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CATH domain | Related DB codes (homologues) |
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1.10.510.10 : Transferase(Phosphotransferase); domain 1 | M00125,M00124,M00131,T00224,M00127,M00129,M00130,M00132,M00136,M00196,M00197,M00198,M00304,M00323,M00325,M00326,M00327,M00328,M00329,M00330,M00331,M00332,M00333,M00339,M00344 | 2.30.30.40 : SH3 type barrels. | M00183,M00043,M00130,T00256,M00304 | 3.30.200.20 : Phosphorylase Kinase; domain 1 | M00125,M00124,M00131,T00224,M00127,M00129,M00130,M00132,M00136,M00196,M00197,M00198,M00304,M00323,M00325,M00326,M00327,M00328,M00329,M00330,M00331,M00332,M00333,M00339,M00344,D00298 |
UniProtKB:Accession Number | Q07912 |
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Entry name | ACK1_HUMAN |
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Activity | ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.,ATP + a protein = ADP + a phosphoprotein. |
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Subunit | Interacts with NEDD4 (via WW3 domain). NEDD4L and EGF promote association with NEDD4 (By similarity). Homodimer. Interacts with AR, CDC42, WWASL and WWOX. Interacts with CSPG4 (activated). Interacts with MERTK (activated), stimulates autophosphorylation. May interact (phosphorylated) with HSP90AB1, maintains kinase activity. Interacts with NPHP1. Interacts with SNX9 (via SH3 domain). Interacts with SRC (via SH2 and SH3 domain). Interacts with EGFR, and this interaction is dependent on EGF stimulation and kinase activity of EGFR. Interacts (via kinase domain) with AKT1. Part of a collagen stimulated complex involved in cell migration composed of CDC42, CRK, TNK2 and BCAR1/p130cas. Interacts with BCAR1/p130cas via SH3 domains. Forms complexes with GRB2 and numerous receptor tyrosine kinases (RTK) including LTK, AXL or PDGFRL, in which GRB2 promotes RTK recruitment by TNK2. |
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Subcellular location | Cell membrane. Nucleus. Endosome. Cell junction, adherens junction (By similarity). Cytoplasmic vesicle membrane, Peripheral membrane protein, Cytoplasmic side. Cytoplasmic vesicle, clathrin-coated vesicle. Membrane, clathrin-coated pit. Note=The Tyr-284 phosphorylated form is found both in the membrane and nucleus. Co-localizes with EGFR on endosomes. Nuclear translocation is CDC42-dependent. |
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Cofactor | Magnesium. |
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Compound table: links to PDB-related databases & PoSSuM |
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| Cofactors | Substrates | Products |
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KEGG-id | C00305 | C00002 | C00585 | C00017 | C00008 | C01167 | C00562 |
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E.C. | 2.7.10.2,2.7.11.1 | 2.7.10.2,2.7.11.1 | 2.7.10.2 | 2.7.11.1 | 2.7.10.2,2.7.11.1 | 2.7.10.2 | 2.7.11.1 |
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Compound | Mg | ATP | [protein]-L-tyrosine | Protein | ADP | [protein]-L-tyrosine phosphate | Phosphoprotein |
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Type | divalent metal (Ca2+, Mg2+) | amine group,nucleotide | aromatic ring (only carbon atom),peptide/protein | peptide/protein | amine group,nucleotide | aromatic ring (only carbon atom),peptide/protein,phosphate group/phosphate ion | peptide/protein,phosphate group/phosphate ion |
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ChEBI | 18420
| 15422
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| 16761
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PubChem | 888
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| 6022
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1u46A01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1u46B01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1u4dA01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1u4dB01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1u54A01 |  |  |  |  |  |  |  | Unbound | Analogue:ACP | Unbound | Unbound | Unbound | Unbound | Unbound |
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1u54B01 |  |  |  |  |  |  |  | Unbound | Analogue:ACP | Unbound | Unbound | Unbound | Unbound | Unbound |
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3eqpA01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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3eqpB01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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3eqrA01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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3eqrB01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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4ewhA01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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4ewhB01 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1u46A02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1u46B02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1u4dA02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1u4dB02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1u54A02 |  |  |  |  |  |  |  | Bound:2x_MG | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1u54B02 |  |  |  |  |  |  |  | Bound:2x_MG | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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3eqpA02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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3eqpB02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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3eqrA02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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3eqrB02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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4ewhA02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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4ewhB02 |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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1cf4B |  |  |  |  |  |  |  | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound |
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references | [1] |
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PubMed ID | 10360579 |
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Journal | Nature |
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Year | 1999 |
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Volume | 399 |
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Pages | 384-8 |
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Authors | Mott HR, Owen D, Nietlispach D, Lowe PN, Manser E, Lim L, Laue ED |
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Title | Structure of the small G protein Cdc42 bound to the GTPase-binding domain of ACK. |
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Related PDB | 1cf4 |
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[2] |
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PubMed ID | 14506255 |
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Journal | J Biol Chem |
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Year | 2003 |
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Volume | 278 |
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Pages | 47713-23 |
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Authors | Yokoyama N, Miller WT |
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Title | Biochemical properties of the Cdc42-associated tyrosine kinase ACK1. Substrate specificity, authphosphorylation, and interaction with Hck. |
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[3] |
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Comments | X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 107-395, PHOSPHORYLATION AT TYR-284. |
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PubMed ID | 15308621 |
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Journal | J Biol Chem |
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Year | 2004 |
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Volume | 279 |
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Pages | 44039-45 |
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Authors | Lougheed JC, Chen RH, Mak P, Stout TJ |
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Title | Crystal structures of the phosphorylated and unphosphorylated kinase domains of the Cdc42-associated tyrosine kinase ACK1. |
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Related PDB | 1u46,1u4d,1u54 |
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Related UniProtKB | Q07912 |
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[4] |
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Comments | X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 117-392 IN COMPLEX WITH INHIBITOR, CATALYTIC ACTIVITY. |
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PubMed ID | 18993068 |
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Journal | Bioorg Med Chem Lett |
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Year | 2008 |
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Volume | 18 |
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Pages | 6352-6 |
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Authors | Kopecky DJ, Hao X, Chen Y, Fu J, Jiao X, Jaen JC, Cardozo MG, Liu J, Wang Z, Walker NP, Wesche H, Li S, Farrelly E, Xiao SH, Kayser F |
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Title | Identification and optimization of N3,N6-diaryl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamines as a novel class of ACK1 inhibitors. |
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Related PDB | 3eqp,3eqr |
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Related UniProtKB | Q07912 |
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[5] |
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Comments | SUBUNIT, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-284, DOMAIN SAM-LIKE. |
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PubMed ID | 20979614 |
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Journal | BMC Biochem |
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Year | 2010 |
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Volume | 11 |
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Pages | 42 |
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Authors | Prieto-Echague V, Gucwa A, Brown DA, Miller WT |
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Title | Regulation of Ack1 localization and activity by the amino-terminal SAM domain. |
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[6] |
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PubMed ID | 20110370 |
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Journal | J Biol Chem |
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Year | 2010 |
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Volume | 285 |
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Pages | 10605-15 |
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Authors | Prieto-Echague V, Gucwa A, Craddock BP, Brown DA, Miller WT |
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Title | Cancer-associated mutations activate the nonreceptor tyrosine kinase Ack1. |
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[7] |
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Comments | PHOSPHORYLATION AT TYR-284, INTERACTION WITH SRC. |
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PubMed ID | 21309750 |
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Journal | Biochem J |
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Year | 2011 |
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Volume | 435 |
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Pages | 355-64 |
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Authors | Chan W, Sit ST, Manser E |
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Title | The Cdc42-associated kinase ACK1 is not autoinhibited but requires Src for activation. |
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[8] |
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PubMed ID | 21637378 |
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Journal | J Signal Transduct |
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Year | 2011 |
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Volume | 2011 |
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Pages | 742372 |
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Authors | Prieto-Echague V, Miller WT |
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Title | Regulation of ack-family nonreceptor tyrosine kinases. |
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[9] |
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PubMed ID | 22929232 |
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Journal | Bioorg Med Chem Lett |
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Year | 2012 |
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Volume | 22 |
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Pages | 6212-7 |
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Authors | Jiao X, Kopecky DJ, Liu J, Liu J, Jaen JC, Cardozo MG, Sharma R, Walker N, Wesche H, Li S, Farrelly E, Xiao SH, Wang Z, Kayser F |
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Title | Synthesis and optimization of substituted furo[2,3-d]-pyrimidin-4-amines and 7H-pyrrolo[2,3-d]pyrimidin-4-amines as ACK1 inhibitors. |
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Related PDB | 4ewh |
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comments | This enzyme belongs to Ack (activated Cdc42-associated kinase) nonreceptor tyrosine kinase family (see [8]). This enzyme is composed of N-terminal sterile alpha motif (SAM) domain, kinase domain, SH3 domain, Cdc42/Rac-interactive domain (CRIB), Clathrin binding motif, region that shares a high homology with Mitogen induced gene6 (Mig6), and C-terminal ubiquitin associated (UBA) domain. The catalytic domain of this enzyme is homologous to that of proto-oncogene tyrosine-protein kinase ABL1 (M00130 in EzCatDB).
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created | updated |
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2011-12-28 | 2012-12-13 |
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