TYROBP

TYROBP
Identifiers
Aliases	TYROBP, DAP12, KARAP, PLOSL, TYRO protein tyrosine kinase binding protein, PLOSL1, transmembrane immune signaling adaptor TYROBP
External IDs	OMIM: 604142; MGI: 1277211; GeneCards: TYROBP
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2L34, 2L35, 4WO1, 4WOL
Gene location (Human)
Chr.	Chromosome 19 (human)
End	35,908,295 bp
Gene location (Mouse)
Chr.	Chromosome 7 (mouse)
End	30,117,010 bp
RNA expression pattern
	Top expressed in
	monocyte; ; granulocyte; ; blood; ; spleen; ; right lung; ; bone marrow; ; periodontal fiber; ; upper lobe of left lung; ; bone marrow cell; ; gallbladder;
	Top expressed in
	granulocyte; ; tibiofemoral joint; ; mesenteric lymph nodes; ; spleen; ; calvaria; ; stroma of bone marrow; ; right lung lobe; ; blood; ; internal carotid artery; ; dermis;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	signaling receptor binding; protein binding; identical protein binding; metal ion binding;
Cellular component	integral component of membrane; cell surface; plasma membrane; integral component of plasma membrane; membrane; secretory granule membrane;
Biological process	integrin-mediated signaling pathway; macrophage activation involved in immune response; cellular defense response; neutrophil activation involved in immune response; intracellular signal transduction; innate immune response; regulation of osteoclast development; signal transduction; regulation of immune response; neutrophil degranulation; osteoclast differentiation; myeloid leukocyte activation; positive regulation of natural killer cell activation; positive regulation of macrophage fusion; protein stabilization; positive regulation of microglial cell mediated cytotoxicity; positive regulation of protein localization to cell surface; positive regulation of osteoclast development; microglial cell activation involved in immune response; positive regulation of gene expression; actin cytoskeleton organization; negative regulation of B cell proliferation; forebrain development; negative regulation of transforming growth factor beta1 production; positive regulation of superoxide anion generation; response to axon injury; apoptotic signaling pathway; positive regulation of hippocampal neuron apoptotic process; negative regulation of long-term synaptic potentiation; positive regulation of neuron death; positive regulation of receptor localization to synapse; apoptotic cell clearance; immune system process;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	7305
	22177
	ENSG00000011600
	ENSMUSG00000030579
	O43914
	O54885
	NM_001173514; NM_001173515; NM_003332; NM_198125
	NM_011662
	NP_001166985; NP_001166986; NP_003323; NP_937758
	NP_035792
	Wikidata
View/Edit Human	View/Edit Mouse

TYRO protein tyrosine kinase-binding protein is an adapter protein that in humans is encoded by the TYROBP gene.

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.

Interactions

TYROBP has been shown to interact with SIRPB1.

Clinical significance

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

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000011600 – Ensembl, May 2017
1 2 3 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

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

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.

This article on a gene on human chromosome 19 is a stub. You can help Wikipedia by adding missing information.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000011600 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000030579 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid9490415-5] 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.

[pmid10888890-6] 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-7] "Entrez Gene: TYROBP TYRO protein tyrosine kinase binding protein".

[pmid10604985-8] 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.

[pmid10940905-9] 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.