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Protein

Methylcytosine dioxygenase TET2

Gene

TET2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Dioxygenase that catalyzes the conversion of the modified genomic base 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC) and plays a key role in active DNA demethylation. Has a preference for 5-hydroxymethylcytosine in CpG motifs. Also mediates subsequent conversion of 5hmC into 5-formylcytosine (5fC), and conversion of 5fC to 5-carboxylcytosine (5caC). Conversion of 5mC into 5hmC, 5fC and 5caC probably constitutes the first step in cytosine demethylation. Methylation at the C5 position of cytosine bases is an epigenetic modification of the mammalian genome which plays an important role in transcriptional regulation. In addition to its role in DNA demethylation, also involved in the recruitment of the O-GlcNAc transferase OGT to CpG-rich transcription start sites of active genes, thereby promoting histone H2B GlcNAcylation by OGT.6 Publications

Catalytic activityi

DNA 5-methylcytosine + 2-oxoglutarate + O2 = DNA 5-hydroxymethylcytosine + succinate + CO2.1 Publication

Cofactori

Protein has several cofactor binding sites:
  • Fe2+1 PublicationNote: Binds 1 Fe2+ ion per subunit.1 Publication
  • Zn2+1 PublicationNote: Binds 3 zinc ions per subunit. The zinc ions have a structural role (PubMed:24315485).1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi1133 – 11331Zinc 11 Publication
Metal bindingi1135 – 11351Zinc 11 Publication
Metal bindingi1193 – 11931Zinc 21 Publication
Metal bindingi1219 – 12191Zinc 1; via pros nitrogen1 Publication
Metal bindingi1221 – 12211Zinc 11 Publication
Binding sitei1261 – 126112-oxoglutarate
Metal bindingi1271 – 12711Zinc 21 Publication
Metal bindingi1273 – 12731Zinc 21 Publication
Metal bindingi1289 – 12891Zinc 31 Publication
Metal bindingi1298 – 12981Zinc 31 Publication
Metal bindingi1358 – 13581Zinc 31 Publication
Binding sitei1374 – 137412-oxoglutarate
Metal bindingi1380 – 13801Zinc 2; via tele nitrogen1 Publication
Metal bindingi1382 – 13821Iron; catalytic1 Publication
Metal bindingi1384 – 13841Iron; catalytic1 Publication
Binding sitei1387 – 13871Substrate
Binding sitei1416 – 141612-oxoglutarate
Metal bindingi1881 – 18811Iron; catalytic1 Publication
Metal bindingi1912 – 19121Zinc 3; via pros nitrogen1 Publication

GO - Molecular functioni

  • DNA binding Source: UniProtKB-KW
  • ferrous iron binding Source: UniProtKB
  • methylcytosine dioxygenase activity Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • 5-methylcytosine catabolic process Source: UniProtKB
  • cell cycle Source: UniProtKB-KW
  • cytosine metabolic process Source: Ensembl
  • DNA demethylation Source: UniProtKB
  • hematopoietic stem cell homeostasis Source: Ensembl
  • hemoglobin metabolic process Source: Ensembl
  • histone H3-K4 trimethylation Source: UniProtKB
  • kidney development Source: Ensembl
  • liver morphogenesis Source: Ensembl
  • myeloid cell differentiation Source: UniProtKB
  • myeloid progenitor cell differentiation Source: Ensembl
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • post-embryonic development Source: Ensembl
  • protein O-linked glycosylation Source: UniProtKB
  • response to organic cyclic compound Source: Ensembl
  • spleen development Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Chromatin regulator, Dioxygenase, Oxidoreductase

Keywords - Biological processi

Cell cycle

Keywords - Ligandi

DNA-binding, Iron, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-5221030. TET1,2,3 and TDG demethylate DNA.
SIGNORiQ6N021.

Names & Taxonomyi

Protein namesi
Recommended name:
Methylcytosine dioxygenase TET2 (EC:1.14.11.n21 Publication)
Gene namesi
Name:TET2
Synonyms:KIAA1546
ORF Names:Nbla00191
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:25941. TET2.

Pathology & Biotechi

Involvement in diseasei

TET2 is frequently mutated in myeloproliferative disorders (MPD). These constitute a heterogeneous group of disorders, also known as myeloproliferative diseases or myeloproliferative neoplasms (MPN), characterized by cellular proliferation of one or more hematologic cell lines in the peripheral blood, distinct from acute leukemia. Included diseases are: essential thrombocythemia, polycythemia vera, primary myelofibrosis (chronic idiopathic myelofibrosis). Bone marrow samples from patients display uniformly low levels of hmC in genomic DNA compared to bone marrow samples from healthy controls as well as hypomethylation relative to controls at the majority of differentially methylated CpG sites.

Polycythemia vera (PV)
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA myeloproliferative disorder characterized by abnormal proliferation of all hematopoietic bone marrow elements, erythroid hyperplasia, an absolute increase in total blood volume, but also by myeloid leukocytosis, thrombocytosis and splenomegaly.
See also OMIM:263300

TET2 is frequently mutated in systemic mastocytosis; also known as systemic mast cell disease. A condition with features in common with myeloproliferative diseases. It is a clonal disorder of the mast cell and its precursor cells. The clinical symptoms and signs of systemic mastocytosis are due to accumulation of clonally derived mast cells in different tissues, including bone marrow, skin, the gastrointestinal tract, the liver, and the spleen.

Myelodysplastic syndrome (MDS)3 Publications
The disease is caused by mutations affecting the gene represented in this entry. Bone marrow samples from patients display uniformly low levels of hmC in genomic DNA compared to bone marrow samples from healthy controls as well as hypomethylation relative to controls at the majority of differentially methylated CpG sites.
Disease descriptionA heterogeneous group of closely related clonal hematopoietic disorders. All are characterized by a hypercellular or hypocellular bone marrow with impaired morphology and maturation, dysplasia of the myeloid, megakaryocytic and/or erythroid lineages, and peripheral blood cytopenias resulting from ineffective blood cell production. Included diseases are: refractory anemia (RA), refractory anemia with ringed sideroblasts (RARS), refractory anemia with excess blasts (RAEB), refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS); chronic myelomonocytic leukemia (CMML) is a myelodysplastic/myeloproliferative disease. MDS is considered a premalignant condition in a subgroup of patients that often progresses to acute myeloid leukemia (AML).
See also OMIM:614286

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi1261 – 12611R → G: Loss of enzyme activity. 1 Publication
Mutagenesisi1262 – 12621R → A: Slightly reduces enzyme activity. 1 Publication
Mutagenesisi1290 – 12901S → A: Reduces enzyme activity; when associated with A-1295. 1 Publication
Mutagenesisi1291 – 12966WSMYYN → GGSGGS: Loss of enzyme activity. 1 Publication
Mutagenesisi1293 – 12942MY → AA: Strongly reduced enzyme activity. Slightly decreased affinity for DNA. 1 Publication
Mutagenesisi1295 – 12951Y → A: Reduces enzyme activity; when associated with A-1290. 1 Publication
Mutagenesisi1303 – 13031S → N: Loss of enzyme activity; when associated with E-1299. 1 Publication
Mutagenesisi1382 – 13821H → Y: Loss of enzyme activity. Still able to enhance histone H2B GlcNAcylation by OGT; when associated with A-1384. Loss of enzyme activity; when associated with V-1384. 2 Publications
Mutagenesisi1384 – 13841D → A: Loss of enzyme activity. Still able to enhance histone H2B GlcNAcylation by OGT; when associated with Y-1382. 2 Publications
Mutagenesisi1384 – 13841D → V: Loss of enzyme activity; when associated with Y-1382. 2 Publications
Mutagenesisi1387 – 13871N → A: Near loss of enzyme activity. 1 Publication
Mutagenesisi1902 – 19021Y → A: Loss of enzyme activity. 1 Publication
Mutagenesisi1904 – 19041H → R: Loss of enzyme activity. 1 Publication

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

MalaCardsiTET2.
MIMi263300. phenotype.
614286. phenotype.
Orphaneti75564. Acquired idiopathic sideroblastic anemia.
86845. Acute myeloid leukemia with multilineage dysplasia.
3318. Essential thrombocythemia.
824. Myelofibrosis with myeloid metaplasia.
729. Polycythemia vera.
98826. Refractory anemia.
86839. Refractory anemia with excess blasts.
PharmGKBiPA162405634.

Polymorphism and mutation databases

BioMutaiTET2.
DMDMi239938839.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 20022002Methylcytosine dioxygenase TET2PRO_0000324588Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei15 – 151PhosphoserineBy similarity
Modified residuei75 – 751PhosphoserineCombined sources
Modified residuei99 – 991PhosphoserineCombined sources
Modified residuei1107 – 11071PhosphoserineCombined sources
Modified residuei1109 – 11091PhosphoserineCombined sources

Post-translational modificationi

May be glycosylated. It is unclear whether interaction with OGT leads to GlcNAcylation. According to a report, it is not GlcNAcylated by OGT (PubMed:23353889). In contrast, another group reports GlcNAcylation by OGT in mouse ortholog.1 Publication

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

EPDiQ6N021.
MaxQBiQ6N021.
PaxDbiQ6N021.
PeptideAtlasiQ6N021.
PRIDEiQ6N021.

PTM databases

iPTMnetiQ6N021.
PhosphoSiteiQ6N021.

Expressioni

Tissue specificityi

Broadly expressed. Highly expressed in hematopoietic cells; highest expression observed in granulocytes. Expression is reduced in granulocytes from peripheral blood of patients affected by myelodysplastic syndromes.2 Publications

Gene expression databases

BgeeiENSG00000168769.
CleanExiHS_TET2.
ExpressionAtlasiQ6N021. baseline and differential.
GenevisibleiQ6N021. HS.

Organism-specific databases

HPAiHPA043135.
HPA051948.

Interactioni

Subunit structurei

Interacts with HCFC1 and OGT.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
OGTO152947EBI-310727,EBI-539828

Protein-protein interaction databases

BioGridi120151. 8 interactions.
IntActiQ6N021. 9 interactions.
STRINGi9606.ENSP00000369351.

Structurei

Secondary structure

1
2002
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi1135 – 11384Combined sources
Helixi1141 – 11444Combined sources
Beta strandi1153 – 11564Combined sources
Helixi1157 – 116812Combined sources
Helixi1172 – 11743Combined sources
Beta strandi1175 – 11828Combined sources
Beta strandi1197 – 12004Combined sources
Beta strandi1209 – 12157Combined sources
Beta strandi1224 – 123411Combined sources
Helixi1238 – 125518Combined sources
Helixi1262 – 12643Combined sources
Turni1278 – 12803Combined sources
Beta strandi1283 – 12886Combined sources
Turni1293 – 12964Combined sources
Turni1299 – 13024Combined sources
Beta strandi1312 – 13143Combined sources
Helixi1316 – 134025Combined sources
Helixi1342 – 13487Combined sources
Turni1349 – 13546Combined sources
Helixi1356 – 13583Combined sources
Beta strandi1362 – 13643Combined sources
Beta strandi1370 – 13767Combined sources
Beta strandi1393 – 13997Combined sources
Helixi1401 – 14033Combined sources
Beta strandi1405 – 14084Combined sources
Beta strandi1416 – 14183Combined sources
Beta strandi1421 – 14233Combined sources
Helixi1432 – 14409Combined sources
Beta strandi1443 – 14464Combined sources
Beta strandi1451 – 14599Combined sources
Beta strandi1844 – 18496Combined sources
Helixi1851 – 18555Combined sources
Beta strandi1862 – 18643Combined sources
Beta strandi1871 – 18744Combined sources
Turni1876 – 18783Combined sources
Beta strandi1881 – 18833Combined sources
Beta strandi1895 – 19028Combined sources
Beta strandi1904 – 19063Combined sources
Helixi1910 – 19134Combined sources
Helixi1914 – 19207Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4NM6X-ray2.03A1129-1480[»]
A1844-1936[»]
5D9YX-ray1.97A1129-1480[»]
A1844-1936[»]
5DEUX-ray1.80A1129-1480[»]
A1844-1935[»]
ProteinModelPortaliQ6N021.
SMRiQ6N021. Positions 1132-1463, 1832-1924.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1290 – 130314Interaction with DNAAdd
BLAST
Regioni1896 – 189832-oxoglutarate binding
Regioni1902 – 19043Substrate binding

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi398 – 41922Pro-richAdd
BLAST
Compositional biasi591 – 969379Gln-richAdd
BLAST
Compositional biasi1523 – 155331Gln-richAdd
BLAST

Sequence similaritiesi

Belongs to the TET family.Curated

Phylogenomic databases

eggNOGiENOG410IE22. Eukaryota.
ENOG410XPWW. LUCA.
GeneTreeiENSGT00510000046514.
HOVERGENiHBG108562.
InParanoidiQ6N021.
PhylomeDBiQ6N021.
TreeFamiTF337563.

Family and domain databases

InterProiIPR024779. 2OGFeDO_noxygenase_dom.
[Graphical view]
PfamiPF12851. Tet_JBP. 1 hit.
[Graphical view]
SMARTiSM01333. Tet_JBP. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q6N021-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEQDRTNHVE GNRLSPFLIP SPPICQTEPL ATKLQNGSPL PERAHPEVNG
60 70 80 90 100
DTKWHSFKSY YGIPCMKGSQ NSRVSPDFTQ ESRGYSKCLQ NGGIKRTVSE
110 120 130 140 150
PSLSGLLQIK KLKQDQKANG ERRNFGVSQE RNPGESSQPN VSDLSDKKES
160 170 180 190 200
VSSVAQENAV KDFTSFSTHN CSGPENPELQ ILNEQEGKSA NYHDKNIVLL
210 220 230 240 250
KNKAVLMPNG ATVSASSVEH THGELLEKTL SQYYPDCVSI AVQKTTSHIN
260 270 280 290 300
AINSQATNEL SCEITHPSHT SGQINSAQTS NSELPPKPAA VVSEACDADD
310 320 330 340 350
ADNASKLAAM LNTCSFQKPE QLQQQKSVFE ICPSPAENNI QGTTKLASGE
360 370 380 390 400
EFCSGSSSNL QAPGGSSERY LKQNEMNGAY FKQSSVFTKD SFSATTTPPP
410 420 430 440 450
PSQLLLSPPP PLPQVPQLPS EGKSTLNGGV LEEHHHYPNQ SNTTLLREVK
460 470 480 490 500
IEGKPEAPPS QSPNPSTHVC SPSPMLSERP QNNCVNRNDI QTAGTMTVPL
510 520 530 540 550
CSEKTRPMSE HLKHNPPIFG SSGELQDNCQ QLMRNKEQEI LKGRDKEQTR
560 570 580 590 600
DLVPPTQHYL KPGWIELKAP RFHQAESHLK RNEASLPSIL QYQPNLSNQM
610 620 630 640 650
TSKQYTGNSN MPGGLPRQAY TQKTTQLEHK SQMYQVEMNQ GQSQGTVDQH
660 670 680 690 700
LQFQKPSHQV HFSKTDHLPK AHVQSLCGTR FHFQQRADSQ TEKLMSPVLK
710 720 730 740 750
QHLNQQASET EPFSNSHLLQ HKPHKQAAQT QPSQSSHLPQ NQQQQQKLQI
760 770 780 790 800
KNKEEILQTF PHPQSNNDQQ REGSFFGQTK VEECFHGENQ YSKSSEFETH
810 820 830 840 850
NVQMGLEEVQ NINRRNSPYS QTMKSSACKI QVSCSNNTHL VSENKEQTTH
860 870 880 890 900
PELFAGNKTQ NLHHMQYFPN NVIPKQDLLH RCFQEQEQKS QQASVLQGYK
910 920 930 940 950
NRNQDMSGQQ AAQLAQQRYL IHNHANVFPV PDQGGSHTQT PPQKDTQKHA
960 970 980 990 1000
ALRWHLLQKQ EQQQTQQPQT ESCHSQMHRP IKVEPGCKPH ACMHTAPPEN
1010 1020 1030 1040 1050
KTWKKVTKQE NPPASCDNVQ QKSIIETMEQ HLKQFHAKSL FDHKALTLKS
1060 1070 1080 1090 1100
QKQVKVEMSG PVTVLTRQTT AAELDSHTPA LEQQTTSSEK TPTKRTAASV
1110 1120 1130 1140 1150
LNNFIESPSK LLDTPIKNLL DTPVKTQYDF PSCRCVEQII EKDEGPFYTH
1160 1170 1180 1190 1200
LGAGPNVAAI REIMEERFGQ KGKAIRIERV IYTGKEGKSS QGCPIAKWVV
1210 1220 1230 1240 1250
RRSSSEEKLL CLVRERAGHT CEAAVIVILI LVWEGIPLSL ADKLYSELTE
1260 1270 1280 1290 1300
TLRKYGTLTN RRCALNEERT CACQGLDPET CGASFSFGCS WSMYYNGCKF
1310 1320 1330 1340 1350
ARSKIPRKFK LLGDDPKEEE KLESHLQNLS TLMAPTYKKL APDAYNNQIE
1360 1370 1380 1390 1400
YEHRAPECRL GLKEGRPFSG VTACLDFCAH AHRDLHNMQN GSTLVCTLTR
1410 1420 1430 1440 1450
EDNREFGGKP EDEQLHVLPL YKVSDVDEFG SVEAQEEKKR SGAIQVLSSF
1460 1470 1480 1490 1500
RRKVRMLAEP VKTCRQRKLE AKKAAAEKLS SLENSSNKNE KEKSAPSRTK
1510 1520 1530 1540 1550
QTENASQAKQ LAELLRLSGP VMQQSQQPQP LQKQPPQPQQ QQRPQQQQPH
1560 1570 1580 1590 1600
HPQTESVNSY SASGSTNPYM RRPNPVSPYP NSSHTSDIYG STSPMNFYST
1610 1620 1630 1640 1650
SSQAAGSYLN SSNPMNPYPG LLNQNTQYPS YQCNGNLSVD NCSPYLGSYS
1660 1670 1680 1690 1700
PQSQPMDLYR YPSQDPLSKL SLPPIHTLYQ PRFGNSQSFT SKYLGYGNQN
1710 1720 1730 1740 1750
MQGDGFSSCT IRPNVHHVGK LPPYPTHEMD GHFMGATSRL PPNLSNPNMD
1760 1770 1780 1790 1800
YKNGEHHSPS HIIHNYSAAP GMFNSSLHAL HLQNKENDML SHTANGLSKM
1810 1820 1830 1840 1850
LPALNHDRTA CVQGGLHKLS DANGQEKQPL ALVQGVASGA EDNDEVWSDS
1860 1870 1880 1890 1900
EQSFLDPDIG GVAVAPTHGS ILIECAKREL HATTPLKNPN RNHPTRISLV
1910 1920 1930 1940 1950
FYQHKSMNEP KHGLALWEAK MAEKAREKEE ECEKYGPDYV PQKSHGKKVK
1960 1970 1980 1990 2000
REPAEPHETS EPTYLRFIKS LAERTMSVTT DSTVTTSPYA FTRVTGPYNR

YI
Length:2,002
Mass (Da):223,811
Last modified:June 16, 2009 - v3
Checksum:i6D740305EE2A8D46
GO
Isoform 2 (identifier: Q6N021-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1137-1165: EQIIEKDEGPFYTHLGAGPNVAAIREIME → GKCQKCTETHGVYPELANLSSDMGFSFFF
     1166-2002: Missing.

Show »
Length:1,165
Mass (Da):130,254
Checksum:i95546FBB1F6FE0FD
GO
Isoform 3 (identifier: Q6N021-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1137-1194: EQIIEKDEGP...KEGKSSQGCP → GLDRRVKLLG...SELATPVRLQ
     1195-2002: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:1,194
Mass (Da):133,481
Checksum:iFDA110D6E8FB7790
GO

Sequence cautioni

The sequence BAA90898 differs from that shown.Contaminating sequence. Potential poly-A sequence.Curated
The sequence BAA90898 differs from that shown. Reason: Frameshift at position 323. Curated
The sequence BAA90898 differs from that shown. Reason: Erroneous termination at position 325. Translated as Gln.Curated
The sequence BAB55391 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti599 – 5991Q → R in BAA90898 (PubMed:14702039).Curated
Sequence conflicti702 – 7021H → Q in CAE45851 (PubMed:17974005).Curated
Sequence conflicti878 – 8781L → S in BAE45750 (PubMed:12880961).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti29 – 291P → R.1 Publication
Corresponds to variant rs12498609 [ dbSNP | Ensembl ].
VAR_039841
Natural varianti34 – 341L → F.2 Publications
Corresponds to variant rs111948941 [ dbSNP | Ensembl ].
VAR_058171
Natural varianti123 – 1231R → H.1 Publication
Corresponds to variant rs773565437 [ dbSNP | Ensembl ].
VAR_058130
Natural varianti145 – 1451S → N in a chronic myelomonocytic leukemia sample; somatic mutation. 1 Publication
Corresponds to variant rs114619974 [ dbSNP | Ensembl ].
VAR_058172
Natural varianti174 – 1741P → H.1 Publication
Corresponds to variant rs146031219 [ dbSNP | Ensembl ].
VAR_058173
Natural varianti218 – 2181V → M.2 Publications
Corresponds to variant rs6843141 [ dbSNP | Ensembl ].
VAR_039842
Natural varianti308 – 3081A → T in chronic myelomonocytic leukemia and acute myeloid leukemia samples. 1 Publication
VAR_058131
Natural varianti312 – 3121N → S in an acute myeloid leukemia sample; somatic mutation. 1 Publication
VAR_058174
Natural varianti355 – 3551G → D.1 Publication
Corresponds to variant rs61744960 [ dbSNP | Ensembl ].
VAR_058132
Natural varianti363 – 3631P → L.1 Publication
Corresponds to variant rs17253672 [ dbSNP | Ensembl ].
VAR_039843
Natural varianti399 – 3991P → L in myelodysplastic/myeloproliferative disorders; a patient positive for mutation F-617 in JAK2. 1 Publication
VAR_058133
Natural varianti429 – 4291G → R.1 Publication
Corresponds to variant rs201642693 [ dbSNP | Ensembl ].
VAR_058134
Natural varianti460 – 4601S → F in a chronic myelomonocytic leukemia sample; somatic mutation. 1 Publication
Corresponds to variant rs376570662 [ dbSNP | Ensembl ].
VAR_058175
Natural varianti666 – 6661D → G in a chronic myelomonocytic leukemia sample; somatic mutation. 1 Publication
VAR_058176
Natural varianti817 – 8171S → T in myelodysplastic/myeloproliferative disorders. 1 Publication
Corresponds to variant rs753786455 [ dbSNP | Ensembl ].
VAR_058135
Natural varianti867 – 8671Y → H.3 Publications
Corresponds to variant rs144386291 [ dbSNP | Ensembl ].
VAR_058177
Natural varianti912 – 9121A → G.
Corresponds to variant rs4145756 [ dbSNP | Ensembl ].
VAR_039844
Natural varianti924 – 9241H → R.1 Publication
Corresponds to variant rs34485921 [ dbSNP | Ensembl ].
VAR_058136
Natural varianti941 – 9411P → S in a chronic myelomonocytic leukemia sample; somatic mutation. 1 Publication
Corresponds to variant rs532738858 [ dbSNP | Ensembl ].
VAR_058178
Natural varianti949 – 9491H → R.1 Publication
Corresponds to variant rs778464072 [ dbSNP | Ensembl ].
VAR_058137
Natural varianti1073 – 10731E → V.1 Publication
VAR_058179
Natural varianti1084 – 10841Q → P.3 Publications
Corresponds to variant rs75056899 [ dbSNP | Ensembl ].
VAR_058180
Natural varianti1135 – 11351C → Y in a myeloproliferative disorder; somatic mutation. 1 Publication
Corresponds to variant rs769422572 [ dbSNP | Ensembl ].
VAR_058181
Natural varianti1167 – 11671R → T in a myelodysplatic/myeloproliferative disorder and a chronic myelomonocytic leukemia sample. 1 Publication
VAR_058138
Natural varianti1175 – 11751I → V in a refractory anemia with ringed sideroblasts sample. 1 Publication
VAR_058139
Natural varianti1204 – 12041S → C in a myeloproliferative disorder; somatic mutation. 1 Publication
VAR_058182
Natural varianti1214 – 12141R → W in a myelodysplastic syndrome; somatic mutation in a chronic myelomonocytic leukemia sample. 2 Publications
Corresponds to variant rs761811530 [ dbSNP | Ensembl ].
VAR_058183
Natural varianti1237 – 12393Missing in a polycythemia vera sample; somatic mutation. 1 Publication
VAR_058140
Natural varianti1242 – 12421D → R Requires 2 nucleotide substitutions. 1 Publication
VAR_058198
Natural varianti1242 – 12421D → V in myeloproliferative disorders. 1 Publication
VAR_058184
Natural varianti1245 – 12451Y → S in a myeloproliferative disorder; somatic mutation. 1 Publication
VAR_058185
Natural varianti1261 – 12611R → C in a myeloproliferative disorder; somatic mutation. 1 Publication
VAR_058186
Natural varianti1261 – 12611R → H in a chronic myelomonocytic leukemia sample; somatic mutation. 1 Publication
Corresponds to variant rs771761785 [ dbSNP | Ensembl ].
VAR_058187
Natural varianti1261 – 12611R → L in a myelodysplastic syndrome. 1 Publication
VAR_058141
Natural varianti1285 – 12851Missing in a myelodysplastic syndrome; somatic mutation. 1 Publication
VAR_058142
Natural varianti1287 – 12871F → L in myelodysplastic/myeloproliferative disorders. 1 Publication
VAR_058143
Natural varianti1291 – 12911W → R in a myelodysplastic syndrome; somatic mutation; abolishes enzyme activity. 2 Publications
VAR_058144
Natural varianti1299 – 12991K → E in a refractory anemia sample. 2 Publications
VAR_058145
Natural varianti1299 – 12991K → N in chronic myelomonocytic leukemia samples. 1 Publication
VAR_058146
Natural varianti1302 – 13021R → G in primary myelofibrosis and chronic myelomonocytic leukemia samples. 2 Publications
VAR_058147
Natural varianti1318 – 13181E → G in chronic myelomonocytic leukemia samples. 1 Publication
VAR_058148
Natural varianti1367 – 13671P → S in a chronic myelomonocytic leukemia sample.
VAR_058149
Natural varianti1396 – 13961C → W in a myelodysplastic syndrome. 1 Publication
VAR_058150
Natural varianti1398 – 13981L → R in a myelodysplastic syndrome; somatic mutation. 1 Publication
VAR_058151
Natural varianti1417 – 14171V → F in a chronic myelomonocytic leukemia sample; somatic mutation. 1 Publication
Corresponds to variant rs749210253 [ dbSNP | Ensembl ].
VAR_058188
Natural varianti1701 – 17011M → I.1 Publication
Corresponds to variant rs62623390 [ dbSNP | Ensembl ].
VAR_058189
Natural varianti1718 – 17181V → L in refractory anemia with ringed sideroblasts; somatic mutation in an acute myeloid leukemia sample. 2 Publications
Corresponds to variant rs142312318 [ dbSNP | Ensembl ].
VAR_058190
Natural varianti1721 – 17211L → W.1 Publication
Corresponds to variant rs34402524 [ dbSNP | Ensembl ].
VAR_058191
Natural varianti1723 – 17231P → S.2 Publications
Corresponds to variant rs146348065 [ dbSNP | Ensembl ].
VAR_058192
Natural varianti1757 – 17571H → D in a chronic myelomonocytic leukemia sample; somatic mutation. 1 Publication
VAR_058152
Natural varianti1762 – 17621I → V.2 Publications
Corresponds to variant rs2454206 [ dbSNP | Ensembl ].
VAR_058193
Natural varianti1778 – 17781H → R.1 Publication
Corresponds to variant rs62621450 [ dbSNP | Ensembl ].
VAR_058194
Natural varianti1811 – 18111C → R in a chronic myelomonocytic leukemia sample; somatic mutation. 1 Publication
VAR_058153
Natural varianti1828 – 18281Q → L in a myeloproliferative disorder; somatic mutation. 1 Publication
VAR_058154
Natural varianti1869 – 18691G → W in an essential thrombocythemia sample. 1 Publication
VAR_058155
Natural varianti1872 – 18721L → P in a refractory anemia with excess blasts sample. 1 Publication
VAR_058156
Natural varianti1873 – 18731I → T in myelodysplastic syndromes, myeloproliferative disorders and chronic myelomonocytic leukemia; somatic mutation in acute myeloid leukemia and chronic myelomonocytic leukemia samples. 5 Publications
Corresponds to variant rs116519313 [ dbSNP | Ensembl ].
VAR_058157
Natural varianti1875 – 18751C → R in a myelodysplastic syndrome; somatic mutation. 1 Publication
VAR_058195
Natural varianti1881 – 18811H → Q in a myelodysplastic syndrome; somatic mutation. 1 Publication
VAR_058196
Natural varianti1881 – 18811H → R in a myeloproliferative disorder; somatic mutation; also in a patient with systemic mastocytosis associated with chronic myelomonocytic leukemia. 2 Publications
VAR_058158
Natural varianti1896 – 18961R → M in a primary acute myeloid leukemia sample; somatic mutation; reduces enzyme activity. 2 Publications
VAR_058159
Natural varianti1896 – 18961R → S in a myeloproliferative disorder; somatic mutation. 1 Publication
VAR_058197
Natural varianti1898 – 18981S → F in a secondary acute myeloid leukemia sample; somatic mutation; loss of enzyme activity. 2 Publications
Corresponds to variant rs767475870 [ dbSNP | Ensembl ].
VAR_058160
Natural varianti1900 – 19001V → A.1 Publication
VAR_058161
Natural varianti1911 – 19166Missing in a myelodysplastic syndrome; somatic mutation. 1 Publication
VAR_058162
Natural varianti1913 – 19131G → D in myelodysplastic syndromes; refractory cytopenia with multilineage dysplasia and ringed sideroblasts; somatic mutation in a patient. 2 Publications
VAR_058163
Natural varianti1919 – 19191A → V in a myeloproliferative disorder; somatic mutation. 1 Publication
VAR_058164
Natural varianti1926 – 19261R → H in a chronic myelomonocytic leukemia sample; somatic mutation. 1 Publication
VAR_058165
Natural varianti1941 – 19411P → S in a chronic myelomonocytic leukemia sample; somatic mutation. 1 Publication
VAR_058166
Natural varianti1962 – 19621P → L in a myelodysplastic syndrome. 1 Publication
Corresponds to variant rs200971953 [ dbSNP | Ensembl ].
VAR_058167
Natural varianti1966 – 19661R → H in a chronic myelomonocytic leukemia sample; somatic mutation. 1 Publication
Corresponds to variant rs754215085 [ dbSNP | Ensembl ].
VAR_058168
Natural varianti1974 – 19741R → M in a chronic myelomonocytic leukemia sample; somatic mutation. 1 Publication
VAR_058169
Natural varianti2000 – 20001R → K.1 Publication
VAR_058170

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1137 – 119458EQIIE…SQGCP → GLDRRVKLLGLKESSILVKK AKVLRDVLLLSGWFAEAAVK RSYCVWCGSELATPVRLQ in isoform 3. 1 PublicationVSP_032282Add
BLAST
Alternative sequencei1137 – 116529EQIIE…REIME → GKCQKCTETHGVYPELANLS SDMGFSFFF in isoform 2. 2 PublicationsVSP_032283Add
BLAST
Alternative sequencei1166 – 2002837Missing in isoform 2. 2 PublicationsVSP_032284Add
BLAST
Alternative sequencei1195 – 2002808Missing in isoform 3. 1 PublicationVSP_032285Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BX640738 mRNA. Translation: CAE45851.1.
AC004069 Genomic DNA. No translation available.
AC026029 Genomic DNA. No translation available.
AK000039 mRNA. Translation: BAA90898.1. Sequence problems.
AK027819 mRNA. Translation: BAB55391.1. Different initiation.
AB075496 mRNA. Translation: BAE45750.1.
BC110509 mRNA. Translation: AAI10510.1.
BC110510 mRNA. Translation: AAI10511.2.
AB046766 mRNA. Translation: BAB13372.1.
CCDSiCCDS3666.1. [Q6N021-2]
CCDS47120.1. [Q6N021-1]
RefSeqiNP_001120680.1. NM_001127208.2. [Q6N021-1]
NP_060098.3. NM_017628.4. [Q6N021-2]
XP_005263139.1. XM_005263082.2. [Q6N021-1]
UniGeneiHs.367639.
Hs.706276.

Genome annotation databases

EnsembliENST00000265149; ENSP00000265149; ENSG00000168769. [Q6N021-3]
ENST00000305737; ENSP00000306705; ENSG00000168769. [Q6N021-2]
ENST00000380013; ENSP00000369351; ENSG00000168769. [Q6N021-1]
ENST00000540549; ENSP00000442788; ENSG00000168769. [Q6N021-1]
GeneIDi54790.
KEGGihsa:54790.
UCSCiuc003hxj.3. human. [Q6N021-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BX640738 mRNA. Translation: CAE45851.1.
AC004069 Genomic DNA. No translation available.
AC026029 Genomic DNA. No translation available.
AK000039 mRNA. Translation: BAA90898.1. Sequence problems.
AK027819 mRNA. Translation: BAB55391.1. Different initiation.
AB075496 mRNA. Translation: BAE45750.1.
BC110509 mRNA. Translation: AAI10510.1.
BC110510 mRNA. Translation: AAI10511.2.
AB046766 mRNA. Translation: BAB13372.1.
CCDSiCCDS3666.1. [Q6N021-2]
CCDS47120.1. [Q6N021-1]
RefSeqiNP_001120680.1. NM_001127208.2. [Q6N021-1]
NP_060098.3. NM_017628.4. [Q6N021-2]
XP_005263139.1. XM_005263082.2. [Q6N021-1]
UniGeneiHs.367639.
Hs.706276.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4NM6X-ray2.03A1129-1480[»]
A1844-1936[»]
5D9YX-ray1.97A1129-1480[»]
A1844-1936[»]
5DEUX-ray1.80A1129-1480[»]
A1844-1935[»]
ProteinModelPortaliQ6N021.
SMRiQ6N021. Positions 1132-1463, 1832-1924.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120151. 8 interactions.
IntActiQ6N021. 9 interactions.
STRINGi9606.ENSP00000369351.

PTM databases

iPTMnetiQ6N021.
PhosphoSiteiQ6N021.

Polymorphism and mutation databases

BioMutaiTET2.
DMDMi239938839.

Proteomic databases

EPDiQ6N021.
MaxQBiQ6N021.
PaxDbiQ6N021.
PeptideAtlasiQ6N021.
PRIDEiQ6N021.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000265149; ENSP00000265149; ENSG00000168769. [Q6N021-3]
ENST00000305737; ENSP00000306705; ENSG00000168769. [Q6N021-2]
ENST00000380013; ENSP00000369351; ENSG00000168769. [Q6N021-1]
ENST00000540549; ENSP00000442788; ENSG00000168769. [Q6N021-1]
GeneIDi54790.
KEGGihsa:54790.
UCSCiuc003hxj.3. human. [Q6N021-1]

Organism-specific databases

CTDi54790.
GeneCardsiTET2.
HGNCiHGNC:25941. TET2.
HPAiHPA043135.
HPA051948.
MalaCardsiTET2.
MIMi263300. phenotype.
612839. gene.
614286. phenotype.
neXtProtiNX_Q6N021.
Orphaneti75564. Acquired idiopathic sideroblastic anemia.
86845. Acute myeloid leukemia with multilineage dysplasia.
3318. Essential thrombocythemia.
824. Myelofibrosis with myeloid metaplasia.
729. Polycythemia vera.
98826. Refractory anemia.
86839. Refractory anemia with excess blasts.
PharmGKBiPA162405634.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IE22. Eukaryota.
ENOG410XPWW. LUCA.
GeneTreeiENSGT00510000046514.
HOVERGENiHBG108562.
InParanoidiQ6N021.
PhylomeDBiQ6N021.
TreeFamiTF337563.

Enzyme and pathway databases

ReactomeiR-HSA-5221030. TET1,2,3 and TDG demethylate DNA.
SIGNORiQ6N021.

Miscellaneous databases

ChiTaRSiTET2. human.
GenomeRNAii54790.
PROiQ6N021.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000168769.
CleanExiHS_TET2.
ExpressionAtlasiQ6N021. baseline and differential.
GenevisibleiQ6N021. HS.

Family and domain databases

InterProiIPR024779. 2OGFeDO_noxygenase_dom.
[Graphical view]
PfamiPF12851. Tet_JBP. 1 hit.
[Graphical view]
SMARTiSM01333. Tet_JBP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTET2_HUMAN
AccessioniPrimary (citable) accession number: Q6N021
Secondary accession number(s): B5MDU0
, Q2TB88, Q3LIB8, Q96JX5, Q9HCM6, Q9NXW0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 18, 2008
Last sequence update: June 16, 2009
Last modified: September 7, 2016
This is version 103 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

Subsequent steps in cytosine demethylation are subject to discussion. According to a first model cytosine demethylation occurs through deamination of 5hmC into 5-hydroxymethyluracil (5hmU) and subsequent replacement by unmethylated cytosine by the base excision repair system. According to another model, cytosine demethylation is rather mediated via conversion of 5hmC into 5fC and 5caC, followed by excision by TDG (PubMed:21817016).1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.