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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)DescriptionActionsGraphical viewLength
Metal bindingi1133Zinc 11 Publication1
Metal bindingi1135Zinc 11 Publication1
Metal bindingi1193Zinc 21 Publication1
Metal bindingi1219Zinc 1; via pros nitrogen1 Publication1
Metal bindingi1221Zinc 11 Publication1
Binding sitei12612-oxoglutarate1
Metal bindingi1271Zinc 21 Publication1
Metal bindingi1273Zinc 21 Publication1
Metal bindingi1289Zinc 31 Publication1
Metal bindingi1298Zinc 31 Publication1
Metal bindingi1358Zinc 31 Publication1
Binding sitei13742-oxoglutarate1
Metal bindingi1380Zinc 2; via tele nitrogen1 Publication1
Metal bindingi1382Iron; catalytic1 Publication1
Metal bindingi1384Iron; catalytic1 Publication1
Binding sitei1387Substrate1
Binding sitei14162-oxoglutarate1
Metal bindingi1881Iron; catalytic1 Publication1
Metal bindingi1912Zinc 3; via pros nitrogen1 Publication1

GO - Molecular functioni

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
  • oxidative demethylation Source: GO_Central
  • 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.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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)DescriptionActionsGraphical viewLength
Mutagenesisi1261R → G: Loss of enzyme activity. 1 Publication1
Mutagenesisi1262R → A: Slightly reduces enzyme activity. 1 Publication1
Mutagenesisi1290S → A: Reduces enzyme activity; when associated with A-1295. 1 Publication1
Mutagenesisi1291 – 1296WSMYYN → GGSGGS: Loss of enzyme activity. 1 Publication6
Mutagenesisi1293 – 1294MY → AA: Strongly reduced enzyme activity. Slightly decreased affinity for DNA. 1 Publication2
Mutagenesisi1295Y → A: Reduces enzyme activity; when associated with A-1290. 1 Publication1
Mutagenesisi1303S → N: Loss of enzyme activity; when associated with E-1299. 1 Publication1
Mutagenesisi1382H → 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 Publications1
Mutagenesisi1384D → A: Loss of enzyme activity. Still able to enhance histone H2B GlcNAcylation by OGT; when associated with Y-1382. 2 Publications1
Mutagenesisi1384D → V: Loss of enzyme activity; when associated with Y-1382. 2 Publications1
Mutagenesisi1387N → A: Near loss of enzyme activity. 1 Publication1
Mutagenesisi1902Y → A: Loss of enzyme activity. 1 Publication1
Mutagenesisi1904H → R: Loss of enzyme activity. 1 Publication1

Keywords - Diseasei

Tumor suppressor

Organism-specific databases

DisGeNETi54790.
MalaCardsiTET2.
MIMi263300. phenotype.
614286. phenotype.
OpenTargetsiENSG00000168769.
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)DescriptionActionsGraphical viewLength
ChainiPRO_00003245881 – 2002Methylcytosine dioxygenase TET2Add BLAST2002

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei15PhosphoserineBy similarity1
Modified residuei75PhosphoserineCombined sources1
Modified residuei99PhosphoserineCombined sources1
Modified residuei1107PhosphoserineCombined sources1
Modified residuei1109PhosphoserineCombined sources1
Modified residuei1682Asymmetric dimethylarginineCombined sources1

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, Methylation, Phosphoprotein

Proteomic databases

EPDiQ6N021.
MaxQBiQ6N021.
PaxDbiQ6N021.
PeptideAtlasiQ6N021.
PRIDEiQ6N021.

PTM databases

iPTMnetiQ6N021.
PhosphoSitePlusiQ6N021.

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 interactors.
IntActiQ6N021. 10 interactors.
STRINGi9606.ENSP00000369351.

Structurei

Secondary structure

12002
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi1135 – 1138Combined sources4
Helixi1141 – 1144Combined sources4
Beta strandi1153 – 1156Combined sources4
Helixi1157 – 1168Combined sources12
Helixi1172 – 1174Combined sources3
Beta strandi1175 – 1182Combined sources8
Beta strandi1197 – 1200Combined sources4
Beta strandi1209 – 1215Combined sources7
Beta strandi1224 – 1234Combined sources11
Helixi1238 – 1255Combined sources18
Helixi1262 – 1264Combined sources3
Turni1278 – 1280Combined sources3
Beta strandi1283 – 1288Combined sources6
Turni1293 – 1296Combined sources4
Turni1299 – 1302Combined sources4
Beta strandi1312 – 1314Combined sources3
Helixi1316 – 1340Combined sources25
Helixi1342 – 1348Combined sources7
Turni1349 – 1354Combined sources6
Helixi1356 – 1358Combined sources3
Beta strandi1362 – 1364Combined sources3
Beta strandi1370 – 1376Combined sources7
Beta strandi1393 – 1399Combined sources7
Helixi1401 – 1403Combined sources3
Beta strandi1405 – 1408Combined sources4
Beta strandi1416 – 1418Combined sources3
Beta strandi1421 – 1423Combined sources3
Helixi1432 – 1440Combined sources9
Beta strandi1443 – 1446Combined sources4
Beta strandi1451 – 1459Combined sources9
Beta strandi1844 – 1849Combined sources6
Helixi1851 – 1855Combined sources5
Beta strandi1862 – 1864Combined sources3
Beta strandi1871 – 1874Combined sources4
Turni1876 – 1878Combined sources3
Beta strandi1881 – 1883Combined sources3
Beta strandi1895 – 1902Combined sources8
Beta strandi1904 – 1906Combined sources3
Helixi1910 – 1913Combined sources4
Helixi1914 – 1920Combined sources7

3D structure databases

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

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1290 – 1303Interaction with DNAAdd BLAST14
Regioni1896 – 18982-oxoglutarate binding3
Regioni1902 – 1904Substrate binding3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi398 – 419Pro-richAdd BLAST22
Compositional biasi591 – 969Gln-richAdd BLAST379
Compositional biasi1523 – 1553Gln-richAdd BLAST31

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)DescriptionActionsGraphical viewLength
Sequence conflicti599Q → R in BAA90898 (PubMed:14702039).Curated1
Sequence conflicti702H → Q in CAE45851 (PubMed:17974005).Curated1
Sequence conflicti878L → S in BAE45750 (PubMed:12880961).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03984129P → R.1 PublicationCorresponds to variant rs12498609dbSNPEnsembl.1
Natural variantiVAR_05817134L → F.2 PublicationsCorresponds to variant rs111948941dbSNPEnsembl.1
Natural variantiVAR_058130123R → H.1 PublicationCorresponds to variant rs773565437dbSNPEnsembl.1
Natural variantiVAR_058172145S → N in a chronic myelomonocytic leukemia sample; somatic mutation. 1 PublicationCorresponds to variant rs114619974dbSNPEnsembl.1
Natural variantiVAR_058173174P → H.1 PublicationCorresponds to variant rs146031219dbSNPEnsembl.1
Natural variantiVAR_039842218V → M.2 PublicationsCorresponds to variant rs6843141dbSNPEnsembl.1
Natural variantiVAR_058131308A → T in chronic myelomonocytic leukemia and acute myeloid leukemia samples. 1 Publication1
Natural variantiVAR_058174312N → S in an acute myeloid leukemia sample; somatic mutation. 1 Publication1
Natural variantiVAR_058132355G → D.1 PublicationCorresponds to variant rs61744960dbSNPEnsembl.1
Natural variantiVAR_039843363P → L.1 PublicationCorresponds to variant rs17253672dbSNPEnsembl.1
Natural variantiVAR_058133399P → L in myelodysplastic/myeloproliferative disorders; a patient positive for mutation F-617 in JAK2. 1 Publication1
Natural variantiVAR_058134429G → R.1 PublicationCorresponds to variant rs201642693dbSNPEnsembl.1
Natural variantiVAR_058175460S → F in a chronic myelomonocytic leukemia sample; somatic mutation. 1 PublicationCorresponds to variant rs376570662dbSNPEnsembl.1
Natural variantiVAR_058176666D → G in a chronic myelomonocytic leukemia sample; somatic mutation. 1 Publication1
Natural variantiVAR_058135817S → T in myelodysplastic/myeloproliferative disorders. 1 PublicationCorresponds to variant rs753786455dbSNPEnsembl.1
Natural variantiVAR_058177867Y → H.3 PublicationsCorresponds to variant rs144386291dbSNPEnsembl.1
Natural variantiVAR_039844912A → G.Corresponds to variant rs4145756dbSNPEnsembl.1
Natural variantiVAR_058136924H → R.1 PublicationCorresponds to variant rs34485921dbSNPEnsembl.1
Natural variantiVAR_058178941P → S in a chronic myelomonocytic leukemia sample; somatic mutation. 1 PublicationCorresponds to variant rs532738858dbSNPEnsembl.1
Natural variantiVAR_058137949H → R.1 PublicationCorresponds to variant rs778464072dbSNPEnsembl.1
Natural variantiVAR_0581791073E → V.1 Publication1
Natural variantiVAR_0581801084Q → P.3 PublicationsCorresponds to variant rs75056899dbSNPEnsembl.1
Natural variantiVAR_0581811135C → Y in a myeloproliferative disorder; somatic mutation. 1 PublicationCorresponds to variant rs769422572dbSNPEnsembl.1
Natural variantiVAR_0581381167R → T in a myelodysplatic/myeloproliferative disorder and a chronic myelomonocytic leukemia sample. 1 Publication1
Natural variantiVAR_0581391175I → V in a refractory anemia with ringed sideroblasts sample. 1 Publication1
Natural variantiVAR_0581821204S → C in a myeloproliferative disorder; somatic mutation. 1 Publication1
Natural variantiVAR_0581831214R → W in a myelodysplastic syndrome; somatic mutation in a chronic myelomonocytic leukemia sample. 2 PublicationsCorresponds to variant rs761811530dbSNPEnsembl.1
Natural variantiVAR_0581401237 – 1239Missing in a polycythemia vera sample; somatic mutation. 1 Publication3
Natural variantiVAR_0581981242D → R Requires 2 nucleotide substitutions. 1 Publication1
Natural variantiVAR_0581841242D → V in myeloproliferative disorders. 1 Publication1
Natural variantiVAR_0581851245Y → S in a myeloproliferative disorder; somatic mutation. 1 Publication1
Natural variantiVAR_0581861261R → C in a myeloproliferative disorder; somatic mutation. 1 Publication1
Natural variantiVAR_0581871261R → H in a chronic myelomonocytic leukemia sample; somatic mutation. 1 PublicationCorresponds to variant rs771761785dbSNPEnsembl.1
Natural variantiVAR_0581411261R → L in a myelodysplastic syndrome. 1 Publication1
Natural variantiVAR_0581421285Missing in a myelodysplastic syndrome; somatic mutation. 1 Publication1
Natural variantiVAR_0581431287F → L in myelodysplastic/myeloproliferative disorders. 1 Publication1
Natural variantiVAR_0581441291W → R in a myelodysplastic syndrome; somatic mutation; abolishes enzyme activity. 2 Publications1
Natural variantiVAR_0581451299K → E in a refractory anemia sample. 2 Publications1
Natural variantiVAR_0581461299K → N in chronic myelomonocytic leukemia samples. 1 Publication1
Natural variantiVAR_0581471302R → G in primary myelofibrosis and chronic myelomonocytic leukemia samples. 2 Publications1
Natural variantiVAR_0581481318E → G in chronic myelomonocytic leukemia samples. 1 Publication1
Natural variantiVAR_0581491367P → S in a chronic myelomonocytic leukemia sample. 1
Natural variantiVAR_0581501396C → W in a myelodysplastic syndrome. 1 Publication1
Natural variantiVAR_0581511398L → R in a myelodysplastic syndrome; somatic mutation. 1 Publication1
Natural variantiVAR_0581881417V → F in a chronic myelomonocytic leukemia sample; somatic mutation. 1 PublicationCorresponds to variant rs749210253dbSNPEnsembl.1
Natural variantiVAR_0581891701M → I.1 PublicationCorresponds to variant rs62623390dbSNPEnsembl.1
Natural variantiVAR_0581901718V → L in refractory anemia with ringed sideroblasts; somatic mutation in an acute myeloid leukemia sample. 2 PublicationsCorresponds to variant rs142312318dbSNPEnsembl.1
Natural variantiVAR_0581911721L → W.1 PublicationCorresponds to variant rs34402524dbSNPEnsembl.1
Natural variantiVAR_0581921723P → S.2 PublicationsCorresponds to variant rs146348065dbSNPEnsembl.1
Natural variantiVAR_0581521757H → D in a chronic myelomonocytic leukemia sample; somatic mutation. 1 Publication1
Natural variantiVAR_0581931762I → V.2 PublicationsCorresponds to variant rs2454206dbSNPEnsembl.1
Natural variantiVAR_0581941778H → R.1 PublicationCorresponds to variant rs62621450dbSNPEnsembl.1
Natural variantiVAR_0581531811C → R in a chronic myelomonocytic leukemia sample; somatic mutation. 1 Publication1
Natural variantiVAR_0581541828Q → L in a myeloproliferative disorder; somatic mutation. 1 Publication1
Natural variantiVAR_0581551869G → W in an essential thrombocythemia sample. 1 Publication1
Natural variantiVAR_0581561872L → P in a refractory anemia with excess blasts sample. 1 Publication1
Natural variantiVAR_0581571873I → T in myelodysplastic syndromes, myeloproliferative disorders and chronic myelomonocytic leukemia; somatic mutation in acute myeloid leukemia and chronic myelomonocytic leukemia samples. 5 PublicationsCorresponds to variant rs116519313dbSNPEnsembl.1
Natural variantiVAR_0581951875C → R in a myelodysplastic syndrome; somatic mutation. 1 Publication1
Natural variantiVAR_0581961881H → Q in a myelodysplastic syndrome; somatic mutation. 1 Publication1
Natural variantiVAR_0581581881H → R in a myeloproliferative disorder; somatic mutation; also in a patient with systemic mastocytosis associated with chronic myelomonocytic leukemia. 2 Publications1
Natural variantiVAR_0581591896R → M in a primary acute myeloid leukemia sample; somatic mutation; reduces enzyme activity. 2 Publications1
Natural variantiVAR_0581971896R → S in a myeloproliferative disorder; somatic mutation. 1 Publication1
Natural variantiVAR_0581601898S → F in a secondary acute myeloid leukemia sample; somatic mutation; loss of enzyme activity. 2 PublicationsCorresponds to variant rs767475870dbSNPEnsembl.1
Natural variantiVAR_0581611900V → A.1 Publication1
Natural variantiVAR_0581621911 – 1916Missing in a myelodysplastic syndrome; somatic mutation. 1 Publication6
Natural variantiVAR_0581631913G → D in myelodysplastic syndromes; refractory cytopenia with multilineage dysplasia and ringed sideroblasts; somatic mutation in a patient. 2 Publications1
Natural variantiVAR_0581641919A → V in a myeloproliferative disorder; somatic mutation. 1 Publication1
Natural variantiVAR_0581651926R → H in a chronic myelomonocytic leukemia sample; somatic mutation. 1 Publication1
Natural variantiVAR_0581661941P → S in a chronic myelomonocytic leukemia sample; somatic mutation. 1 Publication1
Natural variantiVAR_0581671962P → L in a myelodysplastic syndrome. 1 PublicationCorresponds to variant rs200971953dbSNPEnsembl.1
Natural variantiVAR_0581681966R → H in a chronic myelomonocytic leukemia sample; somatic mutation. 1 PublicationCorresponds to variant rs754215085dbSNPEnsembl.1
Natural variantiVAR_0581691974R → M in a chronic myelomonocytic leukemia sample; somatic mutation. 1 Publication1
Natural variantiVAR_0581702000R → K.1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0322821137 – 1194EQIIE…SQGCP → GLDRRVKLLGLKESSILVKK AKVLRDVLLLSGWFAEAAVK RSYCVWCGSELATPVRLQ in isoform 3. 1 PublicationAdd BLAST58
Alternative sequenceiVSP_0322831137 – 1165EQIIE…REIME → GKCQKCTETHGVYPELANLS SDMGFSFFF in isoform 2. 2 PublicationsAdd BLAST29
Alternative sequenceiVSP_0322841166 – 2002Missing in isoform 2. 2 PublicationsAdd BLAST837
Alternative sequenceiVSP_0322851195 – 2002Missing in isoform 3. 1 PublicationAdd BLAST808

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
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4NM6X-ray2.03A1129-1480[»]
A1844-1936[»]
5D9YX-ray1.97A1129-1480[»]
A1844-1936[»]
5DEUX-ray1.80A1129-1480[»]
A1844-1935[»]
ProteinModelPortaliQ6N021.
SMRiQ6N021.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120151. 8 interactors.
IntActiQ6N021. 10 interactors.
STRINGi9606.ENSP00000369351.

PTM databases

iPTMnetiQ6N021.
PhosphoSitePlusiQ6N021.

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.
DisGeNETi54790.
GeneCardsiTET2.
HGNCiHGNC:25941. TET2.
HPAiHPA043135.
HPA051948.
MalaCardsiTET2.
MIMi263300. phenotype.
612839. gene.
614286. phenotype.
neXtProtiNX_Q6N021.
OpenTargetsiENSG00000168769.
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: November 30, 2016
This is version 106 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.