Cloning the cDNA for a new human zinc finger protein defines a group of closely related krüppel like transcription factors. (1998 Nov)
cloning the cDNA for a new human zinc finger protein defines a group of closely related krüppel like transcription factors . We have identified a novel zinc finger protein that has been named ubiquitous krüppel like factor ( UKLF ) based on structural considerations and the pattern of gene expression . UKLF was isolated by the polymerase chain reaction approach using degenerate oligonucleotides corresponding to the DNA binding domain of erythroid krüppel like factor ( EKLF ) and cDNA prepared from human vascular endothelial cells . The carboxyl terminal portion of UKLF contains three zinc fingers of the Cys2 His2 type and binds in vitro to the caccc motif of the beta globin promoter and to the Sp1 recognition sequence . The amino terminal portion of UKLF consists of a hydrophobic region rich in serines and a negatively charged segment with several glutamic acid residues . The first 47 amino acids of the acidic region are nearly identical to the amino terminal portion of another krüppel like factor , the so called core promoter binding protein ( CPBP ) or Zf9 . Like CPBP / Zf9 , UKLF can function as a transcription activator in co transfection assays . however , this activity is lost when the highly conserved amino terminal segment is deleted . these findings indicate that UKLF and CPBP / Zf9 represent a distinct subgroup of closely related krüppel like activators of transcription . mapping of the UKLF gene to chromosome 2 suggested that UKLF and CPBP …

Zinc finger transcription factors designed for bispecific coregulation of erbb2 and erbb3 receptors : insights into ErbB receptor biology. (2005 Oct)
Zinc finger transcription factors designed for bispecific coregulation of erbb2 and erbb3 receptors : insights into ErbB receptor biology . signaling through the ErbB family of tyrosine kinase receptors in normal and cancer derived cell lines contributes to cell growth and differentiation . In this work , we altered the levels of erbb2 and erbb3 receptors , individually and in combination , by using 6 finger and 12 finger synthetic zinc finger protein artificial transcription factors ( ATFs ) in an epidermoid squamous cell carcinoma line , A431 . We successfully designed 12 finger ATFs capable of coregulating erbb3 and ICAM 1 or erbb2 and erbb3 . With ATFs , the effects of changes in erbb2 and erbb3 receptor levels were evaluated by using cell proliferation , cell migration , and cell signaling assays . Cell proliferation was increased when erbb2 and erbb3 were both overexpressed . Cell migration on collagen was decreased when erbb2 was down regulated , yet migration on laminin was significantly increased with erbb3 overexpression . erbb2 and erbb3 overexpression also stimulated the phosphatidylinositol 3 kinase and mitogen activated protein kinase pathways . Our ATF approach has elucidated differences in ErbB receptor mediated proliferation , migration , and intracellular signaling that cannot be explained merely by the presence or absence of particular ErbB receptors and emphasizes the dynamic nature of the ErbB signaling system . The transcription factor approach developed here provides a gene economical route to the regulation of multiple genes and may be important …

Influence of parenteral zinc and actinomycin D on tissue zinc uptake and the synthesis of a zinc binding protein. (1975 Aug)
influence of parenteral zinc and actinomycin D on tissue zinc uptake and the synthesis of a zinc binding protein . parenterally administered zinc markedly increased the incorporation of 14 C cystine and 65 Zn into a low molecular weight zinc binding protein ( ZnBP ) isolated from liver cytoplasm of rats fed an adequate amount of zinc . This zinc load significantly increased the zinc content in the liver . The increase in hepatic zinc content was inhibited by actinomycin D indicating that DNA dependent RNA synthesis is required for zinc uptake into liver . antinomycin D also produced a concomitant decrease in ZnBP synthesis indicating that this protein may be involved in the uptake mechanism in cells . Zinc repletion also stimulated the synthesis of hepatic ZnBP in zinc deficient rats . This stimulation was also prevented by prior administration of actinomycin D . A similar effect was observed in the intestinal mucosal cells . The data collectively indicate that the control of the synthesis of ZnBP which occurs at the transcriptional level of protein synthesis is responsive to zinc status and thus may have a function in zinc metabolism .

Zinc binding stabilizes mitochondrial tim10 in a reduced and import competent state kinetically. (2005 Oct)
Zinc binding stabilizes mitochondrial tim10 in a reduced and import competent state kinetically . tim10 and all the small Tim proteins of the mitochondrial intermembrane space contain a consensus twin CX3C Zn2 finger motif . while disulphide bond formation between the Cys residues of this motif is essential for complex formation by the small Tim proteins , the specific role of Zn2 binding during the import and assembly of these proteins is not clear . In this study , we investigated the effects of the biologically relevant thiol disulphide redox molecule , glutathione , and Zn2 binding on the oxidative folding of yeast mitochondrial tim10 using both biochemical and biophysical methods in vitro . We show that , whilst oxidized tim10 cannot be reduced by reduced glutathione , reduced tim10 is effectively oxidized at levels of glutathione comparable to those found in the cytosol . The oxidized tim10 generated in the presence of glutathione is competent for complex formation with its partner protein Tim9 , confirming it has a native fold . The standard redox potential of tim10 at pH 7 . 4 was determined to be 0 . 32 V , confirming that tim10 is a much stronger reductant than glutathione ( 0 . 26 V , at pH 7 . 4 ) and could therefore be oxidized rapidly by oxidized glutathione in the cytosol . however , we found that Zn2 binding can stabilize the reduced tim10 , decreasing the rate of the oxidative folding more than tenfold …

Transcriptional activation by the papillomavirus E6 zinc finger oncoprotein. (1990 Jul)
transcriptional activation by the papillomavirus E6 zinc finger oncoprotein . The introduction of the bovine ( BPV ) or human papillomavirus E6 gene into susceptible cells can result in their transformation , but there are few clues to the mechanism of action of the E6 gene . The characteristic features of E6 proteins are their small size ( approximately 150 amino acids ) and the potential to form two large zinc fingers . To determine if E6 can function as a transcription factor , the BPV E6 gene was fused to the sequence specific DNA binding peptide encoded by the BPV E2 gene . This chimeric E6 E2 protein trans activated promoters that incorporated E2 binding elements in both rodent cells and saccharomyces cerevisiae . In the absence of E6 E2 localization to the target promoter , trans activation did not occur . alteration of the cysteine residues at the base of each finger abrogated the transcriptional activity of the E6 E2 hybrids . these data demonstrated that the BPV E6 gene encodes a transcription activation domain and imply that a specific structure of the protein , most likely the zinc fingers , is critical for this function . since these cysteine mutants are also transformation defective , E6 transcriptional functions may be required for its oncogenic activity .

Molecular cloning of a zinc finger protein which binds to the heptamer of the signal sequence for V ( D … (1994 Jan)
molecular cloning of a zinc finger protein which binds to the heptamer of the signal sequence for V ( D ) J recombination . The somatic V ( D ) J recombination for the assembly of the Ig and TCR genes is mediated by the recombination signal sequences ( Rss ) and the V ( D ) J recombinase . A cDNA clone was isolated from a lambda gt11 expression library made from mouse thymocyte poly ( A ) RNA , using the Rss as a ligand . The deduced amino acid sequence of the putative protein , designated recognition component ( Rc ) , reveals a pair of Cys2 His2 zinc fingers followed by a Glu and Asp rich acidic domain . In addition , there are five copies of the Ser / Thr Pro X Arg / Lys sequence , which are putative DNA binding units . The zinc finger acidic domain structures present in Rc are also found in several enhancer binding proteins , such as those for the kappa B motif of the Ig kappa light chain enhancer or related sequences . bacterial fusion proteins for Rc bind preferentially to the Rss heptamer and to the kappa B motif . The dual affinities of Rc for the Rss heptamer and the kappa B motif suggest a possible link between Ig transcription and somatic recombination . The formation of multiple gel shifted DNA protein complexes for Rc and its DNA ligand suggests that these complexes tend to …

Low intracellular zinc induces oxidative DNA damage , disrupts p53 , nfkappa B , and AP1 DNA binding , and … (2002 Dec)
Low intracellular zinc induces oxidative DNA damage , disrupts p53 , nfkappa B , and AP1 DNA binding , and affects DNA repair in a rat glioma cell line . approximately 10 of the U . S . population ingests 50 of the current recommended daily allowance for zinc . We investigate the effect of zinc deficiency on DNA damage , expression of DNA repair enzymes , and downstream signaling events in a cell culture model . Low zinc inhibited cell growth of rat glioma C6 cells and increased oxidative stress . Low intracellular zinc increased DNA single strand breaks ( comet assay ) . Zinc deficient C6 cells also exhibited an increase in the expression of the zinc containing DNA repair proteins p53 and apurinic endonuclease ( APE ) . repletion with zinc restored cell growth and reversed DNA damage . APE is a multifunctional protein that not only repairs DNA but also controls DNA binding activity of many transcription factors that may be involved in cancer progression . The ability of the transcription factors p53 , nuclear factor kappab , and activator protein 1 ( AP1 ) to bind to consensus DNA sequences was decreased markedly with zinc deficiency , as assayed by electrophoretic mobility shift assays . Thus , low intracellular zinc status causes oxidative DNA damage and induces DNA repair protein expression , but binding of p53 and important downstream signals leading to proper DNA repair are lost without zinc .

Combining structure based design with phage display to create new Cys ( 2 ) His ( 2 ) zinc finger … (2000 Oct)
combining structure based design with phage display to create new Cys ( 2 ) His ( 2 ) zinc finger dimers . background : several strategies have been reported for the design and selection of novel DNA binding proteins . Most of these studies have used Cys ( 2 ) His ( 2 ) zinc finger proteins as a framework , and have focused on constructs that bind DNA in a manner similar to zif268 , with neighboring fingers connected by a canonical ( krüppel type ) linker . This linker does not seem ideal for larger constructs because only modest improvements in affinity are observed when more than three fingers are connected in this manner . Two strategies have been described that allow the productive assembly of more than three canonically linked fingers on a DNA site : connecting sets of fingers using linkers ( covalent ) , or assembling sets of fingers using dimerization domains ( non covalent ) . results : using a combination of structure based design and phage display , we have developed a new dimerization system for Cys ( 2 ) His ( 2 ) zinc fingers that allows the assembly of more than three fingers on a desired target site . Zinc finger constructs employing this new dimerization system have high affinity and good specificity for their target sites both in vitro and in vivo . constructs that recognize an asymmetric binding site as heterodimers can be obtained through substitutions in the zinc …

DNA target selectivity by the vitamin D3 receptor : mechanism of dimer binding to an asymmetric repeat element. (1993 Aug)
DNA target selectivity by the vitamin D3 receptor : mechanism of dimer binding to an asymmetric repeat element . The 1 , 25 dihydroxyvitamin D3 receptor , like other members of the nuclear receptor superfamily , forms dimers in solution that are probably stabilized by a dyad symmetrical interface formed by the ligand binding domain . This receptor , however , recognizes DNA targets that are not dyad symmetric but rather are organized as direct repeats of a hexameric sequence with a characteristic 3 bp spacing . using molecular modeling and site directed mutagenesis , we have identified regions within the vitamin D3 receptor zinc finger region that confer selectivity for direct repeats with appropriate spacing . reflecting the organization of the DNA target , these regions , mapping to the tip of the first zinc finger module and the N and C termini of the second finger module , direct asymmetrical protein protein contacts . A stereochemical model is proposed for these interactions .

Gene regulation in planta by plant derived engineered zinc finger protein transcription factors. (2005 Apr)
Gene regulation in planta by plant derived engineered zinc finger protein transcription factors . The ability to modify plant traits is of great commercial potential in agricultural biotechnology . To this end we have engineered plant based zinc finger protein transcription factors ( ZFP TFs ) that minimize the use of non plant DNA sequences . This novel architecture supports the use of tandem arrays of zinc finger DNA recognition domains such that the ZFP TF binds a contiguous DNA target site thus emulating the design of ZFP TFs described previously for mammalian gene regulation . We show that this plant based ZFP TF architecture supports high affinity DNA binding while allowing the specificity of the DNA protein interaction to be determined by the amino acid sequences of the recognition helices . This plant based backbone thus supports the use of previously characterized DNA recognition helices originally identified in a mammalian ZFP context without using mammalian DNA sequences . moreover , we show that plant based ZFP TFs employing this new architecture can up regulate endogenous ADH activity by 20 fold in transgenic arabidopsis . Thus plant based ZFP TFs are shown to be potent regulators of gene expression in vivo .

CDNA cloning , DNA binding , and evolution of mammalian transcription factor IIIA. (2002 Jan)
cDNA cloning , DNA binding , and evolution of mammalian transcription factor IIIA . cDNA for rat transcription factor IIIA ( tfiiia ) was cloned by degenerate PCR and rapid amplification of cDNA ends . This cDNA coded for a protein with nine Cys ( 2 ) His ( 2 ) zinc fingers and a non finger C terminal tail ; 63 amino acid ( aa ) sequence identity was observed with the xenopus tfiiia zinc finger region . recombinant rat protein containing only the nine fingers afforded dnase I protection of the identical nucleotides protected by xenopus laevis native tfiiia on the xenopus 5S RNA gene internal control region . A putative mouse tfiiia clone was identified in an expressed sequence tag database by sequence similarity to rat tfiiia . recombinant nine finger protein from this clone afforded dnase I protection of the xenopus 5S rRNA gene like the native frog protein as did a recombinant nine finger form of a putative human tfiiia clone . these DNA binding results demonstrate that these clones code for the respective mammalian tfiiias . rodent and human tfiiias share about 87 aa sequence identity in their zinc finger regions and have evolved to about the same extent as X . laevis and xenopus borealis tfiiias . A monoclonal antibody against human p53 tumor suppressor bound to rat and mouse tfiiia but not to human tfiiia in western blots . The N terminal regions of rodent and human tfiiia do not contain the …

Identification of DNA recognition sequences and protein interaction domains of the multiple Zn finger protein Roaz. (1998 Nov)
identification of DNA recognition sequences and protein interaction domains of the multiple Zn finger protein Roaz . Roaz , a rat C2H2 zinc finger protein , plays a role in the regulation of olfactory neuronal differentiation through its interaction with the Olf 1 / EBF transcription factor family . An additional role for the Roaz / Olf 1 / EBF heterodimeric protein is suggested by its ability to regulate gene activation at a distinct promoter lacking Olf 1 / EBF binding sites . using an in vitro binding site selection assay ( selex ) , we demonstrate that Roaz protein binds to novel inverted perfect or imperfect repeats of gcaccc separated by 2 bp . We show that Roaz is capable of binding to a canonical consensus recognition sequence with high affinity ( Kd 3 nM ) . analysis of the structural requirement for protein dimerization and DNA binding by Roaz reveals the role of specific zinc finger motifs in the Roaz protein for homodimerization and heterodimerization with the Olf 1 / EBF transcription factor . The DNA binding domain of Roaz is mapped to the N terminal 277 amino acids , containing the first seven zinc finger motifs , which confers weak monomeric binding to a single half site and a stronger dimeric binding to the inverted repeat in a binding site dependent manner . Full length protein can form dimers on both the inverted repeat and direct repeat but not on a single half site . these findings …

Metal and DNA binding properties and mutational analysis of the transcription activating factor , B , of coliphage 186 : … (1997 Aug)
metal and DNA binding properties and mutational analysis of the transcription activating factor , B , of coliphage 186 : a prokaryotic C4 zinc finger protein . coliphage 186 B is a 72 amino acid protein belonging to the Ogr family of analogous transcription factors present in P2 like phage , which contain a Cys X2 Cys X22 Cys X4 Cys presumptive zinc finger motif . The molecular characterization of these proteins has been hampered by their insolubility , a difficulty overcome in the present study by obtaining B as a soluble cadmium containing derivative ( CdB ) . atomic absorption spectroscopy showed the presence of one atom of cadmium per molecule of purified CdB . The UV absorption spectrum revealed a shoulder at 250 nm , characteristic of CysS Cd ( II ) ligand to metal charge transfer transitions , and the difference absorption coefficient after acidification ( delta epsilon 248 , 24 mM 1 cm 1 ) indicated the presence of a Cd ( Cys S ) 4 center . Gel mobility shift analysis of CdB with a 186 late promoter demonstrated specific DNA binding ( KD , app 3 4 microm ) and the protein was shown to activate transcription in vitro from a promoter reporter plasmid construct . The B DNA binding site was mapped by gel shift and dnaase I cleavage protection experiments to an area between 70 and 43 relative to the transcription start site , coincident with the consensus sequence , gttgt N8 …

The transactivation domain within cysteine / histidine rich region 1 of CBP comprises two novel zinc binding modules. (2000 Jun)
The transactivation domain within cysteine / histidine rich region 1 of CBP comprises two novel zinc binding modules . cAMP response element binding protein binding protein ( CBP ) is a transcriptional coactivator that interacts with a number of DNA binding proteins and cofactor proteins involved in the regulation of transcription . relatively little is known about the structure of CBP , but it has been noted that it contains three domains that are rich in cysteine and histidine ( CH1 , CH2 , and CH3 ) . The sequence of CH2 conforms to that of a leukemia associated protein domain ( PHD finger ) , and it has been postulated that this and both CH1 and CH3 may be zinc finger domains . This has not , however , been demonstrated experimentally . We have studied CH1 and show that it is composed of two novel zinc binding modules , which we term zinc bundles . Each bundle contains the sequence Cys X ( 4 ) Cys X ( 8 ) His X ( 3 ) Cys , and we show that a synthetic peptide comprising one zinc bundle from CH1 can fold in a zinc dependent manner . CH3 also appears to contain two zinc bundles , one with the variant sequence Cys X ( 2 ) Cys X ( 9 ) His X ( 3 ) Cys , and we demonstrate that this variant motif also undergoes Zn ( II ) induced folding . CH1 acts as …

Variations of the C2H2 zinc finger motif in the yeast genome and classification of yeast zinc finger proteins. (1997 Jul)
variations of the C2H2 zinc finger motif in the yeast genome and classification of yeast zinc finger proteins . The prosite pattern Zinc finger C2H2 was extended to permit the detection of all C2H2 zinc fingers and their parent proteins in the recently completed sequence of the yeast genome . additionally , a new computer program was written that extracts other zinc binding motifs ( non C2H2 fingers ) , overlapping with the classical zinc finger pattern , from the found set of yeast C2H2 fingers . The complete and correct detection of all fingers is a prerequisite for the classification of the yeast zinc finger proteins in functional terms . The detected 53 yeast C2H2 zinc finger proteins do not contain finger clusters with 10 or more repeats , as is frequently found in higher eukaryotes . Only three proteins contain four or more fingers in a cluster . moreover , nearly all 27 yeast proteins with tandem arrays of two or three finger domains can be classified into nine subgroups with high sequence conservation in their finger clusters , in particular of their DNA recognition helices . these results and application of the recently elaborated finger / DNA recognition rules suggest that the yeast proteins belonging to the same subgroup may recognize identical or very similar DNA sites .

Zinc binding to major human seminal coagulum proteins. (1989 Dec)
Zinc binding to major human seminal coagulum proteins . In vitro binding of zinc to proteins of the human ejaculate and of the various male accessory gland secretions was evaluated . The proteins were separated by sodium dodecyl sulfate gel electrophoresis and transferred to nitrocellulose filters that were subsequently incubated with 65zncl2 . High levels of zinc binding were observed to approximately 20 protein bands ( 14 to 70 kDa ) of the coagulated seminal plasma . there was only low binding to proteins of the spermatozoa and virtually no binding to any protein of the epididymal and prostatic fluids . When sperm liquefaction was allowed to occur , 65zncl2 binding to high molecular weight proteins decreased rapidly , and after 15 min only the binding to proteins of molecular weights less than 25 kDa remained . In addition , zinc concentration was determined both in the centrifugate and in the supernatant after centrifugation of the coagulum . Zinc concentrations in the centrifugate and the supernatant were , respectively , 147 / 72 micrograms / g and 31 / 22 micrograms / g . The whole supernatant contained only 12 / 4 of total sperm zinc . finally , in highly viscous sperm samples the concentration of zinc was not significantly different from that in normally liquefying sperm ( 167 / 87 micrograms / ml compared to 188 / 107 micrograms / ml ) . The main extracellular targets of prostatic zinc in humans are the secreted seminal vesicle proteins …

Identification of candidate target genes for EVI 1 , a zinc finger oncoprotein , using a novel selection strategy. (1998 Nov)
identification of candidate target genes for EVI 1 , a zinc finger oncoprotein , using a novel selection strategy . We have sought to identify and isolate target genes for the zinc finger protein , EVI 1 , which has been implicated in the genesis of myelogenous leukemia both in mouse and human . We have approached this with a two step selection : we first selected for genomic fragments of mouse DNA that bind to the protein with high affinity ; second , we employed cDNA hybrid selection to identify gene sequences contained within these fragments . We show that we have constructed a sublibrary of genomic fragments that contains a significant fraction of the EVI 1 binding sites in the mouse genome . Our data has allowed us to estimate that there are approximately 4300 binding sites per haploid genome in the mouse . We further demonstrate that by using cDNA hybrid selection , it is relatively straightforward to isolate cdnas that correspond to genes embedded in the EVI 1 binding sublibrary . several of these are novel , but are represented in databases of anonymous human or mouse cdnas ( expressed sequence tags ) . One selected gene is itpr2 , encoding the inositol trisphosphate type two receptor , which is transcriptionally regulated during myelopoiesis . finally , using a chimeric EVI 1 VP16 fusion protein under the control of a tetracycline regulated system , we have shown that this chimeric activator can directly regulate itpr2 .

Characterization of the thermosensitive ts453 reovirus mutant : increased dsrna binding of sigma 3 protein correlates with interferon resistance. (1998 Aug)
characterization of the thermosensitive ts453 reovirus mutant : increased dsrna binding of sigma 3 protein correlates with interferon resistance . The mutation harbored by the reovirus ts453 thermosensitive mutant has been assigned to the S4 gene encoding the major outer capsid protein sigma 3 . previous gene sequencing has identified a nonconservative amino acid substitution located near the zinc finger of sigma 3 protein in the mutant . coexpression in COS cells of the sigma 3 protein presenting this amino acid substitution ( N16K ) , together with the other major capsid protein mu 1 , has also revealed an altered interaction between the two proteins ; this altered interaction prevents the sigma 3 dependent cleavage of mu 1 to mu 1C . This could explain the lack of outer capsid assembly observed during ts453 virus infection at nonpermissive temperature . In the present study , we pursued the characterization of this mutant sigma 3 protein . although the N16K mutation is located close to the zinc finger region , it did not affect the ability of the protein to bind zinc . In contrast , this mutation , as well as mutations within the zinc finger motif itself , can increase the binding of the protein to double stranded RNA ( dsrna ) . It also appears that the N16K mutant protein is more efficiently transported to the nucleus than the wild type protein , an observation consistent with the postulated role of dsrna binding in sigma 3 nuclear …

Nucleolin modulates the subcellular localization of GDNF inducible zinc finger protein 1 and its roles in transcription and cell proliferation. (2007 Oct)
nucleolin modulates the subcellular localization of GDNF inducible zinc finger protein 1 and its roles in transcription and cell proliferation . GZF1 is a zinc finger protein induced by glial cell line derived neurotrophic factor ( GDNF ) . It is a sequence specific transcriptional repressor with a BTB / POZ ( broad complex , tramtrack , Bric a brac / poxvirus and zinc finger ) domain and ten zinc finger motifs . In the present study , we used immunoprecipitation and mass spectrometry to identify nucleolin as a GZF1 binding protein . deletion analysis revealed that zinc finger motifs 1 4 of GZF1 mediate its association with nucleolin . When zinc fingers 1 4 were deleted from GZF1 or nucleolin expression was knocked down by short interference RNA ( sirna ) , nuclear localization of GZF1 was impaired . these results suggest that nucleolin is involved in the proper subcellular distribution of GZF1 . In addition , overexpression of nucleolin moderately inhibited the transcriptional repressive activity of GZF1 whereas knockdown of nucleolin expression by sirna enhanced its activity . Thus , the repressive activity of GZF1 is modulated by the level at which nucleolin is expressed . finally , we found that knockdown of GZF1 and nucleolin expression markedly impaired cell proliferation . these findings suggest that the physiological functions of GZF1 may be regulated by the protein s association with nucleolin .

FYVE finger proteins as effectors of phosphatidylinositol 3 phosphate. (1999 Jun)
FYVE finger proteins as effectors of phosphatidylinositol 3 phosphate . phosphatidylinositol 3 phosphate ( ptdins ( 3 ) P ) , generated via the phosphorylation of phosphatidylinositol by phosphatidylinositol 3 kinase ( PI 3 kinase ) , plays an essential role in intracellular membrane traffic . The underlying mechanism is still not understood in detail , but the recent identification of the FYVE finger as a protein domain that binds specifically to ptdins ( 3 ) P provides a number of potential effectors for ptdins ( 3 ) P . The FYVE finger ( named after the first letter of the four proteins containing it ; fab1p , YOTB , vac1p and EEA1 ) is a double zinc binding domain that is conserved in more than 30 proteins from yeast to mammals . It is found in several proteins involved in intracellular traffic , and FYVE finger mutations that affect zinc binding are associated with the loss of function of several of these proteins . The interaction of FYVE fingers with ptdins ( 3 ) P may serve three alternative functions : first , to recruit cytosolic FYVE finger proteins to ptdins ( 3 ) P containing membranes ( in concert with accessory molecules ) ; second , to enrich for membrane bound FYVE finger proteins into ptdins ( 3 ) P containing microdomains within the membrane ; and third , to modulate the activity of membrane bound FYVE finger proteins .