FYB1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesFYB1, ADAP, PRO0823, SLAP-130, SLAP130, FYB, FYN binding protein, THC3, FYN binding protein 1
External IDsOMIM: 602731 MGI: 1346327 HomoloGene: 22664 GeneCards: FYB1
Orthologs
SpeciesHumanMouse
Entrez

2533

23880

Ensembl

ENSG00000082074

ENSMUSG00000022148

UniProt

O15117

O35601

RefSeq (mRNA)

NM_001243093
NM_001465
NM_199335
NM_001349333
NM_018594

NM_001278269
NM_011815

RefSeq (protein)

NP_001230022
NP_001456
NP_955367
NP_001336262
NP_061064

NP_001265198
NP_035945

Location (UCSC)Chr 5: 39.11 – 39.27 MbChr 15: 6.55 – 6.69 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

FYN binding protein (FYB-120/130), also known as FYB, ADAP (Adhesion and degranulation-promoting adapter protein), and SLAP-130 (SLP-76-associated phosphoprotein) is a protein that is encoded by the FYB gene in humans.[5] The protein is expressed in T cells, monocytes, mast cells, macrophages, NK cells, but not B cells.[6][7][8][9] FYB is a multifunctional protein involved in post-activation T cell signaling, lymphocyte cytokine production, cell adhesion, and actin remodeling.[7][8][9][10][11]

Structure

Two isoforms of FYB with different lengths of 120 and 130 kDa (FYB-120 and FYB-130) exist.[8] The 130kDa version has an extra insertion of 46 amino acids and is preferentially expressed in peripheral T cells.[8] The FYB protein has a variety of binding domains: a non-structured N-terminal region, a proline-rich region, two SH3 domains, a FPPP-motif which binds the ENA/VASP protein family, and other tyrosine-based signaling motifs.[11]

Function

FYB is critical for activation and proliferation of T-helper cells (CD4+) and required for chemokine signal transduction in T-helper cells and cytotoxic T cells (CD8+).[11]

FYB regulates cytokine production in T cells as well as in activated NK cells through the FYN-ADAP axis.[9] In T cells, after TCR stimulation, a unique region of FYB, pYDGI, allows phosphorylation of the protein by FYN.[9] After being phosphorylated, ADAP can bind to Carma1, causing NF-κB translocation into the nucleus and cytokine production.[9]

In mast cells, FYB regulates cell adhesion as well as degranulation.[7] In T cells, FYB allows for cell adhesion and migration through blood vessels through the SLP-76-FYB-SKAP1 complex.[10] After being phosphorylated by FYN, FYB can bind to SLP-76.[7] This binding of FYB and SLP-76 regulates "outside-in signaling" or the transfer of signals from outside the cell to inside the cell by integrin.[10] FYB can also bind to SKAP1, which allows SKAP1 to upregulate integrin activity through interactions with Rap1.[8][10] The bacteria Yersinia can interfere with this pathway in macrophages through the secretion of YopH (Yersinia protein tyrosine phosphatase) into the macrophage, which de-phosphorylates FYB and SKAP1, leading to a decrease in integrin activity that results in an inhibition of adhesion, phagocytosis, and cytotoxicity.[8]

FYB is also an important protein for actin remodeling of immune cells.[11] This is thought to occur through the binding of proteins of the ENA/VASP protein family to the FPPPP-motif of the FYB protein.[11]

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000082074 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000022148 - 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. ↑ "Entrez Gene: FYB FYN binding protein (FYB-120/130)".
  6. ↑ Schraven B, Marie-Cardine A, Koretzky G (June 1997). "Molecular analysis of the fyn-complex: cloning of SKAP55 and SLAP-130, two novel adaptor proteins which associate with fyn and may participate in the regulation of T cell receptor-mediated signaling". Immunology Letters. 57 (1–3): 165–169. doi:10.1016/s0165-2478(97)00053-9. PMID 9232446.
  7. 1 2 3 4 Griffiths EK, Penninger JM (June 2002). "Communication between the TCR and integrins: role of the molecular adapter ADAP/Fyb/Slap". Current Opinion in Immunology. 14 (3): 317–322. doi:10.1016/s0952-7915(02)00334-5. PMID 11973129.
  8. 1 2 3 4 5 6 Wang H, Rudd CE (October 2008). "SKAP-55, SKAP-55-related and ADAP adaptors modulate integrin-mediated immune-cell adhesion". Trends in Cell Biology. 18 (10): 486–493. doi:10.1016/j.tcb.2008.07.005. PMC 3512129. PMID 18760924.
  9. 1 2 3 4 5 Gerbec ZJ, Thakar MS, Malarkannan S (2015-09-16). "The Fyn-ADAP Axis: Cytotoxicity Versus Cytokine Production in Killer Cells". Frontiers in Immunology. 6: 472. doi:10.3389/fimmu.2015.00472. PMC 4584950. PMID 26441977.
  10. 1 2 3 4 Zhang Y, Wang H (April 2012). "Integrin signalling and function in immune cells". Immunology. 135 (4): 268–275. doi:10.1111/j.1365-2567.2011.03549.x. PMC 3372743. PMID 22211918.
  11. 1 2 3 4 5 Dadwal N, Mix C, Reinhold A, Witte A, Freund C, Schraven B, Kliche S (2021-07-06). "The Multiple Roles of the Cytosolic Adapter Proteins ADAP, SKAP1 and SKAP2 for TCR/CD3 -Mediated Signaling Events". Frontiers in Immunology. 12: 703534. doi:10.3389/fimmu.2021.703534. PMC 8290198. PMID 34295339.

Further reading

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.