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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q6N021: Variant p.Lys1299Glu

Methylcytosine dioxygenase TET2
Gene: TET2
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Variant information Variant position: help 1299 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Lysine (K) to Glutamate (E) at position 1299 (K1299E, p.Lys1299Glu). 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: help Change from large size and basic (K) to medium size and acidic (E) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 1 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: help In a refractory anemia sample; loss of monoubiquitination, chromatin binding and 5-methylcytosine demethylase activity in vivo, when tested in a heterologous system. Any additional useful information about the variant.


Sequence information Variant position: help 1299 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 2002 The length of the canonical sequence.
Location on the sequence: help ETCGASFSFGCSWSMYYNGC K FARSKIPRKFKLLGDDPKEE 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human                         ETCGASFSFGCSWSMYYNGCKFARSKIPRKFKLLGDDPKEE

Mouse                         ETCGASFSFGCSWSMYYNGCKFARSKKPRKFRLHGAEPKEE

Sequence annotation in neighborhood: help 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.
TypePositionsDescription
Chain 1 – 2002 Methylcytosine dioxygenase TET2
Region 1290 – 1303 Interaction with DNA
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.
Turn 1299 – 1302



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; Crystal structure of TET2-DNA complex: insight into TET-mediated 5mC oxidation.
Hu L.; Li Z.; Cheng J.; Rao Q.; Gong W.; Liu M.; Shi Y.G.; Zhu J.; Wang P.; Xu Y.;
Cell 155:1545-1555(2013)
Cited for: X-RAY CRYSTALLOGRAPHY (2.03 ANGSTROMS) OF 1129-1480 AND 1844-1936 IN COMPLEX WITH DNA; IRON; N-OXALYOLGLYCINE AND ZINC; CATALYTIC ACTIVITY; FUNCTION; CHARACTERIZATION OF VARIANTS ARG-1291; GLU-1299; MET-1896 AND PHE-1898; MUTAGENESIS OF ARG-1261; ARG-1262; SER-1290; 1291-TRP--ASN-1296; 1293-MET-TYR-1294; TYR-1295; SER-1303; HIS-1382; ASP-1384; ASN-1387; TYR-1902 AND HIS-1904; Mutation in TET2 in myeloid cancers.
Delhommeau F.; Dupont S.; Della Valle V.; James C.; Trannoy S.; Masse A.; Kosmider O.; Le Couedic J.-P.; Robert F.; Alberdi A.; Lecluse Y.; Plo I.; Dreyfus F.J.; Marzac C.; Casadevall N.; Lacombe C.; Romana S.P.; Dessen P.; Soulier J.; Viguie F.; Fontenay M.; Vainchenker W.; Bernard O.A.;
N. Engl. J. Med. 360:2289-2301(2009)
Cited for: VARIANTS VAL-1175; 1237-PRO--SER-1239 DEL; GLU-1299; GLY-1302; TRP-1869; PRO-1872; THR-1873; MET-1896 AND PHE-1898;
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.