Molecule Information

General Information of the Molecule (ID: Mol00178)

• Name: Methylcytosine dioxygenase TET2 (TET2) ,Homo sapiens
• Synonyms: KIAA1546; Nbla00191
• Molecule Type: Protein
• Gene Name: TET2
• Gene ID: 54790
• Location: chr4:105145875-105279816[+]
• Sequence:
  MEQDRTNHVEGNRLSPFLIPSPPICQTEPLATKLQNGSPLPERAHPEVNGDTKWHSFKSY
  YGIPCMKGSQNSRVSPDFTQESRGYSKCLQNGGIKRTVSEPSLSGLLQIKKLKQDQKANG
  ERRNFGVSQERNPGESSQPNVSDLSDKKESVSSVAQENAVKDFTSFSTHNCSGPENPELQ
  ILNEQEGKSANYHDKNIVLLKNKAVLMPNGATVSASSVEHTHGELLEKTLSQYYPDCVSI
  AVQKTTSHINAINSQATNELSCEITHPSHTSGQINSAQTSNSELPPKPAAVVSEACDADD
  ADNASKLAAMLNTCSFQKPEQLQQQKSVFEICPSPAENNIQGTTKLASGEEFCSGSSSNL
  QAPGGSSERYLKQNEMNGAYFKQSSVFTKDSFSATTTPPPPSQLLLSPPPPLPQVPQLPS
  EGKSTLNGGVLEEHHHYPNQSNTTLLREVKIEGKPEAPPSQSPNPSTHVCSPSPMLSERP
  QNNCVNRNDIQTAGTMTVPLCSEKTRPMSEHLKHNPPIFGSSGELQDNCQQLMRNKEQEI
  LKGRDKEQTRDLVPPTQHYLKPGWIELKAPRFHQAESHLKRNEASLPSILQYQPNLSNQM
  TSKQYTGNSNMPGGLPRQAYTQKTTQLEHKSQMYQVEMNQGQSQGTVDQHLQFQKPSHQV
  HFSKTDHLPKAHVQSLCGTRFHFQQRADSQTEKLMSPVLKQHLNQQASETEPFSNSHLLQ
  HKPHKQAAQTQPSQSSHLPQNQQQQQKLQIKNKEEILQTFPHPQSNNDQQREGSFFGQTK
  VEECFHGENQYSKSSEFETHNVQMGLEEVQNINRRNSPYSQTMKSSACKIQVSCSNNTHL
  VSENKEQTTHPELFAGNKTQNLHHMQYFPNNVIPKQDLLHRCFQEQEQKSQQASVLQGYK
  NRNQDMSGQQAAQLAQQRYLIHNHANVFPVPDQGGSHTQTPPQKDTQKHAALRWHLLQKQ
  EQQQTQQPQTESCHSQMHRPIKVEPGCKPHACMHTAPPENKTWKKVTKQENPPASCDNVQ
  QKSIIETMEQHLKQFHAKSLFDHKALTLKSQKQVKVEMSGPVTVLTRQTTAAELDSHTPA
  LEQQTTSSEKTPTKRTAASVLNNFIESPSKLLDTPIKNLLDTPVKTQYDFPSCRCVEQII
  EKDEGPFYTHLGAGPNVAAIREIMEERFGQKGKAIRIERVIYTGKEGKSSQGCPIAKWVV
  RRSSSEEKLLCLVRERAGHTCEAAVIVILILVWEGIPLSLADKLYSELTETLRKYGTLTN
  RRCALNEERTCACQGLDPETCGASFSFGCSWSMYYNGCKFARSKIPRKFKLLGDDPKEEE
  KLESHLQNLSTLMAPTYKKLAPDAYNNQIEYEHRAPECRLGLKEGRPFSGVTACLDFCAH
  AHRDLHNMQNGSTLVCTLTREDNREFGGKPEDEQLHVLPLYKVSDVDEFGSVEAQEEKKR
  SGAIQVLSSFRRKVRMLAEPVKTCRQRKLEAKKAAAEKLSSLENSSNKNEKEKSAPSRTK
  QTENASQAKQLAELLRLSGPVMQQSQQPQPLQKQPPQPQQQQRPQQQQPHHPQTESVNSY
  SASGSTNPYMRRPNPVSPYPNSSHTSDIYGSTSPMNFYSTSSQAAGSYLNSSNPMNPYPG
  LLNQNTQYPSYQCNGNLSVDNCSPYLGSYSPQSQPMDLYRYPSQDPLSKLSLPPIHTLYQ
  PRFGNSQSFTSKYLGYGNQNMQGDGFSSCTIRPNVHHVGKLPPYPTHEMDGHFMGATSRL
  PPNLSNPNMDYKNGEHHSPSHIIHNYSAAPGMFNSSLHALHLQNKENDMLSHTANGLSKM
  LPALNHDRTACVQGGLHKLSDANGQEKQPLALVQGVASGAEDNDEVWSDSEQSFLDPDIG
  GVAVAPTHGSILIECAKRELHATTPLKNPNRNHPTRISLVFYQHKSMNEPKHGLALWEAK
  MAEKAREKEEECEKYGPDYVPQKSHGKKVKREPAEPHETSEPTYLRFIKSLAERTMSVTT
  DSTVTTSPYAFTRVTGPYNRYI
• Function: 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.
• Uniprot ID: TET2_HUMAN
• Ensembl ID: ENSG00000168769
• HGNC ID: HGNC:25941

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 3 drug(s) in total

Dasatinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Chronic myeloid leukemia [1]

• Resistant Disease: Chronic myeloid leukemia [ICD-11: 2A20.0]
• Resistant Drug: Dasatinib
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Lin-CD34+CD38- cells; Bone; Homo sapiens (Human); N.A.
• In Vitro Model: Lin-CD34-CD38- CML cells; Bone; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Annexin V assay
• Mechanism Description: The up-regulation of miR29a-3p observed in CML LSCs led to the down-regulation of its target TET2 and conferred TkI-resistance to CML LSCs in vitro.

Imatinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Chronic myeloid leukemia [1]

• Resistant Disease: Chronic myeloid leukemia [ICD-11: 2A20.0]
• Resistant Drug: Imatinib
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Lin-CD34+CD38- cells; Bone; Homo sapiens (Human); N.A.
• In Vitro Model: Lin-CD34-CD38- CML cells; Bone; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Annexin V assay
• Mechanism Description: The up-regulation of miR29a-3p observed in CML LSCs led to the down-regulation of its target TET2 and conferred TkI-resistance to CML LSCs in vitro.

Ponatinib

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Chronic myeloid leukemia [1]

• Resistant Disease: Chronic myeloid leukemia [ICD-11: 2A20.0]
• Resistant Drug: Ponatinib
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Identified from the Human Clinical Data
• In Vitro Model: Lin-CD34+CD38- cells; Bone; Homo sapiens (Human); N.A.
• In Vitro Model: Lin-CD34-CD38- CML cells; Bone; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Annexin V assay
• Mechanism Description: The up-regulation of miR29a-3p observed in CML LSCs led to the down-regulation of its target TET2 and conferred TkI-resistance to CML LSCs in vitro.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Chronic myeloid leukemia [ICD-11: 2A20]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Whole blood
• The Specified Disease: Myelofibrosis
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 6.77E-03; Fold-change: -8.90E-01; Z-score: -2.00E+00
• The Studied Tissue: Whole blood
• The Specified Disease: Polycythemia vera
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 8.69E-07; Fold-change: -4.39E-01; Z-score: -8.52E-01

References

• Ref 1: Deregulated expression of miR-29a-3p, miR-494-3p and miR-660-5p affects sensitivity to tyrosine kinase inhibitors in CML leukemic stem cells. Oncotarget. 2017 Jul 25;8(30):49451-49469. doi: 10.18632/oncotarget.17706.