ELM - Detail for LIG_MYND

Accession:	ELME000341
Functional site class:	MYND domain binding motif.
Functional site description:	The MYND domain is a zinc binding domain that is involved in protein-protein interactions mainly in the context of transcriptional regulation. It is named after Myeloid, Nervy, and DEAF-1, which are the three most characterized proteins that contain the MYND domain. Only a small number of MYND domain containing proteins have been identified and they are involved in various biological processes such as cell proliferation, apoptosis, adhesion, migration, and tumorigenesis and oxygen homeostasis. MYND domain typically binds a proline-rich motif in their interacting partners, however they have different binding specificities.
ELMs with same func. site:	LIG_MYND_1 LIG_MYND_2 LIG_MYND_3
ELM Description:	The PxLE motif is recognized by a MYND type zinc finger (PF01753) of PHD2 (Q9GZT9). The HSP90 co-chaperones p23 (Q15185) and FKBP38 (Q14318) contain this motif and it is similar to other MYND domain-binding motifs. Mutagenesis experiments inside or in the vicinity of the motif have revealed that the Pro, Leu, and Glu residues found in the core motif are strictly defined, i.e. mutations to other amino acids either reduce or abolish binding to PHD2. Moreover, a hydrophobic residue such as Met, Val or Leu preceding the PxLE is required for proper binding. The wild-card position ‘x’ was shown to tolerate amino acids such as Pro, Asp, Ala, or Leu. Finally, one or more acidic residues preceding the motif seem to have a positive effect on the binding affinity (Song,2013).
Pattern:	`[LMV]P.LE`
Pattern Probability:	`0.0000844`
Present in taxon:	Eukaryota
Interaction Domain:	zf-MYND (PF01753) MYND finger (Stochiometry: 1 : 1)

MYND domain binding motif.

The MYND domain is a zinc binding domain that is involved in protein-protein interactions mainly in the context of transcriptional regulation. It is named after Myeloid, Nervy, and DEAF-1, which are the three most characterized proteins that contain the MYND domain. Only a small number of MYND domain containing proteins have been identified and they are involved in various biological processes such as cell proliferation, apoptosis, adhesion, migration, and tumorigenesis and oxygen homeostasis. MYND domain typically binds a proline-rich motif in their interacting partners, however they have different binding specificities.

ELMs with same func. site:

LIG_MYND_1 LIG_MYND_2 LIG_MYND_3

ELM Description:

The PxLE motif is recognized by a MYND type zinc finger (PF01753) of PHD2 (Q9GZT9). The HSP90 co-chaperones p23 (Q15185) and FKBP38 (Q14318) contain this motif and it is similar to other MYND domain-binding motifs. Mutagenesis experiments inside or in the vicinity of the motif have revealed that the Pro, Leu, and Glu residues found in the core motif are strictly defined, i.e. mutations to other amino acids either reduce or abolish binding to PHD2. Moreover, a hydrophobic residue such as Met, Val or Leu preceding the PxLE is required for proper binding. The wild-card position ‘x’ was shown to tolerate amino acids such as Pro, Asp, Ala, or Leu. Finally, one or more acidic residues preceding the motif seem to have a positive effect on the binding affinity (Song,2013).

[LMV]P.LE

0.0000844

Eukaryota

zf-MYND (PF01753) MYND finger (Stochiometry: 1 : 1)

The MYND domain is a cysteine-rich structure present in proteins generally implicated in gene regulation and associated with cancers. Some of the MYND domain containing proteins are BS69, Nervy (a transcriptional corepressor), the chimeric fusion protein of acute myelogenous leukemia (AML) and ETO (a nuclear protein that interacts with corepressor molecules), the bone morphogenesis protein receptor-associated molecule1 (BRAM1), SET and MYND domain-containing proteins (SMYD), RACK7, PDCD2, deformed epidermal auto regulatory factor-1 (DEAF-1). The structures of the MYND domain in these proteins demonstrate a tandem zinc-binding motif organized in cross-brace topology (Kateb,2013).
A variant of MYND domain is also found to exist in prolyl hydroxylase domain protein 2 (PHD2) that catalyzes proline hydroxylation of HIFα subunits. Prolyl hydroxylation is an ancient mechanism to transduce changes in oxygen concentration to changes in cellular function. Among the three PHD isoforms, PHD2 is a distinct one as it is predicted to have a MYND-type zinc finger at its N-terminal. It is also the one that is most closely related to the single ancestral PHD and has the capacity to hydroxylate HIF-1α, which is connected to HSP90 pathway (Huang,2002). Depending upon the variations in amino acid sequence of MYND domain, there exist different binding specificities for MYND domain containing proteins and it acts as a scaffold for different cellular and viral protein-protein interactions.
MYND domains usually recognize proline-rich motifs in their partners. The MYND domain of BS69 has been shown to bind viral tumour antigens E1A and EBNA2 as well as with cellular partners such as MGA through a PxLxP motif (Ansieau,2002). The MYND domain of BS69 contains a set of positively charged residues at its C-terminus, which is crucial for interaction with PxLxP ligands. Other MYND domain containing proteins such as RACK7, ETO and DEAF-1, which lack these charged residues fail to interact with the PxLxP motif. The co-repressor-binding MYND domain-containing proteins such as DEAF-1 and ETO have higher degree of sequence similarity and similar binding mode. They can bind to another proline-rich motif PPPLI (Liu,2007). The MYND-type Zinc Finger of PHD2 binds a PxLE motif, which is so far found to exist in HSP90 co-chaperones p23 and FKBP38 (Song,2013).

Biological Process:
Protein Folding (also annotated in these classes: LIG_TPR )
Peptidyl-Proline Hydroxylation (also annotated in class: )
Chaperone Cofactor-Dependent Protein Refolding (also annotated in class: )
Cellular Compartment:
Cytosol (also annotated in these classes: )
Nucleus (also annotated in these classes: )
Molecular Function:
Protein Binding (also annotated in these classes: )