CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-011539
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Activated CDC42 kinase 1 
Protein Synonyms/Alias
 ACK-1; Tyrosine kinase non-receptor protein 2 
Gene Name
 TNK2 
Gene Synonyms/Alias
 ACK1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
194KDLRLLEKLGDGSFGubiquitination[1]
Reference
 [1] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 126 385 Protein kinase.
 DOMAIN 386 448 SH3.
 DOMAIN 454 466 CRIB.
 DOMAIN 958 996 UBA.
 NP_BIND 132 140 ATP.
 REGION 1 110 SAM-like domain.
 REGION 623 652 Required for interaction with SRC.
 REGION 632 635 Required for interaction with NEDD4 (By
 REGION 733 876 EBD domain (By similarity).
 ACT_SITE 252 252 Proton acceptor.
 BINDING 158 158 ATP.
 MOD_RES 284 284 Phosphotyrosine; by SRC and
 MOD_RES 518 518 Phosphotyrosine.
 MOD_RES 724 724 Phosphoserine.
 MOD_RES 827 827 Phosphotyrosine.
 MOD_RES 859 859 Phosphotyrosine.
 MOD_RES 872 872 Phosphotyrosine.
 MOD_RES 881 881 Phosphoserine.  
Keyword
 3D-structure; Alternative splicing; ATP-binding; Cell junction; Cell membrane; Coated pit; Complete proteome; Cytoplasmic vesicle; Endocytosis; Endosome; Kinase; Magnesium; Membrane; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; SH3 domain; Transferase; Tyrosine-protein kinase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1038 AA 
Protein Sequence
MLEARPPRTQ GSDAAGAAAG RGLRALLLSL TAAAGIWGSM GERSAYQRLA GGEEGPQRLG 60
GGRMQPEEGT GWLLELLSEV QLQQYFLRLR DDLNVTRLSH FEYVKNEDLE KIGMGRPGQR 120
RLWEAVKRRK ALCKRKSWMS KVFSGKRLEA EFPPHHSQST FRKTSPAPGG PAGEGPLQSL 180
TCLIGEKDLR LLEKLGDGSF GVVRRGEWDA PSGKTVSVAV KCLKPDVLSQ PEAMDDFIRE 240
VNAMHSLDHR NLIRLYGVVL TPPMKMVTEL APLGSLLDRL RKHQGHFLLG TLSRYAVQVA 300
EGMGYLESKR FIHRDLAARN LLLATRDLVK IGDFGLMRAL PQNDDHYVMQ EHRKVPFAWC 360
APESLKTRTF SHASDTWMFG VTLWEMFTYG QEPWIGLNGS QILHKIDKEG ERLPRPEDCP 420
QDIYNVMVQC WAHKPEDRPT FVALRDFLLE AQPTDMRALQ DFEEPDKLHI QMNDVITVIE 480
GRAENYWWRG QNTRTLCVGP FPRNVVTSVA GLSAQDISQP LQNSFIHTGH GDSDPRHCWG 540
FPDRIDELYL GNPMDPPDLL SVELSTSRPP QHLGGVKREP PPRPPQPAFF TQKPTYDPVS 600
EDQDPLSSDF KRLGLRKPGL PRGLWLAKPS ARVPGTKASR GSGAEVTLID FGEEPVVPAL 660
RPCAPSLAQL AMDACSLLDE TPPQSPTRAL PRPLHPTPVV DWDARPLPPP PAYDDVAQDE 720
DDFEICSINS TLVGAGVPAG PSQGQTNYAF VPEQARPPPP LEDNLFLPPQ GGGKPPSSAQ 780
TAEIFQALQQ ECMRQLQAPA GSPAPSPSPG GDDKPQVPPR VPIPPRPTRP HVQLSPAPPG 840
EEETSQWPGP ASPPRVPPRE PLSPQGSRTP SPLVPPGSSP LPPRLSSSPG KTMPTTQSFA 900
SDPKYATPQV IQAPGPRAGP CILPIVRDGK KVSSTHYYLL PERPSYLERY QRFLREAQSP 960
EEPTPLPVPL LLPPPSTPAP AAPTATVRPM PQAALDPKAN FSTNNSNPGA RPPPPRATAR 1020
LPQRGCPGDG PEAGRPADKI QMVEQLFGLG LRPRGECHKV LEMFDWNLEQ AGCHLLGSWG 1080
PAHHKR 1086 
Gene Ontology
 GO:0005912; C:adherens junction; IEA:UniProtKB-SubCell.
 GO:0030424; C:axon; IEA:Compara.
 GO:0030136; C:clathrin-coated vesicle; IDA:UniProtKB.
 GO:0005905; C:coated pit; IDA:UniProtKB.
 GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
 GO:0030425; C:dendrite; IEA:Compara.
 GO:0005768; C:endosome; ISS:UniProtKB.
 GO:0070436; C:Grb2-EGFR complex; IDA:BHF-UCL.
 GO:0030426; C:growth cone; IEA:Compara.
 GO:0043025; C:neuronal cell body; IEA:Compara.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0005154; F:epidermal growth factor receptor binding; IDA:BHF-UCL.
 GO:0005095; F:GTPase inhibitor activity; TAS:ProtInc.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; TAS:ProtInc.
 GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
 GO:0004712; F:protein serine/threonine/tyrosine kinase activity; IDA:UniProtKB.
 GO:0050699; F:WW domain binding; ISS:BHF-UCL.
 GO:0007166; P:cell surface receptor signaling pathway; TAS:UniProtKB.
 GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
 GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
 GO:2000369; P:regulation of clathrin-mediated endocytosis; IDA:UniProtKB.
 GO:0007264; P:small GTPase mediated signal transduction; TAS:ProtInc. 
Interpro
 IPR015116; Cdc42_binding_dom_like.
 IPR021619; Inhibitor_Mig-6.
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
 IPR001452; SH3_domain.
 IPR008266; Tyr_kinase_AS.
 IPR020635; Tyr_kinase_cat_dom. 
Pfam
 PF09027; GTPase_binding
 PF11555; Inhibitor_Mig-6
 PF07714; Pkinase_Tyr 
SMART
 SM00326; SH3
 SM00219; TyrKc 
PROSITE
 PS50108; CRIB
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00109; PROTEIN_KINASE_TYR
 PS50002; SH3
 PS50030; UBA 
PRINTS
 PR00109; TYRKINASE.