UniProtKB/Swiss-Prot Q9UPP1: Variant p.Phe315Ser

Histone lysine demethylase PHF8
Gene: PHF8
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Variant information Variant position:

315 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.

LP/P: likely pathogenic or pathogenic.
LB/B: likely benign or benign.
US: uncertain significance

Residue change:

From Phenylalanine (F) to Serine (S) at position 315 (F315S, p.Phe315Ser). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties:

Change from large size and aromatic (F) to small size and polar (S) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-2 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:

Lowest score: -4 (low probability of substitution).
Highest score: 11 (high probability of substitution).

More information can be found on the following page
Variant description:

In MRXSSD; abolishes histone methyltransferase activity; reduces transcriptional activation activity. Any additional useful information about the variant.
Other resources:

Links to websites of interest for the variant.

Variant rs121918524 [ dbSNP | Ensembl ]

Sequence information Variant position:

315 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

1060 The length of the canonical sequence.
Location on the sequence:

VLKGEKIFYLIRPTNANLTL F ECWSSSSNQNEMFFGDQVDK The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         VLKGEKIFYLIRPTNANLTLFECWSSSSNQNEMFFGDQVDK

Mouse                         VLKGEKIFYLIRPTNANLTLFECWSSSSNQNEMFFGDQVEK

Zebrafish                     VLRGEKIFYLIRPTAANLSLFERWSSSSNQNELFFGDQVDM

Sequence annotation in neighborhood:

The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:

Type: the type of sequence feature.
Positions: endpoints of the sequence feature.
Description: contains additional information about the feature.

Type	Positions	Description
Chain	1 – 1060	Histone lysine demethylase PHF8
Domain	231 – 387	JmjC
Binding site	300 – 300
Helix	309 – 319

Literature citations
The X-linked mental retardation gene PHF8 is a histone demethylase involved in neuronal differentiation.
Qiu J.; Shi G.; Jia Y.; Li J.; Wu M.; Li J.; Dong S.; Wong J.;
Cell Res. 20:908-918(2010)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANT MRXSSD SER-315; A functional link between the histone demethylase PHF8 and the transcription factor ZNF711 in X-linked mental retardation.
Kleine-Kohlbrecher D.; Christensen J.; Vandamme J.; Abarrategui I.; Bak M.; Tommerup N.; Shi X.; Gozani O.; Rappsilber J.; Salcini A.E.; Helin K.;
Mol. Cell 38:165-178(2010)
Cited for: FUNCTION; DOMAIN PHD-FINGER; INTERACTION WITH ZNF711; CHARACTERIZATION OF VARIANT MRXSSD SER-315; MUTAGENESIS OF HIS-283; PHF8 targets histone methylation and RNA polymerase II to activate transcription.
Fortschegger K.; de Graaf P.; Outchkourov N.S.; van Schaik F.M.; Timmers H.T.; Shiekhattar R.;
Mol. Cell. Biol. 30:3286-3298(2010)
Cited for: FUNCTION; DOMAIN PHD-FINGER; CHARACTERIZATION OF VARIANT MRXSSD SER-315; PHF8 activates transcription of rRNA genes through H3K4me3 binding and H3K9me1/2 demethylation.
Feng W.; Yonezawa M.; Ye J.; Jenuwein T.; Grummt I.;
Nat. Struct. Mol. Biol. 17:445-450(2010)
Cited for: FUNCTION; CATALYTIC ACTIVITY; SUBCELLULAR LOCATION; INTERACTION WITH POLR1B AND UBTF; CHARACTERIZATION OF VARIANT MRXSSD SER-315; MUTAGENESIS OF TYR-43 AND 283-HIS--ASP-285; Histone H4K20/H3K9 demethylase PHF8 regulates zebrafish brain and craniofacial development.
Qi H.H.; Sarkissian M.; Hu G.Q.; Wang Z.; Bhattacharjee A.; Gordon D.B.; Gonzales M.; Lan F.; Ongusaha P.P.; Huarte M.; Yaghi N.K.; Lim H.; Garcia B.A.; Brizuela L.; Zhao K.; Roberts T.M.; Shi Y.;
Nature 466:503-507(2010)
Cited for: FUNCTION; DOMAIN PHD-FINGER; CHARACTERIZATION OF VARIANT MRXSSD SER-315; MUTAGENESIS OF TYR-43; TYR-50 AND TRP-65; PHF8 mediates histone H4 lysine 20 demethylation events involved in cell cycle progression.
Liu W.; Tanasa B.; Tyurina O.V.; Zhou T.Y.; Gassmann R.; Liu W.T.; Ohgi K.A.; Benner C.; Garcia-Bassets I.; Aggarwal A.K.; Desai A.; Dorrestein P.C.; Glass C.K.; Rosenfeld M.G.;
Nature 466:508-512(2010)
Cited for: FUNCTION; SUBCELLULAR LOCATION; DOMAIN PHD-FINGER; INTERACTION WITH SETD1A; HCFC1 AND E2F1; CHARACTERIZATION OF VARIANT MRXSSD SER-315; PHOSPHORYLATION AT SER-69 AND SER-120; MUTAGENESIS OF SER-69; SER-120 AND HIS-283; Histone demethylase KDM5C is a SAHA-sensitive central hub at the crossroads of transcriptional axes involved in multiple neurodevelopmental disorders.
Poeta L.; Padula A.; Attianese B.; Valentino M.; Verrillo L.; Filosa S.; Shoubridge C.; Barra A.; Schwartz C.E.; Christensen J.; van Bokhoven H.; Helin K.; Lioi M.B.; Collombat P.; Gecz J.; Altucci L.; Di Schiavi E.; Miano M.G.;
Hum. Mol. Genet. 28:4089-4102(2019)
Cited for: FUNCTION; CHARACTERIZATION OF VARIANT MRXSSD SER-315; MUTAGENESIS OF ARG-943; Structural insights into a novel histone demethylase PHF8.
Yu L.; Wang Y.; Huang S.; Wang J.; Deng Z.; Zhang Q.; Wu W.; Zhang X.; Liu Z.; Gong W.; Chen Z.;
Cell Res. 20:166-173(2010)
Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 122-483 IN COMPLEX WITH IRON AND ALPHA-KETOGLUTARATE; FUNCTION; CHARACTERIZATION OF VARIANT MRXSSD SER-315; Screening of mutations in the PHF8 gene and identification of a novel mutation in a Finnish family with XLMR and cleft lip/cleft palate.
Koivisto A.M.; Ala-Mello S.; Lemmelae S.; Komu H.A.; Rautio J.; Jaervelae I.;
Clin. Genet. 72:145-149(2007)
Cited for: VARIANT MRXSSD SER-315;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.