Structural and Functional Insights into the Human Börjeson-Forssman-Lehmann Syndrome-associated Protein PHF6

Z, Liu; Li, Fudong; Ruan, Ke; Zhang, Jiahai; Mei, Yide; Wu, Jihui; Shi, Yunyu

doi:10.1074/jbc.m113.535351

Cited by 64 publications

(76 citation statements)

References 50 publications

(39 reference statements)

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“…Extensive hydrophobic interactions hold the globular structure of this region, which is important for its function 12 . Phe1662 is fully buried at the core, stabilizing the structure of this PHDlike domain while Gly1652 is partially buried (Fig.…”

Section: Kmt2b Is Constrained For Missense and Predicted Protein Trunmentioning

confidence: 99%

“…p.Phe1662Leu and p.Gly1652Asp occur within a PHD-like domain (residues 1574-1688), predicted to facilitate interaction with DNA, protein-protein interaction and recognition of methylated/unmethylated lysines [12][13][14] . Extensive hydrophobic interactions hold the globular structure of this region, which is important for its function 12 .…”

Section: Kmt2b Is Constrained For Missense and Predicted Protein Trunmentioning

confidence: 99%

“…Through national and international collaborations (Online Methods, Supplementary Fig. 1), a further 10 cases (Patients 11,12,15,18,19,20,23,24, 25, 26a) were subsequently ascertained.…”

Section: Chromosomal Microdeletions and Intragenic Kmt2b Sequence Varmentioning

confidence: 99%

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Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia

Meyer¹,

Carss²,

Rankin³

et al. 2016

Nat Genet

193

253

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Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine methyltransferases. Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-

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Section: Kmt2b Is Constrained For Missense and Predicted Protein Trunmentioning

confidence: 99%

Section: Kmt2b Is Constrained For Missense and Predicted Protein Trunmentioning

confidence: 99%

See 1 more Smart Citation

Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia

Meyer¹,

Carss²,

Rankin³

et al. 2016

Nat Genet

193

253

View full text Add to dashboard Cite

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“…We previously reported that residues 152-171 of PHF6 can directly interact with RBBP4 (RbAp48) in GST pulldown assays in vitro (20). ITC was conducted using a synthetic optimized PHF6 peptide (residues 157-171) to titrate RBBP4 (Fig.…”

Section: Phf6 Binds To Rbbp4/rbap48 Forming a Stable Complex-mentioning

confidence: 99%

“…Furthermore, in our previous work, we showed that the PHF6 protein can directly interact with the NuRD complex component RBBP4 and that the interaction is mediated by the nucleolar localization sequence (NoLS) composed of NLS3 and NLS4 of PHF6 (20). To study the molecular basis of this interaction, we subsequently determined the crystal structure of RBBP4 in complex with a PHF6 peptide (residues 157-171).…”

mentioning

confidence: 99%

Structural Basis of Plant Homeodomain Finger 6 (PHF6) Recognition by the Retinoblastoma Binding Protein 4 (RBBP4) Component of the Nucleosome Remodeling and Deacetylase (NuRD) Complex

Zhang

et al. 2015

Journal of Biological Chemistry

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Background:The PHF6 gene is mutated in patients with Börjeson-Forssman-Lehmann syndrome, T-cell acute lymphoblastic leukemia, and acute myeloid leukemia. The PHF6 protein is a newly identified interactor with the NuRD complex. Results: The complex structure of the NoLS region of PHF6 bound to RBBP4 was solved. Conclusion: By interacting with the RBBP4 component, PHF6 associates with the NuRD complex. Significance: Association with the NuRD complex implicates a role for PHF6 in chromatin structure modulation and gene regulation.

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Females with de novo aberrations in PHF6: Clinical overlap of Borjeson–Forssman–Lehmann with Coffin–Siris syndrome

Zweier¹,

Rittinger²,

Bader³

et al. 2014

American J of Med Genetics Pt C

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Recently, de novo aberrations in PHF6 were identified in females with intellectual disability and with a distinct phenotype including a characteristic facial gestalt with bitemporal narrowing, prominent supraorbital ridges, synophrys, a short nose and dental anomalies, tapering fingers with brachytelephalangy, clinodactyly and hypoplastic nails, short toes with hypoplastic nails, and linear skin hyperpigmentation. In adolescent or older patients, this phenotype overlaps but is not identical with Borjeson-Forssman-Lehmann syndrome in males, caused by X-linked recessive mutations in PHF6. In younger girls there seems to be a striking phenotypic overlap with Coffin-Siris syndrome, which is characterized by intellectual disability, sparse hair and hypoplastic nails. This review will summarize and characterize the female phenotype caused by de novo aberrations in PHF6 and will discuss the overlapping and distinguishing features with Coffin-Siris syndrome.

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Structural and Functional Insights into the Human Börjeson-Forssman-Lehmann Syndrome-associated Protein PHF6

Cited by 64 publications

References 50 publications

Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia

Mutations in the histone methyltransferase gene KMT2B cause complex early-onset dystonia

Structural Basis of Plant Homeodomain Finger 6 (PHF6) Recognition by the Retinoblastoma Binding Protein 4 (RBBP4) Component of the Nucleosome Remodeling and Deacetylase (NuRD) Complex

Females with de novo aberrations in PHF6: Clinical overlap of Borjeson–Forssman–Lehmann with Coffin–Siris syndrome

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