DB code: M00335
| RLCP classification | 3.103.130000.1162 : Transfer | |
|---|---|---|
| CATH domain | 1.10.150.- : DNA polymerase; domain 1 | |
| 3.30.200.20 : Phosphorylase Kinase; domain 1 | ||
| 1.10.510.10 : Transferase(Phosphotransferase); domain 1 | Catalytic domain | |
| 2.30.30.40 : SH3 type barrels. | ||
| 4.10.680.10 : Activated P21cdc42hs Kinase; Chain B | ||
| -.-.-.- : | ||
| -.-.-.- : | ||
| 1.10.8.- : Helicase, Ruva Protein; domain 3 | ||
| E.C. | 2.7.10.2 2.7.11.1 | |
| CSA | ||
| M-CSA | ||
| MACiE | ||
| CATH domain | Related DB codes (homologues) |
|---|---|
| 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 |
| Uniprot Enzyme Name | UniprotKB | Protein name | Synonyms | RefSeq | Pfam |
|---|---|---|---|---|
| Q07912 |
Activated CDC42 kinase 1
|
ACK-1
EC 2.7.10.2 EC 2.7.11.1 Tyrosine kinase non-receptor protein 2 |
NP_001010938.1
(Protein)
NM_001010938.1 (DNA/RNA sequence) NP_005772.3 (Protein) NM_005781.4 (DNA/RNA sequence) |
PF09027
(GTPase_binding)
PF11555 (Inhibitor_Mig-6) PF07714 (Pkinase_Tyr) [Graphical View] |
| KEGG enzyme name |
|---|
|
Non-specific protein-tyrosine kinase
(EC 2.7.10.2 ) ACK1 (EC 2.7.10.2 ) ACK2 (EC 2.7.10.2 ) Cytoplasmic protein tyrosine kinase (EC 2.7.10.2 ) Protein-tyrosine kinase (ambiguous) (EC 2.7.10.2 ) TNK1 (EC 2.7.10.2 ) Non-specific serine/threonine protein kinase (EC 2.7.11.1 ) protein kinase (phosphorylating) (EC 2.7.11.1 ) protein phosphokinase (EC 2.7.11.1 ) protein serine kinase (EC 2.7.11.1 ) protein serine-threonine kinase (EC 2.7.11.1 ) protein-serine kinase (EC 2.7.11.1 ) serine kinase (EC 2.7.11.1 ) serine protein kinase (EC 2.7.11.1 ) serine(threonine) protein kinase (EC 2.7.11.1 ) serine/threonine protein kinase (EC 2.7.11.1 ) |
| UniprotKB: Accession Number | Entry name | Activity | Subunit | Subcellular location | Cofactor |
|---|---|---|---|---|---|
| Q07912 | ACK1_HUMAN | ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. ATP + a protein = ADP + a phosphoprotein. | 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. | 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. | Magnesium. |
| KEGG Pathways | Map code | Pathways | E.C. |
|---|
| Compound table | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cofactors | Substrates | Products | Intermediates | ||||||||||
| KEGG-id | C00305 | C00002 | C00585 | C00017 | C00008 | C01167 | C00562 | ||||||
| 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
|
||||||
| Compound | Mg | ATP | [protein]-L-tyrosine | Protein | ADP | [protein]-L-tyrosine phosphate | Phosphoprotein | ||||||
| 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 | ||||||
| ChEBI |
18420 18420 |
15422 15422 |
16761 16761 |
||||||||||
| PubChem |
888 888 |
5957 5957 |
6022 6022 |
||||||||||
| 1u46A01 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1u46B01 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1u4dA01 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1u4dB01 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1u54A01 |
|
|
|
|
|
Unbound | Analogue:ACP | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1u54B01 |
|
|
|
|
|
Unbound | Analogue:ACP | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3eqpA01 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3eqpB01 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3eqrA01 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3eqrB01 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 4ewhA01 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 4ewhB01 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1u46A02 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1u46B02 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1u4dA02 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1u4dB02 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1u54A02 |
|
|
|
|
|
Bound:2x_MG | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1u54B02 |
|
|
|
|
|
Bound:2x_MG | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3eqpA02 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3eqpB02 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3eqrA02 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 3eqrB02 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 4ewhA02 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 4ewhB02 |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| 1cf4B |
|
|
|
|
|
Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | Unbound | |
| Reference for Active-site residues | ||
|---|---|---|
| resource | references | E.C. |
| Literature [3] & Swiss-prot;Q07912 | ||
| Active-site residues | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| PDB | Catalytic residues | Cofactor-binding residues | Modified residues | Main-chain involved in catalysis | Comment | |||||
| 1u46A01 |
|
|
|
|
|
invisible 134-137, 160-167 | ||||
| 1u46B01 |
|
|
|
|
|
invisible 134-137, 160-170 | ||||
| 1u4dA01 |
|
|
|
|
|
invisible 160-170 | ||||
| 1u4dB01 |
|
|
|
|
|
invisible 161-169 | ||||
| 1u54A01 |
|
|
|
|
|
invisible 135-137, 161-169 | ||||
| 1u54B01 |
|
|
|
|
|
invisible 135-137, 161-168 | ||||
| 3eqpA01 |
|
|
|
|
|
invisible 161-166 | ||||
| 3eqpB01 |
|
|
|
|
|
invisible 161-166 | ||||
| 3eqrA01 |
|
|
|
|
|
invisible 162-167 | ||||
| 3eqrB01 |
|
|
|
|
|
|||||
| 4ewhA01 |
|
|
|
|
|
|||||
| 4ewhB01 |
|
|
|
|
|
|||||
| 1u46A02 |
|
|
|
|
|
ASP 252;ARG 256 | ASN 257;ASP 270 (Magnesium binding) | TYR 284 (Auto-Phospholyration) | invisible 280, 287-291 | |
| 1u46B02 |
|
|
|
|
|
ASP 252;ARG 256 | ASN 257;ASP 270 (Magnesium binding) | TYR 284 (Auto-Phospholyration) | invisible 223-224 | |
| 1u4dA02 |
|
|
|
|
|
ASP 252;ARG 256 | ASN 257;ASP 270 (Magnesium binding) | TYR 284 (Auto-Phospholyration) | invisible 280-281, 287-291 | |
| 1u4dB02 |
|
|
|
|
|
ASP 252;ARG 256 | ASN 257;ASP 270 (Magnesium binding) | TYR 284 (Auto-Phospholyration) | invisible 222-224 | |
| 1u54A02 |
|
|
|
|
|
ASP 252;ARG 256 | ASN 257;ASP 270 (Magnesium binding) | PTR 284 (Auto-Phospholyration) | invisible 291 | |
| 1u54B02 |
|
|
|
|
|
ASP 252;ARG 256 | ASN 257;ASP 270 (Magnesium binding) | TYR 284 (Auto-Phospholyration) | ||
| 3eqpA02 |
|
|
|
|
|
ASP 252;ARG 256 | ASN 257;ASP 270 (Magnesium binding) | TYR 284 (Auto-Phospholyration) | ||
| 3eqpB02 |
|
|
|
|
|
ASP 252;ARG 256 | ASN 257;ASP 270 (Magnesium binding) | TYR 284 (Auto-Phospholyration) | ||
| 3eqrA02 |
|
|
|
|
|
ASP 252;ARG 256 | ASN 257;ASP 270 (Magnesium binding) | TYR 284 (Auto-Phospholyration) | ||
| 3eqrB02 |
|
|
|
|
|
ASP 252;ARG 256 | ASN 257;ASP 270 (Magnesium binding) | TYR 284 (Auto-Phospholyration) | ||
| 4ewhA02 |
|
|
|
|
|
ASP 252;ARG 256 | ASN 257;ASP 270 (Magnesium binding) | PTR 284 (Auto-Phospholyration) | ||
| 4ewhB02 |
|
|
|
|
|
ASP 252;ARG 256 | ASN 257;ASP 270 (Magnesium binding) | PTR 284 (Auto-Phospholyration) | ||
| 1cf4B |
|
|
|
|
|
|||||
| References for Catalytic Mechanism | ||
|---|---|---|
| References | Sections | No. of steps in catalysis |
| References | |
|---|---|
| [1] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 10360579 |
| Journal | Nature |
| Year | 1999 |
| Volume | 399 |
| Pages | 384-8 |
| Authors | Mott HR, Owen D, Nietlispach D, Lowe PN, Manser E, Lim L, Laue ED |
| Title | Structure of the small G protein Cdc42 bound to the GTPase-binding domain of ACK. |
| Related PDB | 1cf4 |
| Related UniProtKB | |
| [2] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 14506255 |
| Journal | J Biol Chem |
| Year | 2003 |
| Volume | 278 |
| Pages | 47713-23 |
| Authors | Yokoyama N, Miller WT |
| Title |
Biochemical properties of the Cdc42-associated tyrosine kinase ACK1. |
| Related PDB | |
| Related UniProtKB | |
| [3] | |
| Resource | |
| Comments |
X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 107-395, |
| Medline ID | |
| PubMed ID | 15308621 |
| Journal | J Biol Chem |
| Year | 2004 |
| Volume | 279 |
| Pages | 44039-45 |
| Authors | Lougheed JC, Chen RH, Mak P, Stout TJ |
| Title | Crystal structures of the phosphorylated and unphosphorylated kinase domains of the Cdc42-associated tyrosine kinase ACK1. |
| Related PDB | 1u46 1u4d 1u54 |
| Related UniProtKB | Q07912 |
| [4] | |
| Resource | |
| Comments |
X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 117-392 IN COMPLEX WITH INHIBITOR, |
| Medline ID | |
| PubMed ID | 18993068 |
| Journal | Bioorg Med Chem Lett |
| Year | 2008 |
| Volume | 18 |
| Pages | 6352-6 |
| 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 |
| Title | Identification and optimization of N3,N6-diaryl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamines as a novel class of ACK1 inhibitors. |
| Related PDB | 3eqp 3eqr |
| Related UniProtKB | Q07912 |
| [5] | |
| Resource | |
| Comments |
SUBUNIT, |
| Medline ID | |
| PubMed ID | 20979614 |
| Journal | BMC Biochem |
| Year | 2010 |
| Volume | 11 |
| Pages | 42 |
| Authors | Prieto-Echague V, Gucwa A, Brown DA, Miller WT |
| Title | Regulation of Ack1 localization and activity by the amino-terminal SAM domain. |
| Related PDB | |
| Related UniProtKB | |
| [6] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 20110370 |
| Journal | J Biol Chem |
| Year | 2010 |
| Volume | 285 |
| Pages | 10605-15 |
| Authors | Prieto-Echague V, Gucwa A, Craddock BP, Brown DA, Miller WT |
| Title | Cancer-associated mutations activate the nonreceptor tyrosine kinase Ack1. |
| Related PDB | |
| Related UniProtKB | |
| [7] | |
| Resource | |
| Comments |
PHOSPHORYLATION AT TYR-284, |
| Medline ID | |
| PubMed ID | 21309750 |
| Journal | Biochem J |
| Year | 2011 |
| Volume | 435 |
| Pages | 355-64 |
| Authors | Chan W, Sit ST, Manser E |
| Title | The Cdc42-associated kinase ACK1 is not autoinhibited but requires Src for activation. |
| Related PDB | |
| Related UniProtKB | |
| [8] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 21637378 |
| Journal | J Signal Transduct |
| Year | 2011 |
| Volume | 2011 |
| Pages | 742372 |
| Authors | Prieto-Echague V, Miller WT |
| Title | Regulation of ack-family nonreceptor tyrosine kinases. |
| Related PDB | |
| Related UniProtKB | |
| [9] | |
| Resource | |
| Comments | |
| Medline ID | |
| PubMed ID | 22929232 |
| Journal | Bioorg Med Chem Lett |
| Year | 2012 |
| Volume | 22 |
| Pages | 6212-7 |
| 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 |
| 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. |
| Related PDB | 4ewh |
| Related UniProtKB | |
| Comments |
|---|
|
This enzyme belongs to Ack (activated Cdc42-associated kinase) nonreceptor tyrosine kinase family (see [8]). The catalytic domain of this enzyme is homologous to that of proto-oncogene tyrosine-protein kinase ABL1 (M00130 in EzCatDB). |
| Created | Updated |
|---|---|
| 2011-12-28 | 2012-12-13 |