FYVE zinc finger | |||||||||
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Identifiers | |||||||||
Symbol | FYVE | ||||||||
Pfam | PF01363 | ||||||||
InterPro | IPR000306 | ||||||||
PROSITE | PDOC50178 | ||||||||
SCOP2 | 1vfy / SCOPe / SUPFAM | ||||||||
OPM superfamily | 59 | ||||||||
OPM protein | 1vfy | ||||||||
CDD | cd00065 | ||||||||
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In molecular biology the FYVE zinc finger domain is named after the four cysteine-rich proteins: Fab 1 (yeast orthologue of PIKfyve), YOTB, Vac 1 (vesicle transport protein), and EEA1, in which it has been found. FYVE domains bind phosphatidylinositol 3-phosphate, [2] in a way dependent on its metal ion coordination and basic amino acids. The FYVE domain inserts into cell membranes in a pH-dependent manner. [3] The FYVE domain has been connected to vacuolar protein sorting and endosome function. [4]
The FYVE domain is composed of two small beta hairpins (or zinc knuckles) followed by an alpha helix. [5] The FYVE finger binds two zinc ions. The FYVE finger has eight potential zinc coordinating cysteine positions and is characterized by having basic amino acids around the cysteines. Many members of this family also include two histidines in a sequence motif:
The FYVE finger is structurally similar to the RING domain and the PHD finger.
The following is a list of human proteins containing this domain:
Peripheral membrane proteins, or extrinsic membrane proteins, are membrane proteins that adhere only temporarily to the biological membrane with which they are associated. These proteins attach to integral membrane proteins, or penetrate the peripheral regions of the lipid bilayer. The regulatory protein subunits of many ion channels and transmembrane receptors, for example, may be defined as peripheral membrane proteins. In contrast to integral membrane proteins, peripheral membrane proteins tend to collect in the water-soluble component, or fraction, of all the proteins extracted during a protein purification procedure. Proteins with GPI anchors are an exception to this rule and can have purification properties similar to those of integral membrane proteins.
Phosphatidylinositol 3-phosphate (PtdIns3P) is a phospholipid found in cell membranes that helps to recruit a range of proteins, many of which are involved in protein trafficking, to the membranes. It is the product of both the class II and III phosphoinositide 3-kinases activity on phosphatidylinositol.
Pleckstrin homology domain or (PHIP) is a protein domain of approximately 120 amino acids that occurs in a wide range of proteins involved in intracellular signaling or as constituents of the cytoskeleton.
Phosphatidylinositol 3,5-bisphosphate is one of the seven phosphoinositides found in eukaryotic cell membranes. In quiescent cells, the PtdIns(3,5)P2 levels, typically quantified by HPLC, are the lowest amongst the constitutively present phosphoinositides. They are approximately 3 to 5-fold lower as compared to PtdIns3P and PtdIns5P levels, and more than 100-fold lower than the abundant PtdIns4P and PtdIns(4,5)P2. PtdIns(3,5)P2 was first reported to occur in mouse fibroblasts and budding yeast S. cerevisiae in 1997. In S. cerevisiae PtdIns(3,5)P2 levels increase dramatically during hyperosmotic shock. The response to hyperosmotic challenge is not conserved in most tested mammalian cells except for differentiated 3T3L1 adipocytes.
Zinc finger FYVE domain-containing protein 9 or SARA is a protein that in humans is encoded by the ZFYVE9 gene. SARA contains a double zinc finger.
The gene EEA1 encodes for the 1400 amino acid protein, Early Endosome Antigen 1.
FYVE, RhoGEF and PH domain-containing protein 1 (FGD1) also known as faciogenital dysplasia 1 protein (FGDY), zinc finger FYVE domain-containing protein 3 (ZFYVE3), or Rho/Rac guanine nucleotide exchange factor FGD1 is a protein that in humans is encoded by the FGD1 gene that lies on the X chromosome. Orthologs of the FGD1 gene are found in dog, cow, mouse, rat, and zebrafish, and also budding yeast and C. elegans. It is a member of the FYVE, RhoGEF and PH domain containing family.
Ras-related protein Rab-5A is a protein that in humans is encoded by the RAB5A gene.
Hepatocyte growth factor-regulated tyrosine kinase substrate is an enzyme that in humans is encoded by the HGS gene.
PIKfyve, a FYVE finger-containing phosphoinositide kinase, is an enzyme that in humans is encoded by the PIKFYVE gene.
Myotubularin-related protein 3 is a protein that in humans is encoded by the MTMR3 gene.
Zinc finger FYVE domain-containing protein 16 is a protein that in humans is encoded by the ZFYVE16 gene.
Zinc finger FYVE domain-containing protein 1 is a protein that in humans is encoded by the ZFYVE1 gene.
The endosomal sorting complexes required for transport (ESCRT) machinery is made up of cytosolic protein complexes, known as ESCRT-0, ESCRT-I, ESCRT-II, and ESCRT-III. Together with a number of accessory proteins, these ESCRT complexes enable a unique mode of membrane remodeling that results in membranes bending/budding away from the cytoplasm. These ESCRT components have been isolated and studied in a number of organisms including yeast and humans. A eukaryotic signature protein, the machinery is found in all eukaryotes and some archaea.
Phosphatidylinositol 5-phosphate (PtdIns5P) is a phosphoinositide, one of the phosphorylated derivatives of phosphatidylinositol (PtdIns), that are well-established membrane-anchored regulatory molecules. Phosphoinositides participate in signaling events that control cytoskeletal dynamics, intracellular membrane trafficking, cell proliferation and many other cellular functions. Generally, phosphoinositides transduce signals by recruiting specific phosphoinositide-binding proteins to intracellular membranes.
FYVE, RhoGEF and PH domain-containing protein 2 (FGD2), also known as zinc finger FYVE domain-containing protein 4 (ZFYVE4), is a protein that in humans is encoded by the FGD2 gene.
RUN and FYVE domain containing 2 (RUFY2) is a protein that in humans is encoded by the RUFY2 gene. The RUFY2 gene is named for two of its domains, the RUN domain and FYVE domains. RUFY2 is a member of the RUFY family of proteins that include RUFY1, RUFY2, RUFY3, and RUFY4. RUFY2 protein has a dynamic role in endosomal membrane trafficking.
Zinc finger, FYVE domain containing 26 is a protein that in humans is encoded by the ZFYVE26 gene.
Zinc finger, FYVE domain containing 27 is a protein that in humans is encoded by the ZFYVE27 gene.
Phosphatidylinositol 3-phosphate-binding protein 2 (Pib2) is a yeast protein involved in the regulation of TORC1 signaling and lysosomal membrane permeabilization. It is essential for the reactivation of TORC1 following exposure to rapamycin or nutrient starvation.