Target Information
Target General Infomation | |||||
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Target ID |
T58470
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Former ID |
TTDR00224
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Target Name |
Cyclin-A2
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Gene Name |
CCNA2
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Synonyms |
Cyclin; Cyclin-A; PCNA; CCNA2
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Target Type |
Discontinued
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Disease | Retinoblastoma [ICD10: C69.2] | ||||
Function |
Auxiliary protein of DNA polymerase delta and is involved in the control of eukaryotic DNA replication by increasing the polymerase's processibility during elongation of the leading strand. Induces a robust stimulatory effect on the 3'- 5' exonuclease and 3'-phosphodiesterase, but not apurinic- apyrimidinic (AP) endonuclease, APEX2 activities. Has to be loaded onto DNA in order to be able to stimulate APEX2. Plays a key role in DNA damage response (DDR) by being conveniently positioned at the replication fork to coordinate DNA replication with DNA repair and DNA damage tolerance pathways. Acts as a loading platform to recruit DDR proteins that allow completion of DNA replication after DNA damage and promote postreplication repair: Monoubiquitinated PCNA leads to recruitment of translesion (TLS) polymerases, while 'Lys-63'-linked polyubiquitination of PCNA is involved in error-free pathway and employs recombination mechanisms to synthesize across the lesion.
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Target Validation |
T58470
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UniProt ID | |||||
Sequence |
MLGNSAPGPATREAGSALLALQQTALQEDQENINPEKAAPVQQPRTRAALAVLKSGNPRG
LAQQQRPKTRRVAPLKDLPVNDEHVTVPPWKANSKQPAFTIHVDEAEKEAQKKPAESQKI EREDALAFNSAISLPGPRKPLVPLDYPMDGSFESPHTMDMSIILEDEKPVSVNEVPDYHE DIHTYLREMEVKCKPKVGYMKKQPDITNSMRAILVDWLVEVGEEYKLQNETLHLAVNYID RFLSSMSVLRGKLQLVGTAAMLLASKFEEIYPPEVAEFVYITDDTYTKKQVLRMEHLVLK VLTFDLAAPTVNQFLTQYFLHQQPANCKVESLAMFLGELSLIDADPYLKYLPSVIAGAAF HLALYTVTGQSWPESLIRKTGYTLESLKPCLMDLHQTYLKAPQHAQQSIREKYKNSKYHG VSLLNPPETLNL |
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Structure |
1E9H; 1FIN; 1FVV; 1GY3; 1H1P; 1H1Q; 1H1R; 1H1S; 1H24; 1H25; 1H26; 1H27; 1H28; 1JST; 1JSU; 1OGU; 1OI9; 1OIU; 1OIY; 1OKV; 1OKW; 1OL1; 1OL2; 1P5E; 1PKD; 1QMZ; 1URC; 1VYW; 2BKZ; 2BPM; 2C4G; 2C5N; 2C5O; 2C5V; 2C5X; 2C6T; 2CCH; 2CCI; 2CJM; 2I40; 2IW6; 2IW8; 2IW9; 2UUE; 2UZB; 2UZD; 2UZE; 2UZL; 2V22; 2WEV; 2WFY; 2WHB; 2WIH; 2WIP; 2WMA; 2WMB; 2WPA; 2WXV; 2X1N; 3EID; 3EJ1; 3EOC; 3F5X; 4BCK; 4BCM; 4BCN; 4BCP; 4CFM; 4CFN; 4CFU; 4CFV; 4CFW; 4CFX; 4EOI; 4EOJ; 4EOK; 4EOL; 4EOM; 4EON; 4EOO; 4EOP; 4EOQ; 4EOR; 4EOS; 4FX3; 1AXC; 1U76; 1U7B; 1UL1; 1VYJ; 1VYM; 1W60; 2ZVK; 2ZVL; 2ZVM; 3P87; 3TBL; 3VKX; 3WGW
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Drugs and Mode of Action | |||||
Inhibitor | 2,5-dichloro-N-p-tolylthiophene-3-sulfonamide | Drug Info | [551239] | ||
3-((3,5-diamino-1H-pyrazol-4-yl)diazenyl)phenol | Drug Info | [528490] | |||
4-(7-Butyl-5H-pyrrolo[2,3-b]pyrazin-6-yl)-phenol | Drug Info | [526504] | |||
4-(phenyldiazenyl)-1H-pyrazole-3,5-diamine | Drug Info | [528490] | |||
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol | Drug Info | [528490] | |||
6-(3-Amino-benzyloxy)-9H-purin-2-ylamine | Drug Info | [526389] | |||
6-(3-Methyl-benzyloxy)-9H-purin-2-ylamine | Drug Info | [526389] | |||
6-(Cyclohex-3-enylmethoxy)-9H-purin-2-ylamine | Drug Info | [526389] | |||
6-Cyclohexylmethoxy-pyrimidine-2,4,5-triamine | Drug Info | [526489] | |||
GW-8510 | Drug Info | [526991] | |||
MERIOLIN 1 | Drug Info | [529275] | |||
MERIOLIN 2 | Drug Info | [529275] | |||
MERIOLIN 3 | Drug Info | [529275] | |||
MERIOLIN 4 | Drug Info | [529275] | |||
MERIOLIN 5 | Drug Info | [529275] | |||
MERIOLIN 6 | Drug Info | [529275] | |||
MERIOLIN 7 | Drug Info | [529275] | |||
MERIOLIN 8 | Drug Info | [529275] | |||
NU-2058 | Drug Info | [527129] | |||
NU-6027 | Drug Info | [526489] | |||
PD-0183812 | Drug Info | [525924] | |||
PURVALANOLA | Drug Info | [529039] | |||
RESCOVITINE | Drug Info | [530612] | |||
Pathways | |||||
KEGG Pathway | DNA replication | ||||
Base excision repair | |||||
Nucleotide excision repair | |||||
Mismatch repair | |||||
Cell cycle | |||||
Hepatitis B | |||||
HTLV-I infection | |||||
PathWhiz Pathway | Nucleotide Excision Repair | ||||
Reactome | E2F mediated regulation of DNA replication | ||||
G0 and Early G1 | |||||
Phospho-APC/C mediated degradation of Cyclin A | |||||
Regulation of APC/C activators between G1/S and early anaphase | |||||
SCF(Skp2)-mediated degradation of p27/p21 | |||||
Senescence-Associated Secretory Phenotype (SASP) | |||||
MSH6 (MutSalpha) | |||||
MSH3 (MutSbeta) | |||||
HDR through Homologous Recombination (HRR) | |||||
Processing of DNA double-strand break ends | |||||
Dual Incision in GG-NER | |||||
Dual incision in TC-NER | |||||
Gap-filling DNA repair synthesis and ligation in TC-NER | |||||
G2 Phase | |||||
Orc1 removal from chromatin | |||||
G1/S-Specific Transcription | |||||
Cyclin A/B1 associated events during G2/M transition | |||||
Cdk2-associated events at S phase entry | |||||
WikiPathways | Senescence and Autophagy in Cancer | ||||
Mismatch repair | |||||
DNA Replication | |||||
G1 to S cell cycle control | |||||
EGF/EGFR Signaling Pathway | |||||
S Phase | |||||
Nifedipine Activity | |||||
Primary Focal Segmental Glomerulosclerosis FSGS | |||||
Retinoblastoma (RB) in Cancer | |||||
Integrated Pancreatic Cancer Pathway | |||||
Nucleotide Excision Repair | |||||
Telomere Maintenance | |||||
Synthesis of DNA | |||||
Mitotic G1-G1/S phases | |||||
Cell Cycle | |||||
Base Excision Repair | |||||
References | |||||
Ref 525924 | J Med Chem. 2000 Nov 30;43(24):4606-16.Pyrido[2,3-d]pyrimidin-7-one inhibitors of cyclin-dependent kinases. | ||||
Ref 526389 | J Med Chem. 2002 Aug 1;45(16):3381-93.Probing the ATP ribose-binding domain of cyclin-dependent kinases 1 and 2 with O(6)-substituted guanine derivatives. | ||||
Ref 526489 | Bioorg Med Chem Lett. 2003 Jan 20;13(2):217-22.4-Alkoxy-2,6-diaminopyrimidine derivatives: inhibitors of cyclin dependent kinases 1 and 2. | ||||
Ref 526504 | J Med Chem. 2003 Jan 16;46(2):222-36.Aloisines, a new family of CDK/GSK-3 inhibitors. SAR study, crystal structure in complex with CDK2, enzyme selectivity, and cellular effects. | ||||
Ref 526991 | Bioorg Med Chem Lett. 2004 Feb 23;14(4):953-7.Discovery and in vitro evaluation of potent TrkA kinase inhibitors: oxindole and aza-oxindoles. | ||||
Ref 527129 | J Med Chem. 2004 Jul 15;47(15):3710-22.N2-substituted O6-cyclohexylmethylguanine derivatives: potent inhibitors of cyclin-dependent kinases 1 and 2. | ||||
Ref 528490 | J Med Chem. 2006 Nov 2;49(22):6500-9.4-arylazo-3,5-diamino-1H-pyrazole CDK inhibitors: SAR study, crystal structure in complex with CDK2, selectivity, and cellular effects. | ||||
Ref 529039 | Biochem J. 2007 Dec 15;408(3):297-315.The selectivity of protein kinase inhibitors: a further update. | ||||
Ref 529275 | J Med Chem. 2008 Feb 28;51(4):737-51. Epub 2008 Jan 31.Meriolins (3-(pyrimidin-4-yl)-7-azaindoles): synthesis, kinase inhibitory activity, cellular effects, and structure of a CDK2/cyclin A/meriolincomplex. |
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