Names & Taxonomy

Uniprot ID:
Q07912
Entry Name:
ACK1_HUMAN
Status:
reviewed
Protein Names:
Activated CDC42 kinase 1 (ACK-1) (EC 2.7.10.2) (EC 2.7.11.1) (Tyrosine kinase non-receptor protein 2)
Gene Names:
TNK2 ACK1
Gene Names Primary:
TNK2
Organism:
Homo sapiens (Human)

Structure

Length:
1038
Sequence:
MQPEEGTGWLLELLSEVQLQQYFLRLRDDLNVTRLSHFEYVKNEDLEKIGMGRPGQRRLWEAVKRRKALCKRKSWMSKVFSGKRLEAEFPPHHSQSTFRKTSPAPGGPAGEGPLQSLTCLIGEKDLRLLEKLGDGSFGVVRRGEWDAPSGKTVSVAVKCLKPDVLSQPEAMDDFIREVNAMHSLDHRNLIRLYGVVLTPPMKMVTELAPLGSLLDRLRKHQGHFLLGTLSRYAVQVAEGMGYLESKRFIHRDLAARNLLLATRDLVKIGDFGLMRALPQNDDHYVMQEHRKVPFAWCAPESLKTRTFSHASDTWMFGVTLWEMFTYGQEPWIGLNGSQILHKIDKEGERLPRPEDCPQDIYNVMVQCWAHKPEDRPTFVALRDFLLEAQPTDMRALQDFEEPDKLHIQMNDVITVIEGRAENYWWRGQNTRTLCVGPFPRNVVTSVAGLSAQDISQPLQNSFIHTGHGDSDPRHCWGFPDRIDELYLGNPMDPPDLLSVELSTSRPPQHLGGVKKPTYDPVSEDQDPLSSDFKRLGLRKPGLPRGLWLAKPSARVPGTKASRGSGAEVTLIDFGEEPVVPALRPCAPSLAQLAMDACSLLDETPPQSPTRALPRPLHPTPVVDWDARPLPPPPAYDDVAQDEDDFEICSINSTLVGAGVPAGPSQGQTNYAFVPEQARPPPPLEDNLFLPPQGGGKPPSSAQTAEIFQALQQECMRQLQAPAGSPAPSPSPGGDDKPQVPPRVPIPPRPTRPHVQLSPAPPGEEETSQWPGPASPPRVPPREPLSPQGSRTPSPLVPPGSSPLPPRLSSSPGKTMPTTQSFASDPKYATPQVIQAPGPRAGPCILPIVRDGKKVSSTHYYLLPERPSYLERYQRFLREAQSPEEPTPLPVPLLLPPPSTPAPAAPTATVRPMPQAALDPKANFSTNNSNPGARPPPPRATARLPQRGCPGDGPEAGRPADKIQMAMVHGVTTEECQAALQCHGWSVQRAAQYLKVEQLFGLGLRPRGECHKVLEMFDWNLEQAGCHLLGSWGPAHHKR
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Cell membrane. Nucleus. Endosome. Cell junction, adherens junction

Function

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.
Catalytic Activity:
ATP + a -L-tyrosine = ADP + a -L-tyrosine phosphate.
Cofactor:
COFACTOR: Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
Enzyme Regulation:
ENZYME REGULATION: Inhibited by AIM-100 (4-amino-5,6-biaryl-furopyrimidine), which suppresses activating phosphorylation at Tyr-284. Repressed by dasatinib.
Active Site:
ACT_SITE 252 252 Proton acceptor.
Cross Reference Drug Bank:
DB00171
Gene Ontology Go:
adherens junction
clathrin-coated vesicle
coated pit
cytoplasm
cytoplasmic vesicle membrane
endosome
extrinsic component of cytoplasmic side of plasma membrane
Grb2-EGFR complex
membrane
nucleus
plasma membrane
ATP binding
epidermal growth factor receptor binding
GTPase inhibitor activity
identical protein binding
metal ion binding
non-membrane spanning protein tyrosine kinase activity
protein serine/threonine kinase activity
protein serine/threonine/tyrosine kinase activity
protein tyrosine kinase activity
WW domain binding
cell differentiation
cell migration
cell surface receptor signaling pathway
endocytosis
innate immune response
negative regulation of GTPase activity
peptidyl-tyrosine autophosphorylation
phosphorylation
positive regulation of peptidyl-tyrosine phosphorylation
regulation of cell proliferation
regulation of clathrin-mediated endocytosis
small GTPase mediated signal transduction
transmembrane receptor protein tyrosine kinase signaling pathway
Gene Ontology Biological Process:
cell differentiation
cell migration
cell surface receptor signaling pathway
endocytosis
innate immune response
negative regulation of GTPase activity
peptidyl-tyrosine autophosphorylation
phosphorylation
positive regulation of peptidyl-tyrosine phosphorylation
regulation of cell proliferation
regulation of clathrin-mediated endocytosis
small GTPase mediated signal transduction
transmembrane receptor protein tyrosine kinase signaling pathway
Gene Ontology Molecular Function:
ATP binding
epidermal growth factor receptor binding
GTPase inhibitor activity
identical protein binding
metal ion binding
non-membrane spanning protein tyrosine kinase activity
protein serine/threonine/tyrosine kinase activity
protein serine/threonine kinase activity
protein tyrosine kinase activity
WW domain binding
Gene Ontology Cellular Component:
adherens junction
clathrin-coated vesicle
coated pit
cytoplasm
cytoplasmic vesicle membrane
endosome
extrinsic component of cytoplasmic side of plasma membrane
Grb2-EGFR complex
membrane
nucleus
plasma membrane
Keywords:
3D-structure
ATP-binding
Alternative splicing
Cell junction
Cell membrane
Coated pit
Complete proteome
Cytoplasmic vesicle
Endocytosis
Endosome
Kinase
Magnesium
Membrane
Metal-binding
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
SH3 domain
Serine/threonine-protein kinase
Transferase
Tyrosine-protein kinase
Ubl conjugation
Interacts With:
Itself; P29972; P56945; P60953-2; Q00610; P07902; Q9HC98; Q7Z3S9; O60880

Publication

PubMed ID:
8497321 14702039 16641997 15489334 10587647 10652228 11278436 14733946 16288044 16137687 16257963 15592455 16247015 17081983 17038317 16472662 17494760 18477472 18435854 18262180 18691976 18669648 19144635 19815557 19369195 20979614 20383201 20333297 20623637 21309750 21169560 20432460 10360579 15308621 18993068 17344846