M00335
type: Enzyme
rlcp: p1162
cath: DNA polymerase; domain 1
cath: Phosphorylase Kinase; domain 1
cath: Transferase(Phosphotransferase); domain 1
cath: SH3 type barrels.
cath: Activated P21cdc42hs Kinase; Chain B
cath: http://ezcatdb.cbrc.jp/EzCatDB/cath/-.-.-.-
cath: Helicase, Ruva Protein; domain 3
ec: https://purl.uniprot.org/enzyme/2.7.10.2
ec: https://purl.uniprot.org/enzyme/2.7.11.1
uniprot: Q07912
kegg enzyme: Non-specific protein-tyrosine kinase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/2.7.10.2
kegg enzyme: ACK1
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/2.7.10.2
kegg enzyme: ACK2
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/2.7.10.2
kegg enzyme: Cytoplasmic protein tyrosine kinase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/2.7.10.2
kegg enzyme: Protein-tyrosine kinase (ambiguous)
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/2.7.10.2
kegg enzyme: TNK1
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/2.7.10.2
kegg enzyme: Non-specific serine/threonine protein kinase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/2.7.11.1
kegg enzyme: protein kinase (phosphorylating)
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/2.7.11.1
kegg enzyme: protein phosphokinase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/2.7.11.1
kegg enzyme: protein serine kinase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/2.7.11.1
kegg enzyme: protein serine-threonine kinase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/2.7.11.1
kegg enzyme: protein-serine kinase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/2.7.11.1
kegg enzyme: serine kinase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/2.7.11.1
kegg enzyme: serine protein kinase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/2.7.11.1
kegg enzyme: serine(threonine) protein kinase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/2.7.11.1
kegg enzyme: serine/threonine protein kinase
  type: KeggEnzyme
  ec: https://purl.uniprot.org/enzyme/2.7.11.1
kegg cofactor: Mg
kegg substrate: ATP
kegg substrate: [protein]-L-tyrosine
kegg substrate: Protein
kegg product: ADP
kegg product: [protein]-L-tyrosine phosphate
kegg product: Phosphoprotein
pdb: 1u46A01
pdb: 1u46B01
pdb: 1u4dA01
pdb: 1u4dB01
pdb: 1u54A01
pdb: 1u54B01
pdb: 3eqpA01
pdb: 3eqpB01
pdb: 3eqrA01
pdb: 3eqrB01
pdb: 4ewhA01
pdb: 4ewhB01
pdb: 1u46A02
pdb: 1u46B02
pdb: 1u4dA02
pdb: 1u4dB02
pdb: 1u54A02
pdb: 1u54B02
pdb: 3eqpA02
pdb: 3eqpB02
pdb: 3eqrA02
pdb: 3eqrB02
pdb: 4ewhA02
pdb: 4ewhB02
pdb: 1cf4B
pdb bound state: Unbound
  compound: ATP
  pdb: 1u46A01
pdb bound state: Unbound
  compound: ATP
  pdb: 1u46B01
pdb bound state: Unbound
  compound: ATP
  pdb: 1u4dA01
pdb bound state: Unbound
  compound: ATP
  pdb: 1u4dB01
pdb bound state: Analogue
  compound: ATP
  pdb: 1u54A01
  ligand het code: ACP
pdb bound state: Analogue
  compound: ATP
  pdb: 1u54B01
  ligand het code: ACP
pdb bound state: Unbound
  compound: ATP
  pdb: 3eqpA01
pdb bound state: Unbound
  compound: ATP
  pdb: 3eqpB01
active site residues resources: Identification and optimization of N3,N6-diaryl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamines as a novel class of ACK1 inhibitors.
active site residues resources: Q07912
references: Regulation of ack-family nonreceptor tyrosine kinases.
references: Regulation of Ack1 localization and activity by the amino-terminal SAM domain.
references: Cancer-associated mutations activate the nonreceptor tyrosine kinase Ack1.
references: The Cdc42-associated kinase ACK1 is not autoinhibited but requires Src for activation.
references: Structure of the small G protein Cdc42 bound to the GTPase-binding domain of ACK.
references: Biochemical properties of the Cdc42-associated tyrosine kinase ACK1. Substrate specificity, authphosphorylation, and interaction with Hck.
references: Crystal structures of the phosphorylated and unphosphorylated kinase domains of the Cdc42-associated tyrosine kinase ACK1.
references: Identification and optimization of N3,N6-diaryl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamines as a novel class of ACK1 inhibitors.
references: Synthesis and optimization of substituted furo[2,3-d]-pyrimidin-4-amines and 7H-pyrrolo[2,3-d]pyrimidin-4-amines as ACK1 inhibitors.
comment: 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).

DNA polymerase; domain 1
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/1.10.150.-

Phosphorylase Kinase; domain 1
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.30.200.20

Transferase(Phosphotransferase); domain 1
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/1.10.510.10
catalytic domain: index.html

SH3 type barrels.
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/2.30.30.40

Activated P21cdc42hs Kinase; Chain B
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/4.10.680.10

Helicase, Ruva Protein; domain 3
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/1.10.8.-

Mg
type: KeggCofactor
references: KEGG:C00305
ec: https://purl.uniprot.org/enzyme/2.7.10.2
ec: https://purl.uniprot.org/enzyme/2.7.11.1
compound type: divalent metal (Ca2+, Mg2+)
references: CHEBI:18420
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

ATP
type: KeggSubstrate
references: KEGG:C00002
ec: https://purl.uniprot.org/enzyme/2.7.10.2
ec: https://purl.uniprot.org/enzyme/2.7.11.1
compound type: amine group
compound type: nucleotide
references: CHEBI:15422
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

[protein]-L-tyrosine
type: KeggSubstrate
references: KEGG:C00585
ec: https://purl.uniprot.org/enzyme/2.7.10.2
compound type: aromatic ring (only carbon atom)
compound type: peptide/protein

Protein
type: KeggSubstrate
references: KEGG:C00017
ec: https://purl.uniprot.org/enzyme/2.7.11.1
compound type: peptide/protein

ADP
type: KeggProduct
references: KEGG:C00008
ec: https://purl.uniprot.org/enzyme/2.7.10.2
ec: https://purl.uniprot.org/enzyme/2.7.11.1
compound type: amine group
compound type: nucleotide
references: CHEBI:16761
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

[protein]-L-tyrosine phosphate
type: KeggProduct
references: KEGG:C01167
ec: https://purl.uniprot.org/enzyme/2.7.10.2
compound type: aromatic ring (only carbon atom)
compound type: peptide/protein
compound type: phosphate group/phosphate ion

Phosphoprotein
type: KeggProduct
references: KEGG:C00562
ec: https://purl.uniprot.org/enzyme/2.7.11.1
compound type: peptide/protein
compound type: phosphate group/phosphate ion

1u46A01
type: Pdb
references: 1u46
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1u46
comment: invisible 134-137, 160-167

1u46B01
type: Pdb
references: 1u46
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1u46
comment: invisible 134-137, 160-170

1u4dA01
type: Pdb
references: 1u4d
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1u4d
comment: invisible 160-170

1u4dB01
type: Pdb
references: 1u4d
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1u4d
comment: invisible 161-169

1u54A01
type: Pdb
references: 1u54
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1u54
comment: invisible 135-137, 161-169

1u54B01
type: Pdb
references: 1u54
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1u54
comment: invisible 135-137, 161-168

3eqpA01
type: Pdb
references: 3eqp
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3eqp
comment: invisible 161-166

3eqpB01
type: Pdb
references: 3eqp
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3eqp
comment: invisible 161-166

3eqrA01
type: Pdb
references: 3eqr
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3eqr
comment: invisible 162-167

1u46A02
type: Pdb
references: 1u46
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1u46
catalytic residue: ASP 252;ARG 256
cofactor binding residue: ASN 257;ASP 270 (Magnesium binding)
modified residue: TYR 284 (Auto-Phospholyration)
comment: invisible 280, 287-291

1u46B02
type: Pdb
references: 1u46
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1u46
catalytic residue: ASP 252;ARG 256
cofactor binding residue: ASN 257;ASP 270 (Magnesium binding)
modified residue: TYR 284 (Auto-Phospholyration)
comment: invisible 223-224

1u4dA02
type: Pdb
references: 1u4d
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1u4d
catalytic residue: ASP 252;ARG 256
cofactor binding residue: ASN 257;ASP 270 (Magnesium binding)
modified residue: TYR 284 (Auto-Phospholyration)
comment: invisible 280-281, 287-291

1u4dB02
type: Pdb
references: 1u4d
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1u4d
catalytic residue: ASP 252;ARG 256
cofactor binding residue: ASN 257;ASP 270 (Magnesium binding)
modified residue: TYR 284 (Auto-Phospholyration)
comment: invisible 222-224

1u54A02
type: Pdb
references: 1u54
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1u54
catalytic residue: ASP 252;ARG 256
cofactor binding residue: ASN 257;ASP 270 (Magnesium binding)
modified residue: PTR 284 (Auto-Phospholyration)
comment: invisible 291

1u54B02
type: Pdb
references: 1u54
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1u54
catalytic residue: ASP 252;ARG 256
cofactor binding residue: ASN 257;ASP 270 (Magnesium binding)
modified residue: TYR 284 (Auto-Phospholyration)

3eqpA02
type: Pdb
references: 3eqp
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3eqp
catalytic residue: ASP 252;ARG 256
cofactor binding residue: ASN 257;ASP 270 (Magnesium binding)
modified residue: TYR 284 (Auto-Phospholyration)

3eqpB02
type: Pdb
references: 3eqp
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3eqp
catalytic residue: ASP 252;ARG 256
cofactor binding residue: ASN 257;ASP 270 (Magnesium binding)
modified residue: TYR 284 (Auto-Phospholyration)

3eqrA02
type: Pdb
references: 3eqr
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3eqr
catalytic residue: ASP 252;ARG 256
cofactor binding residue: ASN 257;ASP 270 (Magnesium binding)
modified residue: TYR 284 (Auto-Phospholyration)

3eqrB02
type: Pdb
references: 3eqr
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:3eqr
catalytic residue: ASP 252;ARG 256
cofactor binding residue: ASN 257;ASP 270 (Magnesium binding)
modified residue: TYR 284 (Auto-Phospholyration)

4ewhA02
type: Pdb
references: 4ewh
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:4ewh
catalytic residue: ASP 252;ARG 256
cofactor binding residue: ASN 257;ASP 270 (Magnesium binding)
modified residue: PTR 284 (Auto-Phospholyration)

4ewhB02
type: Pdb
references: 4ewh
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:4ewh
catalytic residue: ASP 252;ARG 256
cofactor binding residue: ASN 257;ASP 270 (Magnesium binding)
modified residue: PTR 284 (Auto-Phospholyration)

Regulation of ack-family nonreceptor tyrosine kinases.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/21637378
journal: J Signal Transduct
volume: 2011
pages: 742372
published year: 2011
authors:
  item: Prieto-Echague V
  item: Miller WT

Regulation of Ack1 localization and activity by the amino-terminal SAM domain.
type: BibliographicResource
comment: SUBUNIT, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-284, DOMAIN SAM-LIKE.
references: http://www.ncbi.nlm.nih.gov/pubmed/20979614
journal: BMC Biochem
volume: 11
pages: 42
published year: 2010
authors:
  item: Prieto-Echague V
  item: Gucwa A
  item: Brown DA
  item: Miller WT

Cancer-associated mutations activate the nonreceptor tyrosine kinase Ack1.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/20110370
journal: J Biol Chem
volume: 285
pages: 10605-15
published year: 2010
authors:
  item: Prieto-Echague V
  item: Gucwa A
  item: Craddock BP
  item: Brown DA
  item: Miller WT

The Cdc42-associated kinase ACK1 is not autoinhibited but requires Src for activation.
type: BibliographicResource
comment: PHOSPHORYLATION AT TYR-284, INTERACTION WITH SRC.
references: http://www.ncbi.nlm.nih.gov/pubmed/21309750
journal: Biochem J
volume: 435
pages: 355-64
published year: 2011
authors:
  item: Chan W
  item: Sit ST
  item: Manser E

Structure of the small G protein Cdc42 bound to the GTPase-binding domain of ACK.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10360579
journal: Nature
volume: 399
pages: 384-8
published year: 1999
authors:
  item: Mott HR
  item: Owen D
  item: Nietlispach D
  item: Lowe PN
  item: Manser E
  item: Lim L
  item: Laue ED
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Biochemical properties of the Cdc42-associated tyrosine kinase ACK1. Substrate specificity, authphosphorylation, and interaction with Hck.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/14506255
journal: J Biol Chem
volume: 278
pages: 47713-23
published year: 2003
authors:
  item: Yokoyama N
  item: Miller WT

Crystal structures of the phosphorylated and unphosphorylated kinase domains of the Cdc42-associated tyrosine kinase ACK1.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 107-395, PHOSPHORYLATION AT TYR-284.
references: http://www.ncbi.nlm.nih.gov/pubmed/15308621
journal: J Biol Chem
volume: 279
pages: 44039-45
published year: 2004
authors:
  item: Lougheed JC
  item: Chen RH
  item: Mak P
  item: Stout TJ
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: Q07912

Identification and optimization of N3,N6-diaryl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamines as a novel class of ACK1 inhibitors.
type: BibliographicResource
comment: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 117-392 IN COMPLEX WITH INHIBITOR, CATALYTIC ACTIVITY.
references: http://www.ncbi.nlm.nih.gov/pubmed/18993068
journal: Bioorg Med Chem Lett
volume: 18
pages: 6352-6
published year: 2008
authors:
  item: Kopecky DJ
  item: Hao X
  item: Chen Y
  item: Fu J
  item: Jiao X
  item: Jaen JC
  item: Cardozo MG
  item: Liu J
  item: Wang Z
  item: Walker NP
  item: Wesche H
  item: Li S
  item: Farrelly E
  item: Xiao SH
  item: Kayser F
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: Q07912

Synthesis and optimization of substituted furo[2,3-d]-pyrimidin-4-amines and 7H-pyrrolo[2,3-d]pyrimidin-4-amines as ACK1 inhibitors.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/22929232
journal: Bioorg Med Chem Lett
volume: 22
pages: 6212-7
published year: 2012
authors:
  item: Jiao X
  item: Kopecky DJ
  item: Liu J
  item: Jaen JC
  item: Cardozo MG
  item: Sharma R
  item: Walker N
  item: Wesche H
  item: Li S
  item: Farrelly E
  item: Xiao SH
  item: Wang Z
  item: Kayser F
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl