FYB

Last updated
FYB1
Protein FYB PDB 1ri9.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases FYB1 , ADAP, PRO0823, SLAP-130, SLAP130, FYB, FYN binding protein, THC3, FYN binding protein 1
External IDs OMIM: 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

Contents

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 Mb Chr 15: 6.55 – 6.69 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/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]

Related Research Articles

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<span class="mw-page-title-main">GRB2</span> Protein-coding gene in the species Homo sapiens

Growth factor receptor-bound protein 2, also known as Grb2, is an adaptor protein involved in signal transduction/cell communication. In humans, the GRB2 protein is encoded by the GRB2 gene.

<span class="mw-page-title-main">ZAP70</span> Protein-coding gene in the species Homo sapiens

ZAP-70 is a protein normally expressed near the surface membrane of lymphocytes. It is most prominently known to be recruited upon antigen binding to the T cell receptor (TCR), and it plays a critical role in T cell signaling.

<span class="mw-page-title-main">Lymphocyte cytosolic protein 2</span> Protein-coding gene in the species Homo sapiens

Lymphocyte cytosolic protein 2, also known as LCP2 or SLP-76, is a signal-transducing adaptor protein expressed in T cells and myeloid cells and is important in the signaling of T-cell receptors (TCRs). As an adaptor protein, SLP-76 does not have catalytic functions, primarily binding other signaling proteins to form larger signaling complexes. It is a key component of the signaling pathways of receptors with immunoreceptor tyrosine-based activation motifs (ITAMs) such as T-cell receptors, its precursors, and receptors for the Fc regions of certain antibodies. SLP-76 is expressed in T-cells and related lymphocytes like natural killer cells.

<span class="mw-page-title-main">Integrin beta 2</span> Mammalian protein found in Homo sapiens

In molecular biology, CD18 is an integrin beta chain protein that is encoded by the ITGB2 gene in humans. Upon binding with one of a number of alpha chains, CD18 is capable of forming multiple heterodimers, which play significant roles in cellular adhesion and cell surface signaling, as well as important roles in immune responses. CD18 also exists in soluble, ligand binding forms. Deficiencies in CD18 expression can lead to adhesion defects in circulating white blood cells in humans, reducing the immune system's ability to fight off foreign invaders.

<span class="mw-page-title-main">Linker for activation of T cells</span> Protein-coding gene in the species Homo sapiens

The Linker for activation of T cells, also known as linker of activated T cells or LAT, is a protein involved in the T-cell antigen receptor signal transduction pathway which in humans is encoded by the LAT gene. Alternative splicing results in multiple transcript variants encoding different isoforms.

<span class="mw-page-title-main">FYN</span> Mammalian protein found in Homo sapiens

Proto-oncogene tyrosine-protein kinase Fyn is an enzyme that in humans is encoded by the FYN gene.

<span class="mw-page-title-main">NCK1</span> Protein-coding gene in the species Homo sapiens

Cytoplasmic protein NCK1 is a protein that in humans is encoded by the NCK1 gene.

<span class="mw-page-title-main">Vasodilator-stimulated phosphoprotein</span> Mammalian protein found in Homo sapiens

Vasodilator-stimulated phosphoprotein is a protein that in humans is encoded by the VASP gene.

<span class="mw-page-title-main">ARHGEF7</span> Protein-coding gene in the species Homo sapiens

Rho guanine nucleotide exchange factor 7 is a protein that in humans is encoded by the ARHGEF7 gene.

<span class="mw-page-title-main">B-cell linker</span> Mammalian protein found in Homo sapiens

B-cell linker (BLNK) protein is expressed in B cells and macrophages and plays a large role in B cell receptor signaling. Like all adaptor proteins, BLNK has no known intrinsic enzymatic activity. Its function is to temporally and spatially coordinate and regulate downstream signaling effectors in B cell receptor (BCR) signaling, which is important in B cell development. Binding of these downstream effectors is dependent on BLNK phosphorylation. BLNK is encoded by the BLNK gene and is also known as SLP-65, BASH, and BCA.

<span class="mw-page-title-main">GRAP2</span> Protein-coding gene in the species Homo sapiens

GRB2-related adapter protein 2 also known as GRB2-related adaptor downstream of Shc (GADS) is a 37 kDa protein that in humans is encoded by the GRAP2 gene.

<span class="mw-page-title-main">ENAH (gene)</span> Protein-coding gene in the species Homo sapiens

Protein enabled homolog is a protein that in humans is encoded by the ENAH gene.

<span class="mw-page-title-main">Enah/Vasp-like</span> Protein-coding gene in the species Homo sapiens

Ena/VASP-like protein is a member of the Ena/VASP family of proteins that in humans is encoded by the EVL gene.

<span class="mw-page-title-main">SKAP2</span> Protein-coding gene in the species Homo sapiens

Src kinase-associated phosphoprotein 2 is an enzyme that in humans is encoded by the SKAP2 gene.

<span class="mw-page-title-main">ITGB1BP1</span> Protein-coding gene in the species Homo sapiens

Integrin beta-1-binding protein 1 is a protein that in humans is encoded by the ITGB1BP1 gene.

<span class="mw-page-title-main">SKAP1</span> Protein-coding gene in the species Homo sapiens

Src kinase-associated phosphoprotein 1 is an adapter protein that in humans is encoded by the SKAP1 gene.

<span class="mw-page-title-main">TXK (gene)</span> Protein-coding gene in the species Homo sapiens

Tyrosine-protein kinase TXK is an enzyme that in humans is encoded by the TXK gene.

<span class="mw-page-title-main">PRAM1</span> Protein-coding gene in the species Homo sapiens

PML-RARA-regulated adapter molecule 1 is a protein that in humans is encoded by the PRAM1 gene.

Rap1 is a small GTPase, which are small cytosolic proteins that act like cellular switches and are vital for effective signal transduction. There are two isoforms of the Rap1 protein, each encoded by a separate gene, RAP1A and RAP1B. Rap1 belongs to Ras-related protein family.

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.

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