ACK1_MOUSE
ID ACK1_MOUSE Reviewed; 1055 AA.
AC O54967; Q0Z844; Q8C2U0; Q8K0K4;
DT 24-OCT-2003, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 2.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Activated CDC42 kinase 1;
DE Short=ACK-1;
DE EC=2.7.10.2;
DE EC=2.7.11.1;
DE AltName: Full=Non-receptor protein tyrosine kinase Ack;
DE AltName: Full=Tyrosine kinase non-receptor protein 2;
GN Name=Tnk2; Synonyms=Ack1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, AND MUTAGENESIS OF LYS-158; TRP-424 AND HIS-464.
RX PubMed=16777958; DOI=10.1073/pnas.0603714103;
RA Galisteo M.L., Yang Y., Urena J., Schlessinger J.;
RT "Activation of the nonreceptor protein tyrosine kinase Ack by multiple
RT extracellular stimuli.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:9796-9801(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RA Her J.-H., Bolen J.B.;
RT "The protein tyrosine kinase Ack is associated with and activated in vivo
RT by CDC42Hs.";
RL Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Brain, and Colon;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 121-1055 (ISOFORM 3).
RC STRAIN=NOD; TISSUE=Thymus;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [5]
RP INTERACTION WITH CDC42, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=16052498; DOI=10.1002/cne.20656;
RA Urena J.M., La Torre A., Martinez A., Lowenstein E., Franco N.,
RA Winsky-Sommerer R., Fontana X., Casaroli-Marano R., Ibanez-Sabio M.A.,
RA Pascual M., Del Rio J.A., de Lecea L., Soriano E.;
RT "Expression, synaptic localization, and developmental regulation of
RT Ack1/Pyk1, a cytoplasmic tyrosine kinase highly expressed in the developing
RT and adult brain.";
RL J. Comp. Neurol. 490:119-132(2005).
RN [6]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=16750431; DOI=10.1016/j.modgep.2006.02.009;
RA La Torre A., del Rio J.A., Soriano E., Urena J.M.;
RT "Expression pattern of ACK1 tyrosine kinase during brain development in the
RT mouse.";
RL Gene Expr. Patterns 6:886-892(2006).
RN [7]
RP FUNCTION, INTERACTION WITH EGFR, SUBCELLULAR LOCATION, DOMAIN EBD AND UBA,
RP AND MUTAGENESIS OF TYR-650.
RX PubMed=17182860; DOI=10.1091/mbc.e06-02-0142;
RA Shen F., Lin Q., Gu Y., Childress C., Yang W.;
RT "Activated Cdc42-associated kinase 1 is a component of EGF receptor
RT signaling complex and regulates EGF receptor degradation.";
RL Mol. Biol. Cell 18:732-742(2007).
RN [8]
RP SUBCELLULAR LOCATION.
RX PubMed=18477472; DOI=10.1016/j.bbrc.2008.05.016;
RA Eley L., Moochhala S.H., Simms R., Hildebrandt F., Sayer J.A.;
RT "Nephrocystin-1 interacts directly with Ack1 and is expressed in human
RT collecting duct.";
RL Biochem. Biophys. Res. Commun. 371:877-882(2008).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-518 (ISOFORMS 2 AND 3), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-113, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [11]
RP INTERACTION WITH NEDD4 AND NEDD4L, UBIQUITINATION, INDUCTION, AND DOMAIN
RP SAM-LIKE AND UBA.
RX PubMed=20086093; DOI=10.1128/mcb.00013-10;
RA Lin Q., Wang J., Childress C., Sudol M., Carey D.J., Yang W.;
RT "HECT E3 ubiquitin ligase Nedd4-1 ubiquitinates ACK and regulates epidermal
RT growth factor (EGF)-induced degradation of EGF receptor and ACK.";
RL Mol. Cell. Biol. 30:1541-1554(2010).
RN [12]
RP FUNCTION, INTERACTION WITH AKT1, AND SUBCELLULAR LOCATION.
RX PubMed=20333297; DOI=10.1371/journal.pone.0009646;
RA Mahajan K., Coppola D., Challa S., Fang B., Chen Y.A., Zhu W., Lopez A.S.,
RA Koomen J., Engelman R.W., Rivera C., Muraoka-Cook R.S., Cheng J.Q.,
RA Schoenbrunn E., Sebti S.M., Earp H.S., Mahajan N.P.;
RT "Ack1 mediated AKT/PKB tyrosine 176 phosphorylation regulates its
RT activation.";
RL PLoS ONE 5:E9646-E9646(2010).
RN [13]
RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT TYR-284 AND TYR-533.
RX PubMed=21169560; DOI=10.1091/mbc.e10-07-0637;
RA Shen H., Ferguson S.M., Dephoure N., Park R., Yang Y., Volpicelli-Daley L.,
RA Gygi S., Schlessinger J., De Camilli P.;
RT "Constitutive activated Cdc42-associated kinase (Ack) phosphorylation at
RT arrested endocytic clathrin-coated pits of cells that lack dynamin.";
RL Mol. Biol. Cell 22:493-502(2011).
RN [14]
RP SUBCELLULAR LOCATION.
RX PubMed=25223282; DOI=10.15252/embr.201438688;
RA Strochlic T.I., Stavrides K.P., Thomas S.V., Nicolas E., O'Reilly A.M.,
RA Peterson J.R.;
RT "Ack kinase regulates CTP synthase filaments during Drosophila oogenesis.";
RL EMBO Rep. 15:1184-1191(2014).
RN [15]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-854, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: Non-receptor tyrosine-protein and serine/threonine-protein
CC kinase that is implicated in cell spreading and migration, cell
CC survival, cell growth and proliferation. Transduces extracellular
CC signals to cytosolic and nuclear effectors. Phosphorylates AKT1, AR,
CC MCF2, WASL and WWOX. Implicated in trafficking and clathrin-mediated
CC endocytosis through binding to epidermal growth factor receptor (EGFR)
CC and clathrin. Binds to both poly- and mono-ubiquitin and regulates
CC ligand-induced degradation of EGFR, thereby contributing to the
CC accumulation of EGFR at the limiting membrane of early endosomes.
CC Downstream effector of CDC42 which mediates CDC42-dependent cell
CC migration via phosphorylation of BCAR1. May be involved both in adult
CC synaptic function and plasticity and in brain development. Activates
CC AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267'
CC and 'Tyr-363' thereby promoting its recruitment to androgen-responsive
CC enhancers (AREs). Phosphorylates WWOX on 'Tyr-287'. Phosphorylates
CC MCF2, thereby enhancing its activity as a guanine nucleotide exchange
CC factor (GEF) toward Rho family proteins. Contributes to the control of
CC AXL receptor levels. Confers metastatic properties on cancer cells and
CC promotes tumor growth by negatively regulating tumor suppressor such as
CC WWOX and positively regulating pro-survival factors such as AKT1 and
CC AR. {ECO:0000269|PubMed:17182860, ECO:0000269|PubMed:20333297}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- SUBUNIT: Homodimer. Interacts with CSPG4 (activated). Interacts with
CC MERTK (activated); stimulates autophosphorylation. May interact
CC (phosphorylated) with HSP90AB1; maintains kinase activity. Interacts
CC with NPHP1. Interacts with SNX9 (via SH3 domain). Interacts with SRC
CC (via SH2 and SH3 domain). Part of a collagen stimulated complex
CC involved in cell migration composed of CDC42, CRK, TNK2 and
CC BCAR1/p130cas. Interacts with BCAR1/p130cas via SH3 domains. Forms
CC complexes with GRB2 and numerous receptor tyrosine kinases (RTK)
CC including LTK, AXL or PDGFRL, in which GRB2 promotes RTK recruitment by
CC TNK2 (By similarity). Interacts with CDC42. Interacts with EGFR, and
CC this interaction is dependent on EGF stimulation and kinase activity of
CC EGFR. Interacts (via kinase domain) with AKT1. Interacts with NEDD4
CC (via WW3 domain). NEDD4L and EGF promote association with NEDD4.
CC {ECO:0000250, ECO:0000269|PubMed:16052498, ECO:0000269|PubMed:17182860,
CC ECO:0000269|PubMed:20086093, ECO:0000269|PubMed:20333297}.
CC -!- INTERACTION:
CC O54967; Q99M51: Nck1; NbExp=2; IntAct=EBI-7780354, EBI-642202;
CC O54967; P16333-1: NCK1; Xeno; NbExp=2; IntAct=EBI-7780354, EBI-15578122;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16777958,
CC ECO:0000269|PubMed:20333297}. Nucleus {ECO:0000269|PubMed:20333297}.
CC Endosome {ECO:0000269|PubMed:17182860}. Cell junction, adherens
CC junction {ECO:0000269|PubMed:18477472}. Cytoplasmic vesicle membrane;
CC Peripheral membrane protein; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q07912}. Cytoplasmic vesicle, clathrin-coated
CC vesicle {ECO:0000250|UniProtKB:Q07912}. Membrane, clathrin-coated pit
CC {ECO:0000269|PubMed:21169560}. Cytoplasm, cytosol
CC {ECO:0000269|PubMed:25223282}. Note=The Tyr-284 phosphorylated form is
CC found both in the membrane and nucleus (PubMed:20333297). Co-localizes
CC with EGFR on endosomes (PubMed:17182860). Nuclear translocation is
CC CDC42-dependent (PubMed:21169560). Detected in long filamentous
CC cytosolic structures where it co-localizes with CTPS1
CC (PubMed:25223282). {ECO:0000269|PubMed:17182860,
CC ECO:0000269|PubMed:20333297, ECO:0000269|PubMed:21169560,
CC ECO:0000269|PubMed:25223282}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O54967-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O54967-2; Sequence=VSP_008657, VSP_008658;
CC Name=3;
CC IsoId=O54967-3; Sequence=VSP_008657;
CC -!- TISSUE SPECIFICITY: Ubiquitously present in all tissues tested. Highly
CC expressed in the adult central nervous system (CNS); hippocampus,
CC neocortex, and cerebellum, both at dendritic spines and presynaptic
CC axon terminals. Levels are strongly increased during enhanced neural
CC activity. {ECO:0000269|PubMed:16052498, ECO:0000269|PubMed:16750431,
CC ECO:0000269|PubMed:16777958}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed at 14 dpc-16 dpc in the
CC forebrain, in the proliferative ventricular zone of the neocortex and
CC hippocampus, and in the cortical and hippocampal plates. Also observed
CC in the septal area, the ganglionic eminence, and in the dorsal thalamus
CC and hypothalamus. In the hindbrain, expressed in many nuclei in the
CC brain stem and in the cerebellar anlage, external granule cell layer,
CC in Purkinje cells and the deep cerebellar nuclei.
CC {ECO:0000269|PubMed:16052498, ECO:0000269|PubMed:16750431}.
CC -!- INDUCTION: Down-regulated by EGF. {ECO:0000269|PubMed:20086093}.
CC -!- DOMAIN: The EBD (EGFR-binding domain) domain is necessary for
CC interaction with EGFR.
CC -!- DOMAIN: The SAM-like domain is necessary for NEDD4-mediated
CC ubiquitination. Promotes membrane localization and dimerization to
CC allow for autophosphorylation.
CC -!- DOMAIN: The UBA domain binds both poly- and mono-ubiquitin.
CC -!- PTM: Autophosphorylation regulates kinase activity. Phosphorylation on
CC Tyr-533 is required for interaction with SRC and is observed during
CC association with clathrin-coated pits (By similarity). {ECO:0000250}.
CC -!- PTM: Polyubiquitinated by NEDD4 and NEDD4L. Degradation can be induced
CC by EGF and is lysosome-dependent. {ECO:0000269|PubMed:20086093}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH31168.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};
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DR EMBL; DQ666696; ABG46266.1; -; mRNA.
DR EMBL; AF037260; AAC04786.1; -; mRNA.
DR EMBL; BC031168; AAH31168.1; ALT_SEQ; mRNA.
DR EMBL; BC052421; AAH52421.1; -; mRNA.
DR EMBL; AK087965; BAC40063.1; -; mRNA.
DR CCDS; CCDS37313.1; -. [O54967-1]
DR CCDS; CCDS49828.1; -. [O54967-2]
DR RefSeq; NP_001103617.1; NM_001110147.1.
DR RefSeq; NP_001276372.1; NM_001289443.1.
DR RefSeq; NP_001334114.1; NM_001347185.1.
DR RefSeq; NP_058068.2; NM_016788.3.
DR AlphaFoldDB; O54967; -.
DR SMR; O54967; -.
DR BioGRID; 206174; 74.
DR DIP; DIP-57223N; -.
DR IntAct; O54967; 3.
DR MINT; O54967; -.
DR STRING; 10090.ENSMUSP00000110777; -.
DR BindingDB; O54967; -.
DR ChEMBL; CHEMBL2079848; -.
DR iPTMnet; O54967; -.
DR PhosphoSitePlus; O54967; -.
DR EPD; O54967; -.
DR jPOST; O54967; -.
DR MaxQB; O54967; -.
DR PaxDb; O54967; -.
DR PeptideAtlas; O54967; -.
DR PRIDE; O54967; -.
DR ProteomicsDB; 285931; -. [O54967-1]
DR ProteomicsDB; 285932; -. [O54967-2]
DR ProteomicsDB; 285933; -. [O54967-3]
DR DNASU; 51789; -.
DR GeneID; 51789; -.
DR KEGG; mmu:51789; -.
DR UCSC; uc007yzc.2; mouse. [O54967-2]
DR CTD; 10188; -.
DR MGI; MGI:1858308; Tnk2.
DR eggNOG; KOG0199; Eukaryota.
DR InParanoid; O54967; -.
DR OrthoDB; 1008736at2759; -.
DR PhylomeDB; O54967; -.
DR BioGRID-ORCS; 51789; 2 hits in 61 CRISPR screens.
DR ChiTaRS; Tnk2; mouse.
DR PRO; PR:O54967; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; O54967; protein.
DR GO; GO:0005912; C:adherens junction; IEA:UniProtKB-SubCell.
DR GO; GO:0030424; C:axon; IDA:MGI.
DR GO; GO:0005905; C:clathrin-coated pit; ISO:MGI.
DR GO; GO:0030136; C:clathrin-coated vesicle; ISO:MGI.
DR GO; GO:0097268; C:cytoophidium; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; IDA:MGI.
DR GO; GO:0005768; C:endosome; IDA:UniProtKB.
DR GO; GO:0031234; C:extrinsic component of cytoplasmic side of plasma membrane; IBA:GO_Central.
DR GO; GO:0070436; C:Grb2-EGFR complex; ISO:MGI.
DR GO; GO:0030426; C:growth cone; IDA:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0043025; C:neuronal cell body; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005154; F:epidermal growth factor receptor binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0004712; F:protein serine/threonine/tyrosine kinase activity; ISO:MGI.
DR GO; GO:0004713; F:protein tyrosine kinase activity; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0050699; F:WW domain binding; IPI:BHF-UCL.
DR GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR GO; GO:0006897; P:endocytosis; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; ISS:UniProtKB.
DR GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:MGI.
DR GO; GO:2000369; P:regulation of clathrin-dependent endocytosis; ISO:MGI.
DR GO; GO:0007286; P:spermatid development; IGI:UniProtKB.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR Gene3D; 4.10.680.10; -; 1.
DR InterPro; IPR030220; Ack1.
DR InterPro; IPR015116; Cdc42-bd-like.
DR InterPro; IPR037085; Cdc42-bd-like_dom_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR021619; Mig-6.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR009060; UBA-like_sf.
DR PANTHER; PTHR14254:SF6; PTHR14254:SF6; 1.
DR Pfam; PF09027; GTPase_binding; 1.
DR Pfam; PF11555; Inhibitor_Mig-6; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF14604; SH3_9; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00326; SH3; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF46934; SSF46934; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell junction; Cell membrane;
KW Coated pit; Cytoplasm; Cytoplasmic vesicle; Endocytosis; Endosome; Kinase;
KW Magnesium; Membrane; Metal-binding; Methylation; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; SH3 domain; Transferase;
KW Tyrosine-protein kinase; Ubl conjugation.
FT CHAIN 1..1055
FT /note="Activated CDC42 kinase 1"
FT /id="PRO_0000088059"
FT DOMAIN 126..385
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 388..448
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 454..466
FT /note="CRIB"
FT DOMAIN 973..1013
FT /note="UBA"
FT REGION 1..110
FT /note="SAM-like domain"
FT REGION 91..110
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 505..548
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 638..667
FT /note="Required for interaction with SRC"
FT REGION 647..650
FT /note="Required for interaction with NEDD4"
FT /evidence="ECO:0000269|PubMed:20086093"
FT REGION 737..855
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 748..891
FT /note="EBD domain"
FT REGION 896..952
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 748..769
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 787..816
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 818..842
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 900..922
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 934..948
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 252
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 132..140
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 158
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 113
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 284
FT /note="Phosphotyrosine; by SRC and autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q07912"
FT MOD_RES 533
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:21169560"
FT MOD_RES 842
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q07912"
FT MOD_RES 854
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 874
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q07912"
FT MOD_RES 887
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q07912"
FT MOD_RES 896
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q07912"
FT VAR_SEQ 515..531
FT /note="REPPPRPPQPAIFTQKT -> KP (in isoform 2 and isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_008657"
FT VAR_SEQ 980..1011
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_008658"
FT MUTAGEN 158
FT /note="K->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:16777958"
FT MUTAGEN 424
FT /note="W->K: Increase in autophosphorylation activity."
FT /evidence="ECO:0000269|PubMed:16777958"
FT MUTAGEN 464
FT /note="H->D: Loss of CDC42-binding and impairment of
FT autophosphorylation."
FT /evidence="ECO:0000269|PubMed:16777958"
FT MUTAGEN 650
FT /note="Y->A: Loss of interaction with NEDD4 and drastic
FT reduction in its ubiquitination."
FT /evidence="ECO:0000269|PubMed:17182860"
FT CONFLICT 57..58
FT /note="RR -> SG (in Ref. 2; AAC04786)"
FT /evidence="ECO:0000305"
FT CONFLICT 531
FT /note="T -> P (in Ref. 1; ABG46266)"
FT /evidence="ECO:0000305"
FT CONFLICT 574
FT /note="K -> E (in Ref. 1; ABG46266)"
FT /evidence="ECO:0000305"
FT CONFLICT 649
FT /note="A -> V (in Ref. 2; AAC04786)"
FT /evidence="ECO:0000305"
FT CONFLICT 818
FT /note="L -> V (in Ref. 3; BAC40063)"
FT /evidence="ECO:0000305"
FT CONFLICT 955
FT /note="A -> T (in Ref. 2; AAH52421 and 3; BAC40063)"
FT /evidence="ECO:0000305"
FT MOD_RES O54967-2:518
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455"
FT MOD_RES O54967-3:518
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455"
SQ SEQUENCE 1055 AA; 116975 MW; 4A029C67C350B89A CRC64;
MQPEEGTGWL LELLSEVQLQ QYFLRLRDDL NITRLSHFEY VKNEDLEKIG MGRPGQRRLW
EAVKRRKAMC KRKSWMSKVF SGKRLEAEFP SQHSQSTFRK PSPTPGSLPG EGTLQSLTCL
IGEKDLRLLE KLGDGSFGVV RRGEWDAPAG KTVSVAVKCL KPDVLSQPEA MDDFIREVNA
MHSLDHRNLI RLYGVVLTLP MKMVTELAPL GSLLDRLRKH QGHFLLGTLS RYAVQVAEGM
AYLESKRFIH RDLAARNLLL ATRDLVKIGD FGLMRALPQN DDHYVMQEHR KVPFAWCAPE
SLKTRTFSHA SDTWMFGVTL WEMFTYGQEP WIGLNGSQIL HKIDKEGERL PRPEDCPQDI
YNVMVQCWAH KPEDRPTFVA LRDFLLEAQP TDMRALQDFE EPDKLHIQMN DVITVIEGRA
ENYWWRGQNT RTLCVGPFPR NVVTSVAGLS AQDISQPLQN SFIHTGHGDS DPRHCWGFPD
RIDELYLGNP MDPPDLLSVE LSTSRPTQHL GRVKREPPPR PPQPAIFTQK TTYDPVSEDP
DPLSSDFKRL GLRKPALPRG LWLAKPSARV PGTKADRSSG GEVTLIDFGE EPVVPTPRPC
APSLAQLAMD ACSLLDKTPP QSPTRALPRP LHPTPVVDWD ARPLPPPPAY DDVAQDEDDF
EVCSINSTLV GAGLPAGPSQ GETNYAFVPE QAQMPPALED NLFLPPQGGG KPPSSVQTAE
IFQALQQECM RQLQVPTGQL TPSPTPGGDD KPQVPPRVPI PPRPTRPRVE LSPAPSGEEE
TSRWPGPASP PRVPPREPLS PQGSRTPSPL VPPGSSPLPH RLSSSPGKTM PTTQSFASDP
KYATPQVIQA PGPRAGPCIL PIVRDGRKVS STHYYLLPER PPYLERYQRF LREAQSPEEP
AALPVPPLLP PPSTPAPAAP TATVRPMPQA APDPKANFST NNSNPGARPP SLRAAARLPQ
RGCPGDGQEA ARPADKVQML QAMVHGVTTE ECQAALQSHS WSVQRAAQYL KVEQLFGLGL
RPRVECHKVL EMFDWNLEQA GCHLLGSCGP AHHKR
