Target General Infomation
Target ID
T63220 (Former ID: TTDI02471)
Target Name
Activated CDC42 kinase 1 (ACK-1)
Synonyms
Tyrosine kinase non-receptor protein 2; ACK1; ACK-1
Gene Name
TNK2
Target Type
Patented-recorded target
[1]
Disease [+] 1 Target-related Diseases +
1 Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Function
Non-receptor tyrosine-protein and serine/threonine-protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. Transduces extracellular signals to cytosolic and nuclear effectors. Phosphorylates AKT1, AR, MCF2, WASL and WWOX. Implicated in trafficking and clathrin-mediated endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. Binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR, thereby contributing to the accumulation of EGFR at the limiting membrane of early endosomes. Downstream effector of CDC42 which mediates CDC42-dependent cell migration via phosphorylation of BCAR1. May be involved both in adult synaptic function and plasticity and in brain development. Activates AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267' and 'Tyr-363' thereby promoting its recruitment to androgen-responsive enhancers (AREs). Phosphorylates WWOX on 'Tyr-287'. Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. Contributes to the control of AXL receptor levels. Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and AR. Phosphorylates WASP.
BioChemical Class
Kinase
UniProt ID
ACK1_HUMAN
EC Number
EC 2.7.10.2
Sequence
MQPEEGTGWLLELLSEVQLQQYFLRLRDDLNVTRLSHFEYVKNEDLEKIGMGRPGQRRLW
EAVKRRKALCKRKSWMSKVFSGKRLEAEFPPHHSQSTFRKTSPAPGGPAGEGPLQSLTCL
IGEKDLRLLEKLGDGSFGVVRRGEWDAPSGKTVSVAVKCLKPDVLSQPEAMDDFIREVNA
MHSLDHRNLIRLYGVVLTPPMKMVTELAPLGSLLDRLRKHQGHFLLGTLSRYAVQVAEGM
GYLESKRFIHRDLAARNLLLATRDLVKIGDFGLMRALPQNDDHYVMQEHRKVPFAWCAPE
SLKTRTFSHASDTWMFGVTLWEMFTYGQEPWIGLNGSQILHKIDKEGERLPRPEDCPQDI
YNVMVQCWAHKPEDRPTFVALRDFLLEAQPTDMRALQDFEEPDKLHIQMNDVITVIEGRA
ENYWWRGQNTRTLCVGPFPRNVVTSVAGLSAQDISQPLQNSFIHTGHGDSDPRHCWGFPD
RIDELYLGNPMDPPDLLSVELSTSRPPQHLGGVKKPTYDPVSEDQDPLSSDFKRLGLRKP
GLPRGLWLAKPSARVPGTKASRGSGAEVTLIDFGEEPVVPALRPCAPSLAQLAMDACSLL
DETPPQSPTRALPRPLHPTPVVDWDARPLPPPPAYDDVAQDEDDFEICSINSTLVGAGVP
AGPSQGQTNYAFVPEQARPPPPLEDNLFLPPQGGGKPPSSAQTAEIFQALQQECMRQLQA
PAGSPAPSPSPGGDDKPQVPPRVPIPPRPTRPHVQLSPAPPGEEETSQWPGPASPPRVPP
REPLSPQGSRTPSPLVPPGSSPLPPRLSSSPGKTMPTTQSFASDPKYATPQVIQAPGPRA
GPCILPIVRDGKKVSSTHYYLLPERPSYLERYQRFLREAQSPEEPTPLPVPLLLPPPSTP
APAAPTATVRPMPQAALDPKANFSTNNSNPGARPPPPRATARLPQRGCPGDGPEAGRPAD
KIQMAMVHGVTTEECQAALQCHGWSVQRAAQYLKVEQLFGLGLRPRGECHKVLEMFDWNL
EQAGCHLLGSWGPAHHKR
Mode of Action [+] 1 Modes of Action +
Inhibitor [+] 7 Inhibitor drugs +
1 BDBM50379214 Drug Info [2]
2 Gefitinib Drug Info [2]
3 US8481733, 106 Drug Info [3]
4 US8481733, 118 Drug Info [3]
5 US8481733, 95 Drug Info [3]
6 ACK-1 inhibitors Drug Info [1]
7 PMID17280833C30 Drug Info [4]
Target Regulators
Target-regulating microRNAs
Target-interacting Proteins
Target Affiliated Biological Pathways
NetPath Pathway [+] 1 NetPath Pathways +
1 TSH Signaling Pathway
PID Pathway [+] 1 PID Pathways +
1 CDC42 signaling events
WikiPathways [+] 3 WikiPathways +
1 G13 Signaling Pathway
2 EGF/EGFR Signaling Pathway
3 Focal Adhesion
References
REF 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2246).
REF 2 Kinase modulators for the treatment of cancer. US9416123.
REF 3 Substituted imidazopyr- and imidazotri-azines. US8481733.
REF 4 Discovery of 4-amino-5,6-biaryl-furo[2,3-d]pyrimidines as inhibitors of Lck: development of an expedient and divergent synthetic route and prelimin... Bioorg Med Chem Lett. 2007 Apr 15;17(8):2305-9.

If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Wang and Dr. Li.