TYROBP

Protein-coding gene in the species Homo sapiens
TYROBP
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

2L34, 2L35, 4WO1, 4WOL

Identifiers
AliasesTYROBP, DAP12, KARAP, PLOSL, TYRO protein tyrosine kinase binding protein, PLOSL1, transmembrane immune signaling adaptor TYROBP
External IDsOMIM: 604142 MGI: 1277211 HomoloGene: 7986 GeneCards: TYROBP
Gene location (Human)
Chromosome 19 (human)
Chr.Chromosome 19 (human)[1]
Chromosome 19 (human)
Genomic location for TYROBP
Genomic location for TYROBP
Band19q13.12Start35,904,401 bp[1]
End35,908,295 bp[1]
Gene location (Mouse)
Chromosome 7 (mouse)
Chr.Chromosome 7 (mouse)[2]
Chromosome 7 (mouse)
Genomic location for TYROBP
Genomic location for TYROBP
Band7 B1|7 17.45 cMStart30,113,185 bp[2]
End30,117,010 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • monocyte

  • blood

  • spleen

  • right lung

  • bone marrow

  • periodontal fiber

  • upper lobe of left lung

  • bone marrow cells

  • gallbladder

  • right coronary artery
Top expressed in
  • spleen

  • calvaria

  • right lung lobe

  • blood

  • internal carotid artery

  • dermis

  • white adipose tissue

  • external carotid artery

  • lip

  • femur
More reference expression data
BioGPS
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
SpeciesHumanMouse
Entrez

7305

22177

Ensembl

ENSG00000011600

ENSMUSG00000030579

UniProt

O43914

O54885

RefSeq (mRNA)

NM_001173514
NM_001173515
NM_003332
NM_198125

NM_011662

RefSeq (protein)

NP_001166985
NP_001166986
NP_003323
NP_937758

NP_035792

Location (UCSC)Chr 19: 35.9 – 35.91 MbChr 7: 30.11 – 30.12 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000011600 – Ensembl, May 2017
  2. ^ a b c 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.
  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.
  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.
  7. ^ "Entrez Gene: TYROBP TYRO protein tyrosine kinase binding protein".
  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.
  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.

External links

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

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.


  • v
  • t
  • e