Learn and talk about PHF8, EC 1.14.11, Genes on chromosome X, Human 2OG oxygenases, Human proteins

PHD finger protein 8

Rendering based on PDB 2WWU.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
2WWU, 3K3N, 3K3O, 3KV4, 4DO0

Identifiers

Symbols

PHF8; JHDM1F; MRXSSD; ZNF422

External IDs

OMIM: 300560 MGI: 2444341 HomoloGene: 49405 GeneCards: PHF8 Gene

EC number

1.14.11.27

Gene Ontology
Molecular function	• chromatin binding • iron ion binding • protein binding • zinc ion binding • oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, 2-oxoglutarate as one donor, and incorporation of one atom each of oxygen into both donors • histone demethylase activity • histone demethylase activity (H3-K9 specific) • methylated histone residue binding • histone demethylase activity (H4-K20 specific) • histone demethylase activity (H3-K36 specific) • histone demethylase activity (H3-K27 specific)
Cellular component	• nucleus • nucleolus
Biological process	• G1/S transition of mitotic cell cycle • transcription, DNA-dependent • brain development • histone H3-K9 demethylation • histone H4-K20 demethylation • positive regulation of transcription, DNA-dependent • positive regulation of transcription from RNA polymerase I promoter • negative regulation of chromatin silencing at rDNA • histone H3-K36 demethylation • histone H3-K27 demethylation
Sources: Amigo / QuickGO

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr HG1433_PATCH:
53.68 – 53.79 Mb

Chr X:
151.52 – 151.63 Mb

PubMed search

[1]

[2]

PHD finger protein 8 is a protein that in humans is encoded by the PHF8 gene.^[1]

1 Function
2 Clinical significance
3 References
4 Further reading
5 External links

Function[edit]

PHF8 belongs to the family of ferrous iron and 2-oxoglutarate dependent oxygenases,^[2] and is active as a histone lysine demethylase with selectivity for the di-and monomethyl states.^[3]

Clinical significance[edit]

Mutations in PHF8 cause Siderius type X-linked mental retardation (XLMR) (OMIM 300263).^[4]^[5]^[6] In addition to moderate mental retardation, features of the Siderius-Hamel syndrome include facial dysmorphism, cleft lip and/or cleft palate, and in some cases microcephaly.^[7]^[8]^[9] A chromosomal microdeletion on Xp11.22 encompassing all of the PHF8 and FAM120C genes and a part of the WNK3 gene was reported in two brothers with autism spectrum disorder in addition to Siderius-type XLMR and cleft lip and palate.^[10]

This catalytic activity is disrupted by clinically known mutations to PHF8, which were found to cluster in its catalytic JmjC domain. The F279S mutation of PHF8, found in 2 Finnish brothers with mild mental retardation, facial dysmorphism and cleft lip/palate,^[9] was found to additionally prevent nuclear localisation of PHF8 overexpressed in human cells.^[3]

The catalytic activity of PHF8 depends on molecular oxygen,^[3] a fact considered important with respect to reports on increased incidence of cleft lip/palate in mice that have been exposed to hypoxia during pregnancy.^[11] In humans, fetal cleft lip and other congenital abnormalities have also been linked to maternal hypoxia, as caused by e.g. maternal smoking,^[12] maternal alcohol abuse or maternal hypertension treatment.^[13]

References[edit]

^ "Entrez Gene: PHF8 PHD finger protein 8".
^ Loenarz, C.; Schofield, C. J. (2008). "Expanding chemical biology of 2-oxoglutarate oxygenases". Nat. Chem. Biol. 4 (3): 152–156. doi:10.1038/nchembio0308-152. PMID 18277970.
^ ^a ^b ^c Loenarz, C.; Ge W., Coleman M. L., Rose N. R., Cooper C. D. O., Klose R. J., Ratcliffe P. J., Schofield, C. J. (2009). "PHF8, a gene associated with cleft lip/palate and mental retardation, encodes for an N{varepsilon}-dimethyl lysine demethylase". Hum. Mol. Genet. 19 (2): 217–22. doi:10.1093/hmg/ddp480. PMID 19843542.
^ Siderius LE, Hamel BC, van Bokhoven H, et al. (2000). "X-linked mental retardation associated with cleft lip/palate maps to Xp11.3-q21.3.". Am. J. Med. Genet. 85 (3): 216–220. doi:10.1002/(SICI)1096-8628(19990730)85:3<216::AID-AJMG6>3.0.CO;2-X. PMID 10398231.
^ "OMIM: Siderius X-linked mental retardation syndrome". Retrieved 2009-10-21.
^ "OMIM: PHD finger protein 8; PHF8". Retrieved 2009-10-21.
^ Abidi, F. E.; Miano, M. G.; Murray, J. C.; Schwartz, C. E. (2007). "A novel mutation in the PHF8 gene is associated with X-linked mental retardation with cleft lip/cleft palate". Clin. Genet. 72 (1): 19–22. doi:10.1111/j.1399-0004.2007.00817.x. PMC 2570350. PMID 17594395.
^ Laumonnier F, Holbert S, Ronce N, et al. (2006). "Mutations in PHF8 are associated with X linked mental retardation and cleft lip/cleft palate.". J. Med. Genet. 42 (10): 780–786. doi:10.1136/jmg.2004.029439. PMC 1735927. PMID 16199551.
^ ^a ^b Koivisto AM, Ala-Mello S, Lemmelä S, et al. (2007). "Screening of mutations in the PHF8 gene and identification of a novel mutation in a Finnish family with XLMR and cleft lip/cleft palate.". Clin. Genet. 72 (2): 145–149. doi:10.1111/j.1399-0004.2007.00836.x. PMID 17661819.
^ Qiao, Y; Liu, X.; Harvard, C.; Hildebrand, M. J.; Rajcan-Separovic, E.; Holden, J. J. A.; Lewis, M. E. S. (2008). "Autism-associated familial microdeletion of Xp11.22". Clin. Genet. 74 (2): 134–144. doi:10.1111/j.1399-0004.2008.01028.x. PMID 18498374.
^ Millicovsky, G.; Johnston, M.C. (1981). "Hyperoxia and hypoxia in pregnancy: simple experimental manipulation alters the incidence of cleft lip and palate in CL/Fr mice". Proc. Natl. Acad. Sci. U.S.A. 78 (9): 5722–5723. doi:10.1073/pnas.78.9.5722. PMC 348841. PMID 6946511.
^ Shi, M.; Wehby, G.L. and Murray, J.C. (2008). "Review on genetic variants and maternal smoking in the etiology of oral clefts and other birth defects". Birth Defects Res., Part C 84 (1): 16–29. doi:10.1002/bdrc.20117. PMC 2570345. PMID 18383123.
^ Hurst, J. A.; Houlston, R.S., Roberts, A., Gould, S.J. and Tingey, W.G. (1995). "Transverse limb deficiency, facial clefting and hypoxic renal damage: an association with treatment of maternal hypertension?". Clin. Dysmorphol. 4 (4): 359–363. PMID 8574428.

External links[edit]

PHF8 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Transcription factors and intracellular receptors

(1) Basic domains

(1.1) Basic leucine zipper (bZIP)	Activating transcription factor (AATF, 1, 2, 3, 4, 5, 6, 7) · AP-1 (c-Fos, FOSB, FOSL1, FOSL2, JDP2, c-Jun, JUNB, JUND) · BACH (1, 2) · BATF · BLZF1 · C/EBP (α, β, γ, δ, ε, ζ) · CREB (1, 3, L1) · CREM · DBP · DDIT3 · GABPA · HLF · MAF (B, F, G, K) · NFE (2, L1, L2, L3) · NFIL3 · NRL · NRF (1, 2, 3) · XBP1

(1.2) Basic helix-loop-helix (bHLH)	ATOH1 · AhR · AHRR · ARNT · ASCL1 · BHLH (2, 9) · BMAL (ARNTL, ARNTL2) · CLOCK · EPAS1 · FIGLA · HAND (1, 2) · HES (5, 6) · HEY (1, 2, L) · HES1 · HIF (1A, 3A) · ID (1, 2, 3, 4) · LYL1 · MESP2 · MXD4 · MYCL1 · MYCN · Myogenic regulatory factors (MyoD, Myogenin, MYF5, MYF6) · Neurogenins (1, 2, 3) · NeuroD (1, 2) · NPAS (1, 2, 3) · OLIG (1, 2) · Pho4 · Scleraxis · SIM (1, 2) · TAL (1, 2) · Twist · USF1

(1.3) bHLH-ZIP	AP-4 · MAX (MXD3) · MITF · MNT · MLX · MXI1 · Myc · SREBP (1, 2)

(1.4) NF-1	NFI (A, B, C, X) · SMAD (R-SMAD (1, 2, 3, 5, 9) - I-SMAD (6, 7) - 4)

(1.5) RF-X	RFX (1, 2, 3, 4, 5, 6, ANK)

(1.6) Basic helix-span-helix (bHSH)	AP-2 (α, β, γ, δ, ε)

(2) Zinc finger DNA-binding domains

(2.1) Nuclear receptor (Cys₄)	subfamily 1 (Thyroid hormone (α, β), CAR, FXR, LXR (α, β), PPAR (α, β/δ, γ), PXR, RAR (α, β, γ), ROR (α, β, γ), Rev-ErbA (α, β), VDR) subfamily 2 (COUP-TF (I, II), Ear-2, HNF4 (α, γ), PNR, RXR (α, β, γ), Testicular receptor (2, 4), TLX) subfamily 3 (Steroid hormone (Androgen, Estrogen (α, β), Glucocorticoid, Mineralocorticoid, Progesterone), Estrogen related (α, β, γ)) subfamily 4 NUR (NGFIB, NOR1, NURR1) · subfamily 5 (LRH-1, SF1) · subfamily 6 (GCNF) · subfamily 0 (DAX1, SHP)

(2.2) Other Cys₄	GATA (1, 2, 3, 4, 5, 6) · MTA (1, 2, 3) · TRPS1

(2.3) Cys₂His₂	General transcription factors (TFIIA, TFIIB, TFIID, TFIIE (1, 2), TFIIF (1, 2), TFIIH (1, 2, 4, 2I, 3A, 3C1, 3C2)) ATBF1 · BCL (6, 11A, 11B) · CTCF · E4F1 · EGR (1, 2, 3, 4) · ERV3 · GFI1 · GLI-Krüppel family (1, 2, 3, REST, S1, S2, YY1) · HIC (1, 2) · HIVEP (1, 2, 3) · IKZF (1, 2, 3) · ILF (2, 3) · KLF (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 17) · MTF1 · MYT1 · OSR1 · PRDM9 · SALL (1, 2, 3, 4) · SP (1, 2, 4, 7, 8) · TSHZ3 · WT1 · Zbtb7 (7A, 7B) · ZBTB (11, 16, 17, 20, 32, 33, 40) · zinc finger (3, 7, 9, 10, 19, 22, 24, 33B, 34, 35, 41, 43, 44, 51, 74, 143, 146, 148, 165, 202, 217, 219, 238, 239, 259, 267, 268, 281, 295, 300, 318, 330, 346, 350, 365, 366, 384, 423, 451, 452, 471, 593, 638, 644, 649, 655)

(2.4) Cys₆	HIVEP1

(2.5) Alternating composition	AIRE · DIDO1 · GRLF1 · ING (1, 2, 4) · JARID (1A, 1B, 1C, 1D, 2) · JMJD1B

(2.6) WRKY	WRKY

(3) Helix-turn-helix domains

(3.1) Homeodomain	ARX · CDX (1, 2) · CRX · CUTL1 · DBX (1, 2) · DLX (3, 4, 5) · EMX (1, 2) · EN (1, 2) · FHL (1, 2, 3) · HESX1 · HHEX · HLX · Homeobox (A1, A2, A3, A4, A5, A7, A9, A10, A11, A13, B1, B2, B3, B4, B5, B6, B7, B8, B9, B13, C4, C5, C6, C8, C9, C10, C11, C12, C13, D1, D3, D4, D8, D9, D10, D11, D12, D13) · HOPX · IRX (1, 2, 3, 4, 5, 6, MKX) · LMX (1A, 1B) · MEIS (1, 2) · MEOX2 · MNX1 · MSX (1, 2) · NANOG · NKX (2-1, 2-2, 2-3, 2-5, 3-1, 3-2, 6-1, 6-2) · NOBOX · PBX (1, 2, 3) · PHF (1, 3, 6, 8, 10, 16, 17, 20, 21A) · PHOX (2A, 2B) · PITX (1, 2, 3) · POU domain (PIT-1, BRN-3: A, B, C, Octamer transcription factor: 1, 2, 3/4, 6, 7, 11) · OTX (1, 2) · PDX1 · SATB2 · SHOX2 · SIX (1, 2, 3, 4, 5) · VAX1 · ZEB (1, 2)

(3.2) Paired box	PAX (1, 2, 3, 4, 5, 6, 7, 8, 9)

(3.3) Fork head / winged helix	E2F (1, 2, 3, 4, 5) · FOX proteins (A1, A2, A3, C1, C2, D3, D4, E1, E3, F1, G1, H1, I1, J1, J2, K1, K2, L2, M1, N1, N3, O1, O3, O4, P1, P2, P3, P4)

(3.4) Heat Shock Factors	HSF (1, 2, 4)

(3.5) Tryptophan clusters	ELF (2, 4, 5) · EGF · ELK (1, 3, 4) · ERF · ETS (1, 2, ERG, SPIB) · ETV (1, 4, 5, 6) · FLI1 · Interferon regulatory factors (1, 2, 3, 4, 5, 6, 7, 8) · MYB · MYBL2

(3.6) TEA domain	transcriptional enhancer factor (1, 2, 3, 4)

(4) β-Scaffold factors with minor groove contacts

(4.1) Rel homology region	NF-κB (NFKB1, NFKB2, REL, RELA, RELB) · NFAT (C1, C2, C3, C4, 5)

(4.2) STAT	STAT (1, 2, 3, 4, 5, 6)

(4.3) p53	p53 · TBX (1, 2, 3, 5, 19, 21, 22, Brachyury, TBR1, TBR2) · TP63

(4.4) MADS box	Mef2 (A, B, C, D) · SRF

(4.6) TATA binding proteins	TBP · TBPL1

(4.7) High-mobility group	BBX · HMGB (1, 2, 3, 4) · HMGN (1, 2, 3, 4) · HNF (1A, 1B) · LEF1 · SOX (1, 2, 3, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14, 15, 18, 21) · SRY · SSRP1 · TCF (3, 4) · TOX (1, 2, 3, 4)

(4.9) Grainyhead	TFCP2

(4.10) Cold-shock domain	CSDA, YBX1

(4.11) Runt	CBF (CBFA2T2, CBFA2T3, RUNX1, RUNX2, RUNX3, RUNX1T1)

(0) Other transcription factors

(0.2) HMGI(Y)	HMGA (1, 2) · HBP1

(0.3) Pocket domain	Rb · RBL1 · RBL2

(0.5) AP-2/EREBP-related factors	Apetala 2 · EREBP · B3

(0.6) Miscellaneous	ARID (1A, 1B, 2, 3A, 3B, 4A) · CAP · IFI (16, 35) · MLL (2, 3, T1) · MNDA · NFY (A, B, C) · Rho/Sigma

see also transcription factor/coregulator deficiencies
B bsyn: dna (repl, cycl, reco, repr) · tscr (fact, tcrg, nucl, rnat, rept, ptts) · tltn (risu, pttl, nexn) · dnab, rnab/runp · stru (domn, 1°, 2°, 3°, 4°)

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PHF8

Contents

Function[edit]

Clinical significance[edit]

References[edit]

Further reading[edit]

External links[edit]

Talk About PHF8

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