UniProtKB/Swiss-Prot Q6N021 : Variant p.Phe1287Leu
Methylcytosine dioxygenase TET2
Gene: TET2
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Variant information
Variant position:
1287
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:
US
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 Leucine (L) at position 1287 (F1287L, p.Phe1287Leu).
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 medium size and hydrophobic (L)
The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:
0
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 myelodysplastic/myeloproliferative disorders; no effect on interaction with DCAF1, monoubiquitination, nor on 5-methylcytosine demethylase activity in vivo, when tested in a heterologous system.
Any additional useful information about the variant.
Sequence information
Variant position:
1287
The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:
2002
The length of the canonical sequence.
Location on the sequence:
EERTCACQGLDPETCGASFS
F GCSWSMYYNGCKFARSKIPR
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 EERTCACQGLDPETCGASFSF GCSWSMYYNGCKFARSKIPR
Mouse ETRNCCCQGENPETCGASFSF GCSWSMYYNGCKFARSKKPR
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 – 2002
Methylcytosine dioxygenase TET2
Binding site
1271 – 1271
Binding site
1273 – 1273
Binding site
1289 – 1289
Binding site
1298 – 1298
Cross
1299 – 1299
Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Alternative sequence
1166 – 2002
Missing. In isoform 2.
Alternative sequence
1195 – 2002
Missing. In isoform 3.
Mutagenesis
1290 – 1290
S -> A. Reduces enzyme activity; when associated with A-1295.
Mutagenesis
1292 – 1292
S -> R. No effect on interaction with DCAF1, monoubiquitination, nor on 5-methylcytosine demethylase activity in vivo, when tested in a heterologous system.
Mutagenesis
1295 – 1295
Y -> A. Reduces enzyme activity; when associated with A-1290.
Mutagenesis
1298 – 1298
C -> Y. Loss of monoubiquitination and of 5-methylcytosine demethylase activity in vivo. No effect on interaction with DCAF1, when tested in a heterologous system.
Mutagenesis
1300 – 1300
F -> S. Loss of interaction with DCAF1, monoubiquitination and of 5-methylcytosine demethylase activity in vivo, when tested in a heterologous system.
Mutagenesis
1303 – 1303
S -> N. Loss of enzyme activity; when associated with E-1299.
Beta strand
1283 – 1288
Literature citations
CRL4(VprBP) E3 ligase promotes monoubiquitylation and chromatin binding of TET dioxygenases.
Nakagawa T.; Lv L.; Nakagawa M.; Yu Y.; Yu C.; D'Alessio A.C.; Nakayama K.; Fan H.Y.; Chen X.; Xiong Y.;
Mol. Cell 57:247-260(2015)
Cited for: INTERACTION WITH DCAF1; MONOUBIQITINATION AT LYS-1299; SUBCELLULAR LOCATION; CHARACTERIZATION OF VARIANTS LEU-1287; ARG-1291; ASN-1299; GLU-1299; GLY-1302 AND GLY-1318; MUTAGENESIS OF SER-1292; CYS-1298 AND PHE-1300;
Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms.
Jankowska A.M.; Szpurka H.; Tiu R.V.; Makishima H.; Afable M.; Huh J.; O'Keefe C.L.; Ganetzky R.; McDevitt M.A.; Maciejewski J.P.;
Blood 113:6403-6410(2009)
Cited for: INVOLVEMENT IN MDS; INVOLVEMENT IN MYELOPROLIFERATIVE DISORDERS; VARIANTS THR-308; LEU-399; THR-817; HIS-867; PRO-1084; THR-1167; LEU-1287; ASN-1299; GLY-1302; GLY-1318; LEU-1718; THR-1873 AND ASP-1913;
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.