Molecule Information

General Information of the Molecule (ID: Mol03011)

• Name: DNA topoisomerase 2-alpha (TOP2A) ,Homo sapiens
• Synonyms: TOP2; TP2A; TOPIIA; TOP2alpha
• Molecule Type: Protein
• Gene Name: TOP2A
• Gene ID: 7153
• Location: chr17: 40,388,525-40,417,896[+]
• Sequence:
  MEVSPLQPVNENMQVNKIKKNEDAKKRLSVERIYQKKTQLEHILLRPDTYIGSVELVTQQ
  MWVYDEDVGINYREVTFVPGLYKIFDEILVNAADNKQRDPKMSCIRVTIDPENNLISIWN
  NGKGIPVVEHKVEKMYVPALIFGQLLTSSNYDDDEKKVTGGRNGYGAKLCNIFSTKFTVE
  TASREYKKMFKQTWMDNMGRAGEMELKPFNGEDYTCITFQPDLSKFKMQSLDKDIVALMV
  RRAYDIAGSTKDVKVFLNGNKLPVKGFRSYVDMYLKDKLDETGNSLKVIHEQVNHRWEVC
  LTMSEKGFQQISFVNSIATSKGGRHVDYVADQIVTKLVDVVKKKNKGGVAVKAHQVKNHM
  WIFVNALIENPTFDSQTKENMTLQPKSFGSTCQLSEKFIKAAIGCGIVESILNWVKFKAQ
  VQLNKKCSAVKHNRIKGIPKLDDANDAGGRNSTECTLILTEGDSAKTLAVSGLGVVGRDK
  YGVFPLRGKILNVREASHKQIMENAEINNIIKIVGLQYKKNYEDEDSLKTLRYGKIMIMT
  DQDQDGSHIKGLLINFIHHNWPSLLRHRFLEEFITPIVKVSKNKQEMAFYSLPEFEEWKS
  STPNHKKWKVKYYKGLGTSTSKEAKEYFADMKRHRIQFKYSGPEDDAAISLAFSKKQIDD
  RKEWLTNFMEDRRQRKLLGLPEDYLYGQTTTYLTYNDFINKELILFSNSDNERSIPSMVD
  GLKPGQRKVLFTCFKRNDKREVKVAQLAGSVAEMSSYHHGEMSLMMTIINLAQNFVGSNN
  LNLLQPIGQFGTRLHGGKDSASPRYIFTMLSSLARLLFPPKDDHTLKFLYDDNQRVEPEW
  YIPIIPMVLINGAEGIGTGWSCKIPNFDVREIVNNIRRLMDGEEPLPMLPSYKNFKGTIE
  ELAPNQYVISGEVAILNSTTIEISELPVRTWTQTYKEQVLEPMLNGTEKTPPLITDYREY
  HTDTTVKFVVKMTEEKLAEAERVGLHKVFKLQTSLTCNSMVLFDHVGCLKKYDTVLDILR
  DFFELRLKYYGLRKEWLLGMLGAESAKLNNQARFILEKIDGKIIIENKPKKELIKVLIQR
  GYDSDPVKAWKEAQQKVPDEEENEESDNEKETEKSDSVTDSGPTFNYLLDMPLWYLTKEK
  KDELCRLRNEKEQELDTLKRKSPSDLWKEDLATFIEELEAVEAKEKQDEQVGLPGKGGKA
  KGKKTQMAEVLPSPRGQRVIPRITIEMKAEAEKKNKKKIKNENTEGSPQEDGVELEGLKQ
  RLEKKQKREPGTKTKKQTTLAFKPIKKGKKRNPWSDSESDRSSDESNFDVPPRETEPRRA
  ATKTKFTMDLDSDEDFSDFDEKTDDEDFVPSDASPPKTKTSPKLSNKELKPQKSVVSDLE
  ADDVKGSVPLSSSPPATHFPDETEITNPVPKKNVTVKKTAAKSQSSTSTTGAKKRAAPKG
  TKRDPALNSGVSQKPDPAKTKNRRKRKPSTSDDSDSNFEKIVSKAVTSKKSKGESDDFHM
  DFDSAVAPRAKSVRAKKPIKYLEESDEDDLF
• Function: Key decatenating enzyme that alters DNA topology by binding to two double-stranded DNA molecules, generating a double-stranded break in one of the strands, passing the intact strand through the broken strand, and religating the broken strand.
• Uniprot ID: TOP2A_HUMAN
• Ensembl ID: ENSG00000131747
• HGNC ID: HGNC:11989

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

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Doxorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Thyroid gland cancer [1]

• Resistant Disease: Thyroid gland cancer [ICD-11: 2D10.0]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Missense mutation; p.R450Q
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Regulation
• In Vitro Model: HTC-C3 cells; Pleural effusion; Homo sapiens (Human); CVCL_1295
• Experiment for Drug Resistance: Cell growth rate assay
• Mechanism Description: Several mutations have been identified in human topoisomerase IIalpha from cell lines which are resistant to anti-topoisomerase II agents. So far, three mutations at amino acids 439, 450 and 803 of DNA topoisomerase IIalpha have been reported in anticancer agent-resistant cell lines. It has been reported that introducing either of the mutations, Arg450Gln or Pro803Ser into the VM-1 cell line results in an enzyme that can confer drug resistance to yeast.

Disease Class: Thyroid gland cancer [1]

• Resistant Disease: Thyroid gland cancer [ICD-11: 2D10.0]
• Resistant Drug: Doxorubicin
• Molecule Alteration: Missense mutation; p.P803S
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Regulation
• In Vitro Model: HTC-C3 cells; Pleural effusion; Homo sapiens (Human); CVCL_1295
• Experiment for Drug Resistance: Cell growth rate assay
• Mechanism Description: Several mutations have been identified in human topoisomerase IIalpha from cell lines which are resistant to anti-topoisomerase II agents. So far, three mutations at amino acids 439, 450 and 803 of DNA topoisomerase IIalpha have been reported in anticancer agent-resistant cell lines. It has been reported that introducing either of the mutations, Arg450Gln or Pro803Ser into the VM-1 cell line results in an enzyme that can confer drug resistance to yeast.

References

• Ref 1: Lack of a point mutation of human DNA topoisomerase II in multidrug-resistant anaplastic thyroid carcinoma cell lines. Cancer Lett. 1997 Jun 3;116(1):33-9.