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13  structures 1441  species 0  interactions 25572  sequences 1027  architectures

Family: FYVE (PF01363)

Summary: FYVE zinc finger

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This is the Wikipedia entry entitled "FYVE domain". More...

FYVE domain Edit Wikipedia article

FYVE zinc finger
Early endosome antigen 1 (EEA1) dimer with lipids.[1]
OPM superfamily59
OPM protein1vfy

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:

R+HHC+XCG, where + represents a charged residue and X any residue

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:


  1. ^ Dumas JJ, Merithew E, Sudharshan E, et al. (November 2001). "Multivalent endosome targeting by homodimeric EEA1". Mol. Cell. 8 (5): 947–58. doi:10.1016/S1097-2765(01)00385-9. PMID 11741531.
  2. ^ Gaullier JM, Simonsen A, D'Arrigo A, Bremnes B, Stenmark H, Aasland R (July 1998). "FYVE fingers bind PtdIns(3)P". Nature. 394 (6692): 432–3. doi:10.1038/28767. PMID 9697764.
  3. ^ He J, Vora M, Haney RM, et al. (September 2009). "Membrane insertion of the FYVE domain is modulated by pH". Proteins. 76 (4): 852–60. doi:10.1002/prot.22392. PMC 2909462. PMID 19296456.
  4. ^ Leevers SJ, Vanhaesebroeck B, Waterfield MD (April 1999). "Signalling through phosphoinositide 3-kinases: the lipids take centre stage". Curr. Opin. Cell Biol. 11 (2): 219–25. doi:10.1016/S0955-0674(99)80029-5. PMID 10209156.
  5. ^ Misra S, Hurley JH (May 1999). "Crystal structure of a phosphatidylinositol 3-phosphate-specific membrane-targeting motif, the FYVE domain of Vps27p". Cell. 97 (5): 657–66. doi:10.1016/S0092-8674(00)80776-X. PMID 10367894.

Further reading

  • Stenmark H, Aasland R, Toh BH, D'Arrigo A (September 1996). "Endosomal localization of the autoantigen EEA1 is mediated by a zinc-binding FYVE finger". J. Biol. Chem. 271 (39): 24048–54. doi:10.1074/jbc.271.39.24048. PMID 8798641.
  • Stenmark H, Aasland R (December 1999). "FYVE-finger proteins--effectors of an inositol lipid". J. Cell Sci. 112 (Pt 23): 4175–83. PMID 10564636.

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

FYVE zinc finger Provide feedback

The FYVE zinc finger is named after four proteins that it has been found in: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two Zn++ ions [1]. The FYVE finger has eight potential zinc coordinating cysteine positions. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. We have included members which do not conserve these histidine residues but are clearly related.

Literature references

  1. Stenmark H, Aasland R, Toh BH, D'Arrigo A; , J Biol Chem 1996;271:24048-24054.: Endosomal localization of the autoantigen EEA1 is mediated by a zinc-binding FYVE finger. PUBMED:8798641 EPMC:8798641

  2. Gaullier JM, Simonsen A, D'Arrigo A, Bremnes B, Stenmark H, Aasland R; , Nature 1998;394:432-433.: FYVE fingers bind PtdIns(3)P. PUBMED:9697764 EPMC:9697764

  3. Stenmark H, Aasland R; , J Cell Sci 1999;112:4175-4183.: FYVE-finger proteins - effectors of an inositol lipid. PUBMED:10564636 EPMC:10564636

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR000306

Zinc finger (Znf) domains are relatively small protein motifs which contain multiple finger-like protrusions that make tandem contacts with their target molecule. Some of these domains bind zinc, but many do not; instead binding other metals such as iron, or no metal at all. For example, some family members form salt bridges to stabilise the finger-like folds. They were first identified as a DNA-binding motif in transcription factor TFIIIA from Xenopus laevis (African clawed frog), however they are now recognised to bind DNA, RNA, protein and/or lipid substrates [ PUBMED:10529348 , PUBMED:15963892 , PUBMED:15718139 , PUBMED:17210253 , PUBMED:12665246 ]. Their binding properties depend on the amino acid sequence of the finger domains and of the linker between fingers, as well as on the higher-order structures and the number of fingers. Znf domains are often found in clusters, where fingers can have different binding specificities. There are many superfamilies of Znf motifs, varying in both sequence and structure. They display considerable versatility in binding modes, even between members of the same class (e.g. some bind DNA, others protein), suggesting that Znf motifs are stable scaffolds that have evolved specialised functions. For example, Znf-containing proteins function in gene transcription, translation, mRNA trafficking, cytoskeleton organisation, epithelial development, cell adhesion, protein folding, chromatin remodelling and zinc sensing, to name but a few [ PUBMED:11179890 ]. Zinc-binding motifs are stable structures, and they rarely undergo conformational changes upon binding their target.

The FYVE zinc finger is named after four proteins that it has been found in: Fab1, YOTB/ZK632.12, Vac1, and EEA1. The FYVE finger has been shown to bind two zinc ions [ PUBMED:8798641 ]. The FYVE finger has eight potential zinc coordinating cysteine positions. Many members of this family also include two histidines in a motif R+HHC+XCG, where + represents a charged residue and X any residue. FYVE-type domains are divided into two known classes: FYVE domains that specifically bind to phosphatidylinositol 3-phosphate in lipid bilayers and FYVE-related domains of undetermined function [ PUBMED:15576038 ]. Those that bind to phosphatidylinositol 3-phosphate are often found in proteins targeted to lipid membranes that are involved in regulating membrane traffic [ PUBMED:11456498 , PUBMED:11739631 , PUBMED:11509568 ]. Most FYVE domains target proteins to endosomes by binding specifically to phosphatidylinositol-3-phosphate at the membrane surface. By contrast, the CARP2 FYVE-like domain is not optimized to bind to phosphoinositides or insert into lipid bilayers. FYVE domains are distinguished from other zinc fingers by three signature sequences: an N-terminal WxxD motif, a basic R(R/K)HHCR patch, and a C-terminal RVC motif.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan zf-FYVE-PHD (CL0390), which has the following description:

Superfamily contains a number of zinc-fingers, of the FYVE/PHD type, which are found in several groups of proteins including myelin-associated oligodendrocytic basic proteins (MOBP) Rabphilins, melanophilins, exophilins and myosin-VIIA and Rab-interacting protein families.

The clan contains the following 13 members:

ADD_ATRX ADD_DNMT3 FYVE FYVE_2 PHD PHD_2 PHD_4 PHD_Oberon RAG2_PHD zf-HC5HC2H zf-HC5HC2H_2 zf-PHD-like zf-piccolo


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Curation and family details

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Seed source: Pfam-B_655 (release 3.0)
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: Bateman A , Armstrong J
Number in seed: 129
Number in full: 25572
Average length of the domain: 70.50 aa
Average identity of full alignment: 32 %
Average coverage of the sequence by the domain: 7.74 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.8 27.8
Trusted cut-off 27.8 27.8
Noise cut-off 27.7 27.7
Model length: 69
Family (HMM) version: 23
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Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the FYVE domain has been found. There are 13 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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