Protein: Activated CDC42 kinase 1 (ACK-1) (EC 2.7.10.2) (EC 2.7.11.1) (Tyrosine kinase non-receptor protein 2) (Q07912)
Organism: Homo sapiens (Human)
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.
Subcellular location: Cell membrane {ECO:0000269|PubMed:20333297, ECO:0000269|PubMed:20979614}. Nucleus {ECO:0000269|PubMed:14733946, ECO:0000269|PubMed:20333297}. Endosome {ECO:0000250|UniProtKB:O54967}. Cell junction, adherens junction {ECO:0000305}. Cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side {ECO:0000269|PubMed:16137687}. Cytoplasmic vesicle, clathrin-coated vesicle {ECO:0000269|PubMed:16137687, ECO:0000269|PubMed:18262180}. Membrane, clathrin-coated pit {ECO:0000269|PubMed:21169560}. Cytoplasm, perinuclear region {ECO:0000269|PubMed:20110370}. Cytoplasm, cytosol {ECO:0000250|UniProtKB:O54967}. Note=The Tyr-284 phosphorylated form is found both in the membrane and nucleus (By similarity). Co-localizes with EGFR on endosomes (PubMed:20333297). Nuclear translocation is CDC42-dependent (By similarity). Detected in long filamentous cytosolic structures where it co-localizes with CTPS1 (By similarity). {ECO:0000250|UniProtKB:O54967, ECO:0000269|PubMed:20333297}.
Interaction partners:
- Cell division control protein 42 homolog
- Growth factor receptor-bound protein 2
- E3 ubiquitin-protein ligase NEDD4-like
- Clathrin heavy chain 1
- Epidermal growth factor receptor
- SH2/SH3 adapter protein NCK1
- Hematopoietic SH2 domain-containing protein
- Heat shock protein HSP 90-alpha
- WW domain-containing oxidoreductase
- Tyrosine-protein kinase HCK
Sequence:
MQPEEGTGWLLELLSEVQLQQYFLRLRDDLNVTRLSHFEYVKNEDLEKIGMGRPGQRRLWEAVKRRKALCKRKSWMSKVFSGKRLEAEFPPHHSQSTFRKTSPAPGGPAGEGPLQSLTCLIGEKDLRLLEKLGDGSFGVVRRGEWDAPSGKTVSVAVKCLKPDVLSQPEAMDDFIREVNAMHSLDHRNLIRLYGVVLTPPMKMVTELAPLGSLLDRLRKHQGHFLLGTLSRYAVQVAEGMGYLESKRFIHRDLAARNLLLATRDLVKIGDFGLMRALPQNDDHYVMQEHRKVPFAWCAPESLKTRTFSHASDTWMFGVTLWEMFTYGQEPWIGLNGSQILHKIDKEGERLPRPEDCPQDIYNVMVQCWAHKPEDRPTFVALRDFLLEAQPTDMRALQDFEEPDKLHIQMNDVITVIEGRAENYWWRGQNTRTLCVGPFPRNVVTSVAGLSAQDISQPLQNSFIHTGHGDSDPRHCWGFPDRIDELYLGNPMDPPDLLSVELSTSRPPQHLGGVKKPTYDPVSEDQDPLSSDFKRLGLRKPGLPRGLWLAKPSARVPGTKASRGSGAEVTLIDFGEEPVVPALRPCAPSLAQLAMDACSLLDETPPQSPTRALPRPLHPTPVVDWDARPLPPPPAYDDVAQDEDDFEICSINSTLVGAGVPAGPSQGQTNYAFVPEQARPPPPLEDNLFLPPQGGGKPPSSAQTAEIFQALQQECMRQLQAPAGSPAPSPSPGGDDKPQVPPRVPIPPRPTRPHVQLSPAPPGEEETSQWPGPASPPRVPPREPLSPQGSRTPSPLVPPGSSPLPPRLSSSPGKTMPTTQSFASDPKYATPQVIQAPGPRAGPCILPIVRDGKKVSSTHYYLLPERPSYLERYQRFLREAQSPEEPTPLPVPLLLPPPSTPAPAAPTATVRPMPQAALDPKANFSTNNSNPGARPPPPRATARLPQRGCPGDGPEAGRPADKIQMAMVHGVTTEECQAALQCHGWSVQRAAQYLKVEQLFGLGLRPRGECHKVLEMFDWNLEQAGCHLLGSWGPAHHKR