EzCatDB: M00335
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DB codeM00335
RLCP classification3.103.130000.1162 : Transfer
CATH domainDomain 11.10.150.- : DNA polymerase; domain 1
Domain 23.30.200.20 : Phosphorylase Kinase; domain 1
Domain 31.10.510.10 : Transferase(Phosphotransferase); domain 1Catalytic domain
Domain 42.30.30.40 : SH3 type barrels.
Domain 54.10.680.10 : Activated P21cdc42hs Kinase; Chain B
Domain 6-.-.-.-
Domain 7-.-.-.-
Domain 81.10.8.- : Helicase, Ruva Protein; domain 3
E.C.2.7.10.2,2.7.11.1

CATH domainRelated DB codes (homologues)
1.10.510.10 : Transferase(Phosphotransferase); domain 1M00125,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 1M00125,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

Enzyme Name
UniProtKBKEGG

Q07912
Protein nameActivated CDC42 kinase 1Non-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)
SynonymsACK-1
EC 2.7.10.2
EC 2.7.11.1
Tyrosine kinase non-receptor protein 2
RefSeqNP_001010938.1 (Protein)
NM_001010938.1 (DNA/RNA sequence)
NP_005772.3 (Protein)
NM_005781.4 (DNA/RNA sequence)
PfamPF09027 (GTPase_binding)
PF11555 (Inhibitor_Mig-6)
PF07714 (Pkinase_Tyr)
[Graphical view]


UniProtKB:Accession NumberQ07912
Entry nameACK1_HUMAN
ActivityATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.,ATP + a protein = ADP + a phosphoprotein.
SubunitInteracts 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.
Subcellular locationCell 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.
CofactorMagnesium.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00305C00002C00585C00017C00008C01167C00562
E.C.2.7.10.2,2.7.11.12.7.10.2,2.7.11.12.7.10.22.7.11.12.7.10.2,2.7.11.12.7.10.22.7.11.1
CompoundMgATP[protein]-L-tyrosineProteinADP[protein]-L-tyrosine phosphatePhosphoprotein
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotidearomatic ring (only carbon atom),peptide/proteinpeptide/proteinamine group,nucleotidearomatic ring (only carbon atom),peptide/protein,phosphate group/phosphate ionpeptide/protein,phosphate group/phosphate ion
ChEBI18420
15422


16761


PubChem888
5957


6022


               
1u46A01UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1u46B01UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1u4dA01UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1u4dB01UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1u54A01UnboundAnalogue:ACPUnboundUnboundUnboundUnboundUnbound
1u54B01UnboundAnalogue:ACPUnboundUnboundUnboundUnboundUnbound
3eqpA01UnboundUnboundUnboundUnboundUnboundUnboundUnbound
3eqpB01UnboundUnboundUnboundUnboundUnboundUnboundUnbound
3eqrA01UnboundUnboundUnboundUnboundUnboundUnboundUnbound
3eqrB01UnboundUnboundUnboundUnboundUnboundUnboundUnbound
4ewhA01UnboundUnboundUnboundUnboundUnboundUnboundUnbound
4ewhB01UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1u46A02UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1u46B02UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1u4dA02UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1u4dB02UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1u54A02Bound:2x_MGUnboundUnboundUnboundUnboundUnboundUnbound
1u54B02Bound:2x_MGUnboundUnboundUnboundUnboundUnboundUnbound
3eqpA02UnboundUnboundUnboundUnboundUnboundUnboundUnbound
3eqpB02UnboundUnboundUnboundUnboundUnboundUnboundUnbound
3eqrA02UnboundUnboundUnboundUnboundUnboundUnboundUnbound
3eqrB02UnboundUnboundUnboundUnboundUnboundUnboundUnbound
4ewhA02UnboundUnboundUnboundUnboundUnboundUnboundUnbound
4ewhB02UnboundUnboundUnboundUnboundUnboundUnboundUnbound
1cf4BUnboundUnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Literature [3] & Swiss-prot;Q07912
pdbCatalytic residuesCofactor-binding residuesModified residuescomment
            
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               
 
 
 
1u46A02ASP 252;ARG 256
ASN 257;ASP 270 (Magnesium binding)
TYR 284 (Auto-Phospholyration)
invisible 280, 287-291
1u46B02ASP 252;ARG 256
ASN 257;ASP 270 (Magnesium binding)
TYR 284 (Auto-Phospholyration)
invisible 223-224
1u4dA02ASP 252;ARG 256
ASN 257;ASP 270 (Magnesium binding)
TYR 284 (Auto-Phospholyration)
invisible 280-281, 287-291
1u4dB02ASP 252;ARG 256
ASN 257;ASP 270 (Magnesium binding)
TYR 284 (Auto-Phospholyration)
invisible 222-224
1u54A02ASP 252;ARG 256
ASN 257;ASP 270 (Magnesium binding)
PTR 284 (Auto-Phospholyration)
invisible 291
1u54B02ASP 252;ARG 256
ASN 257;ASP 270 (Magnesium binding)
TYR 284 (Auto-Phospholyration)
 
3eqpA02ASP 252;ARG 256
ASN 257;ASP 270 (Magnesium binding)
TYR 284 (Auto-Phospholyration)
 
3eqpB02ASP 252;ARG 256
ASN 257;ASP 270 (Magnesium binding)
TYR 284 (Auto-Phospholyration)
 
3eqrA02ASP 252;ARG 256
ASN 257;ASP 270 (Magnesium binding)
TYR 284 (Auto-Phospholyration)
 
3eqrB02ASP 252;ARG 256
ASN 257;ASP 270 (Magnesium binding)
TYR 284 (Auto-Phospholyration)
 
4ewhA02ASP 252;ARG 256
ASN 257;ASP 270 (Magnesium binding)
PTR 284 (Auto-Phospholyration)
 
4ewhB02ASP 252;ARG 256
ASN 257;ASP 270 (Magnesium binding)
PTR 284 (Auto-Phospholyration)
 
1cf4B 
 
 
 


references
[1]
PubMed ID10360579
JournalNature
Year1999
Volume399
Pages384-8
AuthorsMott HR, Owen D, Nietlispach D, Lowe PN, Manser E, Lim L, Laue ED
TitleStructure of the small G protein Cdc42 bound to the GTPase-binding domain of ACK.
Related PDB1cf4
[2]
PubMed ID14506255
JournalJ Biol Chem
Year2003
Volume278
Pages47713-23
AuthorsYokoyama N, Miller WT
TitleBiochemical properties of the Cdc42-associated tyrosine kinase ACK1. Substrate specificity, authphosphorylation, and interaction with Hck.
[3]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 107-395, PHOSPHORYLATION AT TYR-284.
PubMed ID15308621
JournalJ Biol Chem
Year2004
Volume279
Pages44039-45
AuthorsLougheed JC, Chen RH, Mak P, Stout TJ
TitleCrystal structures of the phosphorylated and unphosphorylated kinase domains of the Cdc42-associated tyrosine kinase ACK1.
Related PDB1u46,1u4d,1u54
Related UniProtKBQ07912
[4]
CommentsX-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 117-392 IN COMPLEX WITH INHIBITOR, CATALYTIC ACTIVITY.
PubMed ID18993068
JournalBioorg Med Chem Lett
Year2008
Volume18
Pages6352-6
AuthorsKopecky 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
TitleIdentification and optimization of N3,N6-diaryl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamines as a novel class of ACK1 inhibitors.
Related PDB3eqp,3eqr
Related UniProtKBQ07912
[5]
CommentsSUBUNIT, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-284, DOMAIN SAM-LIKE.
PubMed ID20979614
JournalBMC Biochem
Year2010
Volume11
Pages42
AuthorsPrieto-Echague V, Gucwa A, Brown DA, Miller WT
TitleRegulation of Ack1 localization and activity by the amino-terminal SAM domain.
[6]
PubMed ID20110370
JournalJ Biol Chem
Year2010
Volume285
Pages10605-15
AuthorsPrieto-Echague V, Gucwa A, Craddock BP, Brown DA, Miller WT
TitleCancer-associated mutations activate the nonreceptor tyrosine kinase Ack1.
[7]
CommentsPHOSPHORYLATION AT TYR-284, INTERACTION WITH SRC.
PubMed ID21309750
JournalBiochem J
Year2011
Volume435
Pages355-64
AuthorsChan W, Sit ST, Manser E
TitleThe Cdc42-associated kinase ACK1 is not autoinhibited but requires Src for activation.
[8]
PubMed ID21637378
JournalJ Signal Transduct
Year2011
Volume2011
Pages742372
AuthorsPrieto-Echague V, Miller WT
TitleRegulation of ack-family nonreceptor tyrosine kinases.
[9]
PubMed ID22929232
JournalBioorg Med Chem Lett
Year2012
Volume22
Pages6212-7
AuthorsJiao 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
TitleSynthesis and optimization of substituted furo[2,3-d]-pyrimidin-4-amines and 7H-pyrrolo[2,3-d]pyrimidin-4-amines as ACK1 inhibitors.
Related PDB4ewh

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).

createdupdated
2011-12-282012-12-13
Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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