . 164 (10): 4991– 5. doi :10.4049/jimmunol.164.10.4991 PMID 10799849 . Tomasello E, Cant C, Bühring HJ, Vély F, André P, Seiffert M, Ullrich A, Vivier E (2000). "Association of signal-regulatory proteins beta with KARAP/DAP-12". Eur. J. Immunol . 30 (8): 2147– 56. doi :10.1002/1521-4141(2000)30:8<2147::AID-IMMU2147>3.0.CO;2-1 . PMID 10940905 . S2CID 84258013 . Bottino C, Falco M, Sivori S, Moretta L, Moretta A, Biassoni R (2001). "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. doi :10.1002/1521-4141(200012)30:12<3569::AID-IMMU3569>3.0.CO;2-E PMID 11169398 . Gingras MC, Lapillonne H, Margolin JF (2002). "TREM-1, MDL-1, and DAP12 expression is associated with a mature stage of myeloid development". Mol. Immunol . 38 (11): 817– 24. doi :10.1016/S0161-5890(02)00004-4 . PMID 11922939 . 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 (2002). "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. doi :10.1086/342259 . PMC 379202 PMID 12080485 . Lucas M, Daniel L, Tomasello E, Guia S, Horschowski N, Aoki N, Figarella-Branger D, Gomez S, Vivier E (2002). "Massive inflammatory syndrome and lymphocytic immunodeficiency in KARAP/DAP12-transgenic mice" . Eur. J. Immunol . 32 (9): 2653– 63. doi :10.1002/1521-4141(200209)32:9<2653::AID-IMMU2653>3.0.CO;2-V PMID 12207350 . Kondo T, Takahashi K, Kohara N, Takahashi Y, Hayashi S, Takahashi H, Matsuo H, Yamazaki M, Inoue K, Miyamoto K, Yamamura T (2002). "Heterogeneity of presenile dementia with bone cysts (Nasu-Hakola disease): three genetic forms". Neurology . 59 (7): 1105– 7. doi :10.1212/wnl.59.7.1105 . PMID 12370476 . S2CID 36364470 . Gilfillan S, Ho EL, Cella M, Yokoyama WM, Colonna M (2002). "NKG2D recruits two distinct adapters to trigger NK cell activation and costimulation" . Nat. Immunol . 3 (12): 1150– 5. doi :10.1038/ni857 . PMID 12426564 . S2CID 5859797 .
